Six-month results following treatment of aggressive periodontitis with antimicrobial photodynamic therapy or amoxicillin and metronidazole

Objective

The use of antibacterial photodynamic therapy (aPDT) additionally to scaling and root planing (SRP) has been shown to positively influence the clinical outcomes. However, at present, it is unknown to what extent aPDT may represent a potential alternative to the use of systemic antibiotics in nonsurgical periodontal therapy in patients with aggressive periodontitis (AP). The aim of this study was to evaluate the outcomes following nonsurgical periodontal therapy and additional use of either aPDT or amoxicillin and metronidazole (AB) in patients with AP.

Material and methods

Thirty-six patients with AP displaying at least three sites with pocket depth (PD) ≥6 mm were treated with SRP and either systemic administration of AB for 7 days or with two episodes of aPDT. The following clinical parameters were evaluated at baseline and at 6 months: plaque index (PI), bleeding on probing (BOP), PD, gingival recession (GR) and clinical attachment level (CAL).

Results

Thirty-five patients have completed the 6-month evaluation. At 6 months, mean PD was statistically significantly reduced in both groups (from 5.0?±?0.8 to 3.0?±?0.6 mm with AB and from 5.1?±?0.5 to 3.9?±?0.8 mm with aPDT (p?p?p?p?=?0.03). Both therapies resulted in statistically significant reductions in all parameters compared to baseline.

Conclusion

While both treatments resulted in statistically significant clinical improvements, AB showed statistically significantly higher PD reduction and lower number of pockets ≥7 mm compared to aPDT.

Clinical relevance

In patients with AP, the two times application of aPDT in conjunction with nonsurgical periodontal therapy cannot be considered an alternative to the systemic use of amoxicillin and metronidazole.     

Antigen expression level threshold tunes the fate of CD8 T cells during primary hepatic immune responses

CD8 T-cell responses to liver-expressed antigens range from deletional tolerance to full effector differentiation resulting in overt hepatotoxicity. The reasons for these heterogeneous outcomes are not well understood. To identify factors that govern the fate of CD8 T cells activated by hepatocyte-expressed antigen, we exploited recombinant adenoassociated viral vectors that enabled us to vary potential parameters determining these outcomes in vivo. Our findings reveal a threshold of antigen expression within the liver as the dominant factor determining T-cell fate, irrespective of T-cell receptor affinity or antigen cross-presentation. Thus, when a low percentage of hepatocytes expressed cognate antigen, high-affinity T cells developed and maintained effector function, whereas, at a high percentage, they became functionally exhausted and silenced. Exhaustion was not irreversibly determined by initial activation, but was maintained by high intrahepatic antigen load during the early phase of the response; cytolytic function was restored when T cells primed under high antigen load conditions were transferred into an environment of low-level antigen expression. Our study reveals a hierarchy of factors dictating the fate of CD8 T cells during hepatic immune responses, and provides an explanation for the different immune outcomes observed in a variety of immune-mediated liver pathologic conditions.The liver is acknowledged to possess unique tolerogenic properties, which have likely evolved to maintain immunological unresponsiveness toward food-derived and microbial antigens that enter the circulation via the gut (1, 2). This tolerogenic capability of the liver is demonstrated in animal models of liver transplantation, in which liver allografts are accepted across complete MHC mismatch barriers and are able to protect other donor tissues from rejection (reviewed in ref. 3). In humans, the tolerogenic hepatic environment is likely to contribute to impaired immune clearance of the hepatitis B virus (HBV) and hepatitis C virus (HCV), which result in persistent infection in a significant proportion of exposed individuals and are associated with major morbidity and mortality. In contrast, effective immune responses to hepatotropic pathogens leading to resolution of infection are observed in most hepatitis A and E virus infections, the majority of individuals infected with HBV during adulthood, and a minority of those infected by HCV (reviewed in refs. 4, 5). The liver is also susceptible to a variety of autoimmune-mediated conditions (6). Collectively, these observations indicate that effective immune responses can be initiated and/or sustained in the liver despite its apparent predisposition toward the generation of tolerance. Unfortunately, there is no small animal model in which to study the parameters that determine the balance between intrahepatic immunity and tolerance in viral hepatitis. Thus, the factors that shape immune outcome have not yet been identified.By studying the fate of antigen-specific CD8 T cells transferred into mice expressing antigen in the liver, it has been shown that, despite being a nonlymphoid organ, the liver is able to support primary CD8 T-cell activation (7). However, depending on the choice of antigen expressed and mode of delivery, the outcome of intrahepatic CD8 T-cell activation has been varied, ranging from deletion and/or functional silencing (8–10) to cytotoxic T lymphocyte (CTL) development (11, 12). This observed diversity of T-cell fates parallels the heterogeneous outcomes of liver-immune interactions observed during hepatotropic viral infections in humans. Thus, reconciliation of these findings holds the potential to yield critical insights into the immunopathological basis of immune-mediated liver disease as well as liver-associated tolerance.In this study, we developed an integrated system in which we manipulated parameters predicted to influence the generation of effector CD8 T cells encountering their cognate antigen on hepatocytes. By identifying three key determinants of the generation of functional effector cells in response to hepatocyte-expressed antigen, this study provides, for the first time to our knowledge, a unified model that explains and predicts the functional outcome of CD8 T-cell activation by liver-expressed antigen and reconciles findings from a number of previous studies that addressed this question.     

Long-term follow-up evaluation of endoscopic sclerotherapy for dilated gastrojejunostomy after gastric bypass

Background

Endoscopic sclerotherapy using sodium morrhuate has been used to treat patients with weight regain after Roux-en-Y gastric bypass whose presumed etiology is loss of restriction due to gastrojejunostomy dilation. Weight loss and stability have been demonstrated in several studies with short-term follow-up evaluation.

Methods

This retrospective review evaluated all the patients who underwent sclerotherapy for a dilated gastrojejunostomy between 2007 and 2012.

Results

The study identified 48 patients with a mean follow-up period of 22 months (range 12–60 months). The mean age of these patients was 47.5 ± 10.5 years, and 92 % were women. The average weight loss from the primary procedure was 132.5 ± 54.82 lb, and the average weight regain from the lowest weight to the maximum weight before sclerotherapy was 46 ± 40.32 lb. The median number of sclerotherapy sessions was two (range 1–4). The pre-procedure mean gastrojejunostomy diameter was 20 ± 3.6 mm, and the mean volume of sodium morrhuate injected per session was 12.8 ± 3.7 ml. The average weight loss from sclerotherapy to the final documented weight was 3.17 ± 19.70 lb, which was not statistically significant. The following variables in the multivariate analysis were not associated with statistically significant weight loss: volume of sodium morrhuate, patient age, gastrojejunostomy diameter, number of sclerotherapy sessions, decrease in gastrojejunostomy diameter between the first and second sessions, and number of follow-up years. Weight stabilization or loss was achieved by 58 % of our cohort, with a mean weight loss of 15.9 ± 14.6 lb in this subgroup.

Conclusion

The long-term follow-up evaluation of patients undergoing sclerotherapy of the gastrojejunostomy for weight regain after gastric bypass showed only a marginal weight loss, which was not statistically significant in our study population, although more than 50 % of the patients achieved weight loss or stabilization.     

Management of ear keloids using custom-molded pressure clips: a preliminary study

Background

The application of mechanical pressure by compression devices has gained popularity in the treatment of keloid scars. In this present study, we analyze the long-term efficacy of our custom-molded pressure clip for ear keloids. Our secondary objective is to identify risk factors for the failure of the treatment in the group of the recurrence.

Methods

The patient group consisted of 9 men and 19 women with a mean age of 27 years and a mean follow-up of 8.5 years. For evaluation of the scars, scoring ratings, Patient and Observer Scar Assessment Scale (POSAS), and SF8-questionnaire have been used.

Results

Follow-up observations showed that 71 % were treated successfully. There were significant differences in the Fitzpatrick scale, cause of the ear keloids, overall opinion, and openness for re-treatment between the recurrence and nonrecurrence group. Furthermore, treatment with our custom-molded pressure ear clip resulted in a statistically significant improvement of all the item scores of the POSAS in both the patient and observer scales. Severe complications such as infections or necrosis were not noted.

Conclusions

In this study, we show that the results of adjuvant pressure therapy with our custom-molded ear clips are comparable with the recurrence rates of other studies recently published. The strength of this study is the long follow-up. Level of Evidence: Level III, therapeutic study     

Identifying wound prevalence using the Mobile Wound Care program

Measuring the prevalence of wounds within health care systems is a challenging and complex undertaking. This is often compounded by the clinicians' training, the availability of the required data to collect, incomplete documentation and lack of reporting of this type of data across the various health care settings. To date, there is little published data on wound prevalence across regions or states. This study aims to identify the number and types of wounds treated in the Gippsland area using the Mobile Wound Care (MWC?) program. The MWC program has enabled clinicians in Gippsland to collect data on wounds managed by district nurses from four health services. The main outcomes measured were patient characteristics, wound characteristics and treatment characteristics of wounds in Gippsland. These data create several clinical and research opportunities. The identification of predominant wound aetiologies in Gippsland provides a basis on which to determine a regional wound prospective and the impact of the regional epidemiology. Training that incorporates best practice guidelines can be tailored to the most prevalent wound types. Clinical pathways that encompass the Australian and New Zealand clinical practice guidelines for the management of venous leg ulcers can be introduced and the clinical and economical outcomes can be quantitatively measured. The MWC allows healing times (days) to be benchmarked both regionally and against established literature, for example, venous leg ulcers.     

Nasogastric tubes: an historical context.

Nurses commonly care for patients with nasogastric tubes. Many authors have addressed the management of nasogastric tubes; however, discussion rarely considers the historical perspective. The purpose of this article is to provide an historical context on nasogastric tubes.     

Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy

Allergen-specific desensitization is the only disease-modifying therapy currently available for the treatment of allergies. These therapies require application of allergen over several years and some may induce life-threatening anaphylactic reactions. An ideal vaccine for desensitization should be highly immunogenic and should alleviate allergic symptoms upon few injections while being nonreactogenic. We describe such a vaccine for the treatment of cat allergy, consisting of the major cat allergen Fel d1 coupled to bacteriophage Qβ-derived virus-like particles (Qβ–Fel d1). Qβ–Fel d1 was highly immunogenic, and a single vaccination was sufficient to induce protection against type I allergic reactions. Allergen-specific immunoglobulin G antibodies were shown to be the critical effector molecules and alleviated symptoms by two distinct mechanisms. Although allergen-induced systemic basophil degranulation was inhibited in an FcγRIIb-dependent manner, inhibition of local mast cell degranulation in tissues occurred independently of FcγRIIb. In addition, treatment with Qβ–Fel d1 abolished IgE memory responses upon antigen recall. Despite high immunogenicity, the vaccine was essentially nonreactogenic and vaccination induced neither local nor systemic anaphylactic reactions in sensitized mice. Moreover, Qβ–Fel d1 did not induce degranulation of basophils derived from human volunteers with cat allergies. These data suggest that vaccination with Qβ–Fel d1 may be a safe and effective treatment for cat allergy.Allergic reactions are associated with several hypersensitivity diseases including asthma, rhinoconjunctivitis, contact dermatitis, urticaria, anaphylaxis, and insect, drug, and food allergy. These diseases can affect all age groups and have reached epidemic proportions worldwide with increasing incidence over the last decades (Holgate, 1999). The most common forms of allergies, such as pollen, house dust, or animal dander allergies, are dependent on type 2 T cell responses (Georas et al., 2005), leading to the generation of IL-4 and IgE. IgE antibodies have a short half-life in serum but are stable if bound to Fcε receptors on circulating basophils and, in particular, tissue mast cells (Vieira and Rajewsky, 1988). Cross-linking of the IgE–FcεI receptor complex on these cells by allergen leads to degranulation within seconds, liberating a variety of preformed inflammatory mediators. The clinical effects attended by such allergic reactions vary according to the site of basophil and mast cell activation. Although inhalation or ingestion of allergens activates mucosal mast cells, i.v. or s.c. antigen entry activates circulating basophils and connective tissue mast cells.Most current therapies for the treatment of allergies block mast cell effector molecules (e.g., histamines) or nonspecifically suppress immune responses (e.g., steroids). Although effective, these treatments fail to affect the immunological conditions causing the allergies. In addition, different vaccination or desensitization strategies have been investigated, including the usage of allergen-derived peptides (Francis and Larché, 2005), recombinant hypoallergenic derivates (Niederberger et al., 2004; Saarne et al., 2005), oligonucleotides with CpG motives (Hessel et al., 2005), or allergen conjugated to carbohydrate-based particles (Andersson et al., 2004). However, only a few disease-modifying therapies for allergy have been approved so far. These immunotherapies consist of either multiple s.c. injections of increasing doses of allergen or multiple sublingual or oral administration of the allergen, resulting in long-term desensitization (Till et al., 2004). Although these allergen-specific immunotherapies have shown successes (Durham and Till, 1998), the procedures are time consuming and require 1–3 yr of regular treatments (Hedlin et al., 1986, 1991). Moreover, this therapy bears a high risk for anaphylactic reactions, especially after administration of higher allergen doses (Cox and Coulter, 1997; Bousquet et al., 1998).The mechanism by which this specific immunotherapy affects allergies is poorly understood. The reduction in allergic symptoms by this treatment has been hypothesized to be at least partly mediated by a shift from Th2 toward a Th1 response or the induction of regulatory T (T reg) cells (Akdis et al., 2005). Alternatively, and not mutually exclusive, the balance between allergen-specific IgE and IgG antibodies may regulate mast cell and basophil activity. In fact, Hulett et al. (1993) identified an FcR, with a binding site for IgG, which regulates high affinity IgE receptor–mediated mast cell activation (Daëron et al., 1995b). It is well established that the FcγRIIb (FcγIIb receptor), expressed on mouse and human basophils and mast cells (Bischoff, 2007), can down-regulate FcεRI signaling by cross-linking of the FcεRI–IgE and FcγRIIb–IgG-Ag complex (Daëron et al., 1995a; Katz, 2002; Bruhns et al., 2005; Kraft and Kinet, 2007; Nimmerjahn and Ravetch, 2008). Indeed, a fusion molecule between the cat allergen Fel d1 and the constant part of IgG1 has recently been shown to inhibit allergic symptoms by cross-linking of FcγRIIb with FcεRI in a mouse model of asthma (Zhu et al., 2005; Terada et al., 2006). In addition to signaling through FcγRIIb, allergen-specific IgG antibodies may sequester allergens and hence prevent their binding to IgE–FcεRI complexes. Moreover, it has been shown that the ratio of allergen-specific IgE and IgG antibodies may affect presentation of allergen-derived epitopes to T cells (Wachholz and Durham, 2004). Thus, allergen-specific antibodies may have multiple ways to modulate allergic responses.We have previously shown that antigens displayed in a repetitive fashion on virus-like particles (VLPs) derived from the coat protein of the bacteriophage Qβ are highly immunogenic in mice (Jegerlehner et al., 2002a,b; Lechner et al., 2002; Spohn et al., 2005) and humans (Maurer et al., 2005; Kündig et al., 2006; Ambühl et al., 2007; Tissot et al., 2008). Because bacterial host RNA is incorporated into the VLPs during self-assembly inside bacteria, Qβ-VLPs provide Toll-like receptor ligands, which induce strong IgG2a/c-dominated antibody responses (Forsbach et al., 2007, 2008; Jegerlehner et al., 2007). In the present study, the major cat allergen Fel d1 was coupled in an oriented fashion to Qβ-VLPs, resulting in a highly repetitive form of the allergen. This vaccine was strongly immunogenic in mice, yielding high and long-lasting antigen-specific serum IgG titers after only a single immunization. Vaccination with Qβ–Fel d1 resulted in strongly reduced immediate type I allergic responses in a mouse model of mast cell degranulation, vascular leakage, and anaphylaxis and completely abolished IgE B cell memory responses upon antigen recall. Strikingly, coupling of Fel d1 to Qβ-VLPs essentially abrogated its ability to induce allergic responses in mice or the degranulation of human basophils derived from allergic individuals. Thus, displaying Fel d1 on VLPs enhanced its immunogenicity and therapeutic efficacy while strongly reducing its reactogenicity.     

Topography of Prostate Cancer Recurrence After Radiation Therapy: A Detailed Mapping Study of Salvage Radical Prostatectomy Specimens

In men who do not respond to initial radiation therapy, accurate knowledge of the site of cancer recurrence or persistence is necessary to understand treatment failure. We evaluated the pathologic characteristics of recurrent/persistent prostate cancer with tumor maps from the whole-mount slides of salvage radical prostatectomies performed between 2000 and 2014. Of 216 consecutive patients, detailed tumor maps were available for 77. Sixty-nine patients (90%) were found to have tumor in the apex, of which 46% occurred in the most apical 3 mm. Fifty-three patients (69%) had tumors at a distance of ≤5 mm from the urethra. Five patients had tumor directly involving the urethra, all of whom had urethral invasion at the apex. Seminal vesicle involvement was seen in 32 patients (42%), two of whom had tumor only in the seminal vesicles. Sixty-two patients (81%) had tumors in the distal apex, periurethral area, or seminal vesicles, that is, areas that are not routinely biopsied. Targeting these areas could improve the accuracy of biopsy when cancer recurrence is suspected.

Below the surface: Parents’ views on the factors that influence treatment adherence in paediatric burn scar management — A qualitative study

Introduction

Parents have a crucial role to play in burn scar management for their children at a time that is extremely stressful for them and their child. Scar management treatments such as pressure garment therapy (PGT) require high levels of adherence. There has been a lack of research into the factors that may influence adherence in paediatric burn scar management. This qualitative research study has investigated parents’ experiences of scar management and their attempts to adhere to treatment at home. The aim of this paper is to outline parents’ views on the factors that influence adherence.

Feasibility of a Kinect®-based rehabilitation strategy after burn injury

Introduction

The advent of consoles that deliver both interactive games and therapy may augment rehabilitation options in burn patients. The Jintronix software combines therapy-specific software and interactive gaming as a form of coaching and records patient performance on the Kinect^® platform. Our objective was to determine the feasibility of a set of Jintronix games and therapy modules in hospitalized adult burn patients.