Successful use of emicizumab in a patient with refractory acquired hemophilia A and acute coronary syndrome requiring percutaneous coronary intervention.

ABSTRACT: We report a patient with a high-titer factor VIII inhibitor refractory to immunosuppression. He initially presented with myocardial infarction requiring percutaneous coronary intervention (PCI) with bare metal stent placement. Despite Feiba prophylaxis, inadequate hemostasis prompted premature discontinuation of dual antiplatelet therapy (DAPT). Fifteen weeks later, the patient presented with a left anterior descending artery in-stent restenosis. This case report examines the Key Clinical Question of how to manage in-stent restenosis in a patient with acquired hemophilia A (AHA). After multidisciplinary discussions including hematology, cardiology, cardiac surgery, laboratory medicine, and pharmacy, emicizumab was initiated to facilitate PCI. Four weeks after emicizumab initiation, the patient underwent successful PCI with drug-eluting stent placement. Five months after discharge, he remains without signs or symptoms of cardiac disease or bleeding on DAPT and emicizumab. This case provides evidence of the potential of emicizumab for bleeding prophylaxis in AHA.

Lipoxin A(4) promotes more complete inflammation resolution in sepsis compared to stable lipoxin A(4) analog.

In sepsis, excessive inflammation may lead to organ injury or a paradoxical immunosuppressed state where the host is unable to clear preexisting infection. Resolution of inflammation is the process which restores tissue homeostasis and ensures that a chronic cycle of infection/inflammation does not occur. Lipoxin A4 (LXA4) is one of a family of lipid mediators with novel inflammation resolution activity. We compared the actions of LXA4 to the stable 15-epi-16-(para-fluorophenoxy)-lipoxin A4 methyl ester (LXA4 analog) in the cecal ligation and puncture (CLP) model of sepsis. Both LXA4 compounds (at 7 µg/kg; i.v.) reduced plasma TNFα and IL-6 concentrations compared to rats given vehicle saline. Neither treatment altered plasma IL-10 compared to CLP given saline, but LXA4 analog, increased plasma IL-10 concentrations compared to rats given LXA4. LXA4 reduced blood bacterial load but the LXA4 analog did not. LXA4 increased 8 day survival and the LXA4 analog did not have a significant effect. To examine possible mechanisms for the differences, we investigated peritoneal leukocyte gene expression of iNOS and macrophage phagocytic ability. Only LXA4 increased the percentage of phagocytic peritoneal macrophages. LXA4 reduced neutrophil gene expression of iNOS compared to CLP rats given vehicle, while the LXA4 analog did not. Our results suggest that at doses which reduced systemic inflammation, only LXA4 inhibited bacterial spread and increased survival. This difference may be due to the shorter-lived compound being able to increase macrophage phagocytosis and reduce neutrophil iNOS expression.

Influence of concurrent anastrozole on acute and late side effects of whole breast radiotherapy.

OBJECTIVES: To retrospectively compare radiation toxicity in patients treated with concurrent anastrozole and whole breast irradiation versus women treated sequentially with whole breast irradiation followed by hormonal suppression. METHODS: The records of 249 consecutive estrogen or progesterone receptor positive breast cancer patients treated with breast-conserving surgery and postoperative whole breast irradiation were reviewed. Of total, 57 patients (the concurrent anastrozole group) received concurrent anastrozole prior to and during radiotherapy. In 126 patients (the sequential group), adjuvant hormone suppression therapy (anastrozole, other aromatase inhibitors, or tamoxifen) was administered after the completion of breast irradiation. In 66, women either concurrent tamoxifen was given with radiation or the sequence of hormonal therapy was not known. These women were excluded from the analysis. RESULTS: The frequency of acute grade 2 radiation dermatitis (24.6% in the concurrent anastrozole group vs. 20.6% in the sequential group; P = 0.55), grade 3 radiation dermatitis (8.8% vs. 7.1%; P = 0.77) and treatment interruptions due to skin reactions (14.0% vs. 11.2%; P = 0.69) did not differ between groups. The rates of clinically detectable breast fibrosis were not different (24.2% vs. 24.7%; P = 0.97). With a median follow-up of 28 months and 30.8 months, respectively, 1 local failure occurred in the concurrent anastrozole group and 5 in the sequential group. CONCLUSIONS: Anastrozole, administered concurrently with whole breast irradiation, did not increase acute or late morbidity when compared with sequential administration of radiation and hormonal suppression therapy.

An in vitro comparison of Profile GT and GTX nickel-titanium rotary instruments in apical transportation and length control in mandibular molar.

INTRODUCTION: Profile GT files have been redesigned and are now marketed as GTX nickel-titanium rotary files. METHODS: A double-digital radiographic technique was used to compare apical transportation (AT) and change in working length (CWL) between Profile GT and GTX rotary files. Mesiobuccal canals of 40 extracted mandibular molars were instrumented by either rotary system. The central axes of preoperative (15 K) and master apical rotary file (30/.04) were digitally superimposed. AutoCAD was used to measure AT at 0, 1, and 3 mm from WL. The distance from the file tip to the set WL indicated any CWL. Analysis of variance test showed no significant differences between groups in AT. RESULTS: CWL in GTX (-0.25 +/- 0.42) group was significantly greater than in Profile GT group (0.17 +/- 0.30). CONCLUSIONS: The AT results indicate that the newly designed GTX rotary instruments are as effective as the older Profile GT instruments.

Reduction in radiation-induced morbidity by use of an intercurrent boost in the management of early-stage breast cancer.

PURPOSE: Electron or photon boost immediately following whole-breast irradiation performed after conservation surgery for early-stage breast cancer is the accepted standard of care. This regimen frequently results in Grade III dermatitis, causing discomfort or treatment interruption. Herein, we compare patients treated with whole-breast irradiation followed by boost compared with a cohort with a planned intercurrent radiation boost. METHODS AND MATERIALS: The records of 650 consecutive breast cancer patients treated at Allegheny General Hospital (AGH) between 2000 and 2008 were reviewed. Selected for this study were 327 patients with T1 or T2 tumors treated with external beam radiotherapy postlumpectomy. One hundred and sixty-nine patients were treated by whole-breast radiotherapy (WBRT) followed by boost at completion. One hundred fifty-eight were treated with a planned intercurrent boost (delivered following 3,600 cGy WBRT). The mean whole breast radiation dose in the conventionally treated group was 5,032 cGy (range, 4500-5400 cGy), and the mean whole breast dose was 5,097 cGy (range, 4860-5040 cGy) in the group treated with a planned intercurrent boost. RESULTS: The occurrence of Grade III dermatitis was significantly reduced in the WBRT/intercurrent boost group compared with the WBRT/boost group (0.6% vs. 8.9%), as was the incidence of treatment interruption (1.9% vs. 14.2%). With a median follow-up of 32 months and 27 months, respectively, no significant difference in local control was identified. CONCLUSIONS: Patients treated with intercurrent boost developed less Grade III dermatitis and unplanned treatment interruptions with similar local control.

A nonsurgical endodontics relational research database: the initial six years of experience.

The purpose of this study was to report results of the initial six years of experience utilizing a nonsurgical root canal treatment (NSRCT) database; to compare patient characteristics, operative procedures, and patient outcomes observed in the database to those observed in other studies; and to discuss the potential benefits of a clinical endodontic database. A total of 7,372 NSRCT cases performed by endodontic residents at the University of Pennsylvania from 2000 to 2006 were evaluated. The odds ratio (OR) for caries and trauma being causative agents for NSRCT in

The comparison of gutta-percha and Resilon penetration into lateral canals with different thermoplastic delivery systems.

The aim of this study was to evaluate the ability of Obtura II (Obtura Spartan, Fenton, MO) and Calamus (Densply, Tulsa, OK) to fill artificially created lateral canals in simulated plastic teeth using standard gutta-percha, Flow 150 gutta-percha (Obtura Spartan, Fenton, MO), and Resilon (Resilon Research, LLC, North Branford, CT). Lateral canals were created at 2, 4, 6, 8, 10, and 12 mm from the apex in plastic teeth. The teeth were divided into eight groups. In group 1, teeth were filled with a single increment of Calamus; in group 2, canals were filled with Calamus in three increments. In group 3, Obtura II was used with a single increment of standard gutta-percha, whereas in group 4 Obtura II was used in three increments. Groups 5 and 6 were similarly filled as in the preceding groups. A multiple-comparison analysis of variance test followed by a Tukey post-hoc test were used to compare filling material penetration into the lateral canals and the experimental groups (p < 0.05). The results indicated that the flow of the filling material into lateral canals is a function of the viscoelastic properties of the filling material rather than the mechanical properties of the delivery systems. Our data also suggest that the Resilon filling material flows better into lateral canals when a single backfill technique is used.

A review of factors influencing treatment planning decisions of single-tooth implants versus preserving natural teeth with nonsurgical endodontic therapy.

One of the major issues confronting the contemporary dental clinician is the treatment decision between extracting a tooth with placement of a dental implant or preserving the natural tooth by root canal treatment. The factors that dictate the correct selection of one procedure over the other for each particular case are not yet established by randomized controlled studies. The aim of this review is to evaluate key factors allowing the clinician to make clinical decisions on the basis of the best evidence and in the patient's best interests. General considerations are discussed that will help the reader analyze clinical studies focused on this problem. Importantly, the major studies published to date indicate that there is no difference in long-term prognosis between single-tooth implants and restored root canal-treated teeth. Therefore, the decision to treat a tooth endodontically or to place a single-tooth implant should be based on other criteria such as prosthetic restorability of the tooth, quality of bone, esthetic demands, cost-benefit ratio, systematic factors, potential for adverse effects, and patient preferences. It can be concluded that endodontic treatment of teeth represents a feasible, practical, and economical way to preserve function in a vast array of cases and that dental implants serve as a good alternative in selected indications in which prognosis is poor.

Instrumentation and obturation of the apical third of root canals: addressing the forgotten dimension.

Modern developments in instrument design and obturation techniques have greatly improved the efficiency of conventional endodontic therapy. Nickel titanium rotary instruments allow the practitioner to prepare canals more quickly and predictably. However, apical preparations by such instruments fail to address the anatomical complexity of the root canal system. Morphologic studies consistently show that canals are mostly oval or irregular in shape; therefore, round preparations by instrumentation result in uninstrumented areas of the root canal system. This is of particular importance in the apical third and in cases of preexisting periapical pathology, where residual bacteria may reside and cause persistent infections. How beneficial are these new instrumentation and obturation techniques to the basic purpose of root canal therapy in eradicating bacteria? This article presents the shortcomings of current instrumentation and obturation techniques and offers possible solutions to improve the outcome of endodontic therapy.

Clinical and scanning electron microscopic features of invasive cervical resorption in a maxillary molar.

This case report presents clinical and morphological features of severe invasive cervical resorption (ICR) involving a maxillary first molar. Surface morphology of the ICR defect that extended into enamel was studied using a scanning electron microscope. The topography and morphology of resorbed enamel and pulpal surfaces are described. The pulpal space was characterized by proliferation of fibrovascular tissue invaded by a number of > or = 15-microm-large dentinoclastlike cells. The vertical orientation and hexagonal geometric outlines of enamel rods indicated that the resorptive defect had extended into the outer surface of enamel. Preferential odontoclastic dissolution of interprismatic enamel was noted. Deposits of a cementumlike substance were noticed on enamel surfaces, indicating that resorptive process was coupled with repair. Complete destruction of dentin was associated with no response by the tooth to cold stimulus, supporting the hydrodynamic theory of dentinal sensitivity. The results of this study indicate that in addition to predentin and cementum, the outer surface enamel may be resistant to the resorptive process as well.

Microscopic periradicular surgery: perioperative predictors for postoperative clinical outcomes and quality of life assessment.

The authors report on data from a self-assessment questionnaire filled out by 199 patients undergoing periradicular microscopic surgery at two private endodontic offices and at graduate endodontic clinics of the University of Pennsylvania. Regression analysis was performed using pain and swelling as dependent variables and age, sex, type of teeth, location, periapical lesion, and remedication as independent variables. Pain and swelling were significantly related to females and younger patients (p < 0.05). The results supported Etodolac as a pre- and postoperative analgesic and use of antibiotics restricted to high-risk patients. Maximum pain and swelling were reported at night and day 1 of the surgery, respectively. Generally, swelling was more often reported than pain. Surgeries in anterior maxilla were related to more pain and swelling. A majority of the patients (67%) rated surgical endodontics more pleasant than expected and found it less painful (46%) or the same (38%) as nonsurgical treatment. The results also point out that patients in general have negative beliefs and limited knowledge about periradicular surgery.

A comparison of LightSpeed LS1 and LightSpeed LSX NiTi rotary instruments in apical transportation and length control in simulated root canals.

In a major design change LightSpeed Technologies Inc. has replaced the U-shape blade design with a spade-shape design in LightSpeed LSX root canal rotary instruments. A double-digital radiographic technique was used to compare apical transportation (AT) and length control (LC) between the two instrument designs. Thirty simulated plastic root canals were instrumented by each rotary system. Digital radiography and AutoCAD 2007 were used to determine the central axes of files at 20, 35, 50, and 70 ISO sizes. By superimposition of central axes with a baseline at size 20, the degree of AT was measured at 0, 1, and 3 mm from working length (WL). The distance from file tips to set WL indicated any loss of LC. ANOVA test showed no significant differences between groups with respect to the degree of AT or LC. No instrument separation was noted. The results indicate that newly designed Lightspeed LSX instruments maintain the same effectiveness regarding AT and LC as that of the LightSpeed LS1 instruments.

For teeth requiring endodontic treatment, what are the differences in outcomes of restored endodontically treated teeth compared to implant-supported restorations?

PURPOSE: The clinical question this systematic review aimed to answer was "What are the differences in outcomes of restored endodontically treated teeth compared to implant-supported restorations? Therefore the aim of this study was to use systematic review to compare the survival of compromised teeth restored with either root canal therapy followed by a crown, or placement of a single-tooth implant. MATERIALS AND METHODS: MEDLINE, EMBASE, and PubMed databases were searched for studies dealing with survival of single-tooth implants and restored endodontically treated teeth. A 2-step screening procedure was used to identify articles that met the inclusion/exclusion criteria. Fifty-five studies related to single-tooth implants and 13 studies related to restored root canal-treated teeth were included. The endpoint analyzed in these studies was the survival rate of the treated tooth or implant. RESULTS: The 95% confidence intervals for the pooled estimates for the single-tooth implants and restored endodontically treated teeth were found overlapping in forest plots for all follow-up periods. This indicated no significant differences in survival between restored root canal-treated teeth and single-tooth implants. CONCLUSIONS: The results of this systematic review indicate that the decision to treat a tooth endodontically or replace it with an implant must be based on factors other than the treatment outcomes of the procedures themselves. Both nonsurgical root canal therapy followed by an appropriate restoration and single-tooth implants are excellent treatment modalities for the treatment of compromised teeth.

A retrospective clinical study of incidence of root canal instrument separation in an endodontics graduate program: a PennEndo database study.

This study investigated the incidence of hand and rotary instrument separation (IS) in the endodontics graduate program at the University of Pennsylvania between 2000 and 2004. In 4,865 endodontic resident cases the incidence of hand and rotary IS was 0.25% and 1.68%, respectively. The odds for rotary IS were seven times more than for hand IS. The probability of separating a file in apical third was 33, and 6 times more likely when compared to coronal and middle thirds of the canals. The highest percentage of IS occurred in mandibular (55.5%) and maxillary (33.3%) molars. Furthermore, the odds of separating a file in molars were 2.9 times greater than premolars. Among the ProFile series 29 rotary instruments, the .06 taper # 5 and # 6 files separated the most. There was no significant difference in IS between the use of torque controlled versus nontorque controlled handpieces, nor between first and second year residency.

A comparison of three methods for preparing centered platforms around separated instruments in curved canals.

This study compared three methods for creating the most centered staging platform (SP) around separated instruments (SI) in curved canals. Green .04 ProFiles, notched at D(3), were separated in the apical third of 42 mesiobuccal canals of maxillary and mandibular molars. Teeth were divided into three groups. SPs were prepared in group 1 with Gates Gliddens (GG) to a size #3; group 2 with LightSpeed to a size 90; and group 3 with incrementally cut rotary .06 ProFiles to size 82. Pre- and postoperative digital radiographs were imported into AutoCAD to measure the deviation of SP from the head of the separated instrument. Pearson's correlation showed a positive relationship between deviation of the SP and the distance of the SI from the elbow of the canal. ANOVA showed that LightSpeed instruments were significantly more effective in preparing a centered staging platform around separated instruments in curved canals when compared to GG drills and ProFiles (p < 0.05).

The clinical significance and management of apical accessory canals in maxillary central incisors.

BACKGROUND: The maxillary central incisor is considered to be the least difficult subject for a clinical endodontic experience. However, the internal anatomy of maxillary central incisors can present a number of variations, including multiple accessory canals. CASE DESCRIPTION: This article highlights the clinical significance and management of accessory canals located in the apical one-third of maxillary central incisors. The authors present two case reports in which failure to detect the accessory canals led to root canal failure and subsequent surgical intervention. Another two case reports present the serendipitous discovery and nonsurgical management of accessory canals during the initial treatment of maxillary incisors. CONCLUSIONS AND CLINICAL IMPLICATIONS: It is important for the clinician to be able to detect the signs suggesting the presence of accessory canals in maxillary central incisors. Failure to do so may lead to a less-than-optimal endodontic treatment outcome.

Nonsurgical ultrasonic endodontic instruments.

The advent of nonsurgical ultrasonic tips has opened up a new horizon in endodontic treatment. There are a number of nonsurgical endodontic ultrasonic systems currently available in the market and it is difficult to renew all of them. Based on similarities among different instrument systems, and attempt has been made to classify instruments into broad categories. This article describes the utility of each type of ultrasonic tip and the principles behind its usage. These instruments may be area specific or use specific, but can be used in an area other than the one for which they are specifically designed if the general principles regarding ultrasonic tips are understood and applied.

Comparison of apical transportation in four Ni-Ti rotary instrumentation techniques.

A new radiographic technique was used to compare apical transportation in four Ni-Ti rotary instrumentation sequences. Mesiobuccal canals of 60 extracted mandibular molars were randomly divided into four groups. Groups 1 and 3 were instrumented by crown-down and groups 2 and 4 by step-back technique with 0.06 ProFiles series 29 to size 6. In groups 3 and 4 Greater Taper files were first used in a crown-down manner. The central axes of initial and final instruments were radiographically superimposed to measure loss of working length (WL) and transportation at 0, 0.5, 1, 3, and 5 mm from WL. ANOVA test showed no significant differences among groups regarding degree of transportation or loss of WL. Transportation was negatively correlated with radius of curvature at 0.5 and 5 mm from WL. The results indicate that the operational sequence of ProFiles or preinstrumentation with GT files has no effect on degree of transportation and loss of WL.

Analysis of continuous-wave obturation using a single-cone and hybrid technique.

This study analyzed the adaptation of gutta-percha to prepared root canal walls using two obturation techniques and determined the influence of the System-B plugger depth on filling adaptation. Fifty-six extracted human mandibular molars were instrumented using Profile NiTi rotary instruments, stratified based on curvature, then randomly distributed into two groups. Group 1 was obturated using the single-cone continuous-wave technique. Group 2 was obturated with a hybrid technique: lateral condensation followed by a continuous-wave down-pack. Based on System-B plugger penetration, teeth were divided into three subgroups: (a) < 3.5 mm, (b) 3.5 to 4.5 mm, and (c) > 4.5 mm. Roots were horizontally sectioned at 1 mm and 3 mm coronal to the apical foramen, stained, and photographed. Four evaluators scored the adaptation of gutta-percha to the prepared canal walls. In 100% (n = 56) of the samples, no statistically significant difference existed between the two obturation methods at 1-mm (x = 1.80, SD +/- 0.69) or 3-mm (x = 1.804, SD +/- 0.69) sections. Best results were obtained with a plugger depth 3.5 to 4.5 mm from the working length.