Evaluation of safety and efficacy as an adjuvant for the chitosan-based vaccine delivery vehicle ViscoGel in a single-blind randomised Phase I/IIa clinical trial

ViscoGel, a chitosan-based hydrogel, has earlier been shown to improve humoral and cell-mediated immune responses in mice. In this study, a Phase I/IIa clinical trial was conducted to primarily evaluate safety and secondarily to study the effects of ViscoGel in combination with a model vaccine, Act-HIB to Haemophilus influenzae type b, administered as a single intramuscular injection. Healthy volunteers of both sexes, ages 22–50 and not previously vaccinated to HIB, were recruited. The trial had two phases. In Phase A, three ascending dose levels of ViscoGel (25, 50 and 75 mg) were evaluated for safety in 3 × 10 subjects. Phase B had a single-blind, randomised, parallel-group design evaluating safety and efficacy in five groups, 20 subjects/group, comparing vaccination with 0.2 μg or 2 μg Act-HIB alone or combined with ViscoGel (50 mg) and one group receiving the standard Act-HIB dose (10 μg). No safety or tolerability concerns were identified. Local, transient reactions at the injection site were the most common adverse events. These were more frequent in groups receiving Act-HIB + ViscoGel, while other AEs were recorded at similar frequency in Act-HIB and Act-HIB + ViscoGel groups. Efficacy was evaluated by measuring serum anti-HIB antibodies and cellular responses in peripheral blood mononuclear cells (PBMC). There was a large variation in baseline anti-HIB antibody titres and no adjuvant effect was observed on the anti-HIB antibody production in groups vaccinated with Act-HIB + ViscoGel. ELISpot analyses revealed increased interferon-γ (IFN-γ) responses to Act-HIB in PBMCs from subjects vaccinated with Act-HIB in combination with ViscoGel, compared to groups receiving Act-HIB alone. Moreover, ViscoGel counteracted an inhibitory effect of Act-HIB vaccination on the IFN-γ response to both the vaccine itself and an irrelevant influenza antigen. In summary, ViscoGel was found to be safe and well-tolerated, supporting further examination of ViscoGel as a new innovative vehicle for vaccine development.     

Clinical and Radiographic Outcomes of Traumatized Immature Permanent Necrotic Teeth after Revascularization/Revitalization Therapy

Introduction

Revascularization treatment is rapidly becoming an accepted treatment alternative for the management of endodontic pathology in immature permanent teeth with necrotic dental pulps. However, the success and timing of clinical resolution of symptoms, and radiographic outcomes of interest, such as continued hard tissue deposition within the root, are largely unknown.

Methods

In this prospective cohort study, 20 teeth were treated with a standardized revascularization treatment protocol and monitored for clinical and radiographic changes for 1 year. Standardized radiographs were collected at regular intervals, and radiographic changes were quantified.

Results

All 20 treated teeth survived during the 12-month follow-up period, and all 20 also met the clinical criteria for success at 12 months. As a group, the treated teeth showed a statistically significant increase in radiographic root width and length and a decrease in apical diameter, although the changes in many cases were quite small (such that the clinical significance is unclear). The within-case percent change in apical diameter after 3 months was 16% and had increased to 79% by 12 months, with 55% (11/20) showing complete apical closure. The within-case percent change in root length averaged less than 1% at 3 months and increased to 5% at 12 months. The within-case percent change in root thickness averaged 3% at 3 months and 21% at 12 months.

Conclusions

Although clinical success was highly predictable with this procedure, clinically meaningful radiographic root thickening and lengthening are less predictable after 1-year of follow-up. Apical closure is the most consistent radiographic finding.     

Amniotic fluid embolism causing severe left ventricular dysfunction and death: Case report and review of the literature

Hemodynamic instability in amniotic fluid embolism has previously been demonstrated only by right heart catheterization. We present detailed documentation obtained by echocardiography and cardiac catheterization of a 35-year-old woman who developed amniotic fluid embolism and died from severe left ventricular dysfunction and wide QRS complex tachycardia despite intensive medical therapy (inotropes) and mechanical (intraaortic balloon pump) support. © 1996 Wiley-Liss, Inc.     

Integrin α3β1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma

We have reported that metastatic human melanoma cells utilize the α_vβ₃ integrin to adhere to lymph node vitronectin (VN). In the present study, the adhesion of human and rat breast carcinoma cells to lymph node tissue was analyzed. We have previously shown a correlation between the metastatic potential of breast carcinoma cells and an RGD-mediated adhesion to cryostat sections of peripheral lymph nodes; this adhesion could be blocked by an antibody to the integrin β₁ subunit. Here, we show that the metastatic breast carcinoma cell were significantly more adherent to fibronectin (FN) expressed by lymph node-derived stromal cells than non-metastatic cells. Metastatic cells also spread more rapidly than non-metastatic cells on FN-coated substrates. Using a combination of immunofluorescence microscopy, immunoprecipitation and blocking assays with integrin-specific antibodies, we found (i) that expression of the α₃β₁ integrin on metastatic mammary carcinoma cells was specifically increased in comparison to non-metastatic cells and (ii) that the α₃β₁ receptor was involved in the increased adhesion of metastatic cells to lymph node FN and in cell spreading on FN-coated substrates. Our data also suggest that the α₅β₁ integrin, which is also expressed on the metastatic cells, did not contribute to this increase in adhesion. Our data implicate the α₃β₁ integrin in adhesion to lymph node stromal cell FN and suggest that metastatic cells of different tissue origins (e.g., melanoma and breast carcinoma) may utilize distinct integrin-ligand combinations to colonize the same target organ. © 1996 Wiley-Liss, Inc.     

Utero-cutaneous fistula following cesarean section: A case report

Utero-cutaneous fistula is a rare pathology. It mostly occurs consecutively to surgical intervention such as Cesarean section. Blood discharge from the cesarean scar during menstruation is a quasi-pathognomonic feature. Imaging modalities, particularly with the injection of contrast material through the cutaneous fistulous opening, confirm the diagnosis. The management is mainly surgical.We report the case of a utero-cutaneous fistula in a 27-year-old lady, with systemic lupus erythematosus. She presented seven months after her third cesarean section with pain and blood discharge from the cutaneous scar during menstruation for four months. A pelvic CT scan with the injection of the contrast material through the cutaneous fistulous opening confirmed the diagnosis of utero-cutaneous fistula. Surgical management was successful.     

Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas

ObjectivesThe eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC.ResultsOur analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively.ConclusionThe overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.