Eu- or hypoglycemic ketosis and ketoacidosis in children: a review.

The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of ß-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and ß-hydroxybutyrate.

Kidney tubular injury induced by valproic acid: systematic literature review.

BACKGROUND: Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury. METHODS: We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered. RESULTS: For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-ß-glucosaminidase, was often noted. CONCLUSIONS: Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. A higher resolution version of the Graphical abstract is available as Supplementary information.

Coronavirus disease 2019, vaccination against coronavirus and immunoglobulin A-mediated diseases: systematic literature review.

Coronavirus disease 2019 (COVID-19) and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been associated with autoimmune phenomena. However, the interplay between COVID-19 or vaccination against SARS-CoV-2 and Berger glomerulonephritis or Henoch-Schönlein vasculitis, two diseases mediated by immunoglobulin A, has never been comprehensively investigated. Therefore, we carried out a systematic review of the literature on this topic. Following databases were used: Google Scholar, Excerpta Medica and the United States National Library of Medicine. Eighty-seven patients with immunoglobulin A-mediated diseases associated with SARS-CoV-2 infection or vaccination against coronavirus were sorted out (53% males, 47% females; 34 17-51 years of age, median and interquartile range): 47 cases of Berger glomerulonephritis and 40 of Henoch-Schönlein vasculitis. Approximately 50% (N = 24) of Berger glomerulonephritis and 10% (N = 4) of Henoch-Schönlein vasculitis patients presented with a pre-existing history of immunoglobulin A-mediated disease. Almost all cases of Berger glomerulonephritis were vaccine-associated (N = 44; 94%), while most cases of Henoch-Schönlein vasculitis were infection-associated (N = 23; 57%). Among vaccine-associated immunoglobulin A diseases, about 90% were associated to mRNA-based vaccines. Our analysis supports the hypothesis that COVID-19 and vaccination against SARS-CoV-2 may trigger or exacerbate an immunoglobulin A-mediated diseases.

Ibuprofen-Associated Hypokalemia and Metabolic Acidosis: Systematic Literature Review.

OBJECTIVE: Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has been occasionally associated with hypokalemia and metabolic acidosis. The objective of this report is to analyze the literature on this issue and to address the underlying pathophysiology. DATA SOURCES: Excerpta Medica, the National Library of Medicine, and Web of Science were searched from inception to July 16, 2021. STUDY SELECTION AND DATA EXTRACTION: Papers reporting individually documented humans on ibuprofen with hypokalemia, acidosis, or both were retained. Data were extracted using a checklist. DATA SYNTHESIS: For the final analysis, we evaluated 41 reports describing 50 cases (26 males and 24 females; 36 adults and 14 children) with often profound hypokalemia, acidosis, or both after ingestion of ibuprofen. Twenty-six cases were acute and 24 long term. Hypokalemia and acidosis occurred not only after ingestion of very high doses but also after ingestion of moderately high or even normal doses of ibuprofen. Laboratory values consistent with an excessive urinary potassium excretion or an altered urinary acidification were often disclosed in most cases. Discontinuation of ibuprofen resulted in a resolution of hypokalemia and acidosis within days in 47 cases. The course was lethal in 3 cases. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review highlights potentially fatal side effects of ibuprofen and can help doctors who are confronted with such a situation. CONCLUSIONS: These data highlight the potential of ibuprofen to occasionally induce hypokalemia and acidosis of renal origin. Discontinuation of ibuprofen results in a resolution within days.

Postcardiotomy effusive-constrictive pericarditis in a 65-year-old man: Noteworthy echocardiographic signs.

Effusive-constrictive pericarditis (eCP) is a rare entity where constriction of the heart occurs through the visceral pericardium, with concomitant presence of a tense effusion in the pericardial space. We present the case of a 65-year-old patient with shortness of breath and pericardial effusion, 4 months after aortic and mitral valve replacement for Streptococcus agalactiae endocarditis. The present report focuses on the echocardiographic features of constrictive pericarditis (CP) and provides a brief overview of the pathophysiology, work-up, and management guidelines.

Elderly woman presenting with multivessel coronary artery disease and Takotsubo syndrome.

Takotsubo syndrome is an acute and often reversible condition, with initial presentation mimicking acute coronary syndrome. Typically, patients present with left ventricular regional wall motion abnormalities, without a corresponding coronary artery obstruction on angiography. Coexistence of a coronary artery disease is possible and may render the distinction between the two entities particularly challenging. We report the case of a 94-year-old woman with chest pain after an emotional upset and acute myocardial injury. Transthoracic echocardiogram (TTE) revealed a severely reduced left ventricular ejection fraction (LVEF) with apical ballooning. Coronary angiogram showed significant stenosis of the distal left main coronary artery and of the mid-left anterior descending artery, as well as a 30%-50% stenosis of the mid-distal right coronary artery. Revascularisation was deferred and antiplatelet as well as heart failure therapy begun. A repeat TTE 6 days later revealed a quasi-normalised LVEF. Ultimately, percutaneous coronary revascularisation of the left main and left anterior descending artery was performed, with favourable outcome at 6-month follow-up.

Kidney Tubular Damage Secondary to Deferasirox: Systematic Literature Review.

Deferasirox is a first-line therapy for iron overload that can sometimes cause kidney damage. To better define the pattern of tubular damage, a systematic literature review was conducted on the United States National Library of Medicine, Excerpta Medica, and Web of Science databases. Twenty-three reports describing 57 individual cases could be included. The majority (n = 35) of the 57 patients were ≤18 years of age and affected by thalassemia (n = 46). Abnormal urinary findings were noted in 54, electrolyte or acid-base abnormalities in 46, and acute kidney injury in 9 patients. Latent tubular damage was diagnosed in 11 (19%), overt kidney tubular damage in 37 (65%), and an acute kidney injury in the remaining nine (16%) patients. Out of the 117 acid-base and electrolyte disorders reported in 48 patients, normal-gap metabolic acidosis and hypophosphatemia were the most frequent. Further abnormalities were, in decreasing order of frequency, hypokalemia, hypouricemia, hypocalcemia, and hyponatremia. Out of the 81 abnormal urinary findings, renal glucosuria was the most frequent, followed by tubular proteinuria, total proteinuria, and aminoaciduria. In conclusion, a proximal tubulopathy pattern may be observed on treatment with deferasirox. Since deferasirox-associated kidney damage is dose-dependent, physicians should prescribe the lowest efficacious dose.

Electrolyte and Acid-Base Disorders Triggered by Aminoglycoside or Colistin Therapy: A Systematic Review.

Aminoglycoside or colistin therapy may alter the renal tubular function without decreasing the glomerular filtration rate. This association has never been extensively investigated. We conducted a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Databases searched included United States National Library of Medicine, Excerpta Medica, and Web of Science. For the final analysis, we evaluated 46 reports, published after 1960, describing 82 cases. A total of 286 electrolyte and acid-base disorders were reported. Hypomagnesemia, hypokalemia, and hypocalcemia were reported in more than three quarter of cases. Further disorders were, in decreasing order of frequency, metabolic alkalosis, hyponatremia, hypophosphatemia, hypouricemia, hypernatremia, and metabolic acidosis. Six electrolyte and acid-base disorders were reported in seven cases, five in 12 cases, four in 16 cases, three in 31 cases, two in 11 cases, and one in five cases. Laboratory features consistent with a loop of Henle/distal tubular dysfunction were noted in 56 (68%), with a proximal tubular dysfunction in three (3.7%), and with a mixed dysfunction in five (6.1%) cases. The laboratory abnormality was unclassified in the remaining 18 (22%) cases. Treatment with aminoglycosides or colistin may trigger a proximal tubular or, more frequently, a loop of Henle/distal tubular dysfunction.

Atypical Bacterial Pathogens and Small-Vessel Leukocytoclastic Vasculitis of the Skin in Children: Systematic Literature Review.

Leukocytoclastic small-vessel vasculitis of the skin (with or without systemic involvement) is often preceded by infections such as common cold, tonsillopharyngitis, or otitis media. Our purpose was to document pediatric (≤18 years) cases preceded by a symptomatic disease caused by an atypical bacterial pathogen. We performed a literature search following the Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines. We retained 19 reports including 22 cases (13 females and 9 males, 1.0 to 17, median 6.3 years of age) associated with a Mycoplasma pneumoniae infection. We did not find any case linked to Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, or Legionella pneumophila. Patients with a systemic vasculitis (N = 14) and with a skin-limited (N = 8) vasculitis did not significantly differ with respect to gender and age. The time to recovery was ≤12 weeks in all patients with this information. In conclusion, a cutaneous small-vessel vasculitis with or without systemic involvement may occur in childhood after an infection caused by the atypical bacterial pathogen Mycoplasma pneumoniae. The clinical picture and the course of cases preceded by recognized triggers and by this atypical pathogen are indistinguishable.

Visualization of the Thebesian veins during coronary angiography in a 57-year-old woman.

A 57-year-old woman was hospitalized due to a type 2 respiratory failure. Electrocardiogram at admission showed inverted T waves in leads V2-V4. Coronary angiogram was performed showing no relevant stenosis. However, this exam allowed visualization of the Thebesian veins outlining the left ventricle.

Transcatheter aortic root replacement with chimney grafts for coronary perfusion: a preliminary test in a three-dimensional-printed root model.

OBJECTIVES: Transcatheter aortic root repair is still not available because of the technical challenge of coronary perfusion. The use of chimney grafts for coronary ostia can be an option and we tested the flow-through coronary chimney grafts deployed in a 3-dimensional-printed root model as part of a transcatheter aortic root repair system. METHODS: A 3-dimensional-printed root was used to test the coronary flow after the deployment of 1 root endograft (28 mm diameter) and two 6-mm diameter 10-cm long coronary chimney grafts. Continuous coronary flows were measured in a bench test at different pressure levels (60, 80 and 100 mmHg) and compared to target coronary flows (250 ml/min at rest for the left and 150 ml/min at rest for the right coronary artery). RESULTS: The computed tomography scan-based root was modified with two 5-mm diameter coronary conduits to overcome the limits of the original 3-dimensional-printed coronary ostia. The root was placed in the hydrodynamic system: adjusted coronary free flow at 60, 80 and 100 mmHg of pressure was 1913, 2200 and 2480 ml/min for left coronary and 1633, 2026 and 2366 ml/min for right coronary, respectively. After endografts deployment, mean chimney graft flow at 60, 80 and 100 mmHg of pressure was 1053 ml/min (-45%), 1306 ml/min (-41%) and 1502 ml/min (-40%) for the left coronary and 1100 ml/min (-33%), 1460 ml/min (-28%) and 1626 ml/min (-31%) for the right coronary, respectively. CONCLUSIONS: In this preliminary study, chimney grafts for transcatheter aortic root repair provided 830% of target flow in the right coronary (-31% of free flow) and 414% of target flow in the left coronary (-42% of free flow) which is more than sufficient for both coronaries in real-life conditions. The potential of this approach should be further explored with specifically designed endografts.

Suitability of 3D-Printed Root Models for the Development of Transcatheter Aortic Root Repair Technologies.

Transcatheter aortic root repair (TARR) is still not available because of the complex anatomy. In order to develop future TARR technologies, a human-derived bench test model is required before performing animal tests. For this purpose, we aimed to validate computed tomography (CT)-derived 3D-printed root models for TARR technologies. Four human CT-derived roots were printed using different resins: Visijet M3 Crystal, Photopolymer gel SUP705, Formlabs flexible resin, and Materialise HeartPrint Flex. A stress test was performed using a 26-mm balloon-expandable Sapien valve deployed in aortic position. The too rigid Visijet M3 Crystal was not tested. Among the others, all but one (HeartPrint Flex, Materialise, Leuven, Belgium) ruptured during the test showing low wall resistances. Further tests were then performed in two roots made of HeartPrint Flex resin. The anatomic validation was performed comparing human CT scan-derived 3D reconstructions and CT scan measurements: a mean difference of 0.57 ± 0.4 mm for aortic annulus diameter and for the distance between the aortic annulus and the coronary ostia was measured. Concerning the coronary arteries, they are of paramount importance for new TARR technologies, and therefore, we tested the coronary flows of the HeartPrint Flex root at different pressure levels. At 60 mm Hg, right and left mean adjusted coronary flows were 471 and 663 ml/min; at 80 mm Hg, right and left mean coronary flows were 551 and 777 ml/min; and at 100 mm Hg, right and left mean coronary flows were 625 and 858 ml/min. In our study, 3D-printed root models correlate well with human anatomy and guarantee physiologic coronary flows for TARR technologies.