Mid-term results of a physiotherapist-led Ponseti service for the management of non-idiopathic and idiopathic clubfoot

BackgroundThe Ponseti method is the preferred treatment for idiopathic clubfoot. Although popularised by orthopaedic surgeons it has expanded to physiotherapists and other health practitioners. This study reviews the results of a physiotherapist-led Ponseti service for idiopathic and non-idiopathic clubfeet and compares these results with those reported by other groups.MethodA prospective cohort of clubfeet (2005–2012) with a minimum 2-year follow-up after correction was reviewed. Physiotherapists treated 91 children—41 patients (69 feet) had non-idiopathic deformities and 50 children (77 feet) were idiopathic. Objective outcomes were evaluated and compared to results from other groups managing similar patient cohorts.ResultsThe mean follow-up was 4.6 years (range 2–8.3 years) for both groups. The non-idiopathic group required a median of 7 casts to correct the clubfoot deformity with an 83 % tenotomy rate compared to a median of 5 casts for the idiopathic group with a 63 % tenotomy rate. Initial correction was achieved in 96 % of non-idiopathic feet and in 100 % of idiopathic feet. Recurrence requiring additional treatment was higher in the non-idiopathic group with 40 % of patients (36 % of feet) sustaining a relapse as opposed to 8 % (6 % feet) in the idiopathic group. Surgery was required in 26 % of relapsed non-idiopathic feet and 6 % of idiopathic.ConclusionsAlthough Ponseti treatment was not as successful in non-idiopathic feet as in idiopathic feet, deformity correction was achieved and maintained in the mid-term for the majority of feet. These results compare favourably to other specialist orthopaedic-based services for Ponseti management of non-idiopathic clubfeet.

Level of evidence

Prognostic Level III.     

Correlates of resistance to HIV-1 infection in homosexual men with high-risk sexual behaviour

OBJECTIVE: To investigate possible correlates of HIV resistance in participants from the Amsterdam Cohort of Homosexual men who have remained HIV seronegative despite high-risk sexual behaviour. DESIGN/METHODS: We studied in vitro HIV-1 susceptibility and adaptive and innate immunity in 29 high-risk seronegative (HRSN) and 15 HIV-negative pre-seroconversion (pre-SC) homosexual men from the same Amsterdam Cohort Study (ACS) who seroconverted to HIV-1 positive during active follow-up. Host genetics were compared between HRSN and HIV-positive ACS participants. RESULTS: We found lower in vitro susceptibility for a CCR5-using (R5) HIV-1 variant, higher RANTES production levels, but no difference in coreceptor expression in HRSN as compared with pre-SC controls. Reduced R5 in vitro susceptibility of two HRSN tested was restored to normal levels by addition of antibodies against beta-chemokines. A higher proportion of HRSN carried the SDF-1 3'A variant and HLA-A*11, A*31 and Cw*15 alleles. ELIspot analysis with HIV-1 peptide stimulation revealed low frequencies of HIV-1-specific CD8 interferon-gamma producing cytotoxic T cells in both HRSN and pre-SC controls. CONCLUSIONS: Low in vitro R5 susceptibility of cells from the HRSN men was due to beta-chemokine mediated inhibition of virus replication. The presence of HIV-1 specific cytotoxic T cells in both HRSN and pre-SC participants may signify exposure to the virus rather than protection from infection. Host genetic characteristics and other factors affecting innate immunity may contribute to differential resistance to HIV-1 infection among exposed seronegative individuals.     

Kidney Function and Plasma Copeptin Levels in Healthy Kidney Donors and Autosomal Dominant Polycystic Kidney Disease Patients

Background and objectives

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney.

Design, setting, participants, & measurements

Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as ¹²⁵I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging.

Results

Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4–15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8–6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6–6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105±17 to 66±10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=−0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=−0.51, P<0.001, respectively).

Conclusions

On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels.     

CD4/CD8 ratio is a promising candidate for non-invasive measurement of liver fibrosis in chronic HCV-monoinfected patients

The extent of liver fibrosis is an important factor in prognosis and clinical decision-making in chronic hepatitis C virus (HCV) infection. We investigated CD4/CD8 ratio in HCV-monoinfected and HIV/HCV-coinfected patients, in order to reveal its relation with liver fibrosis. CD4/CD8 ratio in the peripheral blood was assessed by flow cytometry in a cohort of 19 HCV-monoinfected, 14 HIV/HCV-coinfected, ten HIV-monoinfected patients and 15 healthy controls. Liver fibrosis was assessed by transient elastography (n?=?25) or by liver biopsy (n?=?8). Coinfection with HIV was associated with decreased CD4/CD8 ratios in chronic HCV-infected patients, despite adequate antiretroviral treatment. Furthermore, HCV-monoinfected patients with F3-F4 liver fibrosis demonstrated much lower CD4/CD8 ratios than patients with F0-F2 fibrosis (1.4 versus 2.5, p?=?0.023). Similarly, we observed a strong negative correlation between the CD4/CD8 ratio and liver stiffness measured by transient elastography (R?=??0.78, p?=?0.0006). ROC analysis revealed that CD4/CD8 ratio as a non-invasive marker for fibrosis is very promising (area under the curve 0.8). Although our study was performed with a relatively small number of patients, our findings suggest that the CD4/CD8 ratio is a promising candidate for non-invasive evaluation of liver fibrosis in HCV-monoinfected patients.     

A region of euchromatin coincides with an extensive tandem repeat on the mouse (Mus musculus) inactive X chromosome

Euchromatic features are largely absent from the human inactive X chromosome (Xi), with the exception of several large tandem repeats that can be detected as euchromatin bands at metaphase. Despite residing megabases apart, these tandem repeats make frequent inactive X-specific interactions. The mouse homologue has been reported for at least one of the tandem repeats, but whether the mouse Xi is also characterized by distinct bands of euchromatin remains unknown. We examined the mouse Xi for the presence of euchromatin bands by examining the pattern of histone H3 dimethylated at lysine 4 and detected two major signals. The first band resides in the subtelomeric region of band XF5 and may correspond to the pseudoautosomal region. The second band localizes to XE3 and coincides with an extensive complex repeat composed of a large tandem and inverted repeat segment as well as several large short interspersed nuclear element (SINE)-rich tandem repeats. Fluorescence in situ hybridization reveals that sequences with homology to the repeat region are scattered along the length of the Y chromosome. Immunofluorescence analysis of histone H3 trimethylated at lysine 9 on metaphase chromosomes indicates that the repeat region corresponds to a band of constitutive heterochromatin on the male X and female active X chromosomes, whereas the euchromatin signal appears to be female specific. These data suggest that the band of euchromatin observed at XE3 is unique to the mouse Xi, comparable to the chromatin arrangement of several large tandem repeats located on the human X chromosome.     

Emerging role of interleukin‐33 in autoimmune diseases

Interleukin‐33 (IL‐33) is a member of the IL‐1 cytokine family. It predominantly induces type 2 immune responses and thus is protective against atherosclerosis and nematode infections but contributes to allergic airway inflammation. Interleukin‐33 also plays a pivotal role in the development of many autoimmune diseases through mechanisms that are still not fully understood. In this review, we focus on the recent advances in understanding of the expression and function of IL‐33 in some autoimmune disorders, aiming to provide insight into its potential role in disease development.