Laser wavelengths and oral implantology

In modern implant dentistry there are several clinical indications for laser surgery. Different laser systems have a considerable spectrum of application in soft and hard peri-implant tissues. The literature was searched for clinical application of different laser wavelengths in peri-implant tissues: second-stage surgery of submerged implants, treatment of infrabony defects, removal of peri-implant hyperplastic overgrowths, and, possibly, the preparation of bone cavities for implant placement. This report describes the state-of-the-art application of different laser systems in modern implant dentistry for the treatment of peri-implant lesions and decontamination of implant surfaces. Our study evaluated in vitro examinations, clinical experience and long-term clinical studies. The exact selection of the appropriate laser system and wavelength was dependent on the scientific evaluation of recent literature and the level of changes in implant and tissue temperatures during laser application. The significant reduction in bacteria on the implant surface and the peri-implant tissues during irradiation and the cutting effects associated with the coagulation properties of the lasers are the main reasons for laser application in the treatment of peri-implant lesions and the successful long-term prognosis of failing oral implants. The various applications of lasers in implant dentistry are dependent on the wavelength and laser-tissue interactions.

Radiation therapy for HIV-associated diffuse large cell non-Hodgkin lymphoma

PURPOSE: To report the clinical experience with external beam radiotherapy (RT) for AIDS-related lymphoma (ARL) with or without the involvement of the central nervous system (CNS) in HIV-infected patients. PATIENTS AND METHODS: Clinical outcome of 24 HIV-seropositive patients with ARL treated with RT from 1995 to 2004 was reviewed, testing factors associated with outcome. RESULTS: After 1 and 5 years, the overall survival was 65% and 35%, respectively. The mean RT dose was 31 Gy after normalization to fractions of daily 2 Gy (range, 7.8-47.2 Gy). Radiotherapy dose was associated with survival in univariate (P = .04) and multivariate analysis (P = .01). Other factors in univariate analysis associated with outcome were viral load (VL), highly active antiretroviral therapy (HAART), ARL stage, and CNS involvement. Patients with CNS involvement achieved complete response in 46% and improved clinical performance was seen in 73%. CONCLUSIONS: After chemotherapy, RT in combination with HAART is highly active, and RT should be encouraged especially after suboptimal responses to induction treatment.

Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document

OBJECTIVES The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection. BACKGROUND A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous. METHODS AND RESULTS Two in-person meetings (held in September 2011 in Washington, DC, and in February 2012 in Rotterdam, The Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and noninterventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints. CONCLUSIONS This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

Empfehlungen zur Diagnostik und Therapie der behavioralen und psychologischen Symptome der Demenz (BPSD)

In patients with dementia, Behavioral and Psychological Symptoms of Dementia (BPSD) are frequent findings that accompany deficits caused by cognitive impairment and thus complicate diagnostics, therapy and care. BPSD are a burden both for affected individuals as well as care-givers, and represent a significant challenge for therapy of a patient population with high degree of multi-morbidity. The goal of this therapy-guideline issued by swiss professional associations is to present guidance regarding therapy of BPSD as attendant symptoms in dementia, based on evidence as well as clinical experience. Here it appears to be of particular importance to take into account professional experience, as at this point for most therapeutic options no sufficiently controlled clinical trials are available. A critical discussion of pharmaco-therapeutic intervention is necessary, as this patient-population is particularly vulnerable for medication side-effects. Finally, a particular emphasis is placed on incorporating and systematically reporting psycho-social and nursing options therapeutic intervention.

Congenital portosystemic shunt: characterization of a multisystem disease

OBJECTIVES Congenital portosystemic shunts (CPSSs) are rare but increasingly recognized as a cause of important multisystem morbidity. We present new cases and a systematic literature review and propose an algorithm for the identification and care of affected patients. METHODS We reviewed the charts of consecutive patients seen in our pediatric liver clinic between 2003 and 2010 and systematically reviewed the literature of cases with CPSS. RESULTS We identified 316 published cases and 12 patients in our own clinic. Of the published cases (177 male), 185 had an extrahepatic and 131 an intrahepatic portosystemic shunt. Diagnosis was made at any age, from prenatal to late adulthood. Cardiac anomalies were found in 22% of patients. The main complications were hyperammonemia/neurological abnormalities (35%), liver tumors (26%), and pulmonary hypertension or hepatopulmonary syndrome (18%). The spectrum of neurological involvement ranged from changes in brain imaging, subtle abnormalities on neuropsychological testing, through learning disabilities to overt encephalopathy. Spontaneous shunt closure occurred mainly in infants with intrahepatic shunts. Therapeutic interventions included shunt closure by surgery or interventional radiology techniques (35%) and liver transplantation (10%) leading to an improvement of symptoms in the majority. These findings mirror the observations in our own patients. CONCLUSIONS In this largest review of the reported clinical experience, we identify that children with CPSS may present with otherwise unexplained developmental delay, encephalopathy, pulmonary hypertension, hypoxemia, or liver tumors. When CPSS is diagnosed, children should be screened for all of these complications. Spontaneous closure of intrahepatic shunts may occur in infancy. Closure of the shunt is indicated in symptomatic patients and is associated with a favorable outcome.

Topographic bone thickness maps for Bonebridge implantations.

Bonebridge™ (BB) implantation relies on optimal anchoring of the bone-conduction implant in the temporal bone. Preoperative position planning has to account for the available bone thickness minimizing unwanted interference with underlying anatomical structures. This study describes the first clinical experience with a planning method based on topographic bone thickness maps (TBTM) for presigmoid BB implantations. The temporal bone was segmented enabling three-dimensional surface generation. Distances between the external and internal surface were color encoded and mapped to a TBTM. Suitable implant positions were planned with reference to the TBTM. Surgery was performed according to the standard procedure (n = 7). Computation of the TBTM and consecutive implant position planning took 70 min on average for a trained technician. Surgical time for implantations under passive TBTM image guidance was 60 min, on average. The sigmoid sinus (n = 5) and dura mater (n = 1) were exposed, as predicted with the TBTM. Feasibility of the TBTM method was shown for standard presigmoid BB implantations. The projection of three-dimensional bone thickness information into a single topographic map provides the surgeon with an intuitive display of the anatomical situation prior to implantation. Nevertheless, TBTM generation time has to be significantly reduced to simplify integration in clinical routine.

POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders.

PURPOSE: To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures. METHODS: Four patients who developed VPA-induced hepatotoxicity were examined for POLG sequence variations. A subsequent chart review was used to describe clinical course prior to and after VPA dosing. RESULTS: Four patients of multiple different ethnicities, age 3-18 years, developed VPA-induced hepatotoxicity. All were given VPA due to intractable partial seizures. Three of the patients had developed epilepsia partialis continua. The time from VPA exposure to liver failure was between 2 and 3 months. Liver failure was reversible in one patient. Molecular studies revealed homozygous p.R597W or p.A467T mutations in two patients. The other two patients showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S. Clinical findings and POLG mutations were diagnostic of Alpers-Huttenlocher syndrome. CONCLUSION: Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers-Huttenlocher syndrome can precipitate liver failure. Our data support an emerging proposal that POLG gene testing should be considered in any child or adolescent who presents or develops intractable seizures with or without status epilepticus or epilepsia partialis continua, particularly when there is a history of psychomotor regression.

Effects of Lipophilic Extract of Viscum album L. and Oleanolic Acid on Migratory Activity of NIH/3T3 Fibroblasts and on HaCat Keratinocytes

Viscum album L. lipophilic extract (VALE) contains pharmacologically active pentacyclic triterpenes that are known to exhibit immunomodulatory, antitumor, and wound healing activity. Preliminary clinical observations indicate that VALE was able to influence cutaneous wound healing in vivo. The objective of this study was to investigate wound closure related properties of VALE in vitro. As measured in a wound healing assay, VALE and its predominant triterpene oleanolic acid (OA) significantly and dose dependently promoted the migration of NIH/3T3 fibroblasts in vitro, thereby leading to an enhanced wound closure. Compared to the negative control, maximal stimulation by 26.1% and 26.2%, respectively, was attained with 10 μg/mL VALE and 1 μg/mL OA. Stimulation of proliferation in NIH/3T3 fibroblasts by VALE and OA could be excluded. At higher concentrations both substances affected proliferation and viability of NIH/3T3 fibroblasts and HaCat keratinocytes. In the toxic range of concentrations of VALE and OA, migration of NIH/3T3 fibroblasts was suppressed. The extent of the stimulatory effect on cell migration of VALE quite closely corresponded to the effect expected by the concentrations of OA contained in the crude extract VALE. These data support the casual observation that Viscum album L. lipophilic extract might modulate wound healing related processes in vivo.

Efficacy and Safety of Natalizumab in Crohn’s Disease Patients Treated at 6 Boston Academic Hospitals

BACKGROUND: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not currently enrolled in a clinical trial. METHODS: A retrospective case review of patients treated with natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts General Hospital, and UMass Medical Center. RESULTS: Data on 69 CD patients on natalizumab were collected. At the start of treatment, patients' disease duration was 12 years. A high proportion of patients were women (68%), presented with perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%), methotrexate (58%), and at least two anti-tumor necrosis factor agent failures (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation had a partial or complete clinical response. Loss of response was 13% after an average of 1 year of treatment. Adverse events were infusion reactions, headaches, fever, and infections. No case of progressive multifocal leukoencephalopathy was observed. CONCLUSIONS: In our clinical experience outside the context of a clinical trial, natalizumab is largely reserved for CD patients with extensive ileocolonic disease who have failed conventional immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug is, however, well tolerated and offers significant clinical improvement for more than a year in one-third of these difficult-to-treat CD patients.

Ultrasound-guided proximal paravertebral anaesthesia in cattle

OBJECTIVE To develop and evaluate a method for ultrasound-guidance in performing the proximal paravertebral block for flank anaesthesia in cattle through a cadaveric study, followed by clinical application. STUDY DESIGN prospective experimental cadaveric study and clinical series. ANIMALS Previously frozen lumbar sections of cows without known spinal abnormalities were used. The clinical case group comprised of ten animals for which a right flank laparotomy was indicated. METHODS Twenty cow cadavers were used to perform ultrasound-guided bilateral injections of 1.0 mL dye (1.0 mL 1% Toluidine Blue in 1% Borax) at the intervertebral foramen at the level of T13, L1 and L2 spinal nerves. Distance and depth of injection, staining of the dorsal and ventral nerve branches, and deviation from the target were evaluated. The investigator's confidence as to visualisation and expected success at staining the nerve was assessed. Ten clinical cases received the ultrasound-guided proximal paravertebral anaesthesia. Analgesic success was evaluated using a 4-grade scoring system at 10 minutes after the injection and during surgery, respectively. Categorical variables were described using frequencies and proportions. RESULTS Both dorsal and ventral branches of the spinal nerves T13, L1 or L2 were at least partially stained in 41% of injections, while in 77% of injections one of the branches was stained. Five out of ten clinical cases had a satisfactory anaesthesia. There was no significant association between confidence at injection and either staining or analgesic success. CONCLUSION Results from the cadaveric and clinical study suggest no significant improvement using ultrasound guidance to perform proximal paravertebral block in cows compared to our previous clinical experience and to references in the literature using the blind method. CLINICAL RELEVANCE Further research should be conducted to improve the ultrasound-guided technique described in this study.

Indication and timing of soft tissue augmentation at maxillary and mandibular incisors in orthodontic patients. A systematic review.

OBJECTIVE To assess the indication and timing of soft tissue augmentation for prevention or treatment of gingival recession when a change in the inclination of the incisors is planned during orthodontic treatment. MATERIALS AND METHODS Electronic database searches of literature were performed. The following electronic databases with no restrictions were searched: MEDLINE, EMBASE, Cochrane, and CENTRAL. Two authors performed data extraction independently using data collection forms. RESULTS No randomized controlled trial was identified. Two studies of low-to-moderate level of evidence were included: one of prospective and retrospective data collection and one retrospective study. Both implemented a periodontal intervention before orthodontics. Thus, best timing of soft tissue augmentation could not be assessed. The limited available data from these studies appear to suggest that soft tissue augmentation of bucco-lingual gingival dimensions before orthodontics may yield satisfactory results with respect to the development or progression of gingival recessions. However, the strength of the available evidence is not adequate in order to change or suggest a possible treatment approach in the daily practice based on solid scientific evidence. CONCLUSIONS Despite the clinical experience that soft tissue augmentation of bucco-lingual gingival dimensions before orthodontic treatment may be a clinically viable treatment option in patients considered at risk, this treatment approach is not based on solid scientific evidence. Moreover, the present data do not allow to draw conclusions on the best timing of soft tissue augmentation when a change in the inclination of the incisors is planned during orthodontic treatment and thus, there is a stringent need for randomized controlled trials to clarify these open issues.

How does the ascending aorta geometry change when it dissects?

OBJECTIVES The purpose of this study is to delineate changes in aortic geometry and diameter due to dissection. BACKGROUND Aortic diameter is the major criterion for elective ascending aortic replacement for dilated ascending aortas to prevent aortic dissection. However, recommendations are made on the basis of clinical experience and observation of diameters of previously dissected aortas. METHODS Six tertiary centers on 2 continents reviewed their acute aortic dissection type A databases, which contained 1,821 patients. Included were all non-Marfan patients with nonbicuspid aortic valves who had undergone computed tomography angiography <2 years before and within 12 h after aortic dissection onset. Aortic geometry before and after dissection onset were compared. RESULTS Altogether, 63 patients were included (27 spontaneous and 36 retrograde dissections, median age 68 [57; 77] years; 54% were men). In all but 1 patient, maximum ascending aortic diameter was <55 mm before aortic dissection onset. The largest increase in diameter and volume induced by the dissection were observed in the ascending aorta (40.1 [36.6; 45.3] mm vs. 52.9 [46.1; 58.6] mm, +12.8 mm; p < 0.001; 124.0 [90.8; 162.5] cm(3) vs. 171.0 [147.0; 197.0] cm(3), +47 cm(3); p < 0.001). Mean aortic arch diameter increased from 39.8 (30.5; 42.6) mm to 46.4 (42.0; 51.6) mm (+6.6 mm; p < 0.001) and descending thoracic aorta diameter from 31.2 (27.0; 33.3) mm to 34.9 (30.9; 39.5) mm (+3.7 mm; p < 0.001). Changes in thoracic aorta geometry were similar for spontaneous and retrograde etiology. CONCLUSIONS Geometry of the thoracic aorta is affected by aortic dissection, leading to an increase in diameter that is most pronounced in the ascending aorta. Both spontaneous and retrograde dissection result in similar aortic geometry changes.

Modeling corrective experiences as motivational mountain pass

Aim: The landscape metaphor allows viewing corrective experiences (CE) as pathway to a state with relatively lower 'tension' (local minimum). However, such local minima are not easily accessible but obstructed by states with relatively high tension (local maxima) according to the landscape metaphor (Caspar & Berger, 2012). For example, an individual with spider phobia has to transiently tolerate high levels of tension during an exposure therapy to access the local minimum of habituation. To allow for more specific therapeutic guidelines and empirically testable hypotheses, we advance the landscape metaphor to a scientific model which bases on motivational processes. Specifically, we conceptualize CEs as available but unusual trajectories (=pathways) through a motivational space. The dimensions of the motivational state are set up by basic motives such as need for agency or attachment. Methods: Dynamic system theory is used to model motivational states and trajectories using mathematical equations. Fortunately, these equations have easy-to-comprehend and intuitive visual representations similar to the landscape metaphor. Thus, trajectories that represent CEs are informative and action guiding for both therapists and patients without knowledge on dynamic systems. However, the mathematical underpinnings of the model allow researchers to deduct hypotheses for empirical testing. Results: First, the results of simulations of CEs during exposure therapy in anxiety disorders are presented and compared to empirical findings. Second, hypothetical CEs in an autonomy-attachment conflict are reported from a simulation study. Discussion: Preliminary clinical implications for the evocation of CEs are drawn after a critical discussion of the proposed model.

The pre- and post-somatic segments of the human type I spiral ganglion neurons--structural and functional considerations related to cochlear implantation.

Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-β2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-β2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-β2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.

Is The Allergen Really Needed in Allergy Immunotherapy?

Immunotherapy for type I allergies is well established and is regarded to be the most efficient treatment option besides allergen avoidance. As of today, different forms of allergen preparations are used in this regard, as well as different routes of application. Virus-like particles (VLPs) represent a potent vaccine platform with proven immunogenicity and clinical efficacy. The addition of toll-like receptor ligands and/or depot-forming adjuvants further enhances activation of innate as well as adaptive immune responses. CpG motifs represent intensively investigated and potent direct stimulators of plasmacytoid dendritic cells and B cells, while T cell responses are enhanced indirectly through increased antigen presentation and cytokine release. This article will focus on the function of VLPs loaded with DNA rich in nonmethylated CG motifs (CpGs) and the clinical experience gained in the treatment of allergic rhinitis, demonstrating clinical efficacy also if administered without allergens. Several published studies have demonstrated a beneficial impact on allergic symptoms by treatment with CpG-loaded VLPs. Subcutaneous injection of VLPs loaded with CpGs was tested with or without the adjuvant alum in the presence or absence of an allergen. The results encourage further investigation of VLPs and CpG motifs in immunotherapy, either as a stand-alone product or as adjuvants for allergen-specific immunotherapy.