We profiled the expression of circulating microRNAs (miRNAs) in mice using Illumina small RNA deep sequencing in order to identify the miRNAs that may potentially be used as biomarkers to distinguish between gram-negative and gram-positive bacterial infections. Recombinant-specific gram-negative pathogen Escherichia coli (Xen14) and gram-positive pathogen Staphylococcus aureus (Xen29) were used to induce bacterial infection in mice at a concentration of 1 × 108 bacteria/100 μL of phosphate buffered saline (PBS). Small RNA libraries generated from the serum of mice after exposure to PBS, Xen14, Xen29, and Xen14 + Xen29 via the routes of subcutaneous injection (I), cut wound (C), or under grafted skin (S) were analyzed using an Illumina HiSeq2000 Sequencer. Following exposure to gram-negative bacteria alone, no differentially expressed miRNA was found in the injection, cut, or skin graft models. Exposure to mixed bacteria induced a similar expression pattern of the circulating miRNAs to that induced by gram-positive bacterial infection. Upon gram-positive bacterial infection, 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed upregulation greater than 4-fold with a p-value < 0.01. Among them, mir-193b-3p, mir-133a-1-3p, and mir-133a-2-3p presented the most common miRNA targets expressed in the mice exposed to gram-positive bacterial infection. This study identified mir-193b-3p, mir-133a-1-3p, and mir-133a-2-3p as potential circulating miRNAs for gram-positive bacterial infections.

To investigate the injury pattern, severity, and mortality of elderly patients hospitalized for treatment of trauma following fall accidents. Data obtained from the Trauma Registry System were retrospectively reviewed for trauma admissions between January 1, 2009 and December 31, 2013 in a Level I trauma center. Of 16,548 registered patients, detailed information was retrieved from the 2,403 elderly patients (aged 65 years and above) with fall accidents and was compared with information from 1,909 adult patients (aged 20–64) with fall accidents. Falls presented the major mechanism for admission (59.9%) in the elderly patients. The number of elderly patients who fell from a height <1 m was greater than that of the adult patients (91.9% vs. 62.5%, respectively, p <0.001). The Injury Severity Score (ISS) (9.3 ± 4.4 vs. 8.3 ± 6.1, respectively, p =0.007) and New Injury Severity Score (NISS) (10.3 ± 6.8 vs. 9.5 ± 8.2, respectively, p <0.001) were significantly higher in the elderly than the adult patients. A significantly larger proportion of the elderly patients were admitted to the ICU (16.2% vs. 13.4%, respectively, p =0.009), and the elderly were found to have longer stays in the intensive care unit (ICU) (8.6 days vs. 7.6 days, respectively, p =0.034) but not in the hospital in general (9.6 days vs. 8.5 days, respectively, p =0.183). Additionally, a significantly higher percentage of the elderly patients sustained subdural hematoma (10.1% vs. 8.2%, respectively, p =0.032) and femoral fracture (50.6% vs. 14.1%, respectively, p <0.001). There were significant differences in in-hospital mortality (18.2% vs. 10.3%, respectively, p =0.031) and length of stay in the hospital (11.6 days vs. 14.9 days, respectively, p =0.037) between the elderly and adult patients with subdural hematoma, but not between those with femoral fracture. Analysis of the data indicates that elderly patients hospitalized for treatment of trauma following fall accidents present with a bodily injury pattern that differs from that of adult patients and have a higher severe injury score, worse outcome, and higher mortality than those of adult patients.

Supermicrosurgical lymphaticovenous anastomosis (LVA) alleviates lymphedema by draining stagnant lymph from the lymphatic vessels into the venous system. Nevertheless, LVA is believed to be unsuitable for treating moderate-to-severe lymphedema presenting diffuse-pattern dermal backflow (DB). Dermal backflow is considered to be the sign of superficial lymphatic functional failure that renders LVA ineffective. Based on a current algorithm, a more invasive vascularized lymph node flap transfer is recommended instead of LVA. This retrospective study aimed to further investigate and possibly challenge this concept. One-hundred patients with unilateral lymphedematous lower limbs who underwent LVA were included. Patients were divided into Group I (10 patients with mild lymphedema) and Group II (90 patients with moderate-to-severe lymphedema). Demographic data and intraoperative findings were recorded. The post-LVA volume reductions by magnetic resonance volumetry were recorded and analyzed. Preoperatively, significant differences were found in BMI (20.6 vs 26.0 kg/m2, p = 0.004) and the volume gained in the lymphedematous limb (396.8 mL vs 1,056.8 mL, p = 0.005) between Groups I and II. Postoperatively, a significant median post-LVA volume reduction (-282.0 mL vs -763.5 mL, p = 0.022) was found in Group II. However, there were no differences in the percentages of post-LVA volume reduction (-43.8% vs -36.4%, p = 0.793) in Groups I and II. The use of supermicrosurgical LVA is as effective at treating moderate-to-severe lymphedema as milder lymphedema. The indication for LVA should be broadened to include such cases.

To examine the circulating microRNA (miRNA) expression profile in a mouse model of diet-induced obesity (DIO) with subsequent weight reduction achieved via low-fat diet (LFD) feeding. Eighteen C57BL/6NCrl male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal %) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal % high-fat diet (HFD) for 12 weeks; and (3) DIO + LFD, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal % LFD for 4 weeks. A switch to LFD feeding led to decreases in body weight, adiposity, and blood glucose levels in DIO mice. Microarray analysis of miRNA using The Mouse & Rat miRNA OneArray® v4 system revealed significant alterations in the expression of miRNAs in DIO and DIO + LFD mice. Notably, 23 circulating miRNAs (mmu-miR-16, mmu-let-7i, mmu-miR-26a, mmu-miR-17, mmu-miR-107, mmu-miR-195, mmu-miR-20a, mmu-miR-25, mmu-miR-15b, mmu-miR-15a, mmu-let-7b, mmu-let-7a, mmu-let-7c, mmu-miR-103, mmu-let-7f, mmu-miR-106a, mmu-miR-106b, mmu-miR-93, mmu-miR-23b, mmu-miR-21, mmu-miR-30b, mmu-miR-221, and mmu-miR-19b) were significantly downregulated in DIO mice but upregulated in DIO + LFD mice. Target prediction and function annotation of associated genes revealed that these genes were predominantly involved in metabolic, insulin signaling, and adipocytokine signaling pathways that directly link the pathophysiological changes associated with obesity and weight reduction. These results imply that obesity-related reductions in the expression of circulating miRNAs could be reversed through changes in metabolism associated with weight reduction achieved through LFD feeding.

Background: Lymphorrhea is probably the most appalling form of lymphedema and is difficult to treat. Intractable lymphorrhea is prone to infection because of skin breakdown. It is believed that supermicrosurgical lymphaticovenous anastomosis is unsuitable for treating such severe disease. Only a few lymphorrhea patients treated with lymphaticovenous anastomosis have been reported. Whether it can be used to treat lymphorrhea has remained inconclusive. Methods: From September of 2015 to June of 2018, 105 patients underwent supermicrosurgical lymphaticovenous anastomosis (n = 746) in the authors’ hospital. These patients are divided into the nonlymphorrhea group (three male and seven female patients) and the nonlymphedema group (lymphedema patients without lymphorrhea) (11 male and 84 female patients). Retrospective chart review with demographic data and intraoperative findings were recorded and analyzed. Post–lymphaticovenous anastomosis outcomes for lymphorrhea patients were also recorded. Results: No significant differences were found in patient age, sex, or affected limbs between these two groups. As for intraoperative findings, no differences were found in the percentage of indocyanine green–enhanced lymphatic vessels (52.7 ± 41.1 percent versus 67.3 ± 36.7 percent; p = 0.227) or the pathologic changes of lymphatic vessels based on the normal, ectasis, contraction, and sclerosis type classification (2.2 ± 1.0 versus 2.1 ± 1.0; p = 0.893) between the lymphorrhea and nonlymphorrhea groups, respectively. The average follow-up period was 14.5 months (range, 3 to 31 months). Five lymphorrhea patients (50 percent) showed complete recovery without relapse; significant lymphorrhea reduction was found in three patients (30 percent), and two patients showed minimal improvements (20 percent). Conclusion: With comparable functional lymphatic vessels identified in lymphorrhea patients, supermicrosurgical lymphaticovenous anastomosis is a viable option for lymphorrhea treatment, with satisfactory results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.