White paper on antimicrobial stewardship in solid organ transplant recipients

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.     

Effects of resistance training of moderate intensity on heart rate variability,body composition,and muscle strength in healthy elderly women

Purpose

The practice of resistance training is recommended as non-pharmacological strategy during aging. In this study, we propose training composed of exercises, leg 180° press, seated row, leg curl, bench press, abduction machine, push down, adduction machine, and curl biceps. Accordingly, this study aimed to determine the effects of dynamic resistance training on autonomic response, muscle strength, and body composition of elderly women without comorbidities.

Methods

Twenty-six healthy older women (65 ± 3 years) were randomly divided into two groups. The Control Group (CG) consisted of 13 subjects not engaged in any physical exercise, while the Training Group (GT) (n = 13) performed 8 strength training exercises with 3 sets of 8 maximum repetitions. Heart rate variability, body composition, and muscle strength were assessed before and after the 12 weeks in both groups.

Results

No significant difference was found in body composition, muscle strength, and heart rate variability between CG and TG before (baseline) 12 weeks of training. Significant differences between pre- and post-training moments were found only in training group. In this sense, results demonstrated improvement (p < 0.05) in body fat mass (23.0 ± 1.2 vs. 20.0 ± 1.1 kg), fat-free mass (38.0 ± 1.5 vs. 42.0 ± 1.4 kg), strength of upper (17.8 ± 1.0 vs. 22.2 ± 1.1 kgf) and lower limbs (27.1 ± 2.4 vs. 34.1 ± 2.5 kgf), and in time and frequency domain measures of heart rate variability, highlighting the indices LF/HF (1.2 ± 0.4 vs. 0.7 ± 0.1).

Conclusions

The dynamic resistance training protocol presented in this study may be regarded as an effective approach to prevent cardiovascular morbidity and mortality in elderly women.

     

Characterization of an acromesomelic dysplasia,Grebe type case: novel mutation affecting the recognition motif at the processing site of GDF5

Acromesomelic dysplasia, Grebe type is a very rare skeletal dysplasia characterized by severe dwarfism with marked micromelia and deformation of the upper and lower limbs, with a proximodistal gradient of severity. CDMP1 gene mutations have been associated with Grebe syndrome, Hunter–Thompson syndrome, Du Pan syndrome and brachydactyly type C. The proband is a 4-year-old boy, born of consanguineous Pakistani parents. Radiographic imaging revealed features typical of Grebe syndrome: severe shortening of the forearms with an acromesomelic pattern following a proximodistal gradient, with distal parts more severely affected than medial parts; hypoplastic hands, with the phalangeal zone more affected than the metacarpal zone; and severe hypoplastic tibial/femoral zones in both limbs. After molecular analyses, the p.Arg377Trp variant in a homozygous pattern was identified in the CDMP1 gene in the affected child. In silico and structural analyses predicted the p.Arg377Trp amino acid change to be pathogenic. Of the 34 mutations described in the CDMP1 gene, four different missense mutations have been associated with Grebe syndrome. The CDMP1 gene encodes growth differentiation factor 5 (GDF5), which plays a role in regulation of limb patterning, joint formation and distal bone growth. Homozygous mutations in the mature domain of GDF5 result in severe limb malformations such as the Grebe type or the Hunter–Thompson type of acromesomelic chondrodysplasia. The p.Arg377Trp mutation is located within the recognition motif at the processing site of GDF5 where the sequence RRKRR changes to WRKRR. The genotype–phenotype correlation allowed not only confirmation of the clinical diagnosis but also appropriate genetic counselling to be offered to this family.     

Expression analysis of genes involved in collagen cross‐linking and its regulation in traumatic anterior shoulder instability

The molecular alterations involved in the capsule deformation presented in shoulder instability patients are poorly understood. Increased TGFβ1 acts as a signal for production of matrix macromolecules by fibrogenic cells at joint injury sites. TGFβ1, through its receptor TGFβR1, regulates genes involved in collagen cross‐linking, such as LOX, PLOD1, and PLOD2. We evaluated TGFβ1, TGFβR1, LOX, PLOD1, and PLOD2 gene expression in the antero‐inferior (macroscopically injured region), antero‐superior and posterior regions of the glenohumeral capsule of 29 shoulder instability patients and eight controls. We observed that PLOD2 expression was increased in the anterior‐inferior capsule region of the patients compared to controls. LOX expression tended to be increased in the posterior portion of patients. Patients with recurrent shoulder dislocation presented upregulation of TGFβR1 in the antero‐inferior capsule portion and of PLOD2 in the posterior region. Conversely, LOX was increased in the posterior portion of the capsule of patients with a single shoulder dislocation episode. In the antero‐inferior, LOX expression was inversely correlated and TGFβR1 was directly correlated with the duration of symptoms. In the posterior region, PLOD2, TGFβ1, and TGFβR1 were directly correlated with the duration of symptoms. In conclusion, PLOD2 expression was increased in the macroscopically injured region of the capsule of patients. Upregulation of TGFβ1, TGFβR1, and PLOD2 seems to be related with the maintenance of disease symptoms, especially in the posterior region. LOX upregulation seems to occur only in the initial phase of the affection. Therefore, TGFβ1, TGFβR1, LOX, and PLOD2 may play a role in shoulder instability. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:510–517, 2016.     

Rehabilitative intervention during and after pediatric hematopoietic stem cell transplantation: An analysis of the existing literature

Hematopoietic stem cell transplantation is a therapeutic strategy for several oncohematological diseases. It increases survival rates but leads to a high incidence of related effects. The objective of this paper was to examine the existing literature on physical exercise interventions among pediatric HSCT recipients to explore the most often utilized rehabilitative assessment and treatment tools. Studies published from 2002 to April 1, 2015 were selected: 10 studies were included. A previous literary review has shown that rehabilitation programs have a positive impact on quality of life. Our analysis identified some significant outcome variables and shared intervention areas.