1,236 research outputs found
The Acute Porphyric Attack: A Difficult Diagnosis for a Potential Lethal Event in Emergency Medicine
The porphyrias are a heterogeneous group of metabolic
disorders due to an inherited (but in some forms the disturbance may
also be acquired) enzymatic deficiency in the metabolic pathway
of heme biosynthesis. The variable degree of block in the heme
biosynthetic pathway due to the enzyme deficiency results in
accumulation of different metabolic intermediates, whose toxicity is
responsible for the peculiar (cutaneous and/or neurovisceral) clinical
pictures observed in each of these diseases. According to the clinical
features, the porphyrias are classified as \u201cacute\u201d (or neuropsychic)
[characterized by acute neurovisceral crises (the acute porphyric
attack) involving the autonomic and/or central nervous system, but
also the liver and the kidney] and \u201con acute\u201d (or dermatological)
(mostly presenting with cutaneous lesions, due to photosensitivity).
The acute porphyrias are often misdiagnosed diseases: the acute
porphyric attack may in fact mimic many other more common medical
and neuropsychiatric conditions; its delayed diagnosis and treatment
(or its inappropriate treatment) may result in a fatal outcome. For
these reasons, many different specialists, such as surgeons,
psychiatrists, gastroenterologists, neurologists, emergency
physicians and dermatologists may be variably involved in the
diagnostic process, especially in those cases presenting with
acute and life-threatening clinical features. An early and definitive
diagnosis is mandatory to improve outcomes and to assure that
potentially harmful drugs are avoided. To date, the availability of an
adequate treatment has significantly improved the outcome of the
acute porphyric attacks, so the knowledge about the management of
these events may be relevant for the physicians working in internal
and emergency medicine units
Development of a rapid LC-MS/MS Method for the determination of emerging fusarium mycotoxins enniatins and beauvericin in human biological fluids
A novel method for the simultaneous determination of enniatins A, A1, B and B1 and beauvericin, both in human urine and plasma samples, was developed and validated. The method consisted of a simple and easy pretreatment, specific for each matrix, followed by solid phase extraction (SPE) and detection by high performance liquid chromatography-tandem mass spectrometry with an electrospray ion source. The optimized SPE method was performed on graphitized carbon black cartridges after suitable dilution of the extracts, which allowed high mycotoxin absolute recoveries (76%-103%) and the removal of the major interferences from the matrix. The method was extensively evaluated for plasma and urine samples separately, providing satisfactory results in terms of linearity (R² of 0.991-0.999), process efficiency (>81%), trueness (recoveries between 85% and 120%), intra-day precision (relative standard deviation, RSD < 18%), inter-day precision (RSD < 21%) and method quantification limits (ranging between 20 ng·L(-)¹ and 40 ng·L(-)¹ in plasma and between 5 ng·L(-)¹ and 20 ng·L(-)¹ in urine). Finally, the highly sensitive validated method was applied to some urine and plasma samples from different donors
Legius syndrome: Case report and review of literature
A 8-month-old child was referred to our Dermatologic Unit for suspected Neurofibromatosis type 1 (NF 1), because of the appearance, since few days after birth, of numerous caf\ue9-au-lait spots (seven larger than 5 mm); no other sign evocative of NF 1 was found. Her family history was remarkable for the presence of multiple caf\ue9-au-lait spots in the mother, the grandfather and two aunts. The family had been already examined for NF 1, but no sign evocative of the disease was found. We then suspected Legius syndrome, a dominant disease characterized by a mild neurofibromatosis 1 phenotype. The diagnosis was confirmed by the finding of a mutation in SPRED1 gene, a feedback regulator of RAS/MAPK signaling. Here, we discuss the differential diagnosis of caf\ue8-au-lait spots and we briefly review the existing literature about Legius syndrome
Kidney Involvement in Acute Hepatic Porphyrias: Pathophysiology and Diagnostic Implications
Porphyrias are a group of rare disorders originating from an enzyme dysfunction in the
pathway of heme biosynthesis. Depending on the specific enzyme involved, porphyrias manifest
under drastically different clinical pictures. The most dramatic presentation of the four congenital
acute hepatic porphyrias (AHPs: acute intermittent porphyria—AIP, ALAD deficiency, hereditary
coproporphyria—HCP, and porphyria variegata—VP) consists of potentially life-threatening neurovisceral
attacks, for which givosiran, a novel and effective siRNA-based therapeutic, has recently
been licensed. Nonetheless, the clinical manifestations of acute porphyrias are multifaceted and do
not limit themselves to acute attacks. In particular, porphyria-associated kidney disease (PAKD) is a
distinct, long-term degenerating condition with specific pathological and clinical features, for which a
satisfactory treatment is not available yet. In PAKD, chronic tubule-interstitial damage has been most
commonly reported, though other pathologic features (e.g., chronic fibrous intimal hyperplasia) are
consistent findings. Given the relevant role of the kidney in porphyrin metabolism, the mechanisms
possibly intervening in causing renal damage in AHPs are different: among others, d-aminolevulinic
acid (ALA)-induced oxidative damage on mitochondria, intracellular toxic aggregation of porphyrins
in proximal tubular cells, and derangements in the delicate microcirculatory balances of the kidney
might be implicated. The presence of a variant of the human peptide transporter 2 (PEPT2), with
a greater affinity to its substrates (including ALA), might confer a greater susceptibility to kidney
damage in patients with AHPs. Furthermore, a possible effect of givosiran in worsening kidney
function has been observed. In sum, the diagnostic workup of AHPs should always include a baseline
evaluation of renal function, and periodic monitoring of the progression of kidney disease in patients
with AHPs is strongly recommended. This review outlines the role of the kidney in porphyrin
metabolism, the available evidence in support of the current etiologic and pathogenetic hypotheses,
and the known clinical features of renal involvement in acute hepatic porphyrias
Unveiling the morphogenetic code: A new path at the intersection of physical energies and chemical signaling
In this editorial, we discuss the remarkable role of physical energies in the control of cell signaling networks and in the specification of the architectural plan of both somatic and stem cells. In particular, we focus on the biological relevance of bioelectricity in the pattern control that orchestrates both developmental and regenerative pathways. To this end, the narrative starts from the dawn of the first studies on animal electricity, reconsidering the pioneer work of Harold Saxton Burr in the light of the current achievements. We finally discuss the most recent evidence showing that bioelectric signaling is an essential component of the informational processes that control pattern specification during embryogenesis, regeneration, or even malignant transformation. We conclude that there is now mounting evidence for the existence of a Morphogenetic Code, and that deciphering this code may lead to unprecedented opportunities for the development of novel paradigms of cure in regenerative and precision medicine
Challenges in diagnosis and management of acute hepatic porphyrias: from an uncommon pediatric onset to innovative treatments and perspectives
Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the
enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks,
characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion,
hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations
and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney
disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent
attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis
of AHP can be made with a test for urinary porphobilinogen, -aminolaevulinic acid and porphyrins using a
single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical
symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as
some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe,
potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations
in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management
of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated
as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based
agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for
the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate
porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges,
and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations
The counterintuitive effect of multiple injuries in severity scoring: a simple variable improves the predictive ability of NISS
<p>Abstract</p> <p>Background</p> <p>Injury scoring is important to formulate prognoses for trauma patients. Although scores based on empirical estimation allow for better prediction, those based on expert consensus, e.g. the New Injury Severity Score (NISS) are widely used. We describe how the addition of a variable quantifying the number of injuries improves the ability of NISS to predict mortality.</p> <p>Methods</p> <p>We analyzed 2488 injury cases included into the trauma registry of the Italian region Emilia-Romagna in 2006-2008 and assessed the ability of NISS alone, NISS plus number of injuries, and the maximum Abbreviated Injury Scale (AIS) to predict in-hospital mortality. Hierarchical logistic regression was used. We measured discrimination through the C statistics, and calibration through Hosmer-Lemeshow statistics, Akaike's information criterion (AIC) and calibration curves.</p> <p>Results</p> <p>The best discrimination and calibration resulted from the model with NISS plus number of injuries, followed by NISS alone and then by the maximum AIS (C statistics 0.775, 0.755, and 0.729, respectively; AIC 1602, 1635, and 1712, respectively). The predictive ability of all the models improved after inclusion of age, gender, mechanism of injury, and the motor component of Glasgow Coma Scale (C statistics 0.889, 0.898, and 0.901; AIC 1234, 1174, and 1167). The model with NISS plus number of injuries still showed the best performances, this time with borderline statistical significance.</p> <p>Conclusions</p> <p>In NISS, the same weight is assigned to the three worst injuries, although the contribution of the second and third to the probability of death is smaller than that of the worst one. An improvement of the predictive ability of NISS can be obtained adjusting for the number of injuries.</p
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