Diagnostic accuracy comparing OPT and CBCT in the detection of non-vital bone changes before tooth extractions in patients with antiresorptive intake.

OBJECTIVES: To compare the diagnostic accuracy in detecting early non-vital bone changes between orthopantomography (OPT) and cone-beam computed tomography (CBCT) in correlation with histopathological findings before tooth extractions in patients with antiresorptive (AR) intake. SUBJECTS: Patients with an indication tooth extraction who had received OPT and CBCT preoperatively while or after undergoing AR treatment were prospectively enrolled over a 24-month period in the progesterone in spontaneous miscarriage (PRISM) trial. Imaging studies were randomly analyzed by three examiners for early non-vital bone changes using specific predefined characteristics and a 5-level scale (1 definite absence of criteria to 5 definite presence of criteria). Sensitivity and specificity values were calculated in correlation with the histopathologically evaluated bone samples at the time point of tooth extraction. RESULTS: One hundred thirty patients with 237 treated extraction sites met the inclusion criteria. For all images evaluated by all examiners, CBCT (430/492; 87.4%; receiver operating characteristic [ROC]: area under the curve [AUC] = 0.88; p < 0.001) was more likely to detect histopathologically confirmed non-vital bone than the OPT (132/492; 26.8%; ROC: AUC = 0.562; p = 0.115). CONCLUSIONS: In the detection of non-vital bone changes, CBCT is superior to OPT in both sensitivity and specificity. Specific imaging characteristics allow for the prediction of early non-vital bone changes already at the time before tooth extractions.

Infants With Trigonocephaly Treated With Fronto-Orbital Remodelling and Endocortical Positioning of Resorbable Plates-A Retrospective Cohort Study Including 101 Patients.

PURPOSE: Fronto-orbital remodeling is the gold standard for surgical treatment of metopic synostosis in many craniofacial centers. For fixation, resorbable materials are widely used. Because of swelling during resorption, the positioning of the plates can be relevant. Therefore, the goal of this study was to investigate whether there are limitations to endocortical positioning of resorbable plates. METHODS: In this retrospective study, all patients with metopic craniosynostosis resulting in trigonocephaly, who were treated with a standardized fronto-orbital remodeling and endocortical positioning of resorbable plates, between February 2012 and December 2019 were included. The endpoint of this study was the postoperative complications that can be attributed to the material used. RESULTS: A total of 101 patients, who were treated at our unit, could be included with a male predominance, 81 (80.2%) boys versus 20 (19.8%) girls. Surgery was performed at a median age of 9 months (±2.56). No complications were seen related to resorbable plates. All patients of our study population were categorized as Whitaker classification I and II. CONCLUSION: This study shows that the risk level in using endocortical resorbable plates positioned on the inner surface of the bone is low. From an aesthetic point of view, we could not detect any disadvantage.

Comparing the Influence of Surgical and Conservative Therapy on Quality of Life in Patients with Early-Stage Medication-Related Osteonecrosis of the Jaw-A Prospective Longitudinal Study.

Background and Objectives: The purpose of this study was to evaluate the impact of surgical and conservative, non-surgical treatment on general health-related (QoL) and oral health-related quality of life (OHRQoL) in patients suffering from AAOMS stage I MRONJ. Materials and Methods: In the course of this prospective clinical study, QoL and OHRQoL using QLQ-C30 and QHIP G14 questionnaire were longitudinally assessed in N = 174 prospectively enrolled patients with indication of treatment of MRONJ stage I over a period of 12 months. Patients received conservative or surgical treatment. The measurement time points were preoperatively (T0), 12 weeks (T1), 6 months (T2) and 1 year after operation (T3). Results: For OHRQoL, no significant (p > 0.05) differences were found between both treatment groups for all timepoints (T0-T3). In the surgical treatment group, OHIP scores of T1, T2 and T3 were significantly lower than baseline measures (T0) (T0-T1 (2.99, p = 0.024), T0-T2 (5.20, p < 0.001), T0-T3 (7.44, p < 0.001)). For conservative treatment group OHIP, scores of T2 and T3 were significantly lower than baseline measures (T0) (T0-T2 (9.09, p = 0.013), T0-T3 (12.79, p < 0.001)). There was no statistically significant effect of time on QLQ-C30 scores in both groups (surgical treatment: F(3, 174) = 1.542, p < 0.205, partial η2 = 0.026; conservative treatment: F(3, 30) = 0.528, p = 0.667, partial η2 = 0.050). QLQ-C30 scores turned out to be significantly lower in the non-surgical group at T1 (p = 0.036) and T3 (p = 0.047) compared to the surgical treatment group. Conclusions: Surgical and conservative treatment of MRONJ stage I significantly improves patients' OHRQoL. Surgical treatment is superior to conservative treatment of MRONJ stage I regarding general QoL. Therefore, surgical treatment of MRONJ stage I should not be omitted for QoL reasons.

Termite evolution: mutualistic associations, key innovations, and the rise of Termitidae.

Termites are a clade of eusocial wood-feeding roaches with > 3000 described species. Eusociality emerged ~ 150 million years ago in the ancestor of modern termites, which, since then, have acquired and sometimes lost a series of adaptive traits defining of their evolution. Termites primarily feed on wood, and digest cellulose in association with their obligatory nutritional mutualistic gut microbes. Recent advances in our understanding of termite phylogenetic relationships have served to provide a tentative timeline for the emergence of innovative traits and their consequences on the ecological success of termites. While all "lower" termites rely on cellulolytic protists to digest wood, "higher" termites (Termitidae), which comprise ~ 70% of termite species, do not rely on protists for digestion. The loss of protists in Termitidae was a critical evolutionary step that fostered the emergence of novel traits, resulting in a diversification of morphology, diets, and niches to an extent unattained by "lower" termites. However, the mechanisms that led to the initial loss of protists and the succession of events that took place in the termite gut remain speculative. In this review, we provide an overview of the key innovative traits acquired by termites during their evolution, which ultimately set the stage for the emergence of "higher" termites. We then discuss two hypotheses concerning the loss of protists in Termitidae, either through an externalization of the digestion or a dietary transition. Finally, we argue that many aspects of termite evolution remain speculative, as most termite biological diversity and evolutionary trajectories have yet to be explored.

Development of osteomyelitis following dental abscesses-influence of therapy and comorbidities.

OBJECTIVES: Bacterial osteomyelitis of the jaw is a severe disease potentially requiring extensive surgical treatment. We have evaluated the incidence rates of bacterial osteomyelitis following dental abscessation associated with primary or secondary tooth extraction. MATERIALS AND METHODS: A retrospective cohort study was designed and included patients with dental abscesses and surgical treatment including the extraction of focus teeth. Patients were either treated with primary removal during acute infection or secondary delayed extraction within an infection-free interval. The primary outcome variable was the occurrence of bacterial osteomyelitis following the abscess. Secondary outcomes were the influence of general disease, antibiotic therapy, and surgical technique. RESULTS: One hundred nine patients were enrolled in the study; 4 patients (3.7%) developed osteomyelitis. Primary tooth extraction was performed on all these patients (p = 0.017). Significant associations of diabetes (p = 0.001), the use of clindamycin (p = 0.025), and transcutaneous incision (p = 0.017) with the incidence of osteomyelitis were detected. CONCLUSIONS: More severe infections may be associated with a higher risk for the development of osteomyelitis following dental abscesses. A history of diabetes and clindamycin therapy might form further predisposing risk factors. Because of the low incidence and the small case number, our data need to be interpreted carefully. CLINICAL RELEVANCE: Osteomyelitis of the jaw is a rare but severe disease that may require extensive therapy and that impairs the quality of life of affected patients. The evaluation of risk factors to enable further reduction of incidence is therefore urgently required.

Do Functional Scores of Flap Donor Sites Recover After Reconstruction of Segmental Jaw Defects?

PURPOSE: The potential for donor-site morbidity in major maxillofacial reconstruction remains a concern. The purpose of this study was to compare the outcome of donor-site morbidity of deep circumflex iliac artery (DCIA) and scapula free flaps after radical treatment of the jaw and flap reconstruction. PATIENTS AND METHODS: We implemented a prospective cohort study design. Patients requiring segmental resection for benign pathology underwent reconstruction with either DCIA or scapula free flaps. The primary predictor variable was the use of DCIA versus scapula free flaps. The primary outcome variables were changes in orthopedic functional scores for both donor sites. The secondary outcome variable was neurosensory recovery at the recipient site. RESULTS: We included 8 patients in this study, comprising 3 women (38%) and 5 men (62%). Orthopedic scores were assigned preoperatively (T0) and at follow-up appointments at 1 to 3 months postoperatively (T1) and 6 to 12 months postoperatively (T2). In patients with DCIA flaps, a significant reduction (P = .0096) in the Larson I score between examination time points T0 and T1 was found. The score then improved on the operated side between T1 and T2 by an average of 29 points and showed no significant difference compared with the T0 level (P = .68). Patients with a scapular graft showed a significant reduction (P = .004) in the Constant-Murley score on the operated side between T0 and T1. The Constant-Murley score again improved significantly (P = .0136) between T1 and T2. Most of the patients (n = 7, 88%) had a neurologically unremarkable local situation of the recipient site at T0. At T1, 1 patient had level A (mild) neurosensory disorder and 1 had level B (moderate). At T2, all patients' initial neurologic scores were restored. CONCLUSIONS: The donor-site morbidity associated with DCIA and scapula flap reconstruction is a short-term condition and returns to baseline by 3 to 6 months postoperatively.

Polymethylmethacrylate patient-matched implants (PMMA-PMI) for complex and revision cranioplasty: analysis of long-term complication rates and patient outcomes.

Objective: Cranioplasty (CP) is associated with high complication rates and patient-matched implants (PMI) are frequently used for CP. However, only limited data are available regarding complication rates of PMI-based CP after complex or failed primary CP. Here we report our experience with the use of polymethylmethacrylate (PMMA) PMI for this purpose.Method: We analyzed all patients with complex or failed primary CP and subsequent implantation of PMMA-PMI between 2010 and 2015 at our institution.Results: A total of 67 patients (29 females, 38 males) with a mean age of 43 years (range: 13-74 years) were included in the study. Primary PMI-CP was performed in 18 patients with destructive or osteolytic bone tumors. Secondary PMI-CP was performed in 49 patients. Complications occurred in 14 patients with an overall complication rate of 21.7% during a mean follow-up of 39.7 ± 23.4 month. Approximately two-thirds of the patients reported a good quality of life after the initial event and subsequent CP. The majority of patients (>90%) was satisfied with the cosmetic result.Conclusion: Surgical CP with PMMA-PMI appears to be a suitable method for patients with failed or complex CP. Complication rates are comparable to those reported for primary CP.

A complete insect from the Late Devonian period.

After terrestrialization, the diversification of arthropods and vertebrates is thought to have occurred in two distinct phases, the first between the Silurian and the Frasnian stages (Late Devonian period) (425-385 million years (Myr) ago), and the second characterized by the emergence of numerous new major taxa, during the Late Carboniferous period (after 345 Myr ago). These two diversification periods bracket the depauperate vertebrate Romer's gap (360-345 Myr ago) and arthropod gap (385-325 Myr ago), which could be due to preservational artefact. Although a recent molecular dating has given an age of 390 Myr for the Holometabola, the record of hexapods during the Early-Middle Devonian (411.5-391 Myr ago, Pragian to Givetian stages) is exceptionally sparse and based on fragmentary remains, which hinders the timing of this diversification. Indeed, although Devonian Archaeognatha are problematic, the Pragian of Scotland has given some Collembola and the incomplete insect Rhyniognatha, with its diagnostic dicondylic, metapterygotan mandibles. The oldest, definitively winged insects are from the Serpukhovian stage (latest Early Carboniferous period). Here we report the first complete Late Devonian insect, which was probably a terrestrial species. Its 'orthopteroid' mandibles are of an omnivorous type, clearly not modified for a solely carnivorous diet. This discovery narrows the 45-Myr gap in the fossil record of Hexapoda, and demonstrates further a first Devonian phase of diversification for the Hexapoda, as in vertebrates, and suggests that the Pterygota diversified before and during Romer's gap.

Reconstruction of the severely atrophic edentulous maxillae with calvarial bone grafts.

OBJECTIVES: Treatment of the severely atrophic maxilla with dental implants is challenging due to the insufficient horizontal and vertical bone volume and centripetal resorption pattern of the maxilla. Bone-augmentation procedures are often necessary prior to implant placement. The objective of this study was to assess the suitability of using calvarial bone grafts to enable implant placement in severely atrophic maxillae. MATERIAL AND METHODS: Seventeen patients with severe atrophic edentulous maxillae were reconstructed with autogenous calvarial bone grafts. After a 4-month healing period, the patients received a total of 134 dental implants, which were left to heal in submerged positions for 3 months before prosthetic rehabilitation was performed. Patients were followed clinically and radiographically for an average observation period of 53.94 months. RESULTS: At the intraoral recipient sites, two infections developed, causing partial loss of the respective bone grafts. Implant placement, however, was possible at all sites. No donor-site complications occurred. Two of 134 implants were lost in two patients prior to prosthetic loading. The implant survival rate was 98.51%. The implant success rate was 87.6%, and a mean marginal bone loss of 0.62 mm (SD 0.77 mm) was documented. CONCLUSIONS: Patients with severe bone atrophy of the edentulous maxilla can be successfully reconstructed with calvarial bone grafts and dental implants and show a stable clinical and radiographic situation after a mean observation period of 53 months.

Shape alloys of nanorods and nanospheres from self-assembly.

Mixtures of anisotropic nanocrystals promise a great diversity of superlattices and phase behaviors beyond those of single-component systems. However, obtaining a colloidal shape alloy in which two different shapes are thermodynamically coassembled into a crystalline superlattice has remained a challenge. Here we present a joint experimental-computational investigation of two geometrically ubiquitous nanocrystalline building blocks-nanorods and nanospheres-that overcome their natural entropic tendency toward macroscopic phase separation and coassemble into three intriguing phases over centimeter scales, including an AB2-type binary superlattice. Monte Carlo simulations reveal that, although this shape alloy is entropically stable at high packing fraction, demixing is favored at experimental densities. Simulations with short-ranged attractive interactions demonstrate that the alloy is stabilized by interactions induced by ligand stabilizers and/or depletion effects. An asymmetry in the relative interaction strength between rods and spheres improves the robustness of the self-assembly process.

The earliest fossil mosquito.

Female mosquitoes are among the most notorious blood-feeding insects, sometimes causing severe allergic responses or vectoring a variety of microbial pathogens.1,2 Hematophagy in insects is likely a feeding shift from plant fluids, with the piercing-sucking mouthparts serving as suitable exaptation for piercing vertebrates' skin. The origins of these habits are mired in an often-poor fossil record for many hematophagous lineages,3,4 particularly those of sufficient age, as to give insights into the paleoecological context in which blood feeding first appeared or even to arrive at gross estimates as to when such shifts have occurred. This is certainly the case for mosquitoes, a clade estimated molecularly to date back to the Jurassic.5 The known Mesozoic Culicidae are Late Cretaceous, assigned to the modern Anophelinae or to the extinct Burmaculicinae, sister to other Culicidae, all with mouthparts of a modern type. Here, we report the discovery, in Lower Cretaceous amber from Lebanon, of two conspecific male mosquitoes unexpectedly with piercing mouthparts, armed with denticulate sharp mandibles and laciniae. These male fossils were likely hematophagous. They represent a lineage that diverged earlier than Burmaculicinae, extending the definitive occurrence of the family into the Early Cretaceous and serving to narrow the ghost-lineage gap for mosquitoes.

The value of prebent reconstruction plates and in-house 3D printing.

INTRODUCTION: Reconstruction plates, prebent on 3D printed models, are a cheap, quick, and safe solution to improve mandibular reconstruction procedures. The European Medical Device Regulation has changed recently and severely affects 3D printing in hospitals. Therefore, its legitimation must be discussed. This retrospective observational Case-Control Study aimed to evaluate the impact of prebent reconstruction plates on the condylar position in the temporomandibular joint after continuity resection of the mandible in oncological cases. MATERIALS AND METHODS: We included patients who underwent segmental mandibular resection without exarticulation of the condyle or history of prior surgery. The patients were divided into groups with prebent plates on a stereolithographic model and intraoperatively bent reconstruction plates. The segmental defects were categorized using the Jewer Classification. Computed Tomography (CT) scans before and after surgery were analyzed using a standardized method to measure the metric movement of the condyles, as well as their angulation to reference planes to quantify positional changes (primary outcome measures). The influence of the defect location, according to the Jewer classification, was evaluated as a secondary outcome measure. RESULTS: 73 patients, including 33 with preformed reconstruction plates, were included. We could show significantly fewer rotational deviations in cases of prefabricated osteosynthesis in the coronal plane (p<0,001) and in the sagittal plane (p<0,027). DISCUSSION: Using preformed reconstruction plates on 3D printed models improves the correct anatomical position of the condyle after mandibular resection. Especially Jewer-class-L defects seem to benefit from individualized reconstruction plates.

Comparison of Different Antibiotic Regimes for Preventive Tooth Extractions in Patients with Antiresorptive Intake-A Retrospective Cohort Study.

In the present study, the impacts on success rates between three different antibiotic regimes in patients receiving preventive tooth extraction during/after antiresorptive treatment were compared. For the retrospective analysis, we enrolled patients who had undergone tooth extraction from 2009 to 2019 according to the specified preventive conditions under antiresorptive therapy. Three antibiotic regimens were distinguished: (Group 1) intravenous for 7 days, (Group 2) oral for 14 days, and (Group 3) oral for 7 days of application. The primary endpoint was the occurrence of medication-related osteonecrosis of the jaw at 12 weeks after surgery. A total of 760 patients and 1143 extraction regions were evaluated (Group 1 n = 719; Group 2 n = 126; Group 3 n = 298). The primary endpoint showed no significant difference in the development of medication-related osteonecrosis of the jaw between the groups studied (Group 1 n = 50/669 (7%); Group 2 n = 9/117 (7%); Group 3 n = 17/281 (6%); p = 0.746). Overall, the success rate was 93% after intervention when preventive measures were followed. With the same success rate, a reduced, oral administration of antibiotics seems to be sufficient regarding the possible spectrum of side effects, the development of resistance and the health economic point of view.

Impact of Salvage Surgery on Health-Related Quality of Life in Oral Squamous Cell Carcinoma: A Prospective Multi-Center Study.

BACKGROUND: Patients with recurrent oral squamous cell carcinoma (OSCC) have limited treatment options. Salvage surgery offers potential curative therapy. The need for extensive ablative surgery together with microvascular reconstruction implies invasive and painful treatment with questionable functional outcome. To address the impact of salvage surgery on the health-related quality of life (HRQoL) of patients suffering from recurrent OSCC, a multi-center prospective analysis was initiated. MATERIAL AND METHODS: Patients with recurrent OSCC from 2015 to 2022 at two German cancer centers were included. Interdisciplinary tumor board decisions determined surgery as the only curative treatment modality. HRQoL, was assessed via a EORTC questionnaire (European Organization for Research and Treatment of Cancer-EORTC: QLQ-C30 and QLQ-H&N35) in dependence of the recurrent tumor stage. Patients completed the questionnaires once before surgery (baseline) and then every 3 months during follow-up or up to the end of treatment. RESULTS: In total, 55 patients were included. The mean follow-up period was 26.7 ± 19.3 months. Global health status showed superior mean scores after 12 months (60.83 ± 22.58) compared to baseline (53.33 ± 26.41) in stage 1 and 2 recurrent tumors. In advanced recurrent tumors' mean scores for global health showed only minor positive differences after 12 months (55.13 ± 22.7) compared to baseline (53.2 ± 25.58). In terms of the mouth pain, mean scores were lower after salvage surgery in small recurrent tumors after 12 months (20.37 ± 17.73) compared to baseline (41.67 ± 33.07; Wilcoxon two-sample signed-rank test p = 0.028). In advanced recurrent tumors, a significant reduction in mean scores was detected 3 months after salvage surgery (29.7 ± 22.94) compared to baseline (47.76 ± 25.77; Wilcoxon two-sample signed-rank test p = 0.003). Up to 12 months, swallowing function was evaluated inferior compared to baseline independent of tumor stage (Mean score recurrent stage I/II: 12-months 48.15 ± 27.57, baseline 28.7 ± 22.87; stage III/IV: 12-months 49.36.42 ± 27.53; baseline 30.13 ± 26.25). CONCLUSION: Improved HRQoL could be obtained in advanced recurrent OSCC after salvage surgery despite reduced swallowing function. In small recurrent tumors, overall, HRQoL was superior to baseline. Salvage surgery positively affected pain burden. For advanced recurrent tumors, important pain relieve could be observed as soon as 3 months after surgery.

Osteoradionecrosis of the Jaw-Comparison between Bone and Soft Tissue Injury and Their Influence on Surgical Outcomes-A Retrospective Cohort Study.

Surgical therapy of osteoradionecrosis of the jaw (ORN) is challenging and requires treatment of the affected hard and soft tissue. To understand how tissue injury after irradiation influences surgical outcomes, the objective of this study was to find out whether (a) bone-related, (b) soft tissue-related, and (c) treatment-related parameters influence the surgical success of patients with ORN. A total of 175 patients (324 lesions) were included in this retrospective, single-center study. All patients were diagnosed with ORN and underwent surgical therapy. The primary outcome was complete soft tissue recovery (mucosa/skin) and the absence of symptoms 3 months after surgery. At the time of follow-up, 58% of patients (189 of 324 lesions) had intact intraoral or extraoral soft tissue. The extent of bone destruction had no effect on treatment success, whereas soft tissue injury due to fibrosis (OR: 0.344; CI 0.142-0.834; p = 0.01818) and xerostomia (OR: 0.163; CI 0.064-0.419; p = 0.00016) increased the probability of treatment failure. Soft tissue reconstruction with a microvascular graft improved therapeutic success compared to local wound closure (OR: 2.998; CI 1.371-6.555; p = 0.006). Thus, for the treatment of ORN, it is extremely important to pay attention not only to the extent of bone destruction but especially to soft tissue defects. Because the extent of soft tissue injury is a predictor for therapeutic success, it should influence the choice of surgical treatment.

Influence of lower third molar anatomic position on postoperative inflammatory complications.

PURPOSE: Postoperative inflammatory conditions, including alveolar osteitis, surgical site infections, and abscess, are frequent complications after surgical removal of impacted mandibular third molars and multiple associated risk factors have been identified. However, few studies have evaluated the influence of extraction difficulty according to anatomic variables on postoperative inflammatory complications. PATIENTS AND METHODS: A retrospective study was performed of 585 surgically removed lower third molars. All molars were classified by a difficulty score (range 3 to 10) according to the anatomic parameters. RESULTS: For 109 third molars (19%), the extraction difficulty was rated noncomplex (score 3 to 4); for 341 (58%), moderate (score 5 to 7); and for 135 (23%), difficult (score 8 to 10). Molars rated as moderate or difficult for extraction were more often accompanied by postoperative infection than molars rated noncomplex (odds ratio 5.3 and 3.9, respectively, P < .0001). CONCLUSIONS: The results from the present study revealed a highly significant correlation between the level of difficulty for surgical removal of lower third molars (predicted by the anatomic variables) and postoperative inflammatory complications.

Cranial vault remodeling in microcephalic osteodysplastic primordial dwarfism type II and craniosynostosis.

This is a survey of the long-term result after various surgical treatments in a child with microcephalic osteodysplastic primordial dwarfism type II (MOPD II) and craniosynostosis. We report a 17-year-old patient with MOPD II but some unusual clinical signs including bilateral knee dislocation, a misplaced upper lobe bronchus, and hypoplasia of the anterior corpus callosum. Because of premature fusion of several cranial sutures, the child developed signs of increased intracranial pressure with somnolence and papilledema. Cranial vault remodeling with fronto-orbital advancement was performed twice at the age of 16 and 21 months to open the abnormally closed suture, increase the intracranial volume, and relieve the elevated intracranial pressure. Following this procedure, the child's neurologic situation recovered significantly. Surgical procedure of fronto-orbital advancement and the performed reoperation in our patient were safe with no major complications intraoperatively and postoperatively with good functional and satisfying aesthetic outcomes in the long-term follow-up, expressed by the patient, his parents, and the surgeons.

Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial.

BACKGROUND: Some patients with severe asthma remain symptomatic and obstructed despite maximal recommended treatment. Tiotropium, a long-acting inhaled anticholinergic agent, might be an effective bronchodilator in such patients. OBJECTIVE: We sought to compare the efficacy and safety of 2 doses of tiotropium (5 and 10 µg daily) administered through the Respimat inhaler with placebo as add-on therapy in patients with uncontrolled severe asthma (Asthma Control Questionnaire score, ≥ 1.5; postbronchodilator FEV1, ≤ 80% of predicted value) despite maintenance treatment with at least a high-dose inhaled corticosteroid plus a long-acting ß2-agonist. METHODS: This was a randomized, double-blind, crossover study with three 8-week treatment periods. The primary end point was peak FEV1 at the end of each treatment period. RESULTS: Of 107 randomized patients (54% female patients; mean, 55 years of age; postbronchodilator FEV1, 65% of predicted value), 100 completed all periods. Peak FEV1 was significantly higher with 5 µg (difference, 139 mL; 95% CI, 96-181 mL) and 10 µg (difference, 170 mL; 95% CI, 128-213 mL) of tiotropium than with placebo (both P < .0001). There was no significant difference between the active doses. Trough FEV1 at the end of the dosing interval was higher with tiotropium (5 µg: 86 mL [95% CI, 41-132 mL]; 10 µg: 113 mL [95% CI, 67-159 mL]; both P < .0004). Daily home peak expiratory flow measurements were higher with both tiotropium doses. There were no significant differences in asthma-related health status or symptoms. Adverse events were balanced across groups except for dry mouth, which was more common on 10 µg of tiotropium. CONCLUSION: The addition of once-daily tiotropium to asthma treatment, including a high-dose inhaled corticosteroid plus a long-acting ß2-agonist, significantly improves lung function over 24 hours in patients with inadequately controlled, severe, persistent asthma.

Influence of Preventive Tooth Extractions on Quality of Life in Patients with Antiresorptive Intake-A Prospective Longitudinal Study.

BACKGROUND: To find out whether preventive tooth extractions in patients on antiresorptive therapy have a direct impact on the patients' overall quality of life (QoL); Methods: QoL using the five-level version of the EuroQol Group's EQ-5D instrument (EQ-5D-5L) was longitudinally assessed in N = 114 prospectively enrolled patients with indication of preventive tooth extraction over a period of 12 months. Patients were stratified as high-risk (malignant disease with bone metastasis or multiple myeloma, with monthly high-dose antiresorptive therapy delivered intravenously [bisphosphonate] or subcutaneously [denosumab]) and low-risk/osteoporosis patients (weekly low-dose antiresorptive therapy administered orally [bisphosphonate] or half-yearly subcutaneously [denosumab]). The measurement time points were 4 weeks preoperatively (T0), 2 months (T1) and 1 year postoperatively (T2), respectively. RESULTS: EQ-5D-5L index scores fell in a range from -0.21 to 1.00 in the low-risk group to 0.15 to 1.00 in the high-risk group. The t-test comparing the baseline index scores of both groups showed EQ-5D-5L index score in the low-risk group (0.708 ± 0.292) to be significantly smaller (p = 0.037) than in the high-risk group (0.807 ± 0.19). ANCOVA showed no significant differences in EQ-5D-5L index scores between the groups at T1 and T2. CONCLUSIONS: Preventive tooth extractions in patients undergoing antiresorptive treatment have no negative effect on QoL. Therefore, if indicated, preventive tooth extraction should not be omitted. Patient-oriented outcome measures are important to obtain a good risk-benefit balance for patient-specific treatment.

A critical assessment of the medication-related osteonecrosis of the jaw classification in stage I patients: a retrospective analysis.

OBJECTIVES: It is unclear whether the extent of intraoral mucosa defects in patients with medication-related osteonecrosis of the jaw indicates disease severity. Therefore, this study investigated whether mucosal lesions correlate with the true extent of osseous defects in stage I patients. MATERIALS AND METHODS: Retrospectively, all patients with stage I medication-related osteonecrosis of the jaw who underwent surgical treatment between April 2018 and April 2019 were enrolled. Preoperatively, the extent of their mucosal lesions was measured in clinical evaluations, and patients were assigned to either the visible or the probeable bone group. Intraoperatively, the extent of necrosis was measured manually and with fluorescence. RESULTS: Fifty-five patients (36 female, 19 male) with 86 lesions (46 visible bone, 40 probeable bone) were enrolled. Intraoperatively, the necrotic le-sions were significantly larger (P<0.001) than the preoperative mucosal lesions in both groups. A significant (P<0.05) but very weak (R2<0.2) relation-ship was noted between the extent of the mucosal lesions and the necrotic bone area. CONCLUSION: Preoperative mucosal defects (visible or probeable) in patients with medication-related osteonecrosis of the jaw do not indicate the extent of bone necrosis or disease severity.