An Evidence-Based Multidisciplinary Approach Focused on Creating Algorithms for Targeted Therapy of Infection-Related Ventilator-Associated Complications (IVACs) Caused by Pseudomonas aeruginosa and Acinetobacter baumannii in Critically Ill Adult Patients

(1) Background: To develop evidence-based algorithms for targeted antibiotic therapy of infection-related ventilator-associated complications (IVACs) caused by non-fermenting Gram-negative pathogens. (2) Methods: A multidisciplinary team of four experts had several rounds of assessments for developing algorithms devoted to targeted antimicrobial therapy of IVACs caused by two non-fermenting Gram-negative pathogens. A literature search was performed on PubMed-MEDLINE (until September 2021) to provide evidence for supporting therapeutic choices. Quality and strength of evidence was established according to a hierarchical scale of the study design. Six different algorithms with associated recommendations in terms of therapeutic choice and dosing optimization were suggested according to the susceptibility pattern of two non-fermenting Gram-negative pathogens: multi-susceptible Pseudomonas aeruginosa (PA), multidrug-resistant (MDR) metallo-beta-lactamase (MBL)-negative-PA, MBL-positive-PA, carbapenem-susceptible Acinetobacter baumannii (AB), and carbapenem-resistant AB. (3) Results: Piperacillin–tazobactam or fourth-generation cephalosporins represent the first therapeutic choice in IVACs caused by multi-susceptible PA. A carbapenem-sparing approach favouring the administration of novel beta-lactam/beta-lactamase inhibitors should be pursued in the management of MDR-MBL-negative PA infections. Cefiderocol should be used as first-line therapy for the management of IVACs caused by MBL-producing-PA or carbapenem-resistant AB. Fosfomycin-based combination therapy, as well as inhaled colistin, could be considered as a reasonable alternative for the management of IVACs due to MDR-PA and carbapenem-resistant AB. (4) Conclusions: The implementation of algorithms focused on prompt revision of antibiotic regimens guided by results of conventional and rapid diagnostic methodologies, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens is strongly suggested.

Abnormal shadow on chest radiograph: a supra – or infradiaphragmatic finding?

Incidental findings on chest X-ray of oncological patients need further evaluation in contrast-enhanced computed tomography (CT). We report two cases of abnormal shadows, detected on radiograph, in patients with breast cancer: the first one projected under the left hemidiaphragm and the second one obscuring the right hemidiaphragm. Both patients were asymptomatic, subjected to a surgery and to a CT. The first scan revealed a 15 mm diameter nodule in left lung with smooth margins and central calcifications. Whereas, the second exam showed a subcapsular, ring, calcified lesion in the liver. In both cases, CT was essential for staging and therapeutic choice.

Cosmetic Applications of Bee Venom

Bee venom (BV) is a typical toxin secreted by stingers of honeybee workers. BV and BV therapy have long been attractive to different cultures, with extensive studies during recent decades. Nowadays, BV is applied to combat several skin diseases, such as atopic dermatitis, acne vulgaris, alopecia, vitiligo, and psoriasis. BV is used extensively in topical preparations as cosmetics and used as dressing for wound healing, as well as in facemasks. Nevertheless, the safety of BV as a therapeutic choice has always been a concern due to the immune system reaction in some people due to BV use. The documented unfavorable impact is explained by the fact that the skin reactions to BV might expand to excessive immunological responses, including anaphylaxis, that typically resolve over numerous days. This review aims to address bee venom therapeutic uses in skin cosmetics.

Predictors of clinical response after rTMS treatment of patients suffering from drug-resistant depression

Repeated transcranial magnetic stimulation (rTMS) is a therapeutic brain-stimulation technique that is particularly used for drug-resistant depressive disorders. European recommendations mention the effectiveness of 30 to 64%. The failure rate of treatment is high and clinical improvement is visible only after a certain period of time. It would thus be useful to have indicators that could anticipate the success of treatment and more effectively guide therapeutic choices. We aimed to find predictive indicators of clinical improvement at 1 month after the start of rTMS treatment among the data collected during the care of patients with drug-resistant depression included in the Neuromodulation Unit of the Esquirol Hospital in Limoges since 2007. In total, 290 patients with a pharmaco-resistant depressive episode, according to the Hamilton Depression Rating Scale (HDRS) (score ≥8), before treatment who underwent a complete course of rTMS treatment and did not object to the use of their collected data were included. The clinical response in routine practice, corresponding to a decrease in the HDRS score of at least 50% from inclusion, was determined and complemented by interquartile analysis. A combination of factors predictive of clinical response during care, such as a short duration of the current depressive episode associated with a higher HDRS agitation item value (or a lower perceived sleepiness value) and a higher number of previous rTMS treatments, were identified as being useful in predicting the efficacy of rTMS treatment in routine clinical practice, thus facilitating the therapeutic choice for patients with drug-resistant depression.

Zirconia in the Service of Anterior Aesthetic Restorations

Introduction: Zirconia appears in odontology fifteen years ago under the form of a screed covered with feldspathic ceramic, as an alternative to the ceramic-metal crown. The success of zirconia stems from its biocompatibility and aesthetic potential in combination with optimized mechanical properties. For years, zirconia was the benchmark for the restoration of the posterior sector. Today translucent zirconia are offered to satisfy aesthetic demands even at the previous level Observation: The 54-year-old HA patient consulted for the replacement of her old ceramic-metal bridge in the anterior sector. Its motif was both aesthetic and functional. The therapeutic choice was directed towards the creation of metal ceramic bridge with a zirconia coping. The clinical steps necessary for this prosthetic design will be detailed step by step. Discussion: Several ceramics are now available to us for aesthetic anterior restorations. However, the choice of the appropriate ceramic is not only guided by aesthetic needs. Other parameters must be taken into consideration such as the situation of the finish line, the height of the stumps ... Zirconia may not seem like the ideal ceramic for anterior restorations. However, when the case requires, we can opt for an "improved" zirconia giving wide aesthetic satisfaction Key words: zirconia, aesthetics, translucency, opacity, density.

New Perspectives on Old and New Therapies of Staphylococcal Skin Infections: The Role of Biofilm Targeting in Wound Healing

Among the most common complications of both chronic wound and surgical sites are staphylococcal skin infections, which slow down the wound healing process due to various virulence factors, including the ability to produce biofilms. Furthermore, staphylococcal skin infections are often caused by methicillin-resistant Staphylococcus aureus (MRSA) and become a therapeutic challenge. The aim of this narrative review is to collect the latest evidence on old and new anti-staphylococcal therapies, assessing their anti-biofilm properties and their effect on skin wound healing. We considered antibiotics, quorum sensing inhibitors, antimicrobial peptides, topical dressings, and antimicrobial photo-dynamic therapy. According to our review of the literature, targeting of biofilm is an important therapeutic choice in acute and chronic infected skin wounds both to overcome antibiotic resistance and to achieve better wound healing.

JQ1 Synergize with Anti-CD47 Antibody to Enhance the Function of Macrophages and Repress the Progression of Burkitt Lymphoma

Background: M2 macrophages, as the most prominent immune cells in Burkitt lymphoma (BL), are promising targets and anti-CD47 antibody could enhance the phagocytosis but be unable to eradicate tumor cells. JQ1, a C-MYC inhibitor, may enhance the function of macrophages and be a choice for combination therapy. Methods: The effect JQ1, on the expression of CD47 was measured. Then the synergy of JQ1 and anti-CD47 antibody was measured using phagocytosis assays. The effect of JQ1 on the polarization of macrophages was also detected. Finally, the efficiency and safety of JQ1 and anti-CD47 antibody combination therapy was explored in a groin orthotopically implanted Raji tumor model. Results: JQ1 could suppress the expression of CD47 on the surface of BL cells, thus synergize with anti-CD47 antibody to enhance the phagocytosis of macrophages. JQ1 could polarize macrophages from M2 to M1 while inhibiting the proliferation, inducing the apoptosis and blocking the cell cycle of BL cells. Finally, JQ1 and anti-CD47 antibody combination therapy could repress the progression of BL in NOD/SCID mice. Conclusions: Macrophages may be a promising target in BL and JQ1 combined with anti-CD47 antibody may be a potential therapeutic choice, providing theoretical basis for the use of this new targeted immunotherapy in clinical practice.

Choose Your Medicine

Choose Your Medicine is the first comprehensive history of the concept of freedom of therapeutic choice in the United States. It draws on legal history and the history of medicine (as well as political, intellectual, cultural, and social history) to examine the ways that persistent but evolving notions of a right to therapeutic choice have affected American law, regulation, and policy from the country’s origins to the present. It describes social movements and legal efforts dedicated to resisting government measures denying individuals an unfettered choice among therapeutic products and methods. The targets of this activism have included, among others, state medical licensing statutes, FDA restrictions on the distribution of unapproved drugs, state and federal prohibitions against medical marijuana, formulary limitations in government insurance programs, abortion restrictions, and prohibitions on physician-assisted suicide. The narrative’s protagonists range from unschooled supporters of botanical medicine in the early nineteenth century to sophisticated cancer patient advocacy groups in the twenty-first. The book considers how all of these examples, taken together, fit within the broader development of the idea of freedom of therapeutic choice in American history and law.

The Right to Be Covered

This chapter explores the paradoxical assertion of freedom of therapeutic choice in the context of reimbursed health care. Cries of “rationing!” and “death panel!” are directed at every suggestion of a limitation on government insurance coverage. This chapter traces the history of the notion of a “right to be reimbursed” for one’s therapeutic choices since the 1930s. It explores the persistent public insistence on “a right to choose one’s doctor” in insurance plans. It describes the history of drug formularies and patients’ resistance to them. The chapter focuses most intensively on the controversy surrounding the FDA’s November 2011 withdrawal of provisional approval of Avastin for the treatment of breast cancer. Conservatives and patient groups used the language of rights to attack this decision even though it did not remove the drug from the market; the protesters’ real fear was that insurance plans would stop reimbursing patients for this use.