Hand injuries in low- and middle-income countries: systematic review of existing literature and call for greater attention.

OBJECTIVES: Hand injuries result in major healthcare costs from lack of productivity and disability. With rapid industrialization, the incidence of hand injuries is expected to rise in low- and middle-income countries (LMICs). However, estimates of burden and validated outcome tools are needed for effective resource allocation in the management of these injuries. STUDY DESIGN: We conducted a systematic review to evaluate the burden of hand injuries in LMICs according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. METHODS: We searched PubMed, Scopus, Embase, Cochrane Library, PAIS International, African Index Medicus, Global Health, IMMEMR, IMSEAR, Wholis and Bdenf, Lilacs, Scielo, WPRIM, and WHO International Clinical Trials Registry Platform to detect eligible articles with no restrictions on length of follow-up, type of hand injury, or date. RESULTS: We included 17 articles after screening 933 eligible articles based on title, abstract, and full-text screening. There was significant heterogeneity and low quality of evidence. All included articles suggest that hand injuries were associated with work limitations for the majority of patients, and residual pain can further limit their activities. Direct and indirect costs related to treatment account for a major healthcare burden with limited evidence on estimates of long-term cost from disability. CONCLUSIONS: The present systematic review highlights the paucity of high-quality data on the epidemiology, management, and burden of hand injuries in LMICs. The data are heterogeneous, and comprehensive metrics are lacking. Because hand injuries can account for a significant proportion of injury-related disability, reducing the overall burden of hand injuries is of utmost importance.

IgE secretion is attenuated by an inhibitor of proteolytic processing of CD23 (Fc epsilonRII).

CD23, the low-affinity IgE receptor, is up-regulated on interleukin (IL)-4-stimulated B cells and monocytes, with a concomitant increase in the release of soluble fragments of CD23 (sCD23) into the medium by proteolytic processing of the surface-bound intact CD23. The effect of inhibition of the processing of CD23 on IgE production in human and mouse cells and in a mouse model in vivo was evaluated. CD23 processing to sCD23 from RPMI 8866 (a human Epstein-Barr virus-transformed B cell line) cell membranes was inhibited by a broad-spectrum matrix-metalloprotease inhibitor, batimastat, with an IC50 of 0.15 microM. Batimastat also inhibited CD23 processing in whole RPMI 8866 cells as well as in IL-4-stimulated purified human monocytes with similar IC50. Batimastat inhibited IgE production from IL-4/anti-CD40-stimulated human tonsil B cells as well as mouse splenic B cells in a manner consistent with inhibition of CD23 processing. Release of soluble fragments of CD23 in the cell supernatants of tonsil B cells was inhibited over the concentration range of 1-10 microM batimastat and intact cell surface CD23 was increased on mouse splenic B cells in the presence of these concentrations of batimastat. IgE production of IL-4-stimulated human peripheral blood mononuclear cells was also blocked by 1-10 microM batimastat, again with comparable inhibition of sCD23 release over the same concentration range. Finally, in a mouse model of IgE production, batimastat inhibited IgE production in response to ovalbumin challenge as determined by serum IgE levels. Taken together, the data support a role of CD23 in IgE production and point to CD23 processing to sCD23 as a therapeutically relevant control point in the regulation of IgE synthesis.