Caffeine and kidney function at two years in former extremely low gestational age neonates.

BACKGROUND: Extremely low gestational age neonates (ELGANs) are at risk for chronic kidney disease. The long-term kidney effects of neonatal caffeine are unknown. We hypothesize that prolonged caffeine exposure will improve kidney function at 22-26 months. METHODS: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates <28 weeks' gestation. Participants included if any kidney outcomes were collected at 22-26 months corrected age. Exposure was post-menstrual age of caffeine discontinuation. PRIMARY OUTCOMES: 'reduced eGFR' <90 ml/min/1.73 m2, 'albuminuria' (>30 mg albumin/g creatinine), or 'elevated blood pressure' (BP) >95th %tile. A general estimating equation logistic regression model stratified by bronchopulmonary dysplasia (BPD) status was used. RESULTS: 598 participants had at least one kidney metric at follow up. Within the whole cohort, postmenstrual age of caffeine discontinuation was not associated with any abnormal measures of kidney function at 2 years. In the stratified analysis, for each additional week of caffeine, the no BPD group had a 21% decreased adjusted odds of eGFR <90 ml/min/1.73m2 (aOR 0.78; CI 0.62-0.99) and the BPD group had a 15% increased adjusted odds of elevated BP (aOR 1.15; CI: 1.05-1.25). CONCLUSIONS: Longer caffeine exposure during the neonatal period is associated with differential kidney outcomes at 22-26 months dependent on BPD status. IMPACT: In participants born <28 weeks' gestation, discontinuation of caffeine at a later post menstrual age was not associated with abnormal kidney outcomes at 22-26 months corrected age. When assessed at 2 years of age, later discontinuation of caffeine in children born <28 weeks' gestation was associated with a greater risk of reduced eGFR in those without a history of BPD and an increased odds of hypertension in those with a history of BPD. More work is necessary to understand the long-term impact of caffeine on the developing kidney.

Preclinical mouse model of a misfolded PNLIP variant develops chronic pancreatitis.

OBJECTIVE: Increasing evidence implicates mutation-induced protein misfolding and endoplasm reticulum (ER) stress in the pathophysiology of chronic pancreatitis (CP). The paucity of animal models harbouring genetic risk variants has hampered our understanding of how misfolded proteins trigger CP. We previously showed that pancreatic triglyceride lipase (PNLIP) p.T221M, a variant associated with steatorrhoea and possibly CP in humans, misfolds and elicits ER stress in vitro suggesting proteotoxicity as a potential disease mechanism. Our objective was to create a mouse model to determine if PNLIP p.T221M causes CP and to define the mechanism. DESIGN: We created a mouse model of Pnlip p.T221M and characterised the structural and biochemical changes in the pancreas aged 1-12 months. We used multiple methods including histochemistry, immunostaining, transmission electron microscopy, biochemical assays, immunoblotting and qPCR. RESULTS: We demonstrated the hallmarks of human CP in Pnlip p.T221M homozygous mice including progressive pancreatic atrophy, acinar cell loss, fibrosis, fatty change, immune cell infiltration and reduced exocrine function. Heterozygotes also developed CP although at a slower rate. Immunoblot showed that pancreatic PNLIP T221M misfolded as insoluble aggregates. The level of aggregates in homozygotes declined with age and was much lower in heterozygotes at all ages. The Pnlip p.T221M pancreas had increased ER stress evidenced by dilated ER, increased Hspa5 (BiP) mRNA abundance and a maladaptive unfolded protein response leading to upregulation of Ddit3 (CHOP), nuclear factor-κB and cell death. CONCLUSION: Expression of PNLIP p.T221M in a preclinical mouse model results in CP caused by ER stress and proteotoxicity of misfolded mutant PNLIP.

Gastrointestinal perforation after bevacizumab: a multi-site, single-institution study with a focus on survival.

BACKGROUND: Bevacizumab-induced gastrointestinal perforation is a rare but potentially devastating adverse event that has generated limited data on overall survival. Yet, such survival data are critical in guiding management. METHODS: This multi-site, single-institution retrospective study focused on all cancer patients who had received bevacizumab and who had suffered a well-documented gastrointestinal perforation from January 1, 2004 through January 20, 2022.The main goal was to report survival outcomes; Kaplan Meier curves and Cox survival models were used for this purpose. RESULTS: Eighty-nine patients are included in this report with a median age of 62 years (range 26-85). Colorectal cancer was the most common malignancy (n = 42). Thirty-nine patients underwent surgery for the perforation. Seventy-eight were deceased at the time of reporting with an overall median survival of all patients of 2.7 months (range 0-45 months), and 32 (36%) died within 30 days of perforation. In univariable survival analyses, no statistically significant associations were observed for age, gender, corticosteroid use, and time since last bevacizumab dose. However, surgically treated patients manifested a better survival (hazard ratio (HR) 0.49 (95% CI 0.31-0.78); p = 0.003). In multivariable analyses, surgery continued to be associated with improved survival (HR 0.47 (95% CI 0.29-0.74); p = 0.002), and corticosteroid use was associated with worse survival (HR 1.75 (95% CI 1.02-2.99); p = 0.04). CONCLUSION: Although gastrointestinal perforation after bevacizumab should be managed on a case-by-case basis, these descriptive survival data can help inform patients, their families, and healthcare providers as challenging management decisions arise.

Olaparib for ovarian cancer: a single-institution, multi-site qualitative study.

PURPOSE: This qualitative study sought to learn patients' perspectives on olaparib - including maintenance olaparib - in their own words. METHODS: Olaparib-treated patients were interviewed by phone. A semi-structured interview guide that focused on symptoms and quality of life was formulated in alignment with the study objective. Interviews were transcribed and analyzed with content analysis. RESULTS: Twenty olaparib-treated patients were interviewed. Four themes emerged: (1) The Long Cancer Journey. Patients prescribed olaparib appear to have had a long cancer journey, sometimes with prior cancer ("I had breast cancer in 1996") and sometimes with a long interval from an ovarian cancer diagnosis; (2) Adherence. Despite this journey, patients were adherent to olaparib ("I set it for an alarm 15 min before I have to take [olaparib] and then exactly when I'm supposed to take it"); (3) Adherence Despite Challenges. Adherence continued despite side effects (although olaparib was "pretty tolerable"). This adherence also continued despite cost ("…for a month's supply, mine was $15,837… and my insurance covered some of it but not near enough"), and (4) Modifications in Perceptions of BRCA Status. Olaparib as cancer therapy influenced perceptions of BRCA mutations ("But I… I have to tell you, I'm grateful that I qualified to be on Lynparza®"). CONCLUSION: Although oral maintenance therapy for ovarian cancer is relatively new, patients appear willing to take olaparib long term; and they seem to take great lengths to remain adherent, despite having sometimes had a long cancer journey.

The Trend of Urinary N Terminal Probrain Natriuretic Peptide in Extremely Low Birth Weight Infants during the Neonatal Period.

OBJECTIVE: N-terminal probrain natriuretic peptide (NT-proBNP) is a biomarker of interest in many cardiopulmonary diseases in extremely low birth weight (ELBW) Infants. However, there is a gap in knowledge about the trend of ELBW infant's urinary NT-proBNP during the neonatal period. AIM: To determine the trend of urinary NT-proBNP during the first 4 weeks of life of an ELBW infant. STUDY DESIGN: We analyzed prospectively enrolled 87 ELBW infants. Urinary NT-proBNP to creatinine ratios were measured on days 1 to 7, 14, and 28 of life. We plotted each study point's means to determine the trend of urinary NT-proBNP over the entire neonatal period. Data were analyzed using the Friedman analysis of variance for comparative analysis of study points. RESULTS: Urinary NT-proBNP/creatinine ratios were significantly elevated on days 1 to 7 (mean 2,452, ± 1,518) than day 14 (mean 747, ± 176), and day 28 (mean 149, ± 54), p = 0.001. Overall, urinary NT-proBNP levels were highest during days 1 to 3 (mean 3,232, ± 1,255) and lowest on day 28 (mean 149, ± 54). CONCLUSION: Urinary NT-proBNP levels are higher during the first week in ELBW infants with a downward trend during the neonatal period, the lowest values at 4 weeks postnatal age. More studies are required to determine the clinical utility of this trend during and beyond the neonatal period. KEY POINTS: · NT-proBNP is a biomarker for monitoring cardiac disease in premature infants.. · The trend of urinary NT-proBNP is unknown in premature infants.. · A trend of urinary NT-proBNP was determined during the first 4 weeks in premature infants..

Nanoliposomal irinotecan (Nal-IRI)-based chemotherapy after irinotecan -based chemotherapy in patients with pancreas cancer.

BACKGROUND: Nanoliposomal irinotecan (Nal-IRI) is a preferred second-line treatment for metastatic pancreas cancer. It is unclear, however, whether patients who had received irinotecan derive benefit. METHODS: Medical records of metastatic pancreas cancer patients who had received irinotecan and then Nal-IRI were reviewed. The primary endpoint was overall survival after the initiation of Nal-IRI (an a priori threshold of >4 months defined success); adverse events and quotes from the medical record on decision-making were also recorded. RESULTS: Sixty four patients met eligibility criteria with a median age of 65 years (range: 36, 80 years). The median overall survival from initiation of Nal-IRI was 5.1 months (95% confidence interval (CI): 4.3, 5.6 months). An exploratory comparison, based on no cancer progression with irinotecan versus progression, showed improved survival with Nal-IRI in the former group: 6.1 months (95% CI: 5.1, 9.3 months) versus 4.3 months (95% CI: 2.3, 4.8 months); p = 0.0006. Nal-IRI adverse events occurred as expected. Qualitative data illustrate several themes, including "limited treatment options," which appeared to drive the decision to prescribe Nal-IRI. CONCLUSION: Nal-IRI might be considered in pancreas cancer patients who had received irinotecan, particularly in the absence of disease progression with the latter.

The impact of fluid balance on outcomes in premature neonates: a report from the AWAKEN study group.

BACKGROUND: We evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study. METHODS: Retrospective analysis of infants <36 weeks' gestational age from the AWAKEN study (N = 1007). FB was defined by percentage of change from birth weight. OUTCOME: Mechanical ventilation (MV) at postnatal day 7. RESULTS: One hundred and forty-nine (14.8%) were on MV at postnatal day 7. The median peak FB was 0% (IQR: -2.9, 2) and occurred on postnatal day 2 (IQR: 1,5). Multivariable models showed that the peak FB (aOR 1.14, 95% CI 1.10-1.19), lowest FB in first postnatal week (aOR 1.12, 95% CI 1.07-1.16), and FB on postnatal day 7 (aOR 1.10, 95% CI 1.06-1.13) were independently associated with MV on postnatal day 7. In a similar analysis, a negative FB at postnatal day 7 protected against the need for MV at postnatal day 7 (aOR 0.21, 95% CI 0.12-0.35). CONCLUSIONS: Positive peak FB during the first postnatal week and more positive FB on postnatal day 7 were independently associated with MV at postnatal day 7. Those with a negative FB at postnatal day 7 were less likely to require MV.

Increased Intact Proinsulin in the Oral Glucose Challenge Sample is an Early Indicator for Future Type 2 Diabetes Development - Case Reports and Evidence from the Literature.

BACKGROUND: Increased intact proinsulin in plasma is a highly specific biomarker for a major disruption of insulin-processing in the pancreatic ß-cells with associated insulin resistance. Increased intact proinsulin in morning fasting plasma indicates not only incipient diabetes, but also increased risk of macrovascular events in the patient - of ten times before an actual diagnosis of diabetes - due to the convergence of ß-cell dysfunction, insulin resistance, and chronic systemic inflammation. This has raised the question as to whether a marked increase in intact proinsulin levels after oral glucose load in healthy subjects might be considered as indicative for ß-cell dysfunction and prediabetes. METHODS: A previous study from 2011 examined, inter alia, intact proinsulin levels in blood samples from twenty healthy study participants at baseline and two hours after an oral glucose tolerance test (OGTT) with 75 g glucose. Seventeen of the participants showed normal glucose levels at baseline and at two hours compared to 4 participants with normal intact proinsulin levels at baseline but increased intact proinsulin levels at two hours. RESULTS: All four patients went on to develop type 2 diabetes in the following 5 years. None of the other subjects from the previous investigation developed type 2 diabetes. CONCLUSIONS: As also confirmed by recent literature, intact proinsulin provides a powerful, easily measured biomarker for ß-cell dysfunction and insulin resistance in type 2 diabetes, as well as risk of future cardiovascular events regardless of the stage of diabetes.

Case series of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy during extracorporeal life support.

Therapeutic hypothermia initiated within 6 hours of birth is currently the standard of care for the management of neonates with hypoxic-ischemic encephalopathy. Neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy are also at risk for severe respiratory failure and need for extracorporeal life support. The risks and benefits of therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support are still not well defined. We report our experience of a case series of six neonates who underwent therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support. We also report long-term neurodevelopmental follow-up from 6 to 24 months and add to the current body of evidence regarding feasibility, clinical experience, and short-term complications.

The impact of fluid balance on outcomes in critically ill near-term/term neonates: a report from the AWAKEN study group.

BACKGROUND: In sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill near-term/term neonates. METHODS: This analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight. PRIMARY OUTCOME: mechanical ventilation (MV) on postnatal day 7. RESULTS: The median peak fluid balance was 1.0% (IQR: -0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5). Nine percent required MV at postnatal day 7. Multivariable models showed the peak fluid balance (aOR 1.12, 95%CI 1.08-1.17), lowest fluid balance in 1st postnatal week (aOR 1.14, 95%CI 1.07-1.22), fluid balance on postnatal day 7 (aOR 1.12, 95%CI 1.07-1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI 0.16-0.67) were independently associated with MV on postnatal day 7. CONCLUSIONS: We describe the impact of fluid balance in critically ill near-term/term neonates over the first postnatal week. Higher peak fluid balance during the first postnatal week and higher fluid balance on postnatal day 7 were independently associated with MV at postnatal day 7.

Renal injury in neonates: use of "omics" for developing precision medicine in neonatology.

Preterm birth is associated with increased risks of morbidity and mortality along with increased healthcare costs. Advances in medicine have enhanced survival for preterm infants but the overall incidence of major morbidities has changed very little. Abnormal renal development is an important consequence of premature birth. Acute kidney injury (AKI) in the neonatal period is multifactorial and may increase lifetime risk of chronic kidney disease.Traditional biomarkers in newborns suffer from considerable confounders, limiting their use for early identification of AKI. There is a need to develop novel biomarkers that can identify, in real time, the evolution of renal dysfunction in an early diagnostic, monitoring and prognostic fashion. Use of "omics", particularly metabolomics, may provide valuable information regarding functional pathways underlying AKI and prediction of clinical outcomes.The emerging knowledge generated by the application of "omics" (genomics, proteomics, metabolomics) in neonatology provides new insights that can help to identify markers of early diagnosis, disease progression, and identify new therapeutic targets. Additionally, omics will have major implications in the field of personalized healthcare in the future. Here, we will review the current knowledge of different omics technologies in neonatal-perinatal medicine including biomarker discovery, defining as yet unrecognized biologic therapeutic targets, and linking of omics to relevant standard indices and long-term outcomes.

The nephrologist of tomorrow: towards a kidney-omic future.

Omics refers to the collective technologies used to explore the roles and relationships of the various types of molecules that make up the phenotype of an organism. Systems biology is a scientific discipline that endeavours to quantify all of the molecular elements of a biological system. Therefore, it reflects the knowledge acquired by omics in a meaningful manner by providing insights into functional pathways and regulatory networks underlying different diseases. The recent advances in biotechnological platforms and statistical tools to analyse such complex data have enabled scientists to connect the experimentally observed correlations to the underlying biochemical and pathological processes. We discuss in this review the current knowledge of different omics technologies in kidney diseases, specifically in the field of pediatric nephrology, including biomarker discovery, defining as yet unrecognized biologic therapeutic targets and linking omics to relevant standard indices and clinical outcomes. We also provide here a unique perspective on the field, taking advantage of the experience gained by the large-scale European research initiative called "Systems Biology towards Novel Chronic Kidney Disease Diagnosis and Treatment" (SysKid). Based on the integrative framework of Systems biology, SysKid demonstrated how omics are powerful yet complex tools to unravel the consequences of diabetes and hypertension on kidney function.

Transforming growth factor-beta 1 produced by vascular smooth muscle cells predicts fibrosis in the gastrocnemius of patients with peripheral artery disease.

BACKGROUND: Lower leg ischemia, myopathy, and limb dysfunction are distinguishing features of peripheral artery disease (PAD). The myopathy of PAD is characterized by myofiber degeneration in association with extracellular matrix expansion, and increased expression of transforming growth factor-beta 1 (TGF-ß1; a pro-fibrotic cytokine). In this study, we evaluated cellular expression of TGF-ß1 in gastrocnemius of control (CTRL) and PAD patients and its relationship to deposited collagen, fibroblast accumulation and limb hemodynamics. METHODS: Gastrocnemius biopsies were collected from PAD patients with claudication (PAD-II; N = 25) and tissue loss (PAD-IV; N = 20) and from CTRL patients (N = 20). TGF-ß1 in slide-mounted specimens was labeled with fluorescent antibodies and analyzed by quantitative wide-field, fluorescence microscopy. We evaluated co-localization of TGF-ß1 with vascular smooth muscle cells (SMC) (high molecular weight caldesmon), fibroblasts (TE-7 antigen), macrophages (CD163), T cells (CD3) and endothelial cells (CD31). Collagen was stained with Masson Trichrome and collagen density was determined by quantitative bright-field microscopy with multi-spectral imaging. RESULTS: Collagen density increased from CTRL to PAD-II to PAD-IV specimens (all differences p < 0.05) and was prominent around microvessels. TGF-ß1 expression increased with advancing disease (all differences p < 0.05), correlated with collagen density across all specimens (r = 0.864; p < 0.001), associated with fibroblast accumulation, and was observed exclusively in SMC. TGF-ß1 expression inversely correlated with ankle-brachial index across PAD patients (r = -0.698; p < 0.001). CONCLUSIONS: Our findings support a progressive fibrosis in the gastrocnemius of PAD patients that is caused by elevated TGF-ß1 production in the SMC of microvessels in response to tissue hypoxia.

Early urinary biomarkers of acute kidney injury in preterm infants.

BACKGROUND: Acute kidney injury (AKI) in the neonatal intensive care setting is multifactorial and is associated with significant morbidity and mortality. This study evaluates the utility of novel urinary biomarkers to predict the development and/or severity AKI in preterm infants. METHODS: We performed a case-control study on a prospective cohort of preterm infants (<32 wk), to compare seven urine biomarkers between 25 infants with AKI and 20 infants without AKI. RESULTS: Infants with AKI had significantly higher neutrophil gelatinase-associated lipocalin (NGAL) (median, control (CTRL) vs. AKI; 0.598 vs. 4.24 µg/ml; P < 0.0001). In contrast, urinary epidermal growth factor (EGF) levels were significantly lower in infants who developed AKI compared to controls (median, CTRL vs. AKI; 0.016 vs. 0.006 µg/ml; P < 0.001). The area under the curve (AUC) for NGAL for prediction of stage I AKI on the day prior to AKI diagnosis (day-1) was 0.91, and for the prediction of stage II/III, AKI was 0.92. Similarly, urine EGF was a predictor of renal injury on day -1 (AUC: 0.97 for stage I and 0.86 for stage II/III AKI). CONCLUSION: Urinary biomarkers may be useful to predict AKI development prior to changes in serum creatinine (SCr) in preterm infants.

Drug-induced acute kidney injury in neonates.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is an independent risk factor for morbidity and mortality in critically ill neonates. Nephrotoxic medication exposure is common in neonates. Nephrotoxicity represents the most potentially avoidable cause of AKI in this population. RECENT FINDINGS: Recent studies in critically ill children revealed the importance of recognizing AKI and potentially modifiable risk factors for the development of AKI such as nephrotoxic medication exposures. Data from critically ill children who have AKI suggest that survivors are at risk for the development of chronic kidney disease. Premature infants are born with incomplete nephrogenesis and are at risk for chronic kidney disease. The use of nephrotoxic medications in the neonatal intensive care unit is very common; yet the effects of medication nephrotoxicity on the short and long-term outcomes remains highly understudied. SUMMARY: The neonatal kidney is predisposed to nephrotoxic AKI. Our ability to improve outcomes for this vulnerable group depends on a heightened awareness of this issue. It is important for clinicians to develop methods to minimize and prevent nephrotoxic AKI in neonates through a multidisciplinary approach aiming at earlier recognition and close monitoring of nephrotoxin-induced AKI.

Metabolomics in pediatric nephrology: emerging concepts.

Metabolomics, the latest of the "omics" sciences, refers to the systematic study of metabolites and their changes in biological samples due to physiological stimuli and/or genetic modification. Because metabolites represent the downstream expression of genome, transcriptome, and proteome, they can closely reflect the phenotype of an organism at a specific time. As an emerging field in analytical biochemistry, metabolomics has the potential to play a major role in monitoring real-time kidney function and detecting adverse renal events. Additionally, small molecule metabolites can provide mechanistic insights into novel biomarkers of kidney diseases, given the limitations of the current traditional markers. The clinical utility of metabolomics in the field of pediatric nephrology includes biomarker discovery, defining as yet unrecognized biological therapeutic targets, linking of metabolites to relevant standard indices and clinical outcomes, and providing a window of opportunity to investigate the intricacies of environment/genetic interplay in specific disease states.

Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure.

Evidence indicates that cerebral blood flow is both increased and diminished in astronauts on return to Earth. Data from ground-based animal models simulating the effects of microgravity have shown that decrements in cerebral perfusion are associated with enhanced vasoconstriction and structural remodeling of cerebral arteries. Based on these results, the purpose of this study was to test the hypothesis that 13 d of spaceflight [Space Transportation System (STS)-135 shuttle mission] enhances myogenic vasoconstriction, increases medial wall thickness, and elicits no change in the mechanical properties of mouse cerebral arteries. Basilar and posterior communicating arteries (PCAs) were isolated from 9-wk-old female C57BL/6 mice for in vitro vascular and mechanical testing. Contrary to that hypothesized, myogenic vasoconstrictor responses were lower and vascular distensibility greater in arteries from spaceflight group (SF) mice (n=7) relative to ground-based control group (GC) mice (n=12). Basilar artery maximal diameter was greater in SF mice (SF: 236±9 µm and GC: 215±5 µm) with no difference in medial wall thickness (SF: 12.4±1.6 µm; GC: 12.2±1.2 µm). Stiffness of the PCA, as characterized via nanoindentation, was lower in SF mice (SF: 3.4±0.3 N/m; GC: 5.4±0.8 N/m). Collectively, spaceflight-induced reductions in myogenic vasoconstriction and stiffness and increases in maximal diameter of cerebral arteries signify that elevations in brain blood flow may occur during spaceflight. Such changes in cerebral vascular control of perfusion could contribute to increases in intracranial pressure and an associated impairment of visual acuity in astronauts during spaceflight.

Toxic Thyroid Adenoma Presenting as Apathetic Hyperthyroidism: A Case Report.

The thyroid gland is an essential endocrine organ that secretes hormones to regulate homeostasis across multiple organ systems throughout the body. It is actively regulated by the hypothalamic-pituitary-thyroid (HPT) axis, where negative feedback modulates the amounts of active hormone being released; thus, lesions that disrupt the proper functioning of this gland or its regulatory mechanisms can be destructive. Toxic thyroid adenomas are usually singular benign functioning nodules in the thyroid gland that cause thyrotoxicosis. Hyperthyroidism is commonly clinically silent, however, in most symptomatic cases, patients will be diagnosed based on abnormal laboratory findings and typical hyperthyroid symptoms. This case report examines an 81-year-old male with an extensive medical history who presented with complaints of new-onset generalized fatigue coupled with bilateral lower extremity muscle cramps. A positron emission tomography (PET) scan for other medical conditions incidentally noted mildly increased uptake in the thyroid gland, prompting a further investigation that resulted in a diagnosis of toxic thyroid adenoma. The patient responded well to treatment with methimazole and has remained in a euthyroid state.

Complications of thoracic endovascular aneurysm repair (TEVAR): A pictorial review.

Thoracic endovascular aneurysm repair (TEVAR) has replaced open surgical repair as the treatment of choice for several aortic conditions. Despite its lower morbidity and mortality, several TEVAR-related complications can occur and some of which may necessitate surgical or endovascular re-intervention. The current article reviews common and rare complications of TEVAR procedure with emphasis on complications identifiable on cross-sectional imaging and potential pitfalls of pre-procedural planning.

Urinary metabolomic markers of aminoglycoside nephrotoxicity in newborn rats.

BACKGROUND: Aminoglycoside exposure is a common cause of acute kidney injury (AKI). Delay in the diagnosis of AKI using conventional biomarkers has been one of the important obstacles in applying early effective interventions. We tested the hypothesis that urinary metabolomics could identify novel early biomarkers for toxic renal injury. METHODS: Three-day-old rats were divided into three groups; they received a single daily injection of vehicle (0.9% NaCl solution) or gentamicin at a dose of 10 or 20 mg/kg/d for 7 d. Urine and blood were collected after 3 and 7 d of injections. Urinary metabolites were evaluated using high-performance liquid chromatography and gas chromatography/mass spectrometry. RESULTS: A distinct urinary metabolic profile characterized by glucosuria, phosphaturia, and aminoaciduria was identified preceding changes in serum creatinine. At both the gentamicin doses, urinary tryptophan was significantly (P < 0.05) increased (fold change: 1.91 and 2.31 after 3 d; 1.81 and 1.93 after 7 d). Similarly, kynurenic acid, a tryptophan metabolite, showed a significant (P < 0.05) decrease (fold change: 0.26 and 0.24 after 3 d; 0.21 and 0.52 after 7 d), suggesting an interruption of the normal tryptophan metabolism pathway. CONCLUSION: We conclude that urinary metabolomic profiling provides a robust approach for identifying early and novel markers of gentamicin-induced AKI.