Evaluation of the relationship between linezolid exposure and hyponatremia

IntroductionAims of this study were (a) to assess the development ratio of hyponatremia during treatment with linezolid and (b) to evaluate the relationship between the risk of hyponatremia and linezolid exposure and patient background.MethodClinical data including linezolid serum concentrations and serum sodium values were collected at Toyama University Hospital and Kyorin University Hospital. Data from 89 patients were used for the analysis, and a nadir serum sodium level ≤130 mmol/L during the treatment with linezolid was defined as hyponatremia. Mann-Whitney's U test was used to evaluate the effects of the area under the time-concentration curve (AUC) of linezolid at the nadir sodium level, clinical characteristics (e.g. laboratory data), and baseline serum sodium levels on the development of hyponatremia.ResultsThe hyponatremia was occurred in 21 of 89 patients (23.6%). Data are compared for baseline and nadir serum sodium levels of patients with and without hyponatremia. In both groups, nadir serum sodium levels were significantly different from those of the baseline values (P < 0.05). The values of AUC_0-12, accumulated AUC, baseline serum sodium levels and age were significantly different between patients with and without hyponatremia (P < 0.05).ConclusionsLinezolid exposure, age, and baseline sodium levels were detected as the risk factors for linezolid-related hyponatremia. Our findings suggest that regular monitoring of serum sodium levels is desirable during treatment with linezolid, especially for the elderly and patients with low serum sodium levels before the start of linezolid administration.     

Analysis of risk factors for multidrug-resistant pathogens and appropriate treatment indications for pneumonia in children with neurologic impairment

IntroductionThe features of pneumonia in children with neurologic impairment (NI) resemble those of healthcare-associated pneumonia is defined as pneumonia occurring in the community associated with healthcare risk factors. There are currently no guidelines for the treatment of pneumonia in children with NI. Here, we assessed whether the guidelines applicable for treating pneumonia in adults could be applied to children with NI.MethodsBetween 2008 and 2019, we enrolled children with NI who developed pneumonia and were treated in the pediatric ward of Kawasaki Medical School Hospital. We evaluated patient characteristics, the frequency of isolation of multidrug-resistant (MDR) pathogens, and clinical outcomes.ResultsMDR pathogens were more frequently isolated from patients receiving tube feeding (TF) and/or with tracheostomy than from patients without these risk factors. Other risk factors, including a history of antibiotic therapy and methicillin-resistant Staphylococcus aureus isolation, recent hospitalization, residence in a nursing home or extended care facility, and low-dose, long-term macrolide therapy, did not significantly affect the frequency of MDR pathogen isolation. In patients receiving TF and/or with tracheostomy, treatment success was achieved in all cases treated with broad-spectrum antibiotics and 72.2% of cases treated with non-broad-spectrum antibiotics (P = 0.007). Conversely, among patients without these risk factors, no such difference was observed.ConclusionsOur findings indicate that the guideline to select antibiotics for treating pneumonia in children with NI should be simpler and more useful than the current guidelines for adult pneumonia, based on risk factor assessment for MDR pathogens.     

Identification and functional characterization of novel telomerase variant alleles in Japanese patients with bone-marrow failure syndromes

As the incidence of bone-marrow failure syndromes (BMFS) is 2-3x higher in East Asia than in the West, we examined peripheral blood or marrow cells of 100 Japanese patients for possible pathogenic mutations in the two main components of the telomere-synthesizing enzyme telomerase (hTERC RNA and hTERT protein) that have recently been implicated in the disease pathogenesis. We analyzed samples collected from 34 patients with acquired aplastic anemia (AA), 66 patients with myelodysplastic syndromes (MDS) and 120 healthy controls. In addition to two polymorphic germ-line sequence changes (n-771A/G and n-714 C insertion) in the promoter region of hTERC and eleven hTERT polymorphisms that were identified in both patients and healthy individuals, we found a novel germ-line C323T mutation in the hTERC RNA in an MDS patient only. This heterozygous C323T mutation abolished telomerase enzymatic activity and functioned in a haploinsufficiency manner to modulate telomerase activity in cells. In summary, this study reports a novel telomerase natural variant that abolishes telomerase function, which may lead to telomere shortening and marrow hypocellularity in patients with BMFS. This study also highlights the rarity of genetic alterations in BMFS patients in Japan, which suggests that other factors may play a more prominent role in the disease pathogenesis in East Asia.     

Ulcerative Colitis and Immunoglobulin G4

Background/Aims

Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4.

Methods

Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients.

Results

UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05).

Conclusions

UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.