Super high‐flux hemodialysis provides comparable effectiveness with high‐volume postdilution online hemodiafiltration in removing protein‐bound and middle‐molecule uremic toxins: A prospective cross‐over randomized controlled trial

Although high‐volume postdilution online hemodiafiltration (ol‐HDF) is superior to high‐flux HD in removing all kinds of uremic toxins and improving survival, this treatment is not available in most HD centers. The present study was conducted to compare the effectiveness in removals of protein‐bound (indoxyl sulfate [IS]), middle‐molecule [beta‐2 microglobulin (B2M) and alpha‐1 microglobulin (A1MG)], and small‐molecule uremic toxins between super high‐flux HD (SHF‐HD), HD with a novel SHF dialyzer and high‐volume postdilution ol‐HDF in a noninferiority fashion. Fifteen prevalent HD patients were randomly allocated into two sequences of 12‐week treatment periods of SHF‐HD treatment and later high‐volume postdilution ol‐HDF period or vice versa. Each treatment period was divided by a wash‐out phase of 4‐week high‐flux HD. Twelve of 15 patients could complete the study. When compared with high‐volume postdilution ol‐HDF (convective volume of 24.4 ± 3.52 L), SHF‐HD provided comparable reduction ratio values of IS, B2M, and A1MG with mean difference of 5.87 (95% confidence interval [CI] ‐1.63, 13.37), 1.98 (95% CI,‐0.21, 4.18), and 22.96 (95% CI, ‐1.91, 47.83), respectively. The spKt/Vurea was not different. The predialysis levels of all uremic toxins at baseline and after 12‐week treatment did not differ between both groups. Although albumin loss in dialysate in SHF‐HD was greater than high‐volume postdilution ol‐HDF, the serum albumin levels after 12‐week SHF‐HD treatment were significantly higher than baseline. In conclusion, SHF‐HD provides noninferior effectiveness to high‐volume postdilution ol‐HDF in removing various uremic toxins with significantly increased serum albumin levels despite higher albumin loss. SHF‐HD might be an effectively alternative treatment when high‐volume postdilution ol‐HDF is not available.     

Effectiveness of fibroblast growth factor 23 lowering modalities in chronic kidney disease: a systematic review and meta-analysis

International Urology and Nephrology - The heightened fibroblast growth factor 23 (FGF23) level in patients with chronic kidney disease (CKD) is associated with increased cardiovascular disease and...     

An Autochthonous Case of Severe Plasmodium knowlesi Malaria in Thailand

A 58-year-old Thai man was infected with Plasmodium knowlesi in Chantaburi Province, eastern Thailand. In addition to pyrexia, the patient developed hypotension, renal failure, jaundice, and severe thrombocytopenia. The parasitemia at the time of admission was 16.67% or ∼503,400 parasites/μL. With artesunate treatment and supportive care, the patient recovered uneventfully. The occurrence of complicated knowlesi malaria in a low-endemic area underscores the risk of high morbidity from this simian malaria.     

Alcohol and alkalosis enhance excystation of Opisthorchis viverrini metacercariae

The northeastern region of Thailand has long been known as an endemic area of the human liver fluke infection which is caused by Opisthorchis viverrini. Humans are infected by ingestion of uncooked cyprinoid fish in traditional dishes such as “koi-pla,” “pla-som,” “pla-jom,” and “pla-ra.” To date, the prevalence of this parasite infection remains high because of cultural behavior and local beliefs. The popular misunderstanding among people in this area is that alcohol, lemon juice, and fish sauce can kill the parasites. Thus, they believe that they can eat raw fish without the risk of infection. This study attempts to clarify the effects of ethyl alcohol and acidosis–alkalosis on O. viverrini metacercariae excystation. Metacercariae of O. viverrini were obtained from infected cyprinoid fish in a natural reservoir. Most metacercariae were obtained from small cyprinoid fish. Metacercariae were divided into three experimental groups and were treated with solutions containing four different concentrations of ethyl alcohol, four different concentrations of salt, and a range of acidic/basic pH. Metacercariae excystation was observed at the assigned times, and the data were then analyzed. Salt had no effect on excystation. Interestingly, the optimal conditions for O. viverrini excystation were pH 9 and 25 % ethyl alcohol. The present study suggests that raw fish should not be eaten while drinking alcohol or when consuming other ingredients with pH 9, because both alcohol and pH 9 could induce O. viverrini metacercariae excystation, leading to the early development of parasites in the hepatobiliary system.     

Comprehensive and long-term outcomes of enzyme replacement therapy followed by stem cell transplantation in children with Gaucher disease type 1 and 3

Background

Gaucher disease (GD) is a lysosomal storage disorder, characterized by hepatosplenomegaly, pancytopenia, bone diseases, with or without neurological symptoms. Plasma glucosylsphingosine (lyso-Gb1), a highly sensitive and specific biomarker for GD, has been used for diagnosis and monitoring the response to treatment. Enzyme replacement therapy (ERT) is an effective treatment for the non-neurologic symptoms of GD. Neuronopathic GD (type 2 and 3) accounts for 60%–70% of the Asian affected population.

Methods

We explored combination therapy of ERT followed by hematopoietic stem cell transplantation (HSCT) and its long-term outcomes in patients with GD type 3 (GD3).

Results

Four patients with GD3 and one with GD type 1 (GD1) underwent HSCT. The types of donor were one matched-related, one matched-unrelated, and three haploidentical. The age at disease onset was 6–18 months and the age at HSCT was 3.8–15 years in the patients with GD3. The latest age at follow-up was 8–22 years, with a post-HSCT duration of 3–14 years. All patients had successful HSCT. Chronic graft-versus-host disease occurred in one patient. The enzyme activities were normalized at 2 weeks post HSCT. Lyso-Gb1 concentrations became lower than the pathological value. All of the patients are still alive and physically independent. Most of them (4/5) returned to school. None of the patients with GD3 had seizures or additional neurological symptoms after HSCT, but showed varying degrees of cognitive impairment.

Conclusions

ERT followed by HSCT could be considered as an alternative treatment for patients with GD3 who have a high risk of fatal neurological progression.     

Comparison of the pharmacodynamics of meropenem in patients with ventilator-associated pneumonia following administration by 3-hour infusion or bolus injection

The time that concentrations in serum are above the MIC (T>MIC) is the pharmacokinetic/pharmacodynamic parameter correlating with the therapeutic efficacy of beta-lactam antibiotics. The aim of this study was to demonstrate the T>MIC of meropenem when administered by a 3-h infusion compared with that when administered by bolus injection. The study was conducted with nine patients with ventilator-associated pneumonia. Each subject received meropenem in three regimens consecutively: (i) bolus injection of 1 g every 8 h for 24 h; (ii) 3-h infusion of 1 g every 8 h for 24 h; and (iii) 3-h infusion of 2 g every 8 h for 24 h. Following bolus injection, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 28.33% +/- 11.67%, 45.89% +/- 22.90%, 57.00% +/- 24.82%, and 74.67% +/- 17.94% of an 8-h interval, respectively. For the 3-h infusion of 1 g of meropenem, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 37.78% +/- 20.57%, 58.11% +/- 24.38%, 72.67% +/- 21.97%, and 93.56% +/- 6.84% of an 8-h interval, respectively. For the 3-h infusion of 2 g of meropenem, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 57.89% +/- 24.26%, 72.89% +/- 22.40%, 85.56% +/- 16.42%, and 98.56% +/- 3.28% of an 8-h interval, respectively. In conclusion, a 3-h infusion resulted in greater T>MICs than those after a bolus injection. For the treatment of infections caused by pathogens with intermediate resistance, a 3-h infusion of 2 g of meropenem every 8 h can provide concentrations in serum above the MIC of 16 microg/ml for almost 60% of an 8-h interval.     

Congenital bronchoesophageal fistula and tracheoesophageal fistula with esophageal atresia.

A case of initial esophageal atresia and tracheoesophageal fistula in a female newborn, later complicated by pneumonia and a second bronchoesophageal fistula, is reported. She was treated surgically by closure of the tracheoesophageal fistula and by end-to-end esophago-esophageal anastomosis. An esophagram at 1 month of age was normal. Three months later she developed severe, persistent right lower lobe pneumonia that required intensive antibiotic therapy and respiratory support. Esophagography was repeated and revealed a second fistula between the right main-stem bronchus and the lower esophagus. The bronchoesophageal fistula was repaired, and a right lower lobectomy was performed. Postoperative recovery was uncomplicated. Histologic examination indicated that the fistula was congenital in origin. To the best of our knowledge, this is the first reported case of a congenital bronchoesophageal fistula coexisting with a tracheoesophageal fistula and esophageal atresia.     

A new circulating recombinant form,CRF15_01B,reinforces the linkage between IDU and heterosexual epidemics in Thailand

HIV-1 subtype B and CRF01_AE have been in circulation in Thailand and Southeast Asia for more than a decade. Initially separated by risk group, the two strains are increasingly intermixed, and two recombinant strains of essentially reciprocal structure have been recently reported. Here we identify additional CRF_01B recombinants and provide the evidence that HIV-1 strains now pass freely between the two high-risk populations. HIV isolates that showed discordance between CRF01_AE and subtype B in multi-region genotyping assays were selected for the study. They were drawn from 3 different cohorts in Thailand representing different risk behaviors and demographic characteristics: a drug user cohort in the north, a family planning clinic attendee cohort in the southeast, and a cohort study of the mucosal virology and immunology of HIV-1 infection in Thailand. The DNA from these isolates was PCR amplified to recover the full HIV-1 genome and subjected to sequencing and phylogenetic analysis. We establish that one particular CRF_01B recombinant, with the external envelope of subtype B and the rest of the genome from CRF01_AE, is circulating widely in Thailand. Termed CRF15_01B (also referred to as CRF15), the strain was primarily heterosexually transmitted, although injecting drug use (IDU) also played a role. In aggregate data from the studies, CRF15 constituted 1.7% of all HIV-1 infections (95% confidence interval 0.5-4.4%) and was dispersed widely in the country. The previously separate heterosexual and IDU epidemics have apparently been bridged by a new CRF. The entry of CRF15 into the mainstream of the epidemic signals new complexity in the long stable molecular picture in Thailand. These recombinants must be considered in ongoing or projected efficacy evaluations of HIV-1 vaccines and antiviral therapies.