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Cutaneous granulomatous reactions are diverse, both from the clinical and the pathological perspective. Most underlying pathophysiological aspects remain elusive. Interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis have been claimed to be reactions to systemic disorders, such as infectious, inflammatory, or neoplastic conditions. Recently, the overarching term "reactive granulomatous dermatitis" has been coined to unify both entities. We herein report two cases of reactive granulomatous dermatitis presenting with the widely known, albeit infrequent "rope sign" and provide clinicopathological correlation. The two patients included a 53-year-old woman with enlarging erythematous plaques and underlying palpable cords on both sides of trunk near axillae (rope sign), and a 51-year-old woman with personal history of rheumatoid arthritis and a palpable cord on the left aspect of the trunk. Pathological findings were compatible with reactive granulomatous dermatitis in both cases. In conclusion, the rope sign represents a strikingly infrequent but decisive diagnostic clue of reactive granulomatous dermatitis.

Muscular hernias are an uncommon condition that typically present as subcutaneous nodules on the legs that appear or enlarge while standing or exercising. They are usually asymptomatic, although they may sometimes be tender or painful and may cause cramps, especially in athletes. Physical examination and ultrasound imaging are the key for determining the diagnosis. We present a 67-year-old woman with tender subcutaneous nodules on both lower legs in which dynamic ultrasound examination confirmed the diagnosis of muscular hernias.

Holocarboxylase synthase (HCS) deficiency is an extremely rare metabolic disorder typically presenting as severe neonatal metabolic acidosis, lethargy, hypotonia, vomiting, and seizures. This report describes two siblings in a family with late-onset forms of HCS deficiency. The younger sister presented at the age of 11 years and manifested as acute metabolic acidosis, which promptly resolved following rehydration and biotin administration. The results of the organic urine profile confirmed multiple carboxylase deficiency, and genetic testing revealed a novel pathogenic variant in the HLCS gene (NM_000411.8) in the homozygous state: c.995A>G; p. (Gln332Arg). No further decompensation was observed for her during the 3-year follow-up period. His older brother was diagnosed at the age of 23 years-old through biochemical tests, without any history of acidotic decompensation. A mini-review of HCS deficiency with late onset (>1 year) or early onset (

Nonketotic hyperglycinemia (NKH) is a rare, autosomal recessive metabolic disorder usually associated with mutations in genes AMT, GLDC or GCSH involved in the glycine cleavage complex. Other genes have been linked with less severe NKH, associated with deficiency of lipoate cofactor such as GLRX5, LIAS, BOLA3. We identified a new case of GLRX5-mediated NKH who presented at 2-month with severe developmental delay and seizures. The initial suspicion was raised by the MRI and then confirmed by glycine measurements in cerebrospinal fluid and blood. Genetic analysis revealed a previously undescribed homozygous variant in the GLRX5 gene [NM_016417.3:c.367G>C; p. (Asp123His)]. Despite medication and supportive care, he died at the age of 4 months after a sudden neurological deterioration. It was decided to limit therapeutic interventions due to the severity of the prognosis. The case was more severe than the previous GLRX5-mediated NKH described, regarding the early age at onset and the severity. Moreover, the genetic variant was located at a potentially crucial site for glutathione binding in the GLRX5 protein. This report, thereby, expands our understanding of NKH’s genetic underpinnings and phenotypic variability, highlighting the crucial role of GLRX5 and other related genes in variant NKH.

Contribution: A multidisciplinary computational framework to support undergraduate engineering education is introduced. It is posed as an open-source tool that students can use to understand and apply computational methods commonly required in engineering problems. Background: This framework development is motivated by past experiences of teaching courses as segregated disciplines within an aerospace engineering curriculum. Reviewing pedagogical approaches shows that current university practices do not adequately emphasize or demonstrate the importance of interdisciplinary relationships. This framework is also motivated by the apparent need for engineering graduates to study these relationships by learning computational engineering via programming, in which proficiency is becoming increasingly important for their future careers. Intended Outcomes: 1) To effectively teach multidisciplinary engineering concepts to students via the integration of cross-disciplinary content from various courses and 2) To improve computational and programming literacy among undergraduate students in engineering studies. Application Design: A multidisciplinary design optimization approach is adopted to develop a framework called Multidisciplinary Aircraft Design Education (MADE), which provides functionalities for studying engineering disciplines within a computational programming environment. MADE makes the related course contents more accessible and intuitive to students by using reactive computational notebooks in lectures, tutorials, and assignments. Findings: MADE is assessed based on the learning outcomes and feedback from undergraduate students of two courses within an aerospace engineering curriculum. These assessments indicate an improved understanding of multidisciplinary concepts and their applications via computational programming, as reflected in the positive responses from the students.

Acute hepatic porphyrias are inherited metabolic disorders of heme biosynthesis characterized by the accumulation of toxic intermediate metabolites responsible for disabling acute neurovisceral attacks. Givosiran is a newly approved siRNA-based treatment of acute hepatic porphyria targeting the first and rate-limiting δ-aminolevulinic acid synthase 1 (ALAS1) enzyme of heme biosynthetic pathway. We described a 72-year old patient who presented with severe inaugural neurological form of acute intermittent porphyria evolving for several years which made her eligible for givosiran administration. On initiation of treatment, the patient developed a major hyperhomocysteinemia (>400 μmol/L) which necessitated to discontinue the siRNA-based therapy. A thorough metabolic analysis in the patient suggests that hyperhomocysteinemia could be attributed to a functional deficiency of cystathionine β-synthase (CBS) enzyme induced by givosiran. Long-term treatment with vitamin B6, a cofactor of CBS, allowed to normalize homocysteinemia while givosiran treatment was maintained. We review the recently published cases of hyperhomocysteinemia in acute hepatic porphyria and its exacerbation under givosiran therapy. We also discuss the benefits of vitamin B6 supplementation in the light of hypothetic pathophysiological mechanisms responsible for hyperhomocysteinemia in these patients. Our results confirmed the importance of monitoring homocysteine metabolism and vitamin status in patients with acute intermittent porphyria in order to improve management by appropriate vitamin supplementation during givosiran treatment.

Plica neuropathica (PN), also known as plica polonica, felting, matting or bird's nest hair, is an acquired hair condition in which hair becomes twisted, leading to the formation of a compact mass. Psychiatric disorders are an important etiologic factor for PN. We report a case of PN in a woman with severe reactive depression and present the trichoscopic findings.

Abstract Primary carnitine deficiency (PCD) is an inherited disease of fatty acid beta‐oxidation with autosomal recessive inheritance. The disease manifests as metabolic decompensation with hypoketotic hypoglycaemia associated with cardiomyopathy, hepatomegaly, rhabdomyolysis, and seizures. Various outcomes are described from asymptomatic adults to dramatic sudden infant death syndrome cases. We present a severe case of PCD decompensation in an 18‐week‐old female. She presented with hypotonia, moaning, diarrhea, and vomiting at the pediatric emergency. Initially suspected as intracranial hypertension, the clinical condition evolved rapidly and caused a reversible cardiac arrest with profound hypoglycemia. Despite carnitine supplementation, she succumbed from cardiac arrhythmia and multivisceral failure 4 days after admission. The genetic analyses showed a PCD with biallelic pathogenic variants of SLC22A5 gene. The case report is notable for the severity of the cardiac damage possibly favored by maternal carnitine deficiency during pregnancy. The analysis of previously published PCD cases highlights (i) the importance of having large access to emergency biochemical tests for early therapeutic care although the disease has unpredictable severity and (ii) the fact that the clinical outcome remains unpredictable if carnitine treatment is initiated late.

Palmoplantar epidermoid cysts can range in clinical presentation from an asymptomatic slowly enlarging mass to a painful nodule. We report two cases: an epidermoid cyst on the sole and another on the palm. This article reviews the possible etiology, diagnosis, and prognosis of palmoplantar epidermoid cysts.

Resumen: Antecedentes y objetivo: La psoriasis es una enfermedad con una gran implicación sistémica en la que se ha descrito una mayor prevalencia de alteraciones de la mucosa oral. El objetivo del estudio fue determinar la prevalencia de alteraciones orales en pacientes con psoriasis y su asociación con las características clínicas y epidemiológicas de la enfermedad. Material y métodos: Se realizó un estudio transversal, incluyendo pacientes con psoriasis y voluntarios sanos entre diciembre de 2019 y febrero de 2020. Se recogieron datos biométricos, comorbilidades asociadas y alteraciones orales detectadas en la exploración física. Además, en los pacientes con psoriasis se registraron las características clínicas de la enfermedad. Resultados: Se incluyeron 100 pacientes con psoriasis y 100 controles. Los pacientes con psoriasis presentaron una mayor prevalencia de alteraciones de la mucosa oral respecto al grupo control (74% frente a 46%, p

Holocarboxylase synthase (HCS) deficiency is an extremely rare metabolic disorder typically presenting as severe neonatal metabolic acidosis, lethargy, hypotonia, vomiting, and seizures. This report describes two siblings in a family with late-onset forms of HCS deficiency. The younger sister presented at the age of 11 years and manifested as acute metabolic acidosis, which promptly resolved following rehydration and biotin administration. The results of the organic urine profile confirmed multiple carboxylase deficiency, and genetic testing revealed a novel pathogenic variant in the HLCS gene (NM_000411.8) in the homozygous state: c.995A>G; p. (Gln332Arg). No further decompensation was observed for her during the 3-year follow-up period. His older brother was diagnosed at the age of 23 years-old through biochemical tests, without any history of acidotic decompensation. A mini-review of HCS deficiency with late onset (>1 year) or early onset (<1 month) revealed that splice variants are associated with late onset, while both variants p. (Leu216Arg) and p. (Leu237Pro) are associated with early onset. However, the majority of genotypes do not show a clear correlation with the timing of HCS deficiency onset. The most significant point here is the description of extremely late-onset cases of HCS deficiency. This can prompt metabolic investigations and raise suspicion of this rare disease in cases of unexplained metabolic acidosis, even beyond early childhood. [ABSTRACT FROM AUTHOR]

Abstract Carney complex is a rare genodermatosis characterized by cardiac and cutaneous myxomas, among other tumors. In the majority of cases, cutaneous myxomas precede the diagnosis of cardiac myxomas, which are the main cause of death in these patients. Despite the fact that the diagnosis of cutaneous myxomas is histopathological, high-frequency ultrasonography plays an essential role in the differential diagnosis with other cutaneous and subcutaneous tumors. The authors of the present study describe, for the first time in the literature, the ultrasonographic features of both variants of cutaneous myxomas, superficial and subcutaneous, in a patient with a Carney complex.

Abstract Background Diagnosing a ureteral colic is sometimes difficult; however, clinicians should not fail to detect a surgical emergency. This is why diagnostic strategies depend on the imaging examinations, especially ultrasound. Prior studies have investigated the accuracy of Point of Care Ultrasound (PoCUS), but there are relatively few. This study aimed to evaluate the performance of the PoCUS in the diagnosis of renal colic. The secondary objective was to evaluate the relationship between the imaging results and the treatment performed. Methods After the clinical evaluation of patients aged > 18 years with suspected ureteral colic, the Emergency Physician (EP) trained in ultrasound performed PoCUS to conclude whether a diagnosis of “renal colic” should be made. A computed tomography (CT) examination was subsequently performed, to determine whether ureteral or bladder lithiasis was present to diagnose a ureteral colic. The patient’s management was decided according to the to degree of urinary tract dilatation, presence of perinephric fluid, size, and localization of stones. Results Of the 12 Eps in our units, seven met the training criteria for the inclusion of patients. A total of 103 patients were analyzed, and the renal colic diagnosis was retained in 85 cases after the CT examination. The accuracy of PoCUS was 91% (86; 95%) for detecting urinary tract dilatation, 83% (76; 90%) for detecting perinephric fluid, and 54% (44; 64%) for detecting lithiasis. Only high urinary tract stones with ≥ 6 mm diameter were surgically managed (p

Alopecia induced by biological therapy is a rare side effect of this type of drugs. A total of 23 patients of psoriasiform eruptions with severe scalp involvement that induced alopecia during anti-tumor necrosis factor (anti-TNF) treatment of non-dermatological conditions have been previously reported. We present a 50-year-old man affected by plaque psoriasis that developed psoriasiform patches with alopecia over his scalp 10 months after initiating treatment with adalimumab. Punch biopsy of the alopecic area on the scalp revealed psoriasiform epidermal changes and alopecia areata-like dermal changes. Along with these findings, there was a dermal inflammatory infiltrate made up of eosinophils and plasma cells. In conclusion, scalp psoriasiform lesions with alopecia in patients treated with anti-TNF agents have been rarely reported. We describe a patient with anti-TNF therapy-related alopecia affected by psoriasis. Our patient has a peculiar histology with features of psoriasis and alopecia areata in addition to eosinophils and plasma cells. This entity may respond to topical treatment. However in patients of severe scalp involvement anti-TNF suspension should be considered.

A 75-year-old man presented to the dermatology clinic with an asymptomatic lesion on his right plantar surface. The lesion had progressively grown for two months. Physical examination revealed an erythematous and slightly scaly nodule measuring 10x10 mm. Dermoscopy examination showed central diffuse erythema with small red globules. A punch-biopsy revealed a proliferation of irregularly branched small vessels with collapsed lumen, extending in an infiltrative pattern in the superficial and deep dermis. Although this is a rare location, a diagnosis of microvenular hemangioma was made.

The cellular receptor Notch1 is a central regulator of T‐cell development, and as a consequence, Notch1 pathway appears upregulated in > 65% of the cases of T‐cell acute lymphoblastic leukemia (T‐ALL). However, strategies targeting Notch1 signaling render only modest results in the clinic due to treatment resistance and severe side effects. While many investigations reported the different aspects of tumor cell growth and leukemia progression controlled by Notch1, less is known regarding the modifications of cellular metabolism induced by Notch1 upregulation in T‐ALL. Previously, glutaminolysis inhibition has been proposed to synergize with anti‐Notch therapies in T‐ALL models. In this work, we report that Notch1 upregulation in T‐ALL induced a change in the metabolism of the important amino acid glutamine, preventing glutamine synthesis through the downregulation of glutamine synthetase (GS). Downregulation of GS was responsible for glutamine addiction in Notch1‐driven T‐ALL both in vitro and in vivo. Our results also confirmed an increase in glutaminolysis mediated by Notch1. Increased glutaminolysis resulted in the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway, a central controller of cell growth. However, glutaminolysis did not play any role in Notch1‐induced glutamine addiction. Finally, the combined treatment targeting mTORC1 and limiting glutamine availability had a synergistic effect to induce apoptosis and to prevent Notch1‐driven leukemia progression. Our results placed glutamine limitation and mTORC1 inhibition as a potential therapy against Notch1‐driven leukemia.

Nonketotic hyperglycinemia (NKH) is a rare, autosomal recessive metabolic disorder usually associated with mutations in genes AMT, GLDC or GCSH involved in the glycine cleavage complex. Other genes have been linked with less severe NKH, associated with deficiency of lipoate cofactor such as GLRX5, LIAS, BOLA3. We identified a new case of GLRX5-mediated NKH who presented at 2-month with severe developmental delay and seizures. The initial suspicion was raised by the MRI and then confirmed by glycine measurements in cerebrospinal fluid and blood. Genetic analysis revealed a previously undescribed homozygous variant in the GLRX5 gene [NM_016417.3:c.367G>C; p. (Asp123His)]. Despite medication and supportive care, he died at the age of 4 months after a sudden neurological deterioration. It was decided to limit therapeutic interventions due to the severity of the prognosis. The case was more severe than the previous GLRX5-mediated NKH described, regarding the early age at onset and the severity. Moreover, the genetic variant was located at a potentially crucial site for glutathione binding in the GLRX5 protein. This report, thereby, expands our understanding of NKH's genetic underpinnings and phenotypic variability, highlighting the crucial role of GLRX5 and other related genes in variant NKH. [ABSTRACT FROM AUTHOR]

Background and objective: Psoriasis is a multisystem disease associated with an increased prevalence of oral lesions. The aim of this study was to determine the prevalence of oral lesions in patients with psoriasis and examine associations with clinical and patient characteristics. Material and methods: We conducted a cross-sectional study of patients with psoriasis and healthy controls seen between December 2019 and February 2020. We recorded biometric data, comorbidities associated with psoriasis, oral examination findings, and clinical characteristics of psoriasis. Results: We studied 100 patients with psoriasis and 100 controls. Oral lesions were more common in the psoriasis group (74% vs 46%, P