Simple method to measure rheological properties of soft surfaces by a micro-needle contact.

We developed a simple method to investigate rheological properties of soft surfaces, such as polymeric liquids and colloidal suspensions, by capturing the images of a metal micro-needle inserted into the surface. At contact, a meniscus-like deformation is formed on the surface. By relating the shape of the deformation to the balance of applied forces, local elasticity and viscosity just inside the surface are obtained. With a facile setup and rapid measurement process, the present method can be implemented to variety of systems, for instance, drying sessile drops and small volume of liquid confined in a capillary.

White Coat Hypertension Persistence in Children and Adolescents: The Pediatric Nephrology Research Consortium Study.

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM. STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We used multivariable generalized linear mixed effect models to estimate the association of baseline characteristics with abnormal ABPM phenotype progression. RESULTS: Eighty-nine patients met the inclusion criteria (median age, 13.9 years; 78% male). Median interval time between ABPM measurements was 14 months. On follow-up ABPM, 61% progressed to an abnormal ABPM phenotype (23% ambulatory hypertension, 38% ambulatory prehypertension). Individuals age 12-17 years and those with stable white coat hypertension had greater proportions progressing to either prehypertension or ambulatory hypertension. In the multivariable models, baseline wake systolic BP index ≥0.9 was significantly associated with higher odds of progressing to ambulatory hypertension (OR 3.07, 95% CI 1.02-9.23). CONCLUSIONS: The majority of the patients with white coat hypertension progressed to an abnormal ABPM phenotype. This study supports the 2017 American Academy of Pediatrics Clinical Practice Guideline's recommendation for follow-up of ABPM in patients with white coat hypertension.

Transient Hyperphosphatasemia Following Pediatric Kidney Transplant.

Introduction Transient hyperphosphatasemia (TH) is a rare benign condition of elevated serum alkaline phosphatase (AP) levels seen in healthy children. TH has been reported to occur in pediatric solid organ transplants, including kidney transplant patients. Little is known about TH in pediatric kidney transplant patients. Objective To evaluate the incidence and natural history of TH in pediatric kidney transplant patients. Methods A retrospective chart review of patients < 18 years of age who underwent kidney transplantation at the University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between 2008 and 2019 was performed to identify patients with TH, defined as an AP level greater than 1,000 IU/L. Exclusion criteria included repeat kidney transplants or kidney transplant as part of a multiorgan transplant. Results One hundred seventy-six patients underwent a solitary kidney transplant, of which 87 were less than 12 years of age. Eleven patients (6.5%) were found to have TH, all of whom were < 12 years of age (12.8%) (median age: 5 years; range: 1 - 11 years). The median AP level prior to transplant was 183 IU/L (range: 104 - 309 IU/L) and the median peak AP was > 2,300 IU/L (range: 1,227 - 4,912 IU/L). The median time from a kidney transplant to the diagnosis of TH was 0.6 years (range: 0.3 to 7.7 years). The median length of time that TH persisted was 0.5 years (range: 0.2 to 0.9 years). The median estimated glomerular filtration rate (GFR) at the time of diagnosis of TH was 84 mL/min/1.73m2 per the bedside Schwartz equation (range: 45 to 152 mL/min/1.73m2). One patient had variable AP levels over nine months prior to resolution; the other 10 patients had a solitary peak of AP prior to resolution. No patient required treatment of elevated AP levels and the TH resolved spontaneously without intervention. No patients had significant abnormalities of markers of metabolic bone disease or were on active vitamin D, calcium, or phosphorus supplements. Two patients reported bone pain, and one patient was found to have avascular necrosis of the hip. Conclusions TH is a relatively common finding following a pediatric kidney transplant in pre-pubertal children less than 12 years of age. It primarily occurs in the first year following a kidney transplant and usually resolves without recurrence within one year of onset.

Sarcoidosis with marked necrosis in enlarged lymph nodes mimics mycobacterial infection: a case report.

BACKGROUND: Sarcoidosis is pathologically characterized by the formation of non-necrotizing epithelioid cell granulomas. However, pathological findings of patients with sarcoidosis have rarely revealed necrosis. We report here on a patient with sarcoidosis which needed to be distinguished from infectious disease because of marked necrosis in the lymph nodes. CASE PRESENTATION: A 46-year-old Japanese woman was referred to our hospital due to a dry cough and appetite loss. A chest X-ray and computed tomography revealed markedly enlarged mediastinal and hilar lymph nodes and hepatosplenomegaly. Surgical biopsy of these lymph nodes was performed in order to make a diagnosis. Pathological findings revealed epithelioid cell granuloma with marked necrosis that suggested infectious etiology such as mycobacterial and fungal infections. In addition to the pathological findings, immunoglobulin A (IgA) antibody for Mycobacterium avium complex (MAC), enlargement of lymph nodes and hepatosplenomegaly indicated disseminated MAC, while sarcoidosis was considered as another important differential diagnosis according to elevated angiotensin-converting enzyme, soluble interleukin-2 receptor and uveitis. While waiting for the results of the cultures of acid-fast bacilli, the symptoms of cough and consumption had worsened, and initiation of therapy was required before the confirmed diagnosis. The therapy for MAC was initiated because it was feared that immunosuppressive therapy containing corticosteroid for sarcoidosis could worsen the patient's condition if MAC infection was the main etiology. However, the treatment for MAC was not effective, and it was clarified that no acid-fast bacilli were cultured in the liquid culture medium, so the diagnosis was corrected to sarcoidosis after reconsideration of clinical and pathological findings. Prednisolone (30 mg/day) was administered orally, and the patient's symptoms and radiological findings improved. CONCLUSION: Sarcoidosis must be considered even if pathological findings reveal marked necrosis, because rare cases of sarcoidosis exhibit extensive necrosis in lymph nodes. It is extremely important to carefully examine the clinical and pathological findings through discussion with the examining pathologist to reach the correct diagnosis.

Eculizumab exposure in children and young adults: indications, practice patterns, and outcomes-a Pediatric Nephrology Research Consortium study.

BACKGROUND: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab. METHODS: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data. RESULTS: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used "off-label" in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy. CONCLUSIONS: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.

Impact of the generation of EGFR-TKIs administered as prior therapy on the efficacy of osimertinib in patients with non-small cell lung cancer harboring EGFR T790M mutation.

BACKGROUND: There are few studies that directly compare the effects of osimertinib on patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) T790M mutation between the generation of prior EGFR tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively reviewed clinical data from the medical records of consecutive patients with advanced NSCLC who had developed resistance to first- or second-generation EGFR-TKIs due to EGFR T790M mutation and were subsequently treated with osimertinib at Juntendo University Hospital. In patients with available tumor samples, target amplicon sequencing analyses were performed to explore the genetic biomarkers. RESULTS: A total of 38 patients with NSCLC harboring EGFR T790M mutation were treated with osimertinib. Eight patients were classified into group A (afatinib followed by osimertinib) and 30 patients were classified into group B (first-generation EGFR-TKI followed by osimertinib). Progression-free survival (PFS) was significantly longer in group A than in group B (median PFS; not reached vs. 11.0 months, P = 0.018). Fourteen patients had available tissue samples collected before osimertinib treatment for target sequencing. In group A we found no additional mutations, other than EGFR T790M mutation. On the other hand, there were three samples in which other mutations emerged, in addition to EGFR T790M mutation, in group B. CONCLUSIONS: PFS of osimertinib was significantly longer in patients with NSCLC harboring EGFR T790M mutation after treatment with afatinib than in patients after treatment with first generation EGFR-TKIs. Additional mutations other than EGFR T790M may affect the efficacy of osimertinib treatment. KEY POINTS: Significant findings of the study: PFS of osimertinib was significantly longer in patients with NSCLC harboring EGFR T790M mutation after treatment with afatinib than in patients after treatment with first generation EGFR-TKIs. WHAT THIS STUDY ADDS: Additional mutations other than EGFR T790M may affect the efficacy of osimertinib treatment.

The use of urinary biomarkers to predict acute kidney injury in children after liver transplant.

BACKGROUND: AKI after pediatric liver transplantation is associated with increased morbidity and mortality. The role of urinary biomarkers for the prediction of AKI in pediatric patients after liver transplantation has not been previously reported. The primary objective of this prospective pilot study was to determine the predictive capabilities of urinary KIM-1, NGAL, TIMP-2, and IGFBP7 for diagnosing AKI. METHODS: Sixteen children undergoing liver transplantation were enrolled in the study over a 19-month time period. The Kidney Disease Improving Outcomes criteria for urine output and serum creatinine were used to define AKI. Predictive ability was evaluated using the area under the curve obtained by ROC analysis. RESULTS: AKI occurred in 6 (37.5%) of the patients between 2 and 4 days after transplant. There were no differences in any of the biomarkers prior to transplant. When obtained within 6 hours after transplant, the area under the ROC curve for predicting AKI was 0.758 (95% CI: 0.458-1.00) for KIM-1, 0.900 (95% CI: 0.724-1.00) for NGAL, and 0.933 (95% CI: 0.812-1.00) for the product of TIMP-2 and IGFBP7 ([TIMP-2]·[IGFBP7]). CONCLUSIONS: Our results show that both NGAL and [TIMP-2]·[IGFBP7] provide significant discrimination for AKI risk following liver transplant in children. Larger studies are needed to determine the optimal time point for measuring these biomarkers and to validate our findings.

Changes in Ambulatory Blood Pressure Phenotype over Time in Children and Adolescents with Elevated Blood Pressures.

OBJECTIVE: To determine the stability of ambulatory blood pressure monitoring (ABPM) over time in children referred for evaluation of elevated BPs and assess for factors predicting change. STUDY DESIGN: This retrospective chart review conducted at Seattle Children's Hospital and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh identified 124 children referred for elevated BPs with 2 ABPM studies at least 6 months apart. All subjects received lifestyle counseling. Subjects with secondary hypertension (HTN) or on antihypertensive medication were excluded. ABPM phenotype was classified using American Heart Association guidelines as showing normal BP, prehypertension, and HTN. Generalized linear mixed effect regression models were used to regress stable, improving, or worsening HTN outcomes at study follow-up on baseline BP index and load variables. RESULTS: The median age of patients was 14.1 years (73% males) and the median interval between studies was 18 months. ABPM phenotype changed in 58 of 124 children, with 16% worsening and 31% improving. Older age was associated with persistence of HTN. Although not significant, decrease in body mass index z-score tracked with sustained normal ambulatory BPs. CONCLUSIONS: Although the sample size is small, our study suggests ABPM phenotype shows variability over time. Further study is required to identify factors supporting risk for progression of ABPM phenotype over time.

Cholestatic Liver Injury Induced by Pembrolizumab in a Patient with Lung Adenocarcinoma.

The anti-programmed cell death-1 protein monoclonal antibody, pembrolizumab is an immune checkpoint inhibitor. While it improves the prognoses of patients with advanced non-small-cell lung cancer, it has been reported to induce various kinds of immune-related adverse events, including hepatotoxicity. Despite the frequency of hepatotoxicity, there is only limited information available regarding the pathophysiology and treatment. We herein report a 48-year-old man with lung adenocarcinoma who was treated with pembrolizumab and developed cholestatic liver injury. In this case, the importance of evaluating the histology of hepatotoxicity and the effectiveness of ursodeoxycholic acid for cholestatic liver injury is indicated.

Osimertinib for patients with EGFR T790M mutation-positive non-small-cell lung cancer and a poor performance status.

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is effective against EGFR T790M mutation-positive non-small-cell lung cancer (NSCLC) in patients who have good performance status (PS). However, the efficacy and safety of osimertinib for patients with poor PS is unknown. METHODS: We retrospectively evaluated the efficacy and safety of osimertinib in patients with EGFR T790M mutation-positive NSCLC who had Eastern Cooperative Oncology Group PS scores of 2-4 and who were administered 80 mg of osimertinib once daily between March 2016 and February 2017. RESULTS: Thirty patients (8 men and 22 women) with EGFR T790M mutation-positive NSCLC were evaluated; their median age was 66 years (range: 39-89 years). Twenty-four and six patients had PS scores of 2 and 3, respectively; none had a PS score of 4. All patients had previously been treated with first- or second-generation EGFR-TKIs. T790M was detected in the tumor samples of 23 patients, the blood samples of two patients, and both the tumor and blood samples of five patients. The overall response rate was 53% (95% confidence interval: 36-70%), and the PS score improvement rate was 63%. The median progression-free survival was 8.2 months (95% confidence interval: 4.3-13.2 months), while the median overall survival time was not reached. No patient required treatment cessation owing to adverse events, and no treatment-related deaths occurred. CONCLUSIONS: Osimertinib therapy demonstrates promising efficacy and acceptable safety in patients with EGFR T790M mutation-positive NSCLC who have poor PS.

Cost-Utility of Antimicrobial Prophylaxis for Treatment of Children With Vesicoureteral Reflux.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR. Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged <6 years diagnosed with VUR after a first UTI, considering these treatment strategies: (1) prophylaxis for all children with VUR, (2) prophylaxis for children with Grade III or Grade IV VUR, (3) prophylaxis for children with Grade IV VUR, and (4) no prophylaxis. Costs and effectiveness were estimated over the patient's lifetime. We used $100,000/QALY gained as the threshold for considering a treatment strategy cost effective. Results: Based on current data and plausible ranges to account for data uncertainty, prophylaxis of children with Grades IV VUR costs $37,903 per QALY gained. Treating children with Grade III and IV VUR costs an additional $302,024 per QALY gained. Treating children with all grades of VUR costs an additional $339,740 per QALY gained. Conclusions: Treating children with Grades I, II, and III VUR with long-term antimicrobial prophylaxis costs substantially more than interventions typically considered economically reasonable. Prophylaxis in children with Grade IV VUR is cost effective.

Ruptured intracranial aneurysm in a patient with autosomal recessive polycystic kidney disease.

Aneurysmal rupture can result in devastating neurological consequences and can be complicated by comorbid disease processes. Patients with autosomal recessive polycystic kidney disease (ARPKD) have a low rate of reported aneurysms, but this may be due to the relative high rate of end-stage illnesses early in childhood. Authors here report the case of a 10-year-old boy with ARPKD who presented with a Hunt and Hess grade V subarachnoid hemorrhage requiring emergency ventriculostomy, embolization, and decompressive craniectomy. Despite initial improvements in his neurological status, the patient succumbed to hepatic failure. Given the catastrophic outcomes of subarachnoid hemorrhage in young patients, early radiographic screening in those with ARPKD may be warranted.

Evaluation and Management of Stage 2 Hypertension in Pediatric Patients.

PURPOSE OF REVIEW: To update the definition and clinical practice of stage 2 hypertension (HTN) in pediatrics. RECENT FINDINGS: The 2017 American Academy of Pediatrics Clinical Practice Guideline (AAP CPG) for Screening and Management of High Blood Pressure in Children and Adolescent includes new normative blood pressure tables for children and adolescents ages 1 to 17 years and new definitions for stage 2 HTN. This review will highlight these aspects as well as new recommendations in the guideline specific to stage 2 HTN. It will outline how the new guideline differs from the previous 2004 guideline, the implications of these differences, and suggested changes in evaluation and management of stage 2 HTN. Lastly, the review will address topics relevant to daily clinical practice including competitive athletic participation, investigation for secondary HTN and HTN comorbidities, and blood pressure-lowering therapy. With the publication of the new AAP CPG introducing revised normative tables, the prevalence of stage 2 HTN in pediatrics is expected to rise. Based on the new guidelines, there is less emphasis on investigation for secondary HTN and more attention to lifestyle modifications for primary HTN. Future research should address whether there is BP level within the stage 2 HTN range above which the approach to evaluation and management should be altered in this heterogeneous patient population.

Development of interstitial pneumonia during treatment with eribulin: a case report.

BACKGROUND: Eribulin is typically used to treat patients with advanced breast cancer, and anti-cancer agents often cause the development of interstitial pneumonia in Japanese patients with advanced cancer. However, few case reports have addressed eribulin-induced interstitial pneumonia. Herein, we report a rare case of interstitial pneumonia-specifically, organized pneumonia-during treatment with eribulin in a patient with advanced breast cancer. CASE PRESENTATION: A 52-year-old Japanese woman was diagnosed as having advanced breast cancer 3 years before the admission described in the present report. She had received eribulin as third-line chemotherapy. Five days after her second treatment with eribulin, she was admitted to our hospital with dyspnea and dry cough. Upon admission, a chest computed tomography scan showed consolidation, with air bronchograms along the bronchovascular bundle of both lower lobes. The patient's serum levels of sialylated carbohydrate antigen Krebs von den Lungen-6 were high, as were her surfactant protein-D levels. There was no evidence of heart failure, renal failure, or infection. Based on the clinical cause, as well as on the findings of organized pneumonia, the patient was diagnosed as having interstitial pneumonia and treated with corticosteroids. After the initiation of steroid treatment, her respiratory condition and chest radiological findings improved. CONCLUSIONS: This case reveals an association between eribulin treatment and interstitial pneumonia. To our knowledge, this is the first case report to describe eribulin-induced organized pneumonia. Clinicians should be aware that interstitial pneumonia can develop during treatment with anti-cancer agents.

The Use of Ambulatory Blood Pressure Monitoring As Standard of Care in Pediatrics.

Hypertension (HTN) is a significant global health problem, responsible for 7.5 million deaths each year worldwide. The prevalence of HTN is increasing in the pediatric population likely attributed to the increase in childhood obesity. Recent work has also shown that blood pressure (BP) tends to track from childhood to adulthood including BP-related target organ damage. In the last 25-30 years, pediatric use of ambulatory blood pressure monitoring (ABPM) has been expanding mainly in the setting of initial elevated BP measurement evaluation, HTN therapy efficacy follow-up, and renal disease. However, there are many clinical areas where ABPM could potentially be used but is currently underutilized. This review summarizes the current knowledge and the uses of pediatric ABPM and explores clinical areas where it can be very useful both to detect HTN and its longitudinal follow-up. And thus, ABPM could serve as a critical tool to potentially prevent early cardiovascular mortality and morbidity in wide variety of populations. With solid data to support ABPM's superiority over clinic BP measurements and these clinical areas for its expansion, ABPM should now be part of standard of care in BP evaluation and management in pediatrics.

Diagnosis and management of white-coat hypertension in children and adolescents: A Midwest Pediatric Nephrology Consortium study.

Although the definition of white-coat hypertension (WCH) in children and adolescents is clearly defined, little is known about how this condition is actually approached clinically. To better understand the contemporary approach to the diagnosis and management of WCH in pediatric patients, the authors surveyed the membership of the Midwest Pediatric Nephrology Consortium. Seventy-four faculty pediatric nephrologists responded to the survey. The survey results demonstrated uniformity in diagnosing WCH, including ambulatory blood pressure monitoring use in 93% of the respondents and a 75% adherence rate according to the 2014 American Heart Association scientific statement on pediatric ambulatory blood pressure monitoring. A total of 85% of respondents would not embark on further diagnostic evaluation once the WCH diagnosis was established, and none would initiate antihypertensive medications. There was a wide variety of practice habits in follow-up of WCH including frequency of office and out-of-office follow-up blood pressure measurements, the setting and timing of physician follow-up, and the role of repeat ambulatory blood pressure monitoring. The results of this survey highlight the need for prospective studies aimed at establishing the optimal approach to pediatric patients with WCH.

Atypical Hemolytic Uremic Syndrome and Chronic Ulcerative Colitis Treated with Eculizumab.

BACKGROUND: Hemolytic-uremic syndrome (HUS) presents with hemolytic anemia, thrombocytopenia, and thrombotic microangiopathy of the kidney and usually results from Shiga-toxin induced activation of the alternative complement pathway. Gastroenteritis is a common feature of the Shiga-toxin producing Escherichia coli HUS, referred to as STEC-HUS. An inherited or acquired complement dysregulation may lead to HUS referred to as non-STEC or atypical (a)HUS. Although gastroenteritis is not a common presentation of aHUS, some patients develop ischemic colitis and may be misdiagnosed as acute appendicitis or acute ulcerative colitis (UC). CASE DIAGNOSIS ­TREATMENT: We present a patient with low circulating complement (C) 3 levels who developed aHUS in the course of chronic active UC. Resolution of renal and gastrointestinal manifestations in response to treatment with eculizumab, a humanized monoclonal antibody against terminal C5 protein suggests the role of alternative complement in the pathogenesis of both, aHUS and UC. CONCLUSION: This case illustrates that dysregulation of the alternative complement pathway may manifest in other organs besides the kidney and that the circulating C3 levels do not correlate with the disease activity or the clinical response to eculizumab.

Neonatal polycystic kidney disease.

This article provides an up-to-date comprehensive review and summary on neonatal polycystic kidney disease (PKD) with emphasis on the differential diagnosis, clinical manifestations, diagnostic techniques, and potential therapeutic approaches for the major causes of neonatal PKD, namely hereditary disease, including autosomal recessive and autosomal dominant PKD and nonhereditary PKD, with particular emphasis on multicystic dysplastic kidney. A brief overview of obstructive cystic dysplasia and simple and complex cysts is also included.

Therapy of acute hypertension in hospitalized children and adolescents.

Acute hypertension (HTN) in hospitalized children and adolescents occurs relatively frequently, and in some cases, if not recognized and treated promptly, it can lead to hypertensive crisis with potentially significant morbidity and mortality. In contrast to adults, where acute HTN is most likely due to uncontrolled primary HTN, children and adolescents with acute HTN are more likely to have secondary HTN. This review will briefly cover evaluation of acute HTN and various age-specific etiologies of secondary HTN and provide more in-depth discussion on treatment targets, potential risks of acute HTN therapy, and available pediatric data on intravenous and oral antihypertensive agents, and it proposes treatment schema including unique therapy of specific secondary HTN scenarios.