Submandibular myofibroma: a case report

Purpose

Myofibroma is a rare benign spindle cell neoplasm, and the aim of the present study was to carry out a literature review and present a clinical case of a patient with a myofibroma in the submandibular region and its management.

Conclusions

Diagnosis of myofibroma can be reached by a histopathologic and immunohistochemical analysis and surgical excision is the treatment of choice.     

How to Regulate Nonbiological Complex Drugs (NBCD) and Their Follow-on Versions: Points to Consider

The aim of this critical review is to reach a global consensus regarding the introduction of follow-on versions of nonbiological complex drugs (NBCD). A nonbiological complex drug is a medicinal product, not being a biological medicine, where the active substance is not a homo-molecular structure, but consists of different (closely related and often nanoparticulate) structures that cannot be isolated and fully quantitated, characterized and/or described by state of the art physicochemical analytical means and where the clinical meaning of the differences is not known. The composition, quality and in vivo performance of NBCD are highly dependent on manufacturing processes of both the active ingredient as well as in most cases the formulation. The challenges posed by the development of follow-on versions of NBCD are illustrated in this paper by discussing the ‘families’ of liposomes, iron–carbohydrate (‘iron–sugar’) drugs and glatiramoids. It is proposed that the same principles for the marketing authorization of copies of NBCD as for biosimilars be used: the need for animal and/or clinical data and the need to show similarity in quality, safety and efficacy. The regulatory approach of NBCD will have to take into consideration the specific characteristics of the drugs, their formulation and manufacturing process and the resulting critical attributes to achieve their desired quality, safety and efficacy. As with the biosimilars, for the NBCD product, family-specific methods should be evaluated and applied where scientifically proven, including sophisticated quality methods, pharmacodynamic markers and animal models. Concerning substitution and interchangeability of NBCD, it is also advisable to take biosimilars as an example, i.e. (1) substitution without the involvement of a healthcare professional should be discouraged to ensure traceability of the treatment of individual patients, (2) keep an individual patient on a specific treatment if the patient is doing well and only switch if unavoidable and (3) monitor the safety and efficacy of the new product if switching occurs.     

Mortality in patients with loss of consciousness at the scene of trauma

Background and aim:

The aim of this study was to evaluate if loss of consciousness at the scene of an accident in patients with thoracic trauma classified by the Abbreviated Injury Scale (AIS) as thorax >2 has a different outcome in respect to immediate hospital discharge, hospitalization, death and type of accident.

Methods:

A prospective study was performed in the Regional Trauma Center of São José do Rio Preto. All patients with scores related to thoracic injury ≥2 were included in this study. Thus, 134 patients with penetrating and 231 with blunt thoracic injuries were evaluated. The chi-square, Fisher's exact and relative risk tests were utilized for statistical analysis with an alpha error greater than 5% (p?Results: A significantly higher number of patients who lost consciousness (35–33.9%) died compared to those who did not lose consciousness (9–3.5%, Fisher's exact test: p?Conclusion: The loss of consciousness at the time of trauma is a warning sign in patients with thoracic injuries whether associated with other types of injuries or not.     

B-1 cells are pivotal for in vivo inflammatory giant cell formation

The mechanisms that govern giant cell (GC) formation in inflammatory, neoplastic and physiologic conditions are far from being understood. Here, we demonstrate that B-1 cells are essential for foreign-body GC formation in the mouse. GCs were analysed on the surface of glass cover slips implanted into the subcutaneous tissue of the animals. It was demonstrated that GCs are almost absent on cover slips implanted into the subcutaneous tissue of BALB/c or CBA/N X-linked immunodeficient mice. As these animals do not have B-1 cells in the peritoneal cavity, they were reconstituted with B-1 cells obtained from cultures of adherent mouse peritoneal cells. Results showed that in B-1-reconstituted animals, the number of GCs on the implant surface surpassed the values obtained with preparations from wild animals. In animals selectively irradiated (pleural and peritoneal cavities) to deplete these cavities of B-1 cells, GCs were also not formed. Enriched suspensions of B-1 cells grown in culture were labelled with [(3)H]-tymidine and injected into the peritoneal cavity of naive mice before implantation of glass cover slips. After 4 days, about 17% of mononuclear cells had their nuclei labelled, and almost 70% of GCs had one or more of their nuclei labelled when analysed by histoautoradiographic technique. A few GCs expressed an immunoglobulin M when analysed by immunostaining and confocal microscopy. Overall, these data demonstrate that B-1 cells are pivotal in the mechanisms of foreign-body GC formation in the mouse.     

Differentiation of Acidithiobacillus ferrooxidans and A. thiooxidans strains based on 16S-23S rDNA spacer polymorphism analysis

Restriction fragment length polymorphism (RFLP) and sequence analyses of the PCR-amplified 16S-23S rDNA intergenic spacer (ITS) were used for differentiating Acidithiobacillus thiooxidans strains from other related acidithiobacilli, including A. ferrooxidans and A. caldus. RFLP fingerprints obtained with AluI, DdeI, HaeIII, HinfI and MspI enabled the differentiation of all Acidithiobacillus reference strains into species groups. The A. thiooxidans strains investigated (metal mine isolates) yielded identical RFLP patterns to the A. thiooxidans type strain (ATCC 19377(T)), except for strain DAMS, which had a distinct pattern for all enzymes tested. Fourteen A. ferrooxidans mine strains were assigned to 3 RFLP groups, the majority of which were grouped with A. ferrooxidans ATCC 23270(T). The spacer region of one representative strain from each of the RFLP groups obtained was subjected to sequence analysis, in addition to eleven additional A. thiooxidans strains isolated from sediment and water samples, and A. caldus DSM 8584(T). The tRNA(IIe) and tRNA(Ala) genes, present in all strains analyzed, showed high sequence similarity. Phylogenetic analysis of the ITS sequences differentiated all three Acidithiobacillus species. Inter- and infraspecific genetic variations detected were mainly due to the size and sequence polymorphism of the ITS3 region. Mantel tests showed no significant correlation between ITS sequence similarity and the geographical origin of strains. The results showed that the 16S-23S rDNA spacer region is a useful target for the development of molecular-based methods aimed at the detection, rapid differentiation and identification of acidithiobacilli.     

Sepsis: from bench to bedside

Sepsis is a syndrome related to severe infections. It is defined as the systemic host response to microorganisms in previously sterile tissues and is characterized by end-organ dysfunction away from the primary site of infection. The normal host response to infection is complex and aims to identify and control pathogen invasion, as well as to start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to both anti-inflammatory and proinflammatory responses. The chain of events that leads to sepsis is derived from the exacerbation of these mechanisms, promoting massive liberation of mediators and the progression of multiple organ dysfunction. Despite increasing knowledge about the pathophysiological pathways and processes involved in sepsis, morbidity and mortality remain unacceptably high. A large number of immunomodulatory agents have been studied in experimental and clinical settings in an attempt to find an efficacious anti-inflammatory drug that reduces mortality. Even though preclinical results had been promising, the vast majority of these trials actually showed little success in reducing the overwhelmingly high mortality rate of septic shock patients as compared with that of other critically ill intensive care unit patients. Clinical management usually begins with prompt recognition, determination of the probable infection site, early administration of antibiotics, and resuscitation protocols based on "early-goal" directed therapy. In this review, we address the research efforts that have been targeting risk factor identification, including genetics, pathophysiological mechanisms and strategies to recognize and treat these patients as early as possible.