All-trans retinoic acid skews monocyte differentiation into interleukin-12-secreting dendritic-like cells

All-trans retinoic acid (ATRA) and retinoid derivatives are essential agents for multiple biological processes. Numerous immune system dysfunctions can occur in the case of retinoid deficiency. Because of the central role of dendritic cells (DCs) in controlling immunity and the wide effects of retinoids on the immune system homeostasis, we investigated the ability of ATRA to influence the differentiation of DCs from circulating peripheral blood monocytes. Human peripheral blood monocytes were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and various concentrations of ATRA. Differentiated cells were assayed for their morphology, phenotype, antigen uptake, allostimulatory capacity and cytokine secretion profile. ATRA (10(-12) mol/l) and GM-CSF drove the differentiation of monocytes into dendritic-like cells (ATRA-DC). ATRA-DCs exhibited DC morphology, had a phenotype of immature DCs, with the expression of CD1a, and upregulation of adhesion and co-stimulatory molecules. ATRA-DCs could induce a proliferative response in naive CD4+ T cells. Although ATRA-DCs retained their antigen-capture capacity, they secreted interleukin (IL)-12p70 without the need for any maturation agent. In addition, ATRA-DCs could drive T cells towards an IL-12-dependent T-helper cell type 1 response with secretion of interferon-gamma. DCs appear to be potential targets for ATRA, giving new insights into the immunomodulatory function of retinoids, with implications potentially related to immunotherapy.     

Two patients with pancreatic apudomas secreting neurotensin and VIP

Two patients have been studied with a two and a half and nine year history of metastatic pancreatic apudoma. In both patients the main feature was chronic watery diarrhoea with remissions after partial tumour resection and streptozotocin therapy. Plasma levels of circulating VIP and neurotensin were persistently raised in both patients. Chromatographic analysis of the plasma showed that a significant proportion of the raised immunoreactivity of both peptides eluted in an identical position to pure VIP and neurotensin. The extremely high concentrations of neurotensin did not appear to result in any feature which would allow distinction from the classical VIPoma syndrome.     

COVID-19 risk index (CRI): a simple and validated emergency department risk score that predicts mortality and the need for mechanical ventilation

Journal of Thrombosis and Thrombolysis - Although certain risk factors have been associated with morbidity and mortality, validated emergency department (ED) derived risk prediction models specific...     

Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional Constipation: A Randomized Clinical Trial

Background:

Polyethylene glycol (PEG) is often considered as the first-line treatment for functional constipation in children. Descurainia sophia (L.) Webb et Berth (D. sophia) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation.

Objectives:

To clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric constipation and to assess its efficacy and side effects.

Patients and Methods:

120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting randomized controlled trial within two parallel-groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day.

Results:

A total of 109 patients completed the study (56 in D. sophia and 53 in PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and 29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5 in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294), respectively. The number of patients who suffered flatulence was less (5, 8.9%) in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P = 0.461). D. sophia taste was less tolerated.

Conclusions:

D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation.     

Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape

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An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly

Introduction: Psoriasis in elderly patients is considered to be of emerging clinical relevance because of the increase in the aged segment of the population. Psoriasis in such a group raises significant management challenges. There is an age-related immunosuppression, a high frequency of comorbidities, and polypharmacy, which enhances the potential risk of drug interactions or side effects when an additional systemic treatment must be administered. Despite the aging of the general population, clinical studies focusing on treatment of geriatric psoriasis are limited. Patients > 65 years are often not included in randomized clinical trials. As a result, the geriatric population affected by moderate-to-severe psoriasis is usually under-treated.

Areas covered: This review focuses on the use of systemic treatments in elderly psoriatic patients and their efficacy and safety data, analyzing the available literature evidences.

Expert opinion: Conventional agents should be carefully evaluated in each patient considering the possible organ impairment, comorbidities, concomitant medications and contraindications. Apremilast is an appropriate treatment for elderly patients. Biologics represent a safe option for a long-term management of psoriasis. Etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and brodalumab have not been associated to a higher risk of adverse events in the elderly.     

Therapies for multidrug resistant and extensively drug-resistant non-fermenting gram-negative bacteria causing nosocomial infections: a perilous journey toward ‘molecularly targeted’ therapy

Introduction: Non-fermenting Gram-negative bacilli are at the center of the antimicrobial resistance epidemic. Acinetobacter baumannii and Pseudomonas aeruginosa are both designated with a threat level to human health of ‘serious’ by the Centers for Disease Control and Prevention. Two other major non-fermenting Gram-negative bacilli, Stenotrophomonas maltophilia and Burkholderia cepacia complex, while not as prevalent, have devastating effects on vulnerable populations, such as those with cystic fibrosis, as well as immunosuppressed or hospitalized patients.

Areas covered: In this review, we summarize the clinical impact, presentations, and mechanisms of resistance of these four major groups of non-fermenting Gram-negative bacilli. We also describe available and promising novel therapeutic options and strategies, particularly combination antibiotic strategies, with a focus on multidrug resistant variants.

Expert commentary: We finally advocate for a therapeutic approach that incorporates in vitro antibiotic susceptibility testing with molecular and genotypic characterization of mechanisms of resistance, as well as pharmacokinetics and pharmacodynamics (PK/PD) parameters. The goal is to begin to formulate a precision medicine approach to antimicrobial therapy: a clinical-decision making model that integrates bacterial phenotype, genotype and patient’s PK/PD to arrive at rationally-optimized combination antibiotic chemotherapy regimens tailored to individual clinical scenarios.     

Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center

Objective

To determine adverse event rates for adult cranial neuro-oncologic surgeries performed at a high-volume quaternary academic center and assess the impact of resident participation on perioperative complication rates.

Effect of Race on the Incidence of Aortic Stenosis and Outcomes of Aortic Valve Replacement in the United States

Objective

To assess the effect of race on the incidence of aortic stenosis (AS) and utilization and outcomes of aortic valve replacement (AVR).