Safely Reducing Unnecessary Radiographs in Suspected Pediatric Musculoskeletal Injuries: A Multidisciplinary Developed Algorithm.

BACKGROUND: While radiographs are a critical component of diagnosing musculoskeletal (MSK) injuries, they are associated with radiation exposure, patient discomfort, and financial costs. Our study initiative was to develop a system to diagnose pediatric MSK injuries efficiently while minimizing unnecessary radiographs. METHODS: This was a quality improvement trial performed prospectively at a single level one trauma center. A multidisciplinary team with leaders from pediatric orthopedics, trauma surgery, emergency medicine, and radiology created an algorithm delineating which x-rays should be obtained for pediatric patients presenting with MSK injuries. The intervention was performed in the following 3 stages: stage 1: retrospective validation of the algorithm, stage 2: implementation of the algorithm, and stage 3: sustainability evaluation. Outcomes measured included number of extra radiographs per pediatric patient and any missed injuries. RESULTS: In stage 1, 295 patients presented to the pediatric emergency department with MSK injuries. A total of 2148 radiographs were obtained, with 801 not indicated per the protocol, for an average of 2.75 unnecessary radiographs per patient. No injuries would have been missed using the protocol. In stage 2, 472 patients had 2393 radiographs with 339 not indicated per protocol, averaging 0.72 unnecessary radiographs per patient, a significant reduction from stage 1 ( P < 0.001). There were no missed injuries identified on follow-up. In stage 3, improvement was sustained for the subsequent 8 months with an average of 0.34 unnecessary radiographs per patient ( P < 0.05). CONCLUSIONS: Sustained reduction of unnecessary radiation to pediatric patients with suspected MSK injuries was accomplished through the development and implementation of a safe and effective imaging algorithm. The multidisciplinary approach, widespread education of pediatric providers, and standardized order sets improved buy-in and is generalizable to other institutions.Level of Evidence: III.

Mismatch repair protein hMSH2-hMSH6 recognizes mismatches and forms sliding clamps within a D-loop recombination intermediate.

High fidelity homologous DNA recombination depends on mismatch repair (MMR), which antagonizes recombination between divergent sequences by rejecting heteroduplex DNA containing excessive nucleotide mismatches. The hMSH2-hMSH6 heterodimer is the first responder in postreplicative MMR and also plays a prominent role in heteroduplex rejection. Whether a similar molecular mechanism underlies its function in these two processes remains enigmatic. We have determined that hMSH2-hMSH6 efficiently recognizes mismatches within a D-loop recombination initiation intermediate. Mismatch recognition by hMSH2-hMSH6 is not abrogated by human replication protein A (HsRPA) bound to the displaced single-stranded DNA (ssDNA) or by HsRAD51. In addition, ATP-bound hMSH2-hMSH6 sliding clamps that are essential for downstream MMR processes are formed and constrained within the heteroduplex region of the D-loop. Moreover, the hMSH2-hMSH6 sliding clamps are stabilized on the D-loop by HsRPA bound to the displaced ssDNA. Our findings reveal similarities and differences in hMSH2-hMSH6 mismatch recognition and sliding-clamp formation between a D-loop recombination intermediate and linear duplex DNA.

A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity.

The homeostatic mechanisms that fail to restrain chronic tissue inflammation in diseases, such as psoriasis vulgaris, remain incompletely understood. We profiled transcriptomes and epitopes of single psoriatic and normal skin-resident T cells, revealing a gradated transcriptional program of coordinately regulated inflammation-suppressive genes. This program, which is sharply suppressed in lesional skin, strikingly restricts Th17/Tc17 cytokine and other inflammatory mediators on the single-cell level. CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, replicates the interleukin-17A (IL-17A), granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon gamma (IFNγ) elevation in psoriatic memory T cells deficient in these transcripts, functionally validating their influence. Combinatoric expression analysis indicates the suppression of specific inflammatory mediators by individual program members. Finally, we find that therapeutic IL-23 blockade reduces Th17/Tc17 cell frequency in lesional skin but fails to normalize this inflammatory-suppressive program, suggesting how treated lesions may be primed for recurrence after withdrawal of treatment.

Treatment of canine atopic dermatitis with cetirizine, a second generation antihistamine: a single-blinded, placebo-controlled study.

Cetirizine and placebo were administered orally as individual agents to 23 dogs with atopic dermatitis. The pruritus was satisfactorily reduced in 4/22 (18%) dogs that completed the trial with cetirizine. Two dogs vomited after administration of the active drug.

Treatment of canine atopic dermatitis with a commercial homeopathic remedy: a single-blinded, placebo-controlled study.

A commercial homeopathic remedy and a placebo were administered orally as individual agents to 18 dogs with atopic dermatitis. The pruritus was reduced by less than 50% in only 2/18 dogs; 1 of these dogs was receiving the homeopathic remedy, the other was receiving the placebo. One dog vomited after administration of the homeopathic remedy.

Bacteria and fungi on the surface and within noninflamed hair follicles of skin biopsy specimens from horses with healthy skin or inflammatory dermatoses.

A retrospective study using light microscopy was performed to assess the prevalence of surface and follicular bacteria and fungi in skin biopsy specimens from 247 horses with inflammatory dermatoses and from 27 horses with healthy skin. Cocci were found on the surface of specimens from 23% (95% confidence interval 18%, 29%) and 7% (95% confidence interval, 0%, 19%), respectively, of horses with skin disease and horses with healthy skin. Of the nine dermatoses with at least 10 cases in our series of horses, bacterial folliculitis had a higher prevalence of surface bacteria (57%; 95% confidence interval 34%, 81%) than the other eight (which all had a prevalence < 30%). There was a significant association between the prevalence of surface cocci and the extent of epidermal hyperkeratosis. Cocci were found in the keratin of noninflamed hair follicles in only 2% of the horses with skin disease, and in none of the horses with healthy skin. Fungal poroconidia were found on the surface of 4% of the horses with skin disease, and on none of the horses with healthy skin. Yeasts were not found.