Vaccine Hesitancy in Central Switzerland: Identifying and Characterizing Undervaccinated Children in a Pediatric Emergency Department.

Vaccinations play an important role in the prevention of potentially fatal diseases. Vaccine hesitancy has become an important problem both in the public discourse and for public health. We aimed to identify and characterize this potentially unvaccinated or incompletely vaccinated group of children presenting to the pediatric emergency department (PED) of the tertiary children's hospital in central Switzerland, a region that has anecdotally been claimed as a hotspot for vaccine hesitancy. All patients presenting to the PED (N = 20,247) between September 2018 and September 2019 were screened for their vaccination status and categorized as incomplete, unvaccinated, or fully vaccinated in a retrospective cohort study. Some 2.6% (n = 526) visits to the PED were not or incompletely vaccinated according to age, or their vaccination status was unknown. Most of the children in the cohort were not critically ill, and the minority had to be hospitalized. Undervaccinated patients were overrepresented in rural areas. Of all cohort visits, 18 (3.4%) patients received opportunistic vaccination in the PED. No cases of vaccine-preventable diseases were observed. In summary, incompletely vaccinated and unvaccinated status was less frequent than initially expected. The PED may play a role in increasing vaccination coverage by providing opportunistic vaccinations.

Determinants of Kidney Failure in Primary Hyperoxaluria Type 1: Findings of the European Hyperoxaluria Consortium.

Introduction: Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G>A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies. Methods: In this retrospective study of 932 patients with PH1 included in the OxalEurope registry, we analyzed genotype-phenotype correlations as well as the impact of nephrocalcinosis, urolithiasis, and urinary oxalate and glycolate excretion on the development of kidney failure, using survival and mixed model analyses. Results: The risk of developing kidney failure was the highest for 175 vitamin-B6 unresponsive ("null") homozygotes and lowest for 155 patients with c.508G>A and c.454T>A (p.Phe152Ile) variants, with a median age of onset of kidney failure of 7.8 and 31.8 years, respectively. Fifty patients with c.731T>C (p.Ile244Thr) homozygote variants had better kidney survival than null homozygotes (P = 0.003). Poor outcomes were found in patients with other potentially vitamin B6-responsive variants. Nephrocalcinosis increased the risk of kidney failure significantly (hazard ratio [HR] 3.17 [2.03-4.94], P < 0.001). Urinary oxalate and glycolate measurements were available in 620 and 579 twenty-four-hour urine collections from 117 and 87 patients, respectively. Urinary oxalate excretion, unlike glycolate, was higher in patients who subsequently developed kidney failure (P = 0.034). However, the 41% intraindividual variation of urinary oxalate resulted in wide confidence intervals. Conclusion: In conclusion, homozygosity for AGXT null variants and nephrocalcinosis were the strongest determinants for kidney failure in PH1.

Pediatric Trauma and Trauma Team Activation in a Swiss Pediatric Emergency Department: An Observational Cohort Study.

BACKGROUND: Trauma is one of the most common causes of death in childhood, but data on severely injured Swiss children are absent from existing national registries. Our aim was to analyze trauma activations and the profiles of critically injured children at a tertiary, non-academic Swiss pediatric emergency department (PED). In the absence of a national pediatric trauma database, this information may help to guide the design of infrastructure, processes within organizations, training, and policies. METHODS: A retrospective analysis of pediatric trauma patients in a prospective resuscitation database over a 2-year period. Critically injured trauma patients under the age of 16 years were included. Patients were described with established triage and injury severity scales. Statistical evaluation included logistic regression analysis. RESULTS: A total of 82 patients matched one or more of the study inclusion criteria. The most frequent age group was 12-15 years, and 27% were female. Trauma team activation (TTA) occurred with 49 patients (59.8%). Falls were the most frequent mechanism of injury, both overall and for major trauma. Road-traffic-related injuries had the highest relative risk of major trauma. In the multivariate analysis, patients receiving medicalized transport were more likely to trigger a TTA, but there was no association between TTA and age, gender, or Injury Severity Score (ISS). Nineteen patients (23.2%) sustained major trauma with an ISS > 15. Injuries of Abbreviated Injury Scale severity 3 or greater were most frequent to the head, followed by abdomen, chest, and extremities. The overall mortality rate in the cohort was 2.4%. Conclusions: Major trauma presentations only comprise a small proportion of the total patient load in the PED, and trauma team activation does not correlate with injury severity. Low exposure to high-acuity patients highlights the importance of deliberate learning and simulation for all professionals in the PED. Our findings indicate that high priority should be given to training in the management of severely injured children in the PED. The leading major trauma mechanisms were preventable, which should prompt further efforts in injury prevention.

Bilateral upper eyelid swelling (Hoagland sign) in Epstein-Barr infectious mononucleosis: prospective experience.

BACKGROUND: The typical presentation of Epstein-Barr virus infectious mononucleosis includes fever, pharyngitis, measles-like rash, jaundice, and enlarged lymph nodes, liver, or spleen. A painless bilateral swelling of the upper eyelid, sometimes with drooping of the lateral aspect, may also occur. This sign, referred to as Hoagland sign, is not or only marginally mentioned in reviews and textbooks. METHODS: Between 2019 and 2021, two of us evaluated all subjects with a positive acute Epstein-Barr virus serology for the typical signs of mononucleosis and for the possible existence of the Hoagland sign. RESULTS: During the mentioned period, the diagnosis of mononucleosis was made in 26 (14 females and 12 males) subjects aged from 9.0 to 33 years. The initial presentation included fever in 24, enlarged cervical lymph nodes in 23, pharyngitis in 21, a palpable liver in 7, a palpable spleen in 7, jaundice in 2, and a measles-like rash in 2 cases. The Hoagland sign was noted in 14 cases. Patients with and without Hoagland sign did not significantly differ with respect to age and sex. CONCLUSIONS: The Hoagland sign is an easily identifiable clinical sign that is common and likely helpful early in the course of Epstein-Barr virus infectious mononucleosis. There is a need to expand awareness of this sign among physicians.

Improved Outcome of Infantile Oxalosis Over Time in Europe: Data From the OxalEurope Registry.

Introduction: Infantile oxalosis is the most severe form of primary hyperoxaluria type 1 (PH1), with onset of end-stage kidney disease (ESKD) during infancy. We aimed to analyze the outcome of these patients as our current understanding is limited owing to a paucity of reports. Methods: A retrospective registry study was conducted using data from the OxalEurope registry. All PH1 patients with ESKD onset at age <1 year were analyzed. Results: We identified 95 patients born between 1980 and 2018 with infantile oxalosis. Median (interquartile range [IQR]) age at ESKD was 0.4 (0.3-0.5) year. There were 4 patients diagnosed by family screening who developed ESKD despite early diagnosis. There were 11 patients who had biallelic missense mutations associated with vitamin B6 responsiveness. Of 89 patients, 27 (30%) died at a median age of 1.4 (0.6-2.0) years (5-year patient survival of 69%). Systemic oxalosis was described in 54 of 56 screened patients (96%). First transplantation was performed at a median age of 1.7 (1.3-2.9) years. In 42 cases, this procedure was a combined liver-kidney transplantation (LKTx), and in 23 cases, liver transplantations (LTx) was part of a sequential procedure. Survival rates of both strategies were similar. Patient survival was significantly higher in patients born after 2000. Intrafamilial phenotypic variability was present in 14 families of patients with infantile oxalosis. Conclusion: Nearly all screened patients with infantile oxalosis developed systemic disease. Mortality is still high but has significantly improved over time and might further improve under new therapies. The intrafamilial phenotypic variability warrants further investigation.

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study.

BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

SwissPedData: Standardising hospital records for the benefit of paediatric research.

BACKGROUND: Improvement of paediatric healthcare is hampered by inefficient processes for generating new evidence. Clinical research often requires extra encounters with patients, is costly, takes place in an artificial situation with a biased selection of patients, and entails long delays until new evidence is implemented into health care. Electronic health records (EHR) contain detailed information on real patients and cover the entirety of patients. However, the use of EHR for research is limited because they are not standardised between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality. AIMS: SwissPedData aims to lay the foundation for a paediatric learning health system in Switzerland by facilitating EHR-based research. In this project, we aimed to assess the way routine clinical data are currently recorded in large paediatric clinics in Switzerland and to develop a national EHR-based set of common data elements (CDEs) that covers all processes of routine paediatric care in hospitals. METHODS: A taskforce of paediatricians from large Swiss children's hospitals reviewed the current status of routine data documentation in paediatric clinical care and the extent of digitalisation. We then used a modified Delphi method to reach a broad consensus on a national EHR-based set of CDEs. RESULTS: All Swiss children's hospitals use EHR to document some or all aspects of care. One hundred and nineteen paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national set of CDEs that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 CDEs: 76 in the main module on general paediatrics and between 11 and 59 CDEs per subspecialty module. Among these, 266 were classified as mandatory, 52 as recommended and 18 as optional. CONCLUSION: SwissPedData is a set of CDEs for information to be collected in EHR of Swiss children's hospitals. It covers all care processes including clinical and paraclinical assessment, diagnosis, treatment, disposition and care site. All participating hospitals agreed to implement SwissPedData in their clinical routine and clinic information systems. This will pave the way for a national paediatric learning health system in Switzerland that enables fast and efficient answers to urgent clinical questions by facilitating high-quality nationwide retrospective and prospective observational studies and recruitment of patients for nested prospective studies and clinical trials.

Clinical data for paediatric research: the Swiss approach : Proceedings of the National Symposium in Bern, Switzerland, Dec 5-6, 2019.

BACKGROUND AND PURPOSE: Continuous improvement of health and healthcare system is hampered by inefficient processes of generating new evidence, particularly in the case of rare diseases and paediatrics. Currently, most evidence is generated through specific research projects, which typically require extra encounters with patients, are costly and entail long delays between the recognition of specific needs in healthcare and the generation of necessary evidence to address those needs. The Swiss Personalised Health Network (SPHN) aims to improve the use of data obtained during routine healthcare encounters by harmonizing data across Switzerland and facilitating accessibility for research. The project "Harmonising the collection of health-related data and biospecimens in paediatric hospitals throughout Switzerland (SwissPedData)" was an infrastructure development project funded by the SPHN, which aimed to identify and describe available data on child health in Switzerland and to agree on a standardised core dataset for electronic health records across all paediatric teaching hospitals. Here, we describe the results of a two-day symposium that aimed to summarise what had been achieved in the SwissPedData project, to put it in an international context, and to discuss the next steps for a sustainable future. The target audience included clinicians and researchers who produce and use health-related data on children in Switzerland. KEY HIGHLIGHTS: The symposium consisted of state-of-the-art lectures from national and international keynote speakers, workshops and plenary discussions. This manuscript summarises the talks and discussions in four sections: (I) a description of the Swiss Personalized Health Network and the results of the SwissPedData project; (II) examples of similar initiatives from other countries; (III) an overview of existing health-related datasets and projects in Switzerland; and (IV) a summary of the lessons learned and future prospective from workshops and plenary discussions. IMPLICATIONS: Streamlined processes linking initial collection of information during routine healthcare encounters, standardised recording of this information in electronic health records and fast accessibility for research are essential to accelerate research in child health and make it affordable. Ongoing projects prove that this is feasible in Switzerland and elsewhere. International collaboration is vital to success. The next steps include the implementation of the SwissPedData core dataset in the clinical information systems of Swiss hospitals, the use of this data to address priority research questions, and the acquisition of sustainable funding to support a slim central infrastructure and local support in each hospital. This will lay the foundation for a national paediatric learning health system in Switzerland.

What are the participants' perspective and the system-based impact of a standardized, inter-professional morbidity/mortality-conferences in a children's hospital?

BACKGROUND: Morbidity and mortality conferences (MMC) are well established but little data exists on inter-professional aspects, system-based outcomes and characteristics in pediatric departments. Our study aim was to analyze the system-based impact and to assess participant's perspectives on standardized, inter-professional MMCs in a children's hospital. METHODS: In a prospective observational analysis the inter-professional MMCs held at a tertiary teaching children's hospital in Switzerland were analyzed for (I) resulting clinical consequences and (II) participants perception on format, usefulness and no-blame atmosphere. RESULTS: Eighteen MMC, discussing 29 cases were analyzed. Twenty-seven clinical errors/problems were identified and 17 clinical recommendations were developed: ten new or changed clinical guidelines, two new therapeutic alternatives, three new teaching activities, and two guidelines on specific diagnostics. Altogether, the 466 participants evaluated the conferences favorably. Little differences were seen in the evaluations of physicians of different disciplines or seniority but non-physicians scored all questions lower than physicians. Overall, three quarters of the participants felt that there was a no-blame culture during the conferences but results varied depending on the cases discussed. CONCLUSIONS: An inter-professional MMC can have relevant impact on clinical practice and affect system-based changes. Inter-professional conferences are profitable for all participants but evaluated differently according to profession. A standardized format and the presence of a moderator are helpful, but not a guarantee for a no-blame culture. Highly emotional cases are a risk factor to relapse to "blame and shame". A time gap between the event and the MMC may have a beneficial effect. KEYWORDS: Inter-professional communication; inter-professional health care; learning from failure; morbidity and mortality conference (MMC); patient safety; psychological safety.

Case Report: Lipoprotein Glomerulopathy Complicated by Atypical Hemolytic Uremic Syndrome.

Lipoprotein glomerulopathy (LPG) is a rare inherited disease caused by mutations in the APOE gene, encoding apolipoprotein E (apoE). Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by overactivation of the alternative complement pathway. Here we report the case of a 21-year-old man with LPG who developed aHUS. A functional complement assay demonstrated an overactivation of the complement system. Complementary genetic analysis revealed a homozygous aHUS risk allele for complement factor-H related 1 (CFHR1), CFHR1*B. To the best of our knowledge, this is the first report of an aHUS in a patient with LPG.

Swiss consensus recommendations on urinary tract infections in children.

The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis. What is Known: • Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age. • Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. What is New: • Vesicoureteric reflux (VUR) remains a risk factor for UTI but per se is neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended. • A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.

Paediatric end-stage renal disease and renal replacement therapy in Switzerland: survival and treatment trends over four decades.

BACKGROUND: Renal replacement therapy for paediatric end-stage renal disease (ESRD) has developed steadily since its introduction five decades ago. Continuous and long-term analysis of patient outcomes is essential for quality control. METHODS: The Swiss Paediatric Renal Registry, founded in 1970, includes patients diagnosed with ESRD, defined as dialysis for more than three months or renal transplantation, at age <20 years. Here we describe the incidence, primary renal disease, treatment modalities and long-term outcomes over 45 years. RESULTS: This paper reports on 367 children and adolescents treated with chronic renal replacement therapy in Switzerland. Incidence was 5.4 per million children per year, with a tendency to increase over time. The primary renal disease was congenital anomalies of the kidney and the urinary tract in 133 (36%), monogenetic hereditary diseases in 122 (33%) and acquired diseases in 112 (31%) patients. The first renal replacement therapy was haemodialysis in 194 (53%), peritoneal dialysis in 116 (32%) and pre-emptive renal transplantation in 57 (15%) patients. Over the years, pre-emptive renal transplantation became more frequent (34% of all first renal replacement therapies in 2006–2015), reducing the duration of dialysis. Median time on dialysis until transplantation decreased from 1.60 years in 1981–90 to 0.34 years in 2010–15. Over the four decades 1970–80, 1981–90,1991–2000 and 2001–10, the one-year graft survival rate improved from 0.76 to 0.80, 0.89 and then 0.96; and the five-year graft survival rate improved from 0.44 to 0.64, 0.84 and 0.89, respectively. The five-year patient survival rates for the four decades were 0.83, 0.99, 0.93 and 0.94; and the 10-year patient survival rates were 0.75, 0.96, 0.88 and 0.94, respectively. In the four cohorts starting renal replacement therapy in the 70s, 80s, 90s and 00s, the number of children alive after five years of renal replacement therapy increased from 15 to 24, 47 and then 45 respectively. In total, 29 patients (8%) died during chronic renal replacement therapy with ESRD before the age of 20 years. CONCLUSION: Over time, a higher number of children on renal replacement therapy survived, graft survival improved, and the duration of dialysis before renal transplantation decreased.

Growth Patterns After Kidney Transplantation in European Children Over the Past 25 Years: An ESPN/ERA-EDTA Registry Study.

BACKGROUND: Improved management of growth impairment might have resulted in less growth retardation after pediatric kidney transplantation (KT) over time. We aimed to analyze recent longitudinal growth data after KT in comparison to previous eras, its determinants, and the association with transplant outcome in a large cohort of transplanted children using data from the European Society for Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry. METHODS: A total of 3492 patients transplanted before 18 years from 1990 to 2012 were included. Height SD scores (SDS) were calculated using recent national or European growth charts. We used generalized equation models to estimate the prevalence of growth deficit and linear mixed models to calculate adjusted mean height SDS. RESULTS: Mean adjusted height post-KT was -1.77 SDS. Height SDS was within normal range in 55%, whereas 28% showed moderate, and 17% severe growth deficit. Girls were significantly shorter than boys, but catch-up growth by 5 years post-KT was observed in both boys and girls. Children <6 years were shortest at KT and showed the greatest increase in height, whereas there was no catch-up growth in children transplanted >12. CONCLUSIONS: Catch-up growth post-KT remains limited, height SDS did not improve over time, resulting in short stature in nearly half of transplanted children in Europe.

Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up.

Primary hyperoxaluria type 2 is a rare inherited disorder of glyoxylate metabolism causing nephrocalcinosis, renal stone formation and ultimately kidney failure. Previously, primary hyperoxaluria type 2 was considered to have a more favorable prognosis than primary hyperoxaluria type 1, but earlier reports are limited by low patient numbers and short follow up periods. Here we report on the clinical, genetic, and biochemical findings from the largest cohort of patients with primary hyperoxaluria type 2, obtained by a retrospective record review of genetically confirmed cases in the OxalEurope registry, a dataset containing 101 patients from eleven countries. Median follow up was 12.4 years. Median ages at first symptom and diagnosis for index cases were 3.2 years and 8.0 years, respectively. Urolithiasis was the most common presenting feature (82.8% of patients). Genetic analysis revealed 18 novel mutations in the GRHPR gene. Of 238 spot-urine analyses, 23 (9.7%) were within the normal range for oxalate as compared to less than 4% of 24-hour urine collections. Median intra-individual variation of 24-hour oxalate excretion was substantial (34.1%). At time of review, 12 patients were lost to follow-up; 45 of the remaining 89 patients experienced chronic kidney disease stage 2 or greater and 22 patients had reached stage 5. Median renal survival was 43.3 years, including 15 kidney transplantations in 11 patients (1 combined with liver transplantation). Renal outcome did not correlate with genotype, biochemical parameters or initially present nephrocalcinosis. Thus, primary hyperoxaluria type 2 is a disease with significant morbidity. Accurate diagnosis by 24-hour urine analysis and genetic testing are required with careful follow-up.

Neonatal Ventilator Associated Pneumonia: A Quality Improvement Initiative Focusing on Antimicrobial Stewardship.

Background and Aims: Neonatal ventilator associated pneumonia (VAP) is a common nosocomial infection and a frequent reason for empirical antibiotic therapy in NICUs. Nonetheless, there is no international consensus regarding diagnostic criteria and management. In a first step, we analyzed the used diagnostic criteria, risk factors and therapeutic management of neonatal VAP by a literature review. In a second step, we aimed to compare suspected vs. confirmed neonatal VAP episodes in our unit according to different published criteria and to analyze interrater-reliability of chest x-rays. Additionally, we aimed to evaluate the development of VAP incidence and antibiotic use after implementation of multifaceted quality improvement changes regarding antimicrobial stewardship and infection control (VAP-prevention-bundle, early-extubation policy, antimicrobial stewardship rounds). Methods: Neonates until 44 weeks of gestation with suspected VAP, hospitalized at our level-III NICU in Lucerne from September 2014 to December 2017 were enrolled. VAP episodes were analyzed according to 4 diagnostic frameworks. Agreement regarding chest x-ray interpretation done by 10 senior physicians was assessed. Annual incidence of suspected and confirmed neonatal VAP episodes and antibiotic days were calculated and compared for the years 2015, 2016, and 2017. Results: 17 studies were identified in our literature review. Overall, CDC-guidelines or similar criteria, requesting radiographic changes as main criteria, are mostly used. Comparison of suspected vs. confirmed neonatal VAP episodes showed a great variance (20.4 vs. 4.5/1,000 ventilator-days). The interrater-reliability of x-ray interpretation was poor (intra-class correlation 0.25). Implemented changes resulted in a gradual decline in annual VAP incidence and antibiotic days from 2015 compared with 2017 (28.8 vs. 7.4 suspected episodes/1,000 ventilator-days, 5.5 vs. 0 confirmed episodes/1,000 ventilator-days and 211 vs. 34.7 antibiotic days/1,000 ventilation-days, respectively). Conclusion: The incidence of suspected VAP and concomitant antibiotic use is much higher than for confirmed VAP, therefore inclusion of suspected episodes should be considered for accurate evaluation. There is a high diagnostic inconsistency and a low reliability of interpretation of chest x-rays regarding VAP. Implementation of combined antimicrobial stewardship and infection control measures may lead to an effective decrease in VAP incidence and antibiotic use.

Membranoproliferative glomerulonephritis and C3 glomerulopathy in children: change in treatment modality? A report of a case series.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) with immune complexes and C3 glomerulopathy (C3G) in children are rare and have a variable outcome, with some patients progressing to end-stage renal disease (ESRD). Mutations in genes encoding regulatory proteins of the alternative complement pathway and of complement C3 (C3) have been identified as concausative factors. METHODS: Three children with MPGN type I, four with C3G, i.e. three with C3 glomerulonephritis (C3GN) and one with dense deposit disease (DDD), were followed. Clinical, autoimmune data, histological characteristics, estimated glomerular filtration rate (eGFR), proteinuria, serum C3, genetic and biochemical analysis were assessed. RESULTS: The median age at onset was 7.3 years and the median eGFR was 72 mL/min/1.73 m2. Six children had marked proteinuria. All were treated with renin-angiotensin-aldosterone system (RAAS) blockers. Three were given one or more immunosuppressive drugs and two eculizumab. At the last median follow-up of 9 years after diagnosis, three children had normal eGFR and no or mild proteinuria on RAAS blockers only. Among four patients without remission of proteinuria, genetic analysis revealed mutations in complement regulator proteins of the alternative pathway. None of the three patients with immunosuppressive treatment achieved partial or complete remission of proteinuria and two progressed to ESRD and renal transplantation. Two patients treated with eculizumab revealed relevant decreases in proteinuria. CONCLUSIONS: In children with MPGN type I and C3G, the outcomes of renal function and response to treatment modality show great variability independent from histological diagnosis at disease onset. In case of severe clinical presentation at disease onset, early genetic and biochemical analysis of the alternative pathway dysregulation is recommended. Treatment with eculizumab appears to be an option to slow disease progression in single cases.

Levamisole in relapsing steroid-sensitive nephrotic syndrome: where do we stand?

Many patients with steroid-sensitive nephrotic syndrome develop a relapsing course; therefore, alternative treatment may be necessary to avoid steroid toxicity. In this issue, a multicenter controlled study in relapsing steroid-sensitive nephrotic syndrome shows the effectiveness of levamisole. Time to first relapse was significantly increased compared with placebo. In addition, possible differential treatment effects were suggested for subgroups: patients with frequent relapses might have a superior response to those with steroid dependency.