Soluble Interleukin-2 Receptor Predicts Treatment Outcome in Patients With Autoimmune Tubulointerstitial Nephritis. A Preliminary Study.

Background: Autoimmune tubulointerstitial nephritis (TIN) is characterized by immune-mediated tubular injury and requires immunosuppressive therapy. However, diagnosing TIN and assessing therapeutic response are challenging for clinicians due to the lack of useful biomarkers. Pathologically, CD4+ T cells infiltrate to renal tubulointerstitium, and soluble interleukin-2 receptor (sIL-2R) has been widely known as a serological marker of activated T cell. Here, we explored the usefulness of serum sIL-2R to predict the treatment outcome in patients with autoimmune TIN. Methods: Study Design: Single-center retrospective observational study. Participants: 62 patients were diagnosed of TIN from 2005 to April 2018 at Hokkaido University Hospital. Among them, 30 patients were diagnosed with autoimmune TIN and treated with corticosteroids. We analyzed the association between baseline characteristics including sIL-2R and the change of estimated glomerular filtration rate (eGFR) after initiation of corticosteroids. Results: The serum sIL-2R level in patients with autoimmune TIN was significantly higher than that in chronic kidney disease patients with other causes. Mean eGFR in autoimmune TIN patients treated with corticosteroids increased from 43.3 ± 20.4 mL/min/1.73 m2 (baseline) to 50.7 ± 19.9 mL/min/1.73 m2 (3 months) (ΔeGFR; 22.8 ± 26.0%). Multivariate analysis revealed that higher sIL-2R (per 100 U/mL, ß = 1.102, P < 0.001) level was independently associated with the renal recovery. In ROC analysis, sIL-2R had the best area under the curve value (0.805) and the cutoff point was 1182 U/mL (sensitivity = 0.90, 1-specificity = 0.45). Conclusions: Our study showed that elevated serum sIL-2R levels might become a potential predictive marker for therapeutic response in autoimmune TIN.

Impact of Early Surgical Intervention of Plastic Surgeons on the Prognosis of Necrotizing Soft Tissue Infection.

Background Necrotizing soft tissue infection (NSTI) is a rare, severe bacterial infection that causes rapidly progressive soft tissue necrosis from the skin to the muscle. The gold standard for treating NSTI is a prompt diagnosis, early surgical debridement of necrotic tissue, and antimicrobial therapy. This study investigated the relationship between the involvement of plastic surgeons and the clinical course of NSTI cases treated at Yokosuka General Hospital Uwamachi. Methodology This study involved 28 patients with NSTI who were treated at Yokosuka General Hospital Uwamachi. Patient background, outcomes (mortality and amputation), and days to the first surgery were compared in the early and nonearly plastic surgery intervention groups. Moreover, the duration of treatment was also compared in surviving patients. Differences between the two groups were analyzed using Fisher's direct probability test, Mann-Whitney U test was used for comparison of continuous variables between the two groups, and Spearman's rank correlation analysis was used for the bivariate correlation coefficient. The significance level was set at <5%. Results There were eight and 20 patients in the early and nonearly plastic surgery intervention groups (14 in later intervention and six in nonintervention), respectively. A difference in the median number of days to the first surgery between the early (zero days) and the nonearly (two days) intervention groups was significant (p = 0.002). In the survival groups, the median treatment duration in the early (n = 8) and nonearly (n = 13) intervention groups was 44 and 82 days, respectively, which was significantly shorter in the early intervention group (p = 0.003). Conclusions The number of days until the first surgery and the length of the treatment period were significantly shorter in the early plastic surgery intervention group than in the nonearly intervention group.

Boxes fabricated from plate-stabilized liquid marbles.

Polyhedral liquid marbles were fabricated using hydrophobic polymer plates in the shape of a circle, a heart and a star as a stabilizer and water as an inner liquid phase. Boxes could be fabricated by the evaporation of the inner water from the liquid marbles. The fabrication efficiency and stability of these boxes as a function of the plate shape were investigated. Functional materials such as polymers and colloidal particles were successfully introduced into the boxes.

Necrotizing soft tissue infection of the thigh associated with retroperitoneal abscess in a patient with locally advanced ascending colon cancer: A case report.

Necrotizing soft tissue infection (NSTI) is a rare but rapidly progressing soft-tissue infection. Few reports of NSTI caused by colon cancer have been published. We present a rare case of NSTI of the thigh associated the retroperitoneal spread of ascending colon cancer. A 64-year-old man had noticed right hip pain since 3 months before admission, he felt pain in the right thigh which was reddening, and he had difficulty in walking. He was referred to Yokosuka general hospital Uwamachi. Anterolateral aspect of his right thigh was reddening and swelling. The patient was diagnosed with a psoas abscess and a NSTI of the right thigh caused by penetration of ascending colon tumor. The patient underwent debridement of severely necrotized tissue in the right thigh, diverting ileostomy and subsequently a right hemicolectomy with reversal of the ileostomy were performed. He was discharged 70 days after the first surgery. Colon cancer can be a cause of retroperitoneal abscess accompanied by NSTI of the thigh. Two-stage surgery was an efficient option in this patient with NSTI of the thigh associated with locally advanced ascending colon cancer.

Multisite Lymphaticovenular Anastomosis Using Vein Graft for Uterine Cancer-Related Lymphedema After Pelvic Lymphadenectomy.

BACKGROUND: Lymphaticovenular anastomosis (LVA) is becoming a treatment option for lymphedema. It is challenging to perform LVA when a lymphatic vessel is too far from a vein to anastomose directly. METHODS: We applied vein grafting for simultaneous multisite LVA (SM-LVA), when there was a considerable distance between a lymphatic vessel and a vein. Five patients with lower extremity lymphedema (LEL) who underwent SM-LVA were included in this study. Feasibility and treatment effect of the method were evaluated. RESULTS: Simultaneous multisite LVA resulted in 35 anastomoses. Vein grafting was performed in 5 of 35 anastomoses with 100% technical success. All LVAs showed good intraoperative anastomosis patency. At 6 months postoperatively, LEL index was significantly lower than preoperative LEL index (251.0 ± 33.0 vs 271.0 ± 38.5, P < .001). CONCLUSION: In SM-LVA surgery, a vein can be harvested from another surgical field without additional invasiveness and is useful for bridging a lymphatic vessel and a distant vein.

Navigation lymphatic supermicrosurgery for the treatment of cancer-related peripheral lymphedema.

BACKGROUND: Lymphatic supermicrosurgery is becoming the treatment of choice for refractory lymphedema. Detection and anastomosis of functional lymphatic vessels are important for lymphatic supermicrosurgery. METHODS: Navigation lymphatic supermicrosurgery was performed using an operating microscope equipped with an integrated near-infrared illumination system (OPMI Pentero Infrared 800; Carl Zeiss, Oberkochen, Germany). Eight patients with extremity lymphedema who underwent navigation lymphatic supermicrosurgery were evaluated. RESULTS: A total of 21 lymphaticovenular anastomoses were performed on 8 limbs through 14 skin incisions. Lymphatic vessels were enhanced by intraoperative microscopic indocyanine green (ICG) lymphography in 12 of the 14 skin incisions, which resulted in early dissection of lymphatic vessels. All anastomoses showed good anastomosis patency after completion of anastomoses. Postoperative extremity lymphedema index decreased in all limbs. CONCLUSIONS: Navigation lymphatic supermicrosurgery, in which lymphatic vessels are visualized with intraoperative microscopic ICG lymphography, allows a lymphatic supermicrosurgeon to find and dissect lymphatic vessels earlier and facilitates successful performance of lymphaticovenular anastomosis.

Modified lambda-shaped lymphaticovenular anastomosis with supermicrosurgical lymphoplasty technique for a cancer-related lymphedema patient.

Supermicrosurgical lymphaticovenular anastomosis (LVA) has become a useful option for the treatment of compression-refractory lymphedema with its effectiveness and less invasiveness. It is important to make as many bypasses as possible for better treatment results of LVA operation. We report a secondary lymphedema case successfully treated using a modified lambda-shaped LVA. A 62-year-old female with secondary lower extremity lymphedema (LEL) refractory to conservative treatments underwent LVA operation. A modified lambda-shaped LVA was performed at the left groin. In modified lambda-shaped LVA, two lymphatic vessels were transected, and both ends of the proximal and distal sides were converged respectively for an end-to-side and end-to-end anastomoses to one vein. Using modified lambda-shaped LVA, four lymph flows of two lymphatic vessels could be bypassed into a vein. Six months after the LVA surgery, her left LEL index decreased from 261 to 247, indicating edematous volume reduction. Modified lambda-shaped LVA effectively bypasses all lymph flows from two lymphatic vessels, when only one large vein can be found in the surgical field.

Induction of SREBP-1c mRNA by differentiation and LXR ligand in human keratinocytes.

The epidermis is an active site of lipid metabolism, and the synthesis of fatty acids and cholesterol is required for cutaneous homeostasis. Liver X receptor-alpha (LXRalpha) and LXRbeta are nuclear receptors that are activated by oxysterols and regulate cholesterol and fatty acid metabolism. LXRs, predominantly LXRbeta, have been shown to be involved in keratinocyte differentiation and epidermal permeability barrier function. Although LXR regulates hepatic lipogenesis by inducing sterol-regulatory element-binding protein-1c (SREBP-1c), SREBP-1c induction by LXR in the epidermis has not been studied. In this study, we report that SREBP-1c mRNA increased during differentiation of human keratinocyte HaCaT cells and that LXR agonist effectively induced expression of LXR target genes, including SREBP-1c and ATP-binding cassette transporter A1, in differentiated HaCaT cells. Differentiation-associated and LXR-enhanced expression of SREBP-1c was also observed in malignant human keratinocyte A431 cells and primary human keratinocytes. A synthetic LXR antagonist inhibited confluency-dependent expression of SREBP-1c. Thus, SREBP-1c expression increases during keratinocyte differentiation, and LXR activation enhances its expression.

Drug-induced hypersensitivity syndrome due to carbamazepine associated with reactivation of human herpesvirus 7.

We report a 63-year-old Japanese man with epilepsy who developed skin eruptions, liver dysfunction, high fever, leukocytosis and atypical lymphocytosis 4 weeks after he had started taking carbamazepine. Titers of human herpesvirus 7 (HHV-7)-specific IgG antibodies were significantly increased and HHV-7 DNA was detected in his serum by polymerase chain reaction. These findings suggested that reactivation of HHV-7 could contribute to the development of drug-induced hypersensitivity syndrome.

Comparative study of the reaction mechanism of family 18 chitinases from plants and microbes.

Hydrolytic mechanisms of family 18 chitinases from rice (Oryza sativa L.) and Bacillus circulans WL-12 were comparatively studied by a combination of HPLC analysis of the reaction products and theoretical calculation of reaction time-courses. All of the enzymes tested produced beta-anomers from chitin hexasaccharide [(GlcNAc)(6)], indicating that they catalyze the hydrolysis through a retaining mechanism. The rice chitinases hydrolyzed predominantly the fourth and fifth glycosidic linkages from the nonreducing end of (GlcNAc)(6), whereas B. circulans chitinase A1 hydrolyzed the second linkage from the nonreducing end. In addition, the Bacillus enzyme efficiently catalyzed transglycosylation, producing significant amounts of chitin oligomers larger than the initial substrate, but the rice chitinases did not. The time-courses of (GlcNAc)(6) degradation obtained by HPLC were analyzed by theoretical calculation, and the subsite structures of the rice chitinases were identified to be (-4)(-3)(-2)(-1)(+1)(+2). From the HPLC profile of the reaction products previously reported [Terwisscha van Scheltinga et al. (1995) Biochemistry 34, 15619-15623], family 18 chitinase from rubber tree (Hevea brasiliensis) was estimated to have the same type of subsite structure. Theoretical analysis of the reaction time-course for the Bacillus enzyme revealed that the enzyme has (-2)(-1) (+1)(+2)(+3)(+4)-type subsite structure, which is identical to that of fungal chitinase from Coccidioides immitis [Fukamizo et al. (2001) Biochemistry 40, 2448-2454]. The Bacillus enzyme also resembled the fungal chitinase in its transglycosylation activity. Minor structural differences between plant and microbial enzymes appear to result in such functional variations, even though all of these chitinases are classified into the identical family of glycosyl hydrolases.