Spontaneous remission in children with IgA nephropathy

Background

Some patients with IgA nephropathy (IgAN) achieve spontaneous remission even when not receiving medication. However, details on such remissions remain unknown. The aim of our study was to clarify this information in the clinical setting of childhood IgAN with minor glomerular abnormalities or focal mesangial proliferation (MGA/FMP).

Methods

This study was a retrospective analysis of 96 children with MGA/FMP who did not receive medication from among the 555 patients with newly diagnosed childhood IgAN treated between January 1972 and December 2000. The Kaplan?CMeier method and Cox proportional hazard model were used for the analysis.

Results

Of the 96 pediatric patients who did not receive medication, 57 (59.4?%) achieved spontaneous remission. The cumulative spontaneous remission rates among these patients were 57.5? and 77.4 % at 5?and 10 years, respectively, from onset. The mean time from onset to remission was 5.9?±?0.4?years. Clinical and histological findings were similar between the remission and non-remission groups. Of the 57 patients with spontaneous remissions, ten (17.5?%) also developed a recurrence of urinary abnormalities. The cumulative recurrence-free rates were 79.9?and 67.9 % at 5 and 10?years, respectively, after remission.

Conclusions

The spontaneous remission rate in childhood IgAN with MGA/FMP was higher than expected. Our results suggest that physicians should consider the potential for spontaneous remission and refrain from very aggressive treatment in IgAN patients with MGA/FMP.     

<Emphasis Type="Italic">KRAS</Emphasis> and <Emphasis Type="Italic">BRAF</Emphasis> Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review

Background

Epidermal growth factor receptor (EGFR) signaling is one of the most promising targets for molecular-targeted therapies in esophageal squamous cell carcinoma (ESCC). Thus, the molecular diagnosis of KRAS and BRAF mutations is clinically important in therapeutic decision making. However, the frequency of KRAS and BRAF mutations in ESCCs remains inconclusive because of the limited sample sizes of previous studies (all N ≤ 80). Pyrosequencing is a nonelectrophoretic nucleotide extension sequencing technology that can be used for mutation testing.

Methods

The frequency of KRAS and BRAF mutations was examined using a nonbiased database of 203 resected ESCCs and a high-throughput pyrosequencing assay.

Results

The validity of the KRAS pyrosequencing method was initially demonstrated by detection of all 4 types of KRAS mutations [c.35G>T (codon 12 GGT>GTT), c.35G>A (codon 12 GGT>GAT), c.34G>T (codon 12 GGT>TGT), c.38G>A mutation (codon 13 GGC>GAC)], which had been previously diagnosed using Scorpion-ARMS technology, in 9 colon cancer tissues (9 of 9; 100 %). Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing. Subsequently, the KRAS mutation was found to be extremely rare (1 of 203; 0.5 %), and the BRAF mutation was absent (0 of 203; 0 %), in the dataset of 203 ESCCs.

Conclusions

These results suggest that KRAS and BRAF mutations play a limited role in the development of ESCC and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in ESCC.

     

Wound blotting: A convenient biochemical assessment tool for protein components in exudate of chronic wounds

Because wound exudate includes secreted proteins that affect wound healing, its biochemical analysis is useful for objective assessment of chronic wounds. Wound blotting allows for collection of fresh exudate by attaching a nitrocellulose membrane onto the wound surface. To determine its applicability for several analysis methods and its executability in clinical wound assessment, this study comprised an animal experiment and clinical case reports. In the animal experiment, full‐thickness wounds were created on the dorsal skin of mice, and exudate samples were collected daily by a conventional method and by wound blotting. Extremely small but adequate volumes of exudate were collected by wound blotting for subsequent analysis in the animal experiments. Immunostaining showed the concentration and distribution of tumor necrosis factor (TNF) α. The activity of alkaline phosphatase was visualized by reaction with chemiluminescent substrate. The TNF distribution analysis indicated three different patterns: wound edge distribution, wound bed distribution, and a mostly negative pattern in both the animal and clinical studies, suggesting association between the TNF distribution pattern and wound healing. Our results indicate that wound blotting is a convenient method for biochemical analysis of exudate and a candidate tool with which to predict the healing/deterioration of chronic ulcers.     

Predictive validity of granulation tissue color measured by digital image analysis for deep pressure ulcer healing: a multicenter prospective cohort study

This multicenter prospective cohort study examined the predictive validity of granulation tissue color evaluated by digital image analysis for deep pressure ulcer healing. Ninety‐one patients with deep pressure ulcers were followed for 3 weeks. From a wound photograph taken at baseline, an image representing the granulation red index (GRI) was processed in which a redder color represented higher values. We calculated the average GRI over granulation tissue and the proportion of pixels exceeding the threshold intensity of 80 for the granulation tissue surface (%GRI80) and wound surface (%wound red index 80). In the receiver operating characteristics curve analysis, most GRI parameters had adequate discriminative values for both improvement of the DESIGN‐R total score and wound closure. Ulcers were categorized by the obtained cutoff points of the average GRI (≤80, >80), %GRI80 (≤55, >55–80, >80%), and %wound red index 80 (≤25, >25–50, >50%). In the linear mixed model, higher classes for all GRI parameters showed significantly greater relative improvement in overall wound severity during the 3 weeks after adjustment for patient characteristics and wound locations. Assessment of granulation tissue color by digital image analysis will be useful as an objective monitoring tool for granulation tissue quality or surrogate outcomes of pressure ulcer healing.     

Submental perforator flap: Location and number of submental perforating vessels

The sites and numbers of submental perforator vessels were examined using a Doppler probe in 21 volunteers. The subcutaneous vascular network from each perforator was studied in three cases of dissection of upper-neck lymph nodes among the volunteers. A perforator from the submental vessels was noted in all 21 volunteers: a single perforator in 13 cases, and double perforators in eight. The main perforator, which had some subdermal branches, was located 31.8 (8.3) mm in front of the facial artery that was palpated at the mandible. Five patients who presented with skin defects on the cheek and the chin had the submental perforator flap reconstructed, excluding the platysma muscle. All flaps covered the wounds. The submental perforator flap was useful for reconstructing skin defects on the cheek and the chin, because the site of the submental perforator was stable and raising the flap was easy, and the colour and texture matches were acceptable.     

Successful perioperative infection control measures after gastroenterological surgery reduced the number of cases of methicillin-resistant Staphylococcus aureus or Clostridioides (Clostridium) difficile infection to almost zero over a 30-year period: a single-department experience

To investigate changes in the incidence of postoperative infections in the surgical department of a teaching hospital. During the 30-year period from September 1987 to August 2017, 11,568 gastroenterological surgical procedures were performed in our surgical department. This 30-year period was divided into seven periods (A–G), ranging from 2 to 7 years each and based on the infection control methods used in each period. We then compared the rates of incisional surgical site infection (SSI) and organ/space SSI; remote infection (RI) including respiratory tract infection (RTI), intravascular catheter-related infection, and urinary tract infection (UTI); and antibiotic-associated colitis caused by methicillin-resistant Staphylococcus aureus (MRSA) enteritis or Clostridioides (Clostridium) difficile-associated disease (CDAD) among the seven periods. In periods B (September 1990–August 1997) and E (November 2004–July 2007), when a unique antibiotic therapy devised in our department was in use, MRSA was isolated from only 0.3% and 0.4% of surgical patients, respectively, and these rates were significantly lower than those in the other periods (p < 0.05). The rate of CDAD increased during period F (August 2007–July 2014), but in period G (August 2014–August 2017), restrictions were placed on the use of antibiotics with a strong anti-anaerobic action and, in this period, the rate of CDAD was only 0.04%, which was significantly lower than that in period F (p < 0.05). Limiting the use of antibiotics that tend to disrupt the intestinal flora may reduce the rates of MRSA infection and CDAD after gastroenterological surgery.     

Dipeptidyl Peptidase-4 Inhibitor (Vildagliptin) Improves Glycemic Control After Meal Tolerance Test by Suppressing Glucagon Release

Aim

We aimed to evaluate changes in insulin and glucagon secretion, as well as glucose levels, with a meal tolerance test (MTT) before and after 6 months of treatment with vildagliptin in a clinical setting.

Materials and Methods

Participants were 15 patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA_1c] over 6.9 % for more than 3 months). MTTs were conducted before and 6 months after addition of vildagliptin (50 mg twice daily [bid]). Blood samples were collected immediately before, and 1 and 2 h after the test meal for measurement of blood glucose concentration, immune-reactive insulin (IRI), and glucagon. HbA_1c was measured at 6 months.

Results

Mean age of participants was 55.5 ± 2.8 years, and ten (66.7 %) were male. Mean HbA_1c significantly improved from 7.6 to 6.8 % at 6 months after addition of vildagliptin. Blood glucose at 1 and 2 h after the test meal was significantly reduced after addition of vildagliptin, while the reduction in glucagon showed borderline significance and IRI showed no difference. In a comparison of blood glucose-related parameters between subgroups based on median glucose change in area under the curve during MTT (ΔAUC_0–2h), glucagon ΔAUC_0–2h was significantly lower in the group with more improved glucose levels (ΔAUC_0–2h ≥65 mg/dL), but that of IRI did not differ.

Conclusion

Suppression of glucagon release by vildagliptin may improve glycemic control without increasing insulin levels in patients with type 2 diabetes.