Alkaptonuria.

Alkaptonuria is a rare inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase activity. The consequent homogentisic acid (HGA) accumulation in body fluids and tissues leads to a multisystemic and highly debilitating disease whose main features are dark urine, ochronosis (HGA-derived pigment in collagen-rich connective tissues), and a painful and severe form of osteoarthropathy. Other clinical manifestations are extremely variable and include kidney and prostate stones, aortic stenosis, bone fractures, and tendon, ligament and/or muscle ruptures. As an autosomal recessive disorder, alkaptonuria affects men and women equally. Debilitating symptoms appear around the third decade of life, but a proper and timely diagnosis is often delayed due to their non-specific nature and a lack of knowledge among physicians. In later stages, patients' quality of life might be seriously compromised and further complicated by comorbidities. Thus, appropriate management of alkaptonuria requires a multidisciplinary approach, and periodic clinical evaluation is advised to monitor disease progression, complications and/or comorbidities, and to enable prompt intervention. Treatment options are patient-tailored and include a combination of medications, physical therapy and surgery. Current basic and clinical research focuses on improving patient management and developing innovative therapies and implementing precision medicine strategies.

The Complex Network of Cytokines and Chemokines in Pediatric Patients with Long-Standing Type 1 Diabetes.

Type 1 diabetes (T1D) is a progressive disorder leading to the development of microangiopathies and macroangiopathies. Numerous cytokines and chemokines are involved in the pathogenesis of T1D complications. The study aimed to assess the presence of complications in patients with long-standing T1D and its relationship with serum biomarker concentrations. We examined 52 T1D subjects, with a disease duration ≥4 years and 39 healthy controls. The group of T1D patients was further divided into subgroups based on the duration of the disease (<7 years and ≥7 years) and the metabolic control assessed by the HbAlc level (<8% and ≥8%). We used Luminex Technology to assess a wide range of biomarker concentrations. A 24 h urine test was done to evaluate the rate of albuminuria. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (IMT). T1D patients showed remarkably higher concentrations of EGF, eotaxin/CCL11, MDC/CCL22, sCD40L, TGF-α, and TNF-α. Moreover, we reported statistically significant correlations between cytokines and IMT. Biomarker concentrations depend on numerous factors such as disease duration, metabolic control, and the presence of complications. Although the majority of pediatric T1D patients do not present signs of overt complications, it is indispensable to conduct the screening for angiopathies already in childhood, as its early recognition may attenuate the further progression of complications.

Development and Implantation of 3D Anatomically Tailored Polypropylene Mesh for Laparoscopic Inguinal Hernia Repair Designed on the Basis of CT Images (the ILAM Study).

OBJECTIVE: The aim of the ILAM (Individualized Laparoscopic Anatomical Mesh) study was to create and implant a fully individualized mesh based on CT scans, taking into account the published body of knowledge about the material and mechanical behavior of the implant for laparoscopic inguinal hernia repair. SUMMARY BACKGROUND DATA: The team creating and conducting this study consisted of surgeons and engineers. A specific project was made and divided into 4 phases. METHODS: The process of development and implantation was divided into 4 milestones: CT scans and modeling based on predefined subgroups, mesh manufacture, certification and clinical evaluation. RESULTS: The result of the study was the first individually designed hernia mesh to have been implanted in a human subject. After 12 months of follow-up, no recurrences or other complications were reported. CONCLUSIONS: The new mesh provides a better anatomic fit to the patients' inguinal region geometry. Mechanical stability is ensured by the multiple contact points between the implant and the tissues, which generate friction forces. Together with the possibility of shape design (proper overlap), the authors believe that there is no need for mesh fixation. If so, the use of such design meshes can change the guidelines in laparoendoscopic hernia repair in the future.

Clinical presentation of 13 children with alkaptonuria.

Until now, only a few studies have focused on the early onset of symptoms of alkaptonuria (AKU) in the pediatric population. This prospective, longitudinal study is a comprehensive approach to the assessment of children with recognized AKU during childhood. The study includes data from 32 visits of 13 patients (five males, eight females; age 4-17 years) with AKU. A clinical evaluation was performed with particular attention to eye, ear, and skin pigmentation, musculoskeletal complaints, magnetic resonance imaging (MRI), and ultrasound (US) imaging abnormalities. The cognitive functioning and adaptive abilities were examined. Molecular genetic analyses were performed. The most common symptoms observed were dark urine (13/13), followed by joint pain (6/13), and dark ear wax (6/13). In 4 of 13 patients the values obtained in the KOOS-child questionnaire were below the reference values. MRI and US did not show degenerative changes in knee cartilages. One child had nephrolithiasis. Almost half of the children with AKU (5/13) presented deficits in cognitive functioning and/or adaptive abilities. The most frequent HGD variants observed in the patients were c.481G>A (p.Gly161Arg) mutation and the c.240A>T (p.His80Gln) polymorphism. The newly described allele of the HGD gene (c.948G>T, p.Val316Phe) which is potentially pathogenic was identified.

Rat bite fever mimicking ANCA-associated vasculitis.

Rat bite fever (RBF) is a rare infectious zoonotic disease caused by two bacterial species: the Gram-negative rod Streptobacillus moniliformis and the Gram-negative coiled rod Spirillum minus. The association between RBF and skin vasculitis and arthritis has been observed. The aim of this paper was to present a case of rat-bite fever with symptoms of skin vasculitis and arthritis, associated with high titers of ANCA antibodies and anti-endothelial cell antibodies suggestive of primary vasculitis. The patient was successfully treated with antibiotics and non-steroidal anti-inflammatory drugs, leading to significant improvement. Based on the presented case, we discuss the differential diagnosis of the signs and the role of infection in the induction of ANCA antibodies. We reviewed the English language literature for cases of RBF presenting with symptoms of vasculitis and/or antibody presence. A literature review was performed in PubMed and Google using the keywords "rat bite fever" AND "vasculitis", "systemic vasculitis", "ANCA", "antiendothelial antibodies". No cases of rat-bite fever with the presence of ANCA antibodies or AECA antibodies in its course have been described thus far. Rat bite fever is a rare disease with nonspecific symptoms. In its course, general weakness, intermittent fever, leukocytoclastic vasculitis, and arthritis are reported. To our knowledge, this is the first reported case of ANCA positivity associated with RBF.

Physical activity and the brain myelin content in humans.

New imaging sequences and biophysical models allow adopting magnetic resonance imaging (MRI) for in vivo myelin mapping in humans. Understanding myelination and remyelination processes in the brain is fundamental from the perspective of proper design of physical exercise and rehabilitation schemes that aim to slow down demyelination in the aging population and to induce remyelination in patients with neurodegenerative diseases. Therefore, in this review we strive to provide a state-of-the art summary of the existing MRI studies in humans focused on the effects of physical activity on myelination/remyelination. We present and discuss four cross-sectional and four longitudinal studies and one case report. Physical activity and an active lifestyle have a beneficial effect on the myelin content in humans. Myelin expansion can be induced in humans throughout the entire lifespan by intensive aerobic exercise. Additional research is needed to determine (1) what exercise intensity (and cognitive novelty, which is embedded in the exercise scheme) is the most beneficial for patients with neurodegenerative diseases, (2) the relationship between cardiorespiratory fitness and myelination, and (3) how exercise-induced myelination affect cognitive abilities.