Intrapartum-related perinatal deaths in births planned in midwifery-led settings in Great Britain: findings and recommendations from the ESMiE confidential enquiry.

OBJECTIVE: To review quality of care in births planned in midwifery-led settings, resulting in an intrapartum-related perinatal death. DESIGN: Confidential enquiry. SETTING: England, Scotland and Wales. SAMPLE: Intrapartum stillbirths and intrapartum-related neonatal deaths in births planned in alongside midwifery units, freestanding midwifery units or at home, sampled from national perinatal surveillance data for 2015/16 (alongside midwifery units) and 2013-16 (freestanding midwifery units and home births). METHODS: Multidisciplinary panels reviewed medical notes for each death, assessing and grading quality of care by consensus, with reference to national standards and guidance. Data were analysed using thematic analysis and descriptive statistics. RESULTS: Sixty-four deaths were reviewed, 30 stillbirths and 34 neonatal deaths. At the start of labour care, 23 women were planning birth in an alongside midwifery unit, 26 in a freestanding midwifery unit and 15 at home. In 75% of deaths, improvements in care were identified that may have made a difference to the outcome for the baby. Improvements in care were identified that may have made a difference to the mother's physical and psychological health and wellbeing in 75% of deaths. Issues with care were identified around risk assessment and decisions about planning place of birth, intermittent auscultation, transfer during labour, resuscitation and neonatal transfer, follow up and local review. CONCLUSIONS: These confidential enquiry findings do not address the overall safety of midwifery-led settings for healthy women with straightforward pregnancies, but suggest areas where the safety of care can be improved. Maternity services should review their care with respect to our recommendations. TWEETABLE ABSTRACT: Confidential enquiry of intrapartum-related baby deaths highlights areas where care in midwifery-led settings can be made even safer.

Mucin-1 Gene Mutation and the Kidney: The Link between Autosomal Dominant Tubulointerstitial Kidney Disease and Focal and Segmental Glomerulosclerosis.

Glomerular diseases are one of the most frequent causes of chronic kidney disease, focal and segmental glomerulosclerosis being one of the commonest glomerulopathies. However, the etiology of this glomerular entity, which merely depicts a morphologic pattern of disease, is often not established and, in most of the patients, remains unknown. Nephrologists tend to assume focal and segmental glomerulosclerosis as a definitive diagnosis. However, despite the increasing knowledge developed in the field, genetic causes of glomerular diseases are currently identified in fewer than 10% of chronic kidney disease subjects. Moreover, unexplained familial clustering among dialysis patients suggests that genetic causes may be underrecognized. Secondary focal and segmental glomerulosclerosis due to genetic mutations mainly located in the podocyte and slit diaphragm can occur from childbirth to adulthood with different clinical presentations, ranging from mild proteinuria and normal renal function to nephrotic syndrome and renal failure. However, this histopathological pattern can also be due to primary defects outside the glomerulus. The present report illustrates an adult case of secondary focal and segmental glomerulosclerosis with a dominant tubulointerstitial damage that led to the pursue of its cause at the tubular level. In this patient with an undiagnosed family history of adult kidney disease, a genetic study unraveled a mutation in the mucin-1 gene and a final diagnosis of adult dominant tubular kidney disease-MUC1 was made.

Pediatric Nandina domestica ingestions reported to poison centers.

Nandina domestica is grown as an ornamental plant in the United States but has also been reported as an invasive plant in a number of states. Parts of the plant, particularly the berries, contain cyanogenic glycosides that convert to hydrogen cyanide when ingested. This investigation characterized N. domestica ingestions involving patients of age 5 years and less reported to Texas poison centers during 2000-2015. There were 875 total N. domestica ingestions. A seasonal pattern was observed with the highest proportion of ingestions occurring in March (18.5%) and April (14.7%). The patients were male in 55.0% of the cases; 40.8% of the patients were of age 1 and 37.0% of age 2. Berries were specifically mentioned in 709 ingestions, of which 57.3% involved one berry and 28.5% an unknown number of berries. The ingestion occurred at the patient's own residence in 92.9% of the cases, and the patient was managed on site in 97.0%. The most frequently reported clinical effects were vomiting (3.7%), abdominal pain (1.0%), diarrhea (0.9%), and nausea (0.7%). In conclusion, N. domestica ingestions among young children generally do not result in serious outcomes and can be managed successfully outside of a healthcare facility.

In Acute IgA Nephropathy, Proteinuria and Creatinine Are in the Spot, but Podocyturia Operates in Silence: Any Place for Amiloride?

IgA nephropathy is the most frequent cause of primary glomerulonephritis, portends erratic patterns of clinical presentation, and lacks specific treatment. In general, it slowly progresses to end-stage renal disease. The clinical course and the response to therapy are usually assessed with proteinuria and serum creatinine. Validated biomarkers have not been identified yet. In this report, we present a case of acute renal injury with proteinuria and microscopic hematuria in a young male. A kidney biopsy disclosed IgA nephropathy. Podocyturia was significantly elevated compared to normal subjects. Proteinuria, renal function, and podocyturia improved promptly after steroids and these variables remained normal after one year of follow-up, when steroids had already been discontinued and patient continued on valsartan and amiloride. Our report demonstrates that podocyturia is critically elevated during an acute episode of IgA nephropathy, and its occurrence may explain the grim long-term prognosis of this entity. Whether podocyturia could be employed in IgA nephropathy as a trustable biomarker for treatment assessment or even for early diagnosis of IgA nephropathy relapses should be further investigated.

Comparison of poisonings managed at military and Veterans Administration hospitals reported to Texas poison centers.

OBJECTIVES: There is little information on poisonings managed at military and Veterans Administration (VA) hospitals. This investigation described and compared poisonings reported to Texas poison centers that were managed at military and VA hospitals. STUDY DESIGN: Retrospective analysis of poison centre data. METHODS: Cases were poisonings among patients aged 18 years or more reported to Texas poison centers during 2000-2015 where management occurred at a military or VA hospital. The distribution of exposures for various demographic and clinical factors was determined for military and veterans hospitals and comparisons were made between the two groups. RESULTS: There were 4353 and 1676 poisonings managed at military and VA hospitals, resepctively. Males accounted for 50.5% of the military hospital patients and 84.9% of the VA hospital patients. The mean age for military hospital patients was 31 years and for VA hospital patients was 50 years. The proportion of poisonings managed at military hospitals and VA hospitals, respectively, were intentional (70.0% vs 64.1%), particularly suspected attempted suicide (57.3% vs 47.7%), and unintentional (25.0% vs 30.5%). More than one substance was reported in 37.7% of military and 33.2% of VA hospital poisonings. The most commonly reported substance categories for poisonings managed at military and VA hospitals, respectively, were analgesics (28.4% vs 19.7%), sedatives/hypnotics/antipsychotics (24.7% vs 23.4%), antidepressants (18.7% vs 19.7%) and alcohol (11.3% vs 10.6%). CONCLUSIONS: A number of differences were observed between poisonings managed at military and VA hospitals. These differing patterns of poisonings may need to be taken into account in the education, prevention and treatment of poisonings at these hospitals and among the populations they serve.

Human exposures to pentobarbital-phenytoin combination veterinary drugs.

A combination of pentobarbital and phenytoin is used as a veterinary euthanasia drug. Because of its lethal effect, this study described pentobarbital-phenytoin combination veterinary drug human exposures reported to Texas poison centers during 2000-2015. Of 66 exposures, 73% involved female and 27% male patients. The distribution by patient age was 3% 0-5 years, 5% 6-19 years, 91% 20+ years, and 2% unknown. The most common routes were ocular (41%), ingestion (32%), injection (23%), and dermal (18%). The exposure reasons were unintentional (77%) and intentional (23%). The exposure site was the workplace (52%), patient's own residence (38%), health-care facility (2%), and other/unknown (9%). The management site was managed on site (48%), at/en route to health-care facility (45%), referred to health-care facility (5%), and other (2%). The medical outcomes were no effect (23%), minor effect (30%), moderate effect (8%), major effect (8%), not followed nontoxic (3%), not followed minimal effects (24%), unable to follow potentially toxic (2%), and unrelated (3%). The most common adverse effects were ocular irritation/pain (18%), drowsiness/lethargy (15%), and coma (9%). The most common treatments were dilution/irrigation (70%), intravenous fluids (21%), and oxygen (14%). This study found few pentobarbital-phenytoin combination veterinary drug exposures were reported to Texas poison centers during a 16-year period. Although meant to be administered intravenously, the most common exposure routes were ocular and ingestion. Many of the exposures appeared to be unintentional and occurred at the workplace.

Increased urinary CD80 excretion and podocyturia in Fabry disease.

BACKGROUND: Certain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT). METHODS: Cross-sectional study including 65 individuals: controls (n = 20) and Fabry patients (n = 45, 23 of them not on ERT and 22 on ERT). Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia. CD80 mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes. RESULTS: Controls and Fabry patients did not differ in age, eGFR and gender. However, UPCR, uCD80 and podocyturia were significantly higher in Fabry patients than in controls. As expected, Fabry patients not on ERT were younger and a higher percentage were females. Non-ERT Fabry patients had less advanced kidney disease than ERT Fabry patients: UPCR was lower and eGFR higher, but uCD80 and podocyturia did not differ between non-ERT or ERT Fabry patients. There was a significant correlation between uCD80 and UPCR in the whole population (r 0.44, p 0.0005) and in Fabry patients (r 0.42, p 0.0046). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uCD80 expression in cultured podocytes. CONCLUSIONS: Fabry disease is characterized by early occurrence of increased uCD80 excretion that appears to be a consequence of glycolipid accumulation. The potential for uCD80 excretion to reflect early, subclinical renal Fabry involvement should be further studied.

Podocyturia: A Clue for the Rational Use of Amiloride in Alport Renal Disease.

No specific or efficient treatment exists for Alport syndrome, an X-linked hereditary disease caused by mutations in collagen type IV, a crucial component of the glomerular basement membrane. Kidney failure is usually a major complication of the disease, and patients require renal replacement therapy early in life. Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and podocyte contraction and ulterior irreversible detachment. Commonly drug-based approaches include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which are employed to reduce proteinuria and thus retard kidney disease progression and cardiovascular morbidity and mortality. However, as any hereditary disease, it is expressed as early as in the intrauterine life, and usually an index case is helpful to detect family-related cases. As no specific treatment exists, pathophysiologically based approaches are useful. The present case illustrates the reduction rate of urinary podocyte loss and proteinuria after amiloride administration and suggests the molecular pathways involved in Alport renal disease. Finally, podocyturia rather than proteinuria should be considered as an earlier biomarker of kidney involvement and disease progression in Alport disease.

Bibliometric analysis of poison center-related research published in peer-review journals.

Poison centers advance knowledge in the field of toxicology through publication in peer-review journals. This investigation describes the pattern of poison center-related publications. Cases were poison center-related research published in peer-review journals during 1995-2014. These were identified through searching the PubMed database, reviewing the tables of contents of selected toxicology journals, and reviewing abstracts of various national and international meetings. The following variables for each publication were identified: year of publication, journal, type of publication (meeting abstract vs. other, i.e. full article or letter to the editor), and the country(ies) of the poison center(s) included in the research. Of the 3147 total publications, 62.1% were meeting abstracts. There were 263 publications in 1995-1999, 536 in 2000-2004, 999 in 2005-2009, and 1349 in 2010-2014. The publications were in 234 different journals. The journals in which the highest number of research was published were Clinical Toxicology (69.7%), Journal of Medical Toxicology (2.2%), and Veterinary and Human Toxicology (2.1%). The research was reported from 62 different countries. The countries with the highest number of publications were the United States (67.9%), United Kingdom (6.5%), Germany (3.9%), France (2.5%), and Italy (2.4%). The number of publications increased greatly over the 20 years. Although the publications were in a large number of journals, a high proportion of the publications were in one journal. While the research came from a large number of countries, the preponderance came from the United States.

Copious Podocyturia without Proteinuria and with Normal Renal Function in a Young Adult with Fabry Disease.

The time for starting a patient with Fabry disease on enzyme replacement therapy is still a matter of debate, particularly when no overt classical clinical signs or symptoms are present. With respect to Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement infusion until signs of renal disease appear as the appearance of proteinuria or an elevation in serum creatinine and the lack of validated biomarkers of early renal damage. In this regard, proteinuria is nowadays considered as an early and appropriate marker of kidney disease and of cardiovascular morbidity and mortality. However, in this report we demonstrate that podocyturia antedates the classical appearance of proteinuria and could be considered as an even earlier biomarker of kidney damage. Podocyturia may be a novel indication for the initiation of therapy in Fabry disease.

Human interleukin-27: wide individual variation in plasma levels and complex inter-relationships with interleukin-17A.

Although it is widely believed that interleukin (IL)-27 is anti-inflammatory, its role in controlling human immune responses is not fully established. In particular, its interactions with T helper type 17 (Th)17 cytokines are unclear. Our aims were to establish the relationships between IL-27 and proinflammatory cytokines, including IL-17A, in human sera and cultures of peripheral blood mononuclear cells. Plasma IL-27 levels in 879 healthy humans from 163 families varied widely, but with relatively low heritability (19%). Despite IL-27 including a subunit encoded by Epstein-Barr virus-induced gene 3 (EBI3), there was no correlation of levels with serological evidence of infection with the virus. Although IL-27 has been reported to inhibit IL-17A production, we demonstrated a strong positive correlation in sera, but lower correlations of IL-27 with other proinflammatory cytokines. We verified that IL-27 inhibited IL-17A production by human peripheral blood T cells in vitro, but not that it stimulated IL-10 secretion. Importantly, addition of IL-17A decreased IL-27 production by stimulated T cells but had the opposite effect on resting T cells. Together, these data suggest a model whereby IL-27 and IL-17A exerts complex reciprocal effects to boost inflammatory responses, but restrain resting cells to prevent inappropriate activation.

Amiloride as an Alternate Adjuvant Antiproteinuric Agent in Fabry Disease: The Potential Roles of Plasmin and uPAR.

Patients with Fabry disease present a higher risk of cardiovascular and kidney morbidity. We present a patient with a past history of biopsy-proven Fabry disease and stage 3 chronic kidney disease. Proteinuria partially dropped from 6.8 g/day to 2.1 g/day despite an aggressive regime which consisted of low-salt diet, agalsidase beta infusions, dual blockade of the renin-angiotensin system, and low-dose maintenance of steroids. As proteinuria is considered a risk marker of cardiovascular disease and of progression of kidney disease, we added amiloride 5 mg/day, a drug with proven effects in podocyte stabilization and proteinuria actions at the distal convoluted tubule. Proteinuria finally decreased to 0.8 g/day. This report highlights the relevance of intervening on proteinuria in a multitarget approach in order to reduce it as much as possible. Due to this pharmacological response, we suggest that although agalsidase beta specific treatment protects the endothelium, the podocyte, and the tubule in Fabry disease and secondary haemodynamic and immunologic pathways are treated with inhibition of the renin-angiotensin system and steroids, amiloride may act as a complementary tool in podocyte stabilization and in proteinuria effects at the distal tubule.

Neonicotinoid insecticide exposures reported to six poison centers in Texas.

Neonicotinoids are a relatively newer class of insecticide. Used primarily in agriculture, neonicotinoids are also used for flea control in domestic animals. Information on human exposures to neonicotinoids is limited. Neonicotinoid exposures reported to Texas poison centers during 2000-2012 were identified and the distribution by selected factors examined. Of 1,142 total exposures, most products contained imidacloprid (77%) or dinotefuran (17%). The exposures were seasonal with half reported during May-August. The most common routes of exposure were ingestion (51%), dermal (44%), and ocular (11%). The distribution by patient age was 5 years or less (28%), 6-19 years (9%), 20 years or more (61%), and unknown (2%); and 64% of the patients were female. Of all, 97% of the exposures were unintentional and 97% occurred at the patient's own residence. The management site was on-site (92%), already at/en route to a health care facility (6%), and referred to a health care facility (2%). The medical outcomes included no effect (22%), minor effect (11%), moderate effect (1%), not followed judged nontoxic (14%), not followed minimal effects (46%), unable to follow potentially toxic (1%), and unrelated effect (4%). The most commonly reported adverse clinical effects were ocular irritation (6%), dermal irritation (5%), nausea (3%), vomiting (2%), oral irritation (2%), erythema (2%), and red eye (2%). The most frequently reported treatments were dilution/wash (85%) and food (6%). In summary, these data suggest that the majority of neonicotinoid exposures reported to the poison centers may be managed outside of health care facilities with few clinical effects expected.

Initially Nondiagnosed Fabry's Disease when Electron Microscopy Is Lacking: The Continuing Story of Focal and Segmental Glomerulosclerosis.

Focal and segmental glomerulosclerosis is classified as either primary or secondary. We present a patient with a past history of biopsy-proven focal and segmental glomerulosclerosis. Despite initial response to dual blockade and steroids, proteinuria raised when steroids were decreased. After the patient was restarted on steroids, proteinuria did not improve. Another biopsy confirmed the previous diagnosis but suggested Fabry's disease, later confirmed by electron microscopy, α-galactosidase A serum and leukocyte deficiency as well as genetic studies. Proteinuria decreased when agalsidase ß was prescribed in parallel with steroid tapering, increased with steroid discontinuation and improved with meprednisone administration. This report highlights the relevance of electron microscopy in kidney biopsy. In glomerulosclerosis, despite specific treatment, secondary hemodynamic and immunologic pathways may contribute to the development of proteinuria and accelerate the renal disease progression due to the primary disease. We discuss possible pathophysiologic pathways involved in proteinuria in Fabry's disease according to the biopsy and the therapeutic response.

Synthetic cannabinoid and marijuana exposures reported to poison centers.

Synthetic cannabinoids have recently gained popularity as a recreational drug because they are believed to result in a marijuana-like high. This investigation compared synthetic cannabinoids and marijuana exposures reported to a large statewide poison center system. Synthetic cannabinoid and marijuana exposures reported to Texas poison centers during 2010 were identified. The distribution of exposures to the two agents with respect to various demographic and clinical factors were compared by calculating the rate ratio (RR) of the synthetic cannabinoid and marijuana percentages for each subgroup and 95% confidence interval (CI). The proportion of synthetic cannabinoid and marijuana exposures, respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38-2.61), 74.9% and 65.7% in male (RR 1.14, 95% CI 0.87-1.51), 40.2% and 56.6% age ≤ 19 years (RR 0.71, 95% CI 0.52-0.98), 79.2% and 58.6% occurring at a residence (RR 1.35, 95% CI 1.02-1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28-1.00), and 59.3% and 41.4% with serious medical outcomes (RR 1.43, 95% CI 1.03-2.05). Compared to marijuana, synthetic cannabinoid exposures were more likely to be used through inhalation, to involve adults, to be used at a residence, and to result in serious outcomes.

Cases of pediatric ingestion of celecoxib reported to Texas poison control centers in 2000-2007.

Little data exist regarding pediatric celecoxib ingestions. This study described the pattern of pediatric celecoxib ingestions reported to poison control centers. Cases were isolated celecoxib ingestions by patients aged 0-5 years during 2000-2007 reported to Texas poison control centers. The distribution of cases was described with respect to demographic and clinical factors. Of the 177 total patients, dose ingested in milligrams was reported for 92 patients. Mean reported dose was 305.5 mg (range 10-2300 mg). Of those 92 cases, distribution by management site was 89.1% on site, 6.5% already at/en route to healthcare facility and 4.3% referred to healthcare facility. Final medical outcome was no effect for 95.7% cases and minor effect for 4.3% cases. Specific clinical effects reported (in only one case each) were rash, abdominal pain, vomiting, agitation/irritability, and drowsiness. All of the pediatric celecoxib ingestions reported to Texas poison control centers resulted in no or minor effect.

Adult metformin ingestions reported to Texas poison control centers, 2000-2006.

Metformin is an oral hypoglycemic agent used in the management of type 2 diabetes mellitus. Limited information exists on adult metformin ingestions reported to poison control centers. The distribution of adult metformin ingestions reported to Texas poison control centers during 2000-2006 was determined for various factors. In addition, triage guidelines for the management of isolated ingestions were drafted. Of 1528 total metformin ingestions, 58% involved coingestants. Of the 264 ingestions of metformin alone, where the final medical outcome was known, dose ingested was reported for 66%. The mean reported dose was 4739 mg (range 500-60,000 mg). Ingestions of < or =2500 mg and >5000 mg reported doses differed with respect to the proportion involving suspected attempted suicide (6% versus 81%), serious final medical outcome (3% versus 19%), and referral to a health care facility (3% versus 83%). Using 5000 mg as a threshold dose for referral to a health care facility, 91% of cases not already at or en route to a health care facility were managed according drafted triage guidelines.