Safety and Immunogenicity of an Adjuvanted Clostridioides difficile Vaccine Candidate in Healthy Adults: A Randomized Placebo-Controlled Phase 1 Study.

Background: This study investigated the safety, reactogenicity, and immunogenicity in healthy subjects of a Clostridioides difficile vaccine candidate with/without adjuvant, targeting toxins A and B.

Methods: In this first-in-human, phase 1, observer-blind study, subjects aged 18-45 years were randomized to receive F2 antigen (n = 10) or placebo (n = 10), and subjects aged 50-70 years to receive F2 antigen plus AS01 adjuvant (n = 45), F2 antigen (n = 45), or placebo (n = 30) in 2 doses 1 month apart. A subcohort (n = 40) received a third dose 15 months later.

An empirical evaluation of approximate and exact regression-based causal mediation approaches for a binary outcome and a continuous or a binary mediator for case-control study designs.

Background: In the causal mediation analysis framework, several parametric regression-based approaches have been introduced in past years for decomposing the total effect of an exposure on a binary outcome into a direct effect and an indirect effect through a target mediator. In this context, a well-known strategy involves specifying a logistic model for the outcome and invoking the rare outcome assumption (ROA) to simplify estimation. Recently, exact estimators for natural direct and indirect effects have been introduced to circumvent the challenges prompted by the ROA.

Combining androgen deprivation and radiation therapy in the treatment of localised prostate cancer: Summary of level 1 evidence and current gaps in knowledge.

•Localized prostate cancer.•Androgen deprivation therapy.•Radiation therapy.

Utility of urinary cytokine levels as predictors of the immunogenicity and reactogenicity of AS01-adjuvanted hepatitis B vaccine in healthy adults.

Plasma cytokines are useful indicators of the inflammatory response to vaccination, and can serve as potential biomarkers of the systemic reactogenicity and immunogenicity of vaccines. Measurement of cytokines in urine may represent a non-invasive alternative to the blood-based markers. To evaluate whether urinary cytokine levels can help predict vaccine responses to an AS01-adjuvanted vaccine, we measured concentrations of 24 cytokines in the urine from 30 hepatitis B virus (HBV)-naïve adults following administration of AS01-adjuvanted HBV surface antigen vaccine (NCT01777295).

A programme for early diagnosis of atrial fibrillation: a multi-centre study in primary care.

Background: Atrial fibrillation (AF) is a morbid disease whose complications can be prevented if prompt and correctly treated.

Objective: To assess the usefulness of an early AF diagnosis programme in at-risk individuals in primary care centres.

Methods: In an open-label, multi-centre, controlled interventional study, individuals with one or more risk factors for AF but without known AF were enrolled.

Current and Emerging DMARDs for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is the most prevalent form of inflammatory arthritis. It is a profoundly serious and severe disease that if it goes untreated could have severe consequences to the joints and health of the patient who carries this diagnosis. The treatment of RA has dramatically changed since the year 2000, with the discovery of the TNFis, then other biologics, and finally the JAKi.

Impact of Neck Dissection in Head and Neck Squamous Cell Carcinomas of Unknown Primary.

Purpose: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP.

Methods: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage.

Antibody avidity, persistence, and response to antigen recall: comparison of vaccine adjuvants.

Differences in innate immune 'imprinting' between vaccine adjuvants may mediate dissimilar effects on the quantity/quality of persisting adaptive responses. We compared antibody avidity maturation, antibody/memory B cell/CD4 T cell response durability, and recall responses to non-adjuvanted fractional-dose antigen administered 1-year post-immunization (Day [D]360), between hepatitis B vaccines containing Adjuvant System (AS)01, AS01, AS03, AS04, or Alum (NCT00805389). Both the antibody and B cell levels ranked similarly (AS01/AS03 > AS04 > Alum) at peak response, at D360, and following their increases post-antigen recall (D390).

Concurrent diagnosis of oropharynx cancer and bone sarcoidosis mimicking metastasis.

Bone location is uncommon in both sarcoidosis and in neck cancer (HNC). Diagnosis of a bone lesion is therefore challenging to distinguish its nature in a patient suffering from both diseases. We report the case of a 69-years-old woman referred for P16 positive HPV-HNC.

Agriculture increases the bioavailability of silicon, a beneficial element for crop, in temperate soils.

Crops may take benefits from silicon (Si) uptake in soil. Plant available Si (PAS) can be affected by natural weathering processes or by anthropogenic forces such as agriculture. The soil parameters that control the pool of PAS are still poorly documented, particularly in temperate climates.

Assessing the effect of genetic markers on drug immunogenicity from a mechanistic model-based approach.

Background: With the growth in use of biotherapic drugs in various medical fields, the occurrence of anti-drug antibodies represents nowadays a serious issue. This immune response against a drug can be due either to pre-existing antibodies or to the novel production of antibodies from B-cell clones by a fraction of the exposed subjects. Identifying genetic markers associated with the immunogenicity of biotherapeutic drugs may provide new opportunities for risk stratification before the introduction of the drug.

Inflammatory parameters associated with systemic reactogenicity following vaccination with adjuvanted hepatitis B vaccines in humans.

Background: Adjuvants like AS01 increase the immunogenicity of vaccines and generally cause increased transient reactogenicity compared with Alum. A phase II randomized trial was conducted to characterize the response to AS01 and Alum adjuvanted vaccines. A post-hoc analysis was performed to examine the associations between reactogenicity and innate immune parameters.

Unilateral or bilateral irradiation in cervical lymph node metastases of unknown primary? A retrospective cohort study.

Introduction: Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation.

Radical cystectomy or bladder preservation with radiochemotherapy in elderly patients with muscle-invasive bladder cancer: Retrospective International Study of Cancers of the Urothelial Tract (RISC) Investigators.

Background: Radical cystectomy (RC) and radiochemotherapy (RCT) are curative options for muscle-invasive bladder cancer (MIBC). Optimal treatment strategy remains unclear in elderly patients.

Material And Methods: Patients aged 80 years old and above with T2-T4aN0-2M0-Mx MIBC were identified in the Retrospective International Study of Cancers of the Urothelial Tract (RISC) database.

Increased levels of circulating platelet-derived microparticles are associated with metastatic cutaneous melanoma.

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden.

[Prevalence and management of pain in patients with metastatic cancer in Franche-Comté].

Introduction: Pain management is a major public health problem, especially in oncology. In order to assess professional practice, the IRFC-FC conducted a survey amongst patients with metastatic osteophilic solid tumor in Franche-Comté. The aims were to assess the pain prevalence, and its characteristics, its management and its impact on patients' quality of life in patients in pain.

Phase I, randomized, observer-blind, placebo-controlled studies to evaluate the safety, reactogenicity and immunogenicity of an investigational non-typeable Haemophilus influenzae (NTHi) protein vaccine in adults.

Background: Non-typeable Haemophilus influenzae (NTHi) is a major cause of various respiratory diseases. The development of an effective vaccine against NTHi mandates new approaches beyond conjugated vaccines as this opportunistic bacterium is non-encapsulated. Here we report on the safety, reactogenicity and immunogenicity of a multi-component investigational vaccine based on three conserved surface proteins from NTHi (proteins D [PD], E [PE] and Pilin A [PilA]) in two observer-blind phase I studies.

Carboplatin-etoposide combination chemotherapy in metastatic castration-resistant prostate cancer: A retrospective study.

The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differentiated neuroendocrine cancers, such as small-cell lung cancer. The aim of this study was to assess the efficacy and tolerability of the carboplatin-etoposide regimen in metastatic castration-resistant prostate cancer (mCRPC). A total of 27 patients treated by carboplatin [area under the curve (AUC)=5] and etoposide (100 mg/m intravenous infusion on days 1-3 or 75 mg orally/day for 10 days) for mCRPC were included for analysis.

Adjuvant Chemotherapy in Rectal Cancer after Chemoradiotherapy.

The aim of this overview was to investigate whether adjuvant chemotherapy has a favourable effect on the outcome of patients with rectal cancer who had preoperative (chemo)radiotherapy. A review of randomised clinical trials that allocated patients between fluorouracil-based and observation or between fluorouracil-based and oxaliplatin-based adjuvant chemotherapy after preoperative (chemo)radiotherapy was carried out, including their corresponding meta-analyses. None of the five randomised trials has shown a significant benefit of fluorouracil-based adjuvant chemotherapy for overall survival or disease-free survival.

Evaluation of a 36 Gy elective node irradiation dose in anal cancer.

Purpose: To retrospectively analyze the efficacy of 36 Gy of elective node irradiation and report patterns of recurrence in patients with anal cancer treated by chemoradiation with the same radiotherapy (RT) treatment scheme.

Methods And Materials: Between January 1996 and December 2013, 142 patients with anal squamous cell cancer were scheduled to receive a dose of 36 Gy of elective node irradiation (ENI) to the inguinal area and whole pelvis over 4 weeks followed after a 2-week gap by a boost dose of 23.4 Gy over 17 days to the macroscopic disease.

Randomized controlled study of the safety and immunogenicity of pneumococcal vaccine formulations containing PhtD and detoxified pneumolysin with alum or adjuvant system AS02V in elderly adults.

Six vaccine formulations containing AS02V or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 μg PhtD-dPly plus AS02V or alum, 8PCV plus AS02V or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated.

Persistence clinical studies: can you believe what you see?

Long-term immunity, evaluated by the persistence of antibody titers, is important to assess duration of protection induced by vaccination. This paper aims at drawing awareness on the risk of misinterpreting persistence results in absence of adjustment for missing or left-censored data. Using simulations, the paper shows that repeated measurement models are an appropriate alternative to control the bias associated to unadjusted persistence results.

A randomized, controlled trial to assess the immunogenicity and safety of a heptavalent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, hib and meningococcal serogroup C combination vaccine administered at 2, 3, 4 and 12-18 months of age.

Background: Combination vaccines offer protection against multiple diseases with fewer injections. This study evaluated the immunogenicity and safety of an investigational diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) heptavalent combination vaccine (heptavalent vaccine) given as 4 doses at 2, 3, 4 and 12-18 months of age.

Methods: In this randomized, open, phase II study (NCT00970307/NCT01171989) conducted in Poland, 421 infants were enrolled to receive the heptavalent vaccine or licensed comparator vaccines.

Phase II study of a three-dose primary vaccination course of DTPa-IPV/Hib-MenC-TT followed by a 12-month Hib-MenC-TT booster in healthy infants.

Aim: To test for immunologic noninferiority of antibody responses to Hib and MenC using a 6-in-1 combination vaccine (DTPa-IPV/Hib-MenC-TT) compared with DTPa-IPV-Hib plus MenC-CRM197, before and after a 12-month Hib-MenC-TT booster.

Methods: Pragmatic open-label, randomized, multicenter, UK study. "6-in-1" group received DTPa-IPV/Hib-MenC-TT at 2, 3 and 4 months; control group received DTPa-IPV-Hib at 2, 3 and 4 months and MenC-CRM197 at 3 and 4 months.