Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome

Background

Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments.

Methods

We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3–6) after the onset of MMF treatment. The characteristics of responder patients (n?=?74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients (n?=?22) were compared by univariate analysis and multivariate logistic regression.

Results

Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8–30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p?=?0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p?=?0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p?=?0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR?=?0.80, 95 % CI [0.69, 0.93], p?<?0.01).

Conclusions

MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug.

     

Is prenatal urethral descent a risk factor for urinary incontinence during pregnancy and the postpartum period?

Introduction and hypothesis

Obstetric trauma during childbirth is considered a major risk factor for postpartum urinary incontinence (UI), particularly stress urinary incontinence. Our aim was to investigate the relation between postpartum UI, mode of delivery, and urethral descent, and to define a group of women who are particularly at risk of postnatal UI.

Methods

A total of 186 women were included their first pregnancy. Validated questionnaires about urinary symptoms during pregnancy, 2 and 12 months after delivery, were administered. Urethral descent was assessed clinically and by ultrasound at inclusion. Multivariate logistic regression analysis was used to determine the risk factors for UI during pregnancy, at 2 months and 1 year after first delivery.

Results

The prevalence of UI was 38.6, 46.5, 35.6, and 34.4 % at inclusion, late pregnancy, 2 months postpartum, and 1 year postpartum respectively. No significant association was found between UI at late pregnancy and urethral descent assessed clinically or by ultrasound. The only risk factor for UI at 2 months postpartum was UI at inclusion (OR 6.27 [95 % CI 2.70–14.6]). The risk factors for UI at 1 year postpartum were UI at inclusion (6.14 [2.22–16.9]), body mass index (BMI), and urethral descent at inclusion, assessed clinically (7.21 [2.20–23.7]) or by ultrasound. The mode of delivery was not associated with urethral descent.

Conclusions

Prenatal urethral descent and UI during pregnancy are risk factors for UI at 1 year postpartum. These results indicate that postnatal UI is more strongly influenced by susceptibility factors existing before first delivery than by the mode of delivery.

     

Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.     

Resident hesitation in the operating room: does uncertainty equal incompetence?

Context

In postgraduate medical programmes, the progressive development of autonomy places residents in situations in which they must cope with uncertainty. We explored the phenomenon of hesitation, triggered by uncertainty, in the context of the operating room in order to understand the social behaviours surrounding supervision and progressive autonomy.

Methods

Nine surgical residents and their supervising surgeons at a Canadian medical school were selected. Each resident–supervisor pair was observed during a surgical procedure and subsequently participated in separate post‐observation, semi‐structured interviews. Constructivist grounded theory was used to guide the collection and analysis of data.

Results

Three hesitation‐related themes were identified: the principle of progress; the meaning of hesitation, and the judgement of competence. Supervisors and residents understood hesitation in the context of a core surgical principle we termed the ‘principle of progress’. This principle reflects the supervisors’ and residents’ shared norm that maintaining progress throughout a surgical procedure is of utmost importance. Resident hesitation was perceived as the first indication of a disruption to this principle and was therefore interpreted by supervisors and residents alike as a sign of incompetence. This interpretation influenced the teaching–learning process during these moments when residents were working at the edge of their abilities.

Conclusions

The principle of progress influences the meaning of hesitation which, in turn, shapes judgements of competence. This has important implications for teaching and learning in direct supervision settings such as surgery. Without efforts to change the perception that hesitation represents incompetence, these potential teaching–learning moments will not fully support progressive autonomy.

     

Perflubron dosing affects ventilator-induced lung injury in rats with previous lung injury

OBJECTIVES: Randomized controlled trials of partial liquid ventilation in acute respiratory distress syndrome have been negative. Reasons for this failure may reside in the use of too large doses of perfluorocarbon. The objective was to evaluate whether various doses of perflubron affect ventilation-induced injury in edematous lungs in different ways. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory of a university. SUBJECTS: Male Wistar rats weighing 300+/-20 g. INTERVENTIONS: Separate groups of rats were injected with alpha-naphtylthiourea to produce mild permeability pulmonary edema. They were then given 0, 7 (low), 13 (moderate), or 20 mL/kg (near functional residual capacity) perflubron doses and mechanically ventilated with a large (33 mL/kg) tidal volume for 15 mins. MEASUREMENTS AND MAIN RESULTS: 125I-albumin distribution space was used to assess lung microvascular permeability. Quasi-static respiratory system pressure-volume curves were analyzed. Administration of low and moderate perflubron doses significantly improved respiratory mechanics and reduced the ventilator-induced permeability alterations to the level observed in rats that were not ventilated. By contrast, a perflubron dose that was near functional residual capacity increased end-inspiratory plateau pressure and aggravated the permeability alterations due to high tidal volume ventilation. CONCLUSIONS: Near functional residual capacity but not low perflubron dose worsens ventilation-induced lung injury of preinjured lungs. This may provide some explanation for the negative results of the recent clinical trials, and it stresses the importance of the amount of perflubron used for partial liquid ventilation.     

Survey of ticks of domestic dogs and cattle in three Caribbean islands

Ticks and the pathogens they transmit can cause high morbidity and mortality in domestic animals. As part of a larger study to determine the tick‐borne pathogens infesting domestic animals and wildlife, the aim of this study was to survey the tick species infesting the canine and cattle populations in Trinidad, Tobago and St. Lucia. A total of 1,990 ticks were collected off 179 dogs in Trinidad (n = 163) and Tobago (n = 16) between June 2016 and 2018. Ticks were also collected from cattle throughout Trinidad (n = 1,098), Tobago (n = 306) and St. Lucia (n = 176). Collected ticks were morphologically identified using standard taxonomic keys. Tick‐infested dogs were characterized as pets (n = 161) or hunting dogs (n = 18). Only two tick species, Rhipicephalus sanguineus (1,926; 96.8%) and Amblyomma ovale (64; 3.2%), were found on the dogs. A total of 169 (94.4%) dogs and 10 (5.6%) dogs were infested with R. sanguineus and A. ovale, respectively. Three dogs (1.7%) were infested with both tick species. Hunting dogs or those closely associated with them were infested with A. ovale. Rhipicephalus sanguineus was widely distributed throughout both islands, whereas A. ovale was restricted to small foci in three rural settlements in both Trinidad (n = 2) and Tobago (n = 1). Rhipicephalus (Boophilus) microplus (n = 1,404) was the only tick species found in cattle from Trinidad (n = 62) and Tobago (n = 20), whilst R. B. microplus (n = 171) and Amblyomma variegatum (n = 5) were found infesting 14 and two heads of cattle, respectively, in St. Lucia. These preliminary findings will aid in determining whether there are links between ticks and tick‐borne pathogens associated with domestic, wildlife species and humans and give further insight into the potential movement of ticks and their pathogens between the human, animal and tropical forest interface.