Severe hypernatremic dehydration in an infant with Netherton syndrome.

Netherthon syndrome is a rare autosomal recessive disease characterized by ichthyosis, the characteristic hair abnormality trichorrhexis invaginata and atopic manifestations. We report a female child with the severe hypernatremic dehydration form of the Netherton syndrome born as the first child of consanguineous parents. Ichthyosis was present at birth. She was admitted to the intensive care unit at the age of 4 days with important loss of weight and dehydration. Severe hypernatremia and convulsions occurred. Despite intensive care the baby died at the age of 11 days. The diagnosis of Netherton syndrome was confirmed by the finding of the pathognomonic hair shaft anomaly trichorrhexis invaginata (bamboo hair) and premature lamellar body secretion and foci of electron-dense material in the intercellular spaces of stratum corneum as relatively specific markers for Netherton syndrome. Netherton syndrome is characterized by a large variability in phenotypic expression. The major neonatal complication is the hypernatremic dehydration, which can be fatal as in this patient or complicated by neurologic signs (intracranial hemorrhage) and secondary sequellae. Molecular studies revealed a mutation in SPINK 5, encoding a serine protease inhibitor. Prenatal diagnosis was performed in the second pregnancy and showed that the fetus was equally affected.     

Factors associated with malaria parasitaemia,malnutrition, and anaemia among HIV-exposed and unexposed Ugandan infants: a cross-sectional survey

An improved methodology is presented here for transgenic Plasmodium berghei lines that express the negative selectable marker yFCU (a bifunctional protein that combines yeast cytosine deaminase and uridyl phosphoribosyl transferase (UPRT)) and substitutes delivery of selection drug 5-fluorocytosine (5FC) by intraperitoneal injection for administration via the drinking water of the mice. The improved methodology is shown to be as effective, less labour-intensive, reduces animal handling and animal numbers required for successful selection thereby contributing to two of the "three Rs" of animal experimentation, namely refinement and reduction.     

Factors associated with consent for organ donation: a retrospective population-based study

Background:Optimizing the approach to and consent of potential organ donors maximizes patient autonomy and the availability of organs for transplants. We set out to identify modifiable factors associated with donation consent.Methods:We conducted a retrospective cohort study of consecutive adults (≥ 18 yr) referred for organ donation in Ontario between April 2013 and June 2019. We analyzed patient clinical data and demographics, data on substitute decision-makers and characteristics of the donation consent approach. Study outcomes were consent for organ donation and approach rate. We evaluated independent associations between consent and approach-and system-level factors.Results:We identified 34 837 referrals for organ donation, of which 6548 (18.8%) substitute decision-makers were approached for consent. Of these, 3927 (60.0% of approaches) consented for organ donation and 1883 (48.0% of consents) patients proceeded to be organ donors. The most common reason substitute decision-makers were not approached for consent in a case with donation potential was a late referral by the health care team (45.2%). Modifiable factors independently associated with consent included a telephone approach for consent (adjusted odds ratio [OR] 0.46, 95% confidence interval [CI] 0.35–0.58) and a collaborative approach by a physician and donation coordinator (adjusted OR 1.26, 95% CI 1.01–1.59).Interpretation:Consent for organ donation was associated with several modifiable factors. Organizations should target interventions to ensure timely referrals to organ donation organizations, increase in-person consent approaches and increase physician participation in the approach process.

Many people die on transplant waiting lists because the demand for organs outstrips supply. Almost 4500 people are on organ transplant waiting lists in Canada. Despite public support for organ donation across Canada,¹ donation rates vary between 8.8 and 21.2 donors per million population, ² and a substantial pool of potential donors is not being realized. ^2,3 The identification, referral and approach of potential donors can be facilitated by policy, legislation and best practices, ^3,4 although the efficacy of interventions is variable across jurisdictions.^5,6 Some comprehensive interventions to increase donor numbers have not changed consent rates,⁷ suggesting that the consent approach process may be a target for improvement.Substitute decision-makers play an important role in the organ donation process, even in jurisdictions with donation consent registries or opt-out consent systems. Substitute decision-makers are almost always asked permission for organ donation, even when there is a registered donation consent,⁸ and their consent rates vary widely.⁹ Substitute decision-makers faced with consent decisions often do so in emotionally charged circumstances, and many do not know the explicit wishes of the patient.¹⁰ Given this context, the process of obtaining consent and the supports provided may have a substantial impact on the decision. Practices have been identified that improve consent rates from substitute decision-makers,¹¹ and these are routinely performed by large, high-performing organ donation organizations. Several epidemiological studies have identified nonmodifiable factors associated with donation consent (e.g., race, age, socioeconomic status and education).^12–15 The persistent variability in consent rates suggests that other modifiable factors may influence a substitute decision-maker’s decision to consent.We aimed to identify modifiable approach-and system-level factors that were associated with positive consent for organ donation in Ontario, Canada.     

Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus: a retrospective study

Background

To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment – diet-only versus additional insulin therapy – were based on the 2010 national Dutch guidelines.

Methods

Retrospective study of the electronic medical files of 820 singleton GDM pregnancies treated between January 2011 and September 2014 in a university and non-university hospital. Pregnancy outcomes were compared between regular care treatment regimens –diet-only versus additional insulin therapy- and pregnancy outcomes of the Northern region of the Netherlands served as a reference population.

Results

A total of 460 women (56 %) met glycaemic control on diet-only and 360 women (44 %) required additional insulin therapy. Between the groups, there were no differences in perinatal complications (mortality, birth trauma, hyperbilirubinaemia, hypoglycaemia), small for gestational age, large for gestational age (LGA), neonate weighing >4200 g, neonate weighing ≥4500 g, Apgar score <7 at 5 min, respiratory support, preterm delivery, and admission to the neonatology department. Neonates born in the insulin-group had a lower birth weight compared with the diet-group (3364 vs. 3467 g, p?=?0.005) and a lower gestational age at birth (p?=?0.001). However, birth weight was not different between the groups when expressed in percentiles, adjusted for gestational age, gender, parity, and ethnicity. The occurrence of preeclampsia and gestational hypertension was comparable between the groups. In the insulin-group, labour was more often induced and more planned caesarean sections were performed (p?=?0.001). Compared with the general obstetric population, the percentage of LGA neonates was higher in the GDM population (11.0 % vs.19.9 %, p?=?<0.001).

Conclusions

Neonatal and obstetric outcomes were comparable either with diet-only or additional insulin therapy. However, compared with the general obstetric population, the incidence of LGA neonates was significantly increased in this GDM cohort.

     

Aortic banding in rat as a model to investigate malnutrition associated with heart failure

Heart failure is a severe pathology, which has displayed a dramatic increase in the occurrence of patients with chronic heart disease in developed countries, as a result of increases in the population's average age and in survival time. This pathology is associated with severe malnutrition, which worsens the prognosis. Although the cachexia associated with chronic heart failure is a well-known complication, there is no reference animal model of malnutrition related to heart failure. This study was designed to evaluate the nutritional status of rats in a model of loss of cardiac function obtained by ascending aortic banding. Cardiac overload led to the development of cardiac hypertrophy, which decompensates to heart failure, with increased brain natriuretic peptide levels. The rats displayed hepatic dysfunction and an associated renal hypotrophy and renal failure, evidenced by the alteration in renal function markers such as citrullinemia, creatininemia, and uremia. Malnutrition has been evidenced by the alteration of protein and amino acid metabolism. A muscular atrophy with decreased protein content and increased amino acid concentrations in both plasma and muscle was observed. These rats with heart failure displayed a multiorgan failure and malnutrition, which reflected the clinical situation of human chronic heart failure.     

A national survey of complications associated with suction lipectomy: a comparative study

In March of 1988, a survey form was sent to all 2695 U.S. and Canadian members of the American Society of Plastic and Reconstructive Surgeons. Nine-hundred and thirty-five members responded, for a response rate of 34.7 percent. The purpose of the survey was to ascertain the total number of major liposuction, dermatolipectomy, and abdominoplasty procedures performed from January of 1984 to January of 1988 and to compare nine specific complications that are associated with these three procedures. The 935 surgeons reported a total of 112,756 procedures performed: major liposuction (75,591), dermatolipectomy (10,603), and abdominoplasty (26,562). Nine major complications were surveyed: mortality, myocardial infarction, cerebrovascular accident or transient ischemic attack, pulmonary thromboembolism, fat embolism, major skin loss, anesthesia complication, transfusion complications, and deep venous thrombosis. The findings in this survey showed, when comparing these three procedures and the nine types of complications, that the complication rate for major suction lipectomy was 0.1 percent, for dermatolipectomy 0.9 percent, and for abdominoplasty 2.0 percent. Fat emboli did not prove to be a significant factor associated with any of the three procedures. However, of the 15 reported deaths (major liposuction 2, dermatolipectomy 2, and abdominoplasty 11), pulmonary thromboembolism was the causative factor in 9 deaths (60 percent). Based on these analyzed data, we feel that major suction lipectomy has a low complication rate and is a reasonably safe procedure.     

Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study

Background

Differentiating cerebral malaria (CM) from other causes of serious illness in African children is problematic, owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia. CM is associated with endothelial activation. In this study we tested the hypothesis that endothelium-derived biomarkers are associated with the pathophysiology of severe malaria and may help identify children with CM.

Methods and Findings

Plasma samples were tested from children recruited with uncomplicated malaria (UM; n = 32), cerebral malaria with retinopathy (CM-R; n = 38), clinically defined CM without retinopathy (CM-N; n = 29), or non-malaria febrile illness with decreased consciousness (CNS; n = 24). Admission levels of angiopoietin-2 (Ang-2), Ang-1, soluble Tie-2 (sTie-2), von Willebrand factor (VWF), its propeptide (VWFpp), vascular endothelial growth factor (VEGF), soluble ICAM-1 (sICAM-1) and interferon-inducible protein 10 (IP-10) were measured by ELISA. Children with CM-R had significantly higher median levels of Ang-2, Ang-2:Ang-1, sTie-2, VWFpp and sICAM-1 compared to children with CM-N. Children with CM-R had significantly lower median levels of Ang-1 and higher median concentrations of Ang-2:Ang-1, sTie-2, VWF, VWFpp, VEGF and sICAM-1 compared to UM, and significantly lower median levels of Ang-1 and higher median levels of Ang-2, Ang-2:Ang-1, VWF and VWFpp compared to children with fever and altered consciousness due to other causes. Ang-1 was the best discriminator between UM and CM-R and between CNS and CM-R (areas under the ROC curve of 0.96 and 0.93, respectively). A comparison of biomarker levels in CM-R between admission and recovery showed uniform increases in Ang-1 levels, suggesting this biomarker may have utility in monitoring clinical response.

Conclusions

These results suggest that endothelial proteins are informative biomarkers of malarial disease severity. These results require validation in prospective studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness.     

Sleep problem but not chronotype is associated with retirement from shift work: a cross-sectional retrospective study

Sleep and Biological Rhythms - The purpose of this study was to investigate the relationship between chronotype, sleep problems and long-term (maladaptive retirement from shift work) and short-term...     

The microbial and metazoan community associated with colonies of Trichodesmium spp.: a quantitative survey

Association with resource-rich particles may benefit a numberof planktonic species in oligotrophic, open-ocean regimes. Thisstudy examined communities of microbes and zooplankton associatedwith colonies of the cyanobacterium Trichodesmium spp. in theSargasso Sea. Trichodesmium colonies and seawater controls werecollected near Bermuda using SCUBA during September 1995, andJune, July and August 1996. Organisms associated with the coloniesand those in the surrounding seawater were enumerated usinglight and fluorescence microscopy. We found that 85% of theTrichodesmiumpuff and tuft colonies examined harbored associated organisms.Associated organisms included bacteria (rod and coccoid), fungi,pennate diatoms, centric diatoms, heterotrophic and autotrophicdinoflagellates, chrysophytes, hypotrich ciliates, amoebae,hydroids, juveniles and nauplii of harpacticoid copepods, andjuvenile decapods. The most common associates (in addition tobacteria) were dinoflagellates (present in 74% of the coloniesexamined), amoebae (50%), ciliates (24%), and diatoms (24%).Numbers of bacteria per colony volume averaged 8.2x10⁸ bacteriaml^-1 (range = 8.1x10⁷ – 3.5 x10⁹ bacteria ml^-1), and thedensity of associated microzooplankton and metazoans averaged6.8x10⁴ organisms ml^-1 (range = 0 – 3.6 x10⁶ organismsml^-1). Associates of Trichodesmium colonies were enriched bytwo to five orders of magnitude over plankton in the surroundingwater. This unique habitat allows for the association of primarilybenthic ciliate, diatom and copepod species and could contributesignificantly to plankton heterogeneity in the open-ocean. Thedistribution of associated organisms was affected by samplecharacteristics such as colony morphology, mucoid matrix structureand colony integrity. The influence of these factors indicatesthat succession or competition between heterotrophic microorganismsultimately determines Trichodesmium microcommunity structure.Similar processes could regulate microbial and metazoan communitiesassociated with other resource-rich microenvironments, suchas marine snow particles.     

Early repolarization with horizontal ST segment may be associated with aborted sudden cardiac arrest: a retrospective case control study

Background

Patients with systemic lupus erythematosus (SLE) have increased cardiovascular morbidity and mortality. Although autopsy studies have documented that the heart is affected in most SLE patients, clinical manifestations occur in less than 10%. QT dispersion is a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function. We compared the increase in QT dispersion in SLE patients with high disease activity and mild or moderate disease activity.

Methods and Results

One hundred twenty-four patients with SLE were enrolled in the study. Complete history and physical exam, ECG, echocardiography, exercise test and SLE disease activity index (SLEDAI) were recorded. Twenty patients were excluded on the basis of our exclusion criteria. The patients were divided to two groups based on SLEDAI: 54 in the high-score group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10). QT dispersion was significantly higher in high-score group (58.31 ± 18.66 vs. 47.90 ± 17.41 respectively; P < 0.004). QT dispersion was not significantly higher in patients who had received hydroxychloroquine (54.17 ± 19.36 vs. 50.82 ± 15.96, P = 0.45) or corticosteroids (53.58 ± 19.16 vs. 50.40 + 11.59, P = 0.47). There was a statistically significant correlation between abnormal echocardiographic findings (abnormalities of pericardial effusion, pericarditis, pulmonary hypertension and Libman-Sacks endocarditis) and SLEADI (P < 0.004).

Conclusions

QT dispersion can be a useful, simple noninvasive method for the early detection of cardiac involvement in SLE patients with active disease. Concerning high chance of cardiac involvement, cardiovascular evaluation for every SLE patient with a SLEDAI higher than 10 may be recommended.

Trial registration

Clinicaltrial.gov registration NCT01031797     

Association of antecedent malnutrition with persistent diarrhoea: a case-control study.

To determine the effect of nutritional state on persistent diarrhoea a case-control study was carried out on 756 children followed up prospectively for 18 months. Children who developed persistent diarrhoea were compared with population controls and controls with acute diarrhoea. The mean weight for age in the children with persistent diarrhoea (69.9%) was significantly lower than that in the population controls (77.0%) and the diarrhoeal controls (76.2%). Weight for age of less than or equal to 70% was associated with persistent diarrhoea in both case-control analyses (population controls, matched odds ratio 3.25; diarrhoeal controls, matched odds ratio 2.46). The corrected odds (multiple logistic regression) in the two analyses were 3.2 (95% confidence interval 1.3 to 8.1) and 3.4 (1.2 to 9.1). Weight for age of less than or equal to 70% increases the risk of persistent diarrhoea. In an underweight child there is a higher risk of diarrhoea becoming persistent. Prevention of malnutrition and intensive management of acute diarrhoea in malnourished children should help reduce the risk of the diarrhoea persisting.