A human donor (cadaveric) observation study of three needle placements in the piriformis muscle.

OBJECTIVE: To compare the safety and accuracy of three dry needling locations in the piriformis muscle using human donors. DESIGN: Observational dissection study of embalmed human donors. METHODS: A licensed physical therapist of 17 years clinical experience and 5 years teaching dry needling placed three needles in a medial, midpoint, and lateral location of 14 piriformis muscles of seven embalmed human donors. Block dissection allowed for observation of tissues the needles traversed and recording of the structures that the needles pierced. RESULTS: The lateral needle pierced piriformis in 3/14 trials, and contacted sciatic nerve in 0/14 trials. The medial needle pierced both piriformis and sciatic nerve in 11/14 trials. The midpoint needle pierced the piriformis in 11/14 trials, and contacted sciatic nerve in 3/14 trials. Fisher's Exact test (p < 0.001) found a nonrandom association between dry needle placement, and dry needle contact. CONCLUSIONS: When dry needling the piriformis, a lateral approach can avoid the sciatic nerve, but cannot accurately pierce the piriformis tendon. Furthermore, while a midpoint and medial approach finds the piriformis muscle with the same accuracy, the midpoint location avoided the sciatic nerve more often.

COVID-19 recovery: tackling the 2-week wait colorectal pathway backlog by optimising CT colonography utilisation.

AIM: To review the indications for computed tomography colonography (CTC) performed on patients referred via the 2-week wait colorectal pathway (2WWCP). MATERIALS AND METHODS: A retrospective study was performed on all patients referred through the 2WWCP between October 2018 and September 2019. The referrals were audited against the National Institute for Health and Care Excellence (NICE) NG12/DG30 guidelines for referral to the 2WWCP, and against the Royal College of Radiologists (RCR) 2017 guidelines for CTC. RESULTS: Over the study period, there were 1,707 2WWCP referrals, and 362 (21.2%) of these patients underwent CTC. The median age was 66 years, and 55% were female. Forty-six patients did not meet the NICE NG12/DG30 guidelines for referral to the 2WWCP, and a further 268, although meeting the NICE guidelines, did not meet the RCR 2017 guidelines for CTC. In total, only 13% of CTCs performed complied with both guidelines. CONCLUSION: This audit demonstrated a significant opportunity to reallocate CTC resources in the recovery stage of the COVID-19 pandemic. To improve outcomes for colorectal cancer (CRC) in the UK, establishing a selective straight-to-test CTC 2WWCP should be considered. Documented consent detailing the risks and benefits of CTC versus colonoscopy should take place in order to assist the patient in making an informed choice.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Impact of Oral Fidaxomicin Administration on the Intestinal Microbiota and Susceptibility to Clostridium difficile Colonization in Mice.

Clostridium difficile infection (CDI), a common cause of hospital-acquired infections, typically occurs after disruption of the normal gut microbiome by broad-spectrum antibiotics. Fidaxomicin is a narrow-spectrum antibiotic that demonstrates a reduced impact on the normal gut microbiota and is approved for the treatment of CDI. To further explore the benefits of this property, we used a murine model to examine the effects of fidaxomicin versus vancomycin on gut microbiota and susceptibility to C. difficile colonization while tracking microbiota recovery over time. Mice were exposed to fidaxomicin or vancomycin by oral gavage for 3 days and subsequently challenged with C. difficile spores at predetermined time points up to 21 days postexposure to antibiotics. Fecal samples were subsequently collected for analysis. Twenty-four hours postchallenge, mice were euthanized and the colon contents harvested. The microbiota was characterized using 16S rRNA gene sequencing. All fidaxomicin-exposed mice (except for one at day 8) were resistant to C. difficile colonization. However, 9 of 15 vancomycin-exposed mice were susceptible to C. difficile colonization until day 12. All vancomycin-exposed mice recovered colonization resistance by day 16. Bacterial diversity was similar prior to antibiotic exposure in both arms and decreased substantially after exposure. A shift in taxonomic structure and composition occurred after both exposures; however, the shift was greater in vancomycin-exposed than in fidaxomicin-exposed mice. In summary, compared with vancomycin, fidaxomicin exposure had less impact on microbiota composition, promoted faster microbial recovery, and had less impact on the loss of C. difficile colonization resistance.

NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.

Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.

Orthodontic retention--three methods trialed.

DESIGN: Single centre randomised controlled trial. INTERVENTION: Patients treated by a single orthodontist were randomised to one of three retention methods: removable vacuum-formed retainer (VFR) covering the palate and the maxillary anterior teeth from canine-to-canine and bonded canine-to-canine retainer in the lower arch (group V-CTC); maxillary VFR combined with stripping of the lower anterior teeth (group V-S); prefabricated positioner covering all erupted teeth in the maxilla and the mandible (group P). All retention appliances were provided within one hour of debonding. OUTCOME MEASURE: Dental study casts were taken before treatment, at appliance removal and five years or more out of retention. Little's irregularity index, intercanine and intermolar width, arch length and overbite/overjet were recorded. RESULTS: Twenty-five patients were randomised to each group with 69 completing the two-year retention period (24 in V-CTC group; 23 in V-S group; 22 in P group). Forty-nine patients were available five years post retention (16 in V-CTC group; 17 in V-S group; 16 in P group). No significant differences were found between the groups. CONCLUSIONS: After five years or more out of retention, the three retention methods had achieved equally favourable clinical results. Thus a maxillary VFR combined with a bonded canine-to-canine retainer in the mandible, a maxillary VFR combined with stripping of the mandibular anterior teeth and a prefabricated positioner can all be recommended.

A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition.

BACKGROUND: High-dose oestrogen (HDE) is effective but toxic in postmenopausal women with advanced breast cancer (ABC). Prolonged oestrogen deprivation sensitises BC cell lines to estrogen and we hypothesised that third-generation aromatase inhibitors (AIs) would sensitise BCs to low-dose estradiol (LDE). METHODS: A single-arm phase II study of LDE (2 mg estradiol valerate daily) in postmenopausal women with estrogen receptor-positive (ER+) ABC. The primary end-point was clinical benefit (CB) rate. If LDE was ineffective, HDE was offered. If LDE was effective, retreatment with the pre-LDE AI was offered on progression. RESULTS: Twenty-one patients were recruited before the trial was closed early due to slow accrual; 19 were assessable for efficacy and toxicity. CB was seen in 5 in 19 patients (26%; 95% confidence interval 9.1-51.2%), all with prolonged SD (median duration 16.8 months; range 11.0-29.6). Treatment was discontinued for toxicity in 4 in 19 patients (21%) and 8 in 11 women without hysterectomy experienced vaginal bleeding (VB). After primary LDE failure, three patients received HDE and one achieved a partial response (PR). Following CB on LDE, four patients restarted pre-LDE AI and three achieved CB including one PR. Those with CB to LDE had a significantly longer duration of first-line endocrine therapy for ABC than those without (54.9 versus 16.8 months; p < 0.01) CONCLUSION: LDE is an effective endocrine option in women with evidence of prolonged sensitivity to AI therapy. LDE is reasonably well tolerated although VB is an issue. Re-challenge with the pre-LDE AI following progression confirms re-sensitisation as a true phenomenon.

Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome.

BACKGROUND: A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet can ameliorate symptoms in adult irritable bowel syndrome (IBS) within 48 h. AIM: To determine the efficacy of a low FODMAP diet in childhood IBS and whether gut microbial composition and/or metabolic capacity are associated with its efficacy. METHODS: In a double-blind, crossover trial, children with Rome III IBS completed a 1-week baseline period. They then were randomised to a low FODMAP diet or typical American childhood diet (TACD), followed by a 5-day washout period before crossing over to the other diet. GI symptoms were assessed with abdominal pain frequency being the primary outcome. Baseline gut microbial composition (16S rRNA sequencing) and metabolic capacity (PICRUSt) were determined. Metagenomic biomarker discovery (LEfSe) compared Responders (≥50% decrease in abdominal pain frequency on low FODMAP diet only) vs. Nonresponders (no improvement during either intervention). RESULTS: Thirty-three children completed the study. Less abdominal pain occurred during the low FODMAP diet vs. TACD [1.1 ± 0.2 (SEM) episodes/day vs. 1.7 ± 0.4, P < 0.05]. Compared to baseline (1.4 ± 0.2), children had fewer daily abdominal pain episodes during the low FODMAP diet (P < 0.01) but more episodes during the TACD (P < 0.01). Responders were enriched at baseline in taxa with known greater saccharolytic metabolic capacity (e.g. Bacteroides, Ruminococcaceae, Faecalibacterium prausnitzii) and three Kyoto Encyclopedia of Genes and Genomes orthologues, of which two relate to carbohydrate metabolism. CONCLUSIONS: In childhood IBS, a low FODMAP diet decreases abdominal pain frequency. Gut microbiome biomarkers may be associated with low FODMAP diet efficacy. ClinicalTrials.gov identifier: NCT01339117.

Preventing community-wide transmission of Cryptosporidium: a proactive public health response to a swimming pool-associated outbreak--Auglaize County, Ohio, USA.

The incidence of recreational water-associated outbreaks in the United States has significantly increased, driven, at least in part, by outbreaks both caused by Cryptosporidium and associated with treated recreational water venues. Because of the parasite's extreme chlorine tolerance, transmission can occur even in well-maintained treated recreational water venues (e.g. pools) and a focal cryptosporidiosis outbreak can evolve into a community-wide outbreak associated with multiple recreational water venues and settings (e.g. childcare facilities). In August 2004 in Auglaize County, Ohio, multiple cryptosporidiosis cases were identified and anecdotally linked to pool A. Within 5 days of the first case being reported, pool A was hyperchlorinated to achieve 99·9% Cryptosporidium inactivition. A case-control study was launched to epidemiologically ascertain the outbreak source 11 days later. A total of 150 confirmed and probable cases were identified; the temporal distribution of illness onset was peaked, indicating a point-source exposure. Cryptosporidiosis was significantly associated with swimming in pool A (matched odds ratio 121·7, 95% confidence interval 27·4-∞) but not with another venue or setting. The findings of this investigation suggest that proactive implementation of control measures, when increased Cryptosporidium transmission is detected but before an outbreak source is epidemiologically ascertained, might prevent a focal cryptosporidiosis outbreak from evolving into a community-wide outbreak.

Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium.

BACKGROUND: Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research. METHODS: In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. RESULTS: We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. CONCLUSIONS: We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.

Vertebroplasty and kyphoplasty are associated with an increased risk of secondary vertebral compression fractures: a population-based cohort study.

UNLABELLED: To better understand the risk of secondary vertebral compression fracture (VCF) following a vertebroplasty or kyphoplasty, we compared patients treated with those procedures to patients with a previous VCF. The risk of subsequent fracture was significantly greater among treatment patients, especially within 90 days of the procedure. INTRODUCTION: Predominantly uncontrolled studies suggest a greater risk of subsequent vertebral compression fractures (VCFs) associated with vertebroplasty/kyphoplasty. To further understand this risk, we conducted a population-based retrospective cohort study using data from a large regional health insurer. METHODS: Administrative claims procedure codes were used to identify patients receiving either a vertebroplasty or kyphoplasty (treatment group) and a comparison group of patients with a primary diagnosis of VCF who did not receive treatment during the same time period. The main outcomes of interest, validated by two independent medical record reviewers, were any new VCFs within (1) 90 days, (2) 360 days, and (3) at adjacent vertebral levels. Multivariable logistic regression examined the association of vertebroplasty/kyphoplasty with new VCFs. RESULTS: Among 48 treatment (51% vertebroplasty, 49% kyphoplasty) and 164 comparison patients, treated patients had a significantly greater risk of secondary VCFs than comparison patients for fractures within 90 days of the procedure or comparison group time point [adjusted odds ratio (OR) = 6.8; 95% confidence interval (CI) 1.7-26.9] and within 360 days (adjusted OR = 2.9; 95% CI 1.1-7.9). CONCLUSIONS: Patients who had undergone vertebroplasty/kyphoplasty had a greater risk of new VCFs compared to patients with prior VCFs who did not undergo either procedure.

Vitamin K prescribing patterns and bone health surveillance in UK children with cystic fibrosis.

BACKGROUND: Bone disease has become an increasingly recognized complication of cystic fibrosis (CF). Although causes of CF bone disease are multifactorial, there has been recent interest in the role of vitamin K in CF bone disease. AIMS AND METHODS: A questionnaire survey of all UK paediatric CF centre dietitians and centre directors was carried out to ascertain current practice with regard to vitamin K prescribing and bone health surveillance. RESULTS: The survey had a 97% response rate representing 3414 CF children. Twenty-three centre directors and 19 dietitians responded, and at least moderate agreement was noted with kappa scores >0.41 for all but one question assessed. Ninety-three per cent centres report that >90% pancreatic insufficient patients receive vitamins A, D and E, yet only 18% centres routinely supplement vitamin K. The majority (60%) report that <10% of their CF patients receive vitamin K, whilst vitamin K dosage varied from 0.3-0.5 to 10 mg day(-1). Only one centre undertook no bone health surveillance, and vitamin D levels are measured in 89%, calcium intake assessed in 82% and dual-energy X-ray absorptiometry scans performed in 61% centres. DISCUSSION: Heterogeneity in both vitamin K prescribing practices and bone health surveillance in CF across the UK were noted, underlining the need for a national consensus on bone health management, as well as acting as a call for longitudinal research into the clinical effectiveness of vitamin K therapy in CF.

Ocular and systemic side effects of brimonidine 0.2% eye drops (Alphagan) in children.

INTRODUCTION: Brimonidine 0.2% (Alphagan) is a topical alpha-2 agonist widely used as an antihypertensive. There have been occasional reports of systemic adverse effects in children including apparent central nervous system depression. There are few data available on the overall safety of brimonidine 0.2% in children. METHODS: Computerised pharmacy records were used to identify all children who had been prescribed brimonidine 0.2% in our eye department between August 1999 and June 2001, and their notes were reviewed. RESULTS: In all, 23 patients were identified from pharmacy records and 22 sets of notes were recovered and reviewed. The mean age at commencement of treatment was 8 years (range 0-14 years). In all, 10 (46%) were treated in one eye and 12 (54%) in both. Brimonidine 0.2% was taken for a mean 14 months (range 1 day-75 months). A total of 14 (64%) patients were already taking a topical beta-blocker when brimonidine 0.2% was commenced and a further four (18%) were being treated with another topical hypotensive agent. Of the 22 patients, six (27%) had to stop brimonidine 0.2% because of adverse side effects (two because of local irritation/allergy, two because of tiredness, and two because of fainting attacks). DISCUSSION: Many topical hypotensive agents are not licensed for use in children and few safety data are available. In this study, 18% of children had systemic adverse effects sufficient to necessitate stopping the drug. It is possible that educational impairment may have passed unnoticed in others. Larger studies are required to investigate this further.

A cost comparison of heart transplantation versus alternative operations for cardiomyopathy.

BACKGROUND: Heart transplantation is an established therapy for cardiomyopathy but is limited by organ shortage and expense. As a result, alternative operations have been proposed including coronary bypass, mitral valve repair, and left ventricular reconstruction. Because it is unknown whether alternative operations are less expensive than replacing the diseased heart, we compared in-hospital costs and early outcome of these operations with elective heart transplantation. METHODS: We compared clinical and financial data of 268 patients with ejection fraction less than 30% who underwent elective heart transplantation (n = 52, UNOS status 2 only), coronary bypass (n = 176), mitral repair (n = 15), or left ventricular reconstruction (n = 25). Data were evaluated for between-group differences, with p less than 0.05 as significant. RESULTS: Preoperative ejection fraction, although similar for heart transplantation (21.2% +/- 1.3%), coronary bypass (25.8% +/- 0.4%), mitral repair (22.9% +/- 1.5%), and left ventricular reconstruction (24.2% +/- 2.1%), was significantly different between the former two (p < 0.001). There was no difference in operative mortality: 5.8% (3 of 52), 3.4% (7 of 176), 6.7% (1 of 15), and 4.0% (1 of 25), respectively (p = 0.8). However, total hospital cost of heart transplantation was significantly greater than all others: $75,992 +/- $5,380, $25,008 +/- $1,446, $32,375 +/- $2,379, and $26,584 +/- $4,076, respectively (p < 0.001). Organ procurement expenses alone comprised 39.7% ($30,169) of total transplant cost. Kaplan-Meier survival analysis failed to show any survival difference between the various groups (p = 0.86) CONCLUSIONS: Compared with heart transplantation, alternative operations yield a comparable early outcome and long-term survival, and are markedly less expensive. The cost of transplantation, which is largely due to procurement expenses, is yet another reason to attempt alternative operations for cardiomyopathy whenever feasible.

A technique for adequate coverage of the proximal suture line during abdominal aortic aneurysm repair.

The proximal suture line is a vulnerable area after abdominal aortic aneurysm repairs. This area has been implicated in various postoperative complications, such as pseudoaneurysm formation, graft-enteric fistula, and suture line disruption. We present a technique that provides safe and adequate coverage of this suture line by using the aneurysm sac. This technique is derived from the z-plasty technique used for scar revision. The technique is illustrated with detailed line drawings. None of the patients in whom we used this technique have had any complications related to the proximal suture line.

Ewing sarcoma and sinonasal neuroectodermal tumors as second malignant tumors after retinoblastoma and other neoplasms.

BACKGROUND: Excesses of various childhood cancers have been reported after retinoblastoma, including a trickle of Ewing sarcoma (ES) and perhaps histologically similar olfactory neuroblastoma, both of which are neural tumors. To update and advance this information, case reports were sought by an extensive review of the literature. PROCEDURE: The search was made through the use of PubMed, and the Web of Science (Citation Index Expanded), keying on primary references. Three sinonasal cancers diagnosed as ES were immunohistochemically stained for MIC-2 protein (positive in ES). RESULTS: Retinoblastoma occurred before ES in ten cases (seven bilateral). In four others, retinoblastoma (three bilateral) developed before sinonasal neural tumors (poorly differentiated). ES also occurred after 14 cancers other than retinoblastoma (five lymphomas, four leukemias, and one each of five miscellaneous cancers). The predominance of retinoblastoma prior to ES differs markedly from the low-frequency of retinoblastoma among childhood cancers in the general population. On the contrary, cancers other than retinoblastoma were proportionate to those in the general population. Previously, retinoblastoma followed by excesses of osteosarcoma and soft tissue sarcomas has been attributed to the action of the inherited RB-1 gene. The sinonasal tumors stained negative for MIC-2 protein. CONCLUSIONS: Heritable retinoblastoma may predispose to ES and perhaps to a subset of poorly differentiated neuroectodermal tumors in the sinonasal region that may be related to olfactory neuroblastoma.

Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response.

OBJECTIVE: Both donor pulmonary macrophages and recipient circulating leukocytes may be involved in reperfusion injury after lung transplantation. By using the macrophage inhibitor gadolinium chloride and leukocyte filters, we attempted to identify the roles of these two populations of cells in lung transplant reperfusion injury. METHODS: With our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 18-hour cold storage and 2-hour blood reperfusion. Measurements of pulmonary artery pressure, lung compliance, and arterial oxygenation were obtained. Group I (n = 8) served as a control. Group II (n = 8) received gadolinium chloride at 14 mg/kg 24 hours before lung harvest. Group III (n = 8) received leukocyte-depleted blood reperfusion by means of a leukocyte filter. RESULTS: The gadolinium chloride group had significantly improved arterial oxygenation and pulmonary artery pressure measurements compared with control subjects and an improved arterial oxygenation compared with the filter group after 30 minutes of reperfusion. After 120 minutes of reperfusion, however, the filter group had significantly improved arterial oxygenation and pulmonary artery pressure measurements compared with the control group and an improved arterial oxygenation compared with the gadolinium chloride group. CONCLUSIONS: Lung transplant reperfusion injury occurs in two phases. The early phase is mediated by donor pulmonary macrophages and is followed by a late injury induced by recipient circulating leukocytes.

Mineralization dynamics of regenerate bone during mandibular osteodistraction.

Distraction osteogenesis offers an alternative approach for the correction of craniofacial deformities, yet little substantive data is available regarding mineralization of the forming regenerate. The purpose of this study was to evaluate, by plain film radiography and digital subtraction radiography, the mineralization dynamics of regenerate bone during osteodistraction. Thirteen skeletally mature male beagle dogs underwent 10 mm of bilateral mandibular distraction osteogenesis, at which time the bone was allowed to consolidate for either 4, 6, or 8 weeks. The tissues were then evaluated clinically and radiographically. The results demonstrate that several different types of regenerate are evident during mineralization of the distraction gap. A classification system is presented based on the length, width, and density of the mineralizing regenerate, as well as the presence or absence of an interzone. It appears that important factors for determining regenerate stability are the presence or absence of an interzone, as well as the width of the regenerate relative to the host bone segments. Finally, in cases where an interzone is present, subtraction radiography may provide a means of evaluating the level of mineralization within the interzone as well as the dynamics of mineralization over the course of distraction and consolidation.