New Ocular Findings in a Patient with a Novel Pathogenic Variant in the FBXO11 Gene

Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA) is a recently described autosomal dominant entity caused by pathogenic variants, mostly de novo, in the FBXO11 gene. It presents in the first years of life with highly variable clinical manifestations. The main features of IDDFBA include borderline-to-severe intellectual disability, behavioral problems, hypotonia, facial dysmorphisms, minor skeletal abnormalities, and recurrent infections. Although eye problems, such as refractive errors, eye misalignment and minor visual changes, have been described in about 48% of patients, a major ocular defect, namely, bilateral optic nerve hypoplasia, has been reported in the literature only once. We report an 8-year-old boy with a novel de novo pathogenic variant in FBXO11 gene (NM_001190274.1: c.1166dup, p.Cys390Metfs∗3) and a complex ophthalmological phenotype, consisting of right microphthalmia, very shallow anterior chamber, and persistent pupillary membrane, right dense nuclear cataract, bilateral optic nerve hypoplasia, and bilateral horizontal manifest nystagmus.info:eu-repo/semantics/publishedVersio

The PML-RAR alpha transcript in long-term follow-up of acute promyelocytic leukemia patients

Background and Objectives. Detection of PML-RAR alpha transcripts by RT-PCR is now established as a rapid and sensitive method for diagnosis of acute promyelocytic leukemia (APL), Although the majority of patients in longterm clinical remission are negative by consecutive reverse transcription polymerase chain reaction (RT-PCR) assays, negative tests are still observed in patients who ultimately relapse. Conversion from negative to positive PCR has been observed after consolidation and found to be a much stronger predictor of relapse. This study reports on 47 APL patients to determine the correlation between minimal residual disease (MRD) status and clinical outcome in our cohort of patients. Design and Methods. The presence of PML-RAR alpha t transcripts was investigated in 47 APL patients (37 adults and 10 children) using a semi-nested reverse transcriptase-polymerase chain reaction to evaluate the prognostic value of RT-PCR tests. Results. All patients achieved complete clinical remission (CCR) following induction treatment with all-trans retinoic acid (ATRA) and chemotherapy (CHT) or ATRA alone. Patients were followed up between 2 and 117.6 months (median: 37 months). Relapses occurred in 11 patients (9 adults and 2 children) between 11.4 and 19 months after diagnosis (median: 15.1 months) while 36 patients (28 adults and 8 children) remained in CCR, Seventy-five percent of patients carried the PML-RARa long isoform (bcr 1/2) which also predominated among the relapsed cases (9 of 11) but did not associate with any adverse outcome (p = 0.37), For the purpose of this analysis, minimal residual disease tests were clustered into four time-intervals: 0-2 months, 3-5 months, 5-9 months and 10-24 months. Interpretation and Conclusions. Children showed persisting disease for longer than adults during the first 2 months of treatment, At 2 months, 10 (50%) of 20 patients who remained in CCR and 4 (80%) of 5 patients who subsequently relapsed were positive. Patients who remained in CCR had repeatedly negative results beyond 5.5 months from diagnosis. A positive MRD test preceded relapse in 3 of 4 tested patients. The ability of a negative test to predict CCR (predictive negative value, PNV) was greater after 6 months (> 83%), while the ability of a positive test to predict relapse (predictive positive value, PPV) was most valuable only beyond 10 months (100%). This study (i) highlights the prognostic value of RT-PCR monitoring after treatment of APL patients but only from the end of treatment, (ii) shows an association between conversion to a positive test and relapse and (iii) suggests that PCR assessments should be carried out at 3-month intervals to provide a more accurate prediction of hematologic relapses but only after the end of treatment, (C) 2001, Ferrata Storti Foundatio

Arthropathy of genetic hemochromatosis: a major and distinctive manifestation of the disease

Genetic hemochromatosis is not a rare disease and represents a frequently underestimated cause of arthropathy. Joint involvement is one of the most frequent manifestations of the disease and presents typical clinical and radiological features that strongly suggest the diagnosis. Joint complaints are often the first clinical manifestation of GH. Their identification may be crucial to establish the diagnosis in the pre-cirrhotic phase and to institute appropriate therapy to prevent organ damage and associated mortality. Recent identification of the genetic defect responsible for the disease is leading to new insights into the pathogenesis of GH and the associated arthropathy

Physical activity and exercise on diabetic foot related outcomes: a systematic review

Background: Diabetic foot is one of the most common complications of diabetes. It has the potential risk of pathologic consequences including infection, ulceration and amputation, but a growing body of evidence suggests that physical activity and exercise may improve diabetic foot outcomes. Objective: To analyze de effects of exercise and physical activity interventions on diabetic foot outcomes. Methods: A comprehensive and systematic search was conducted according to PRISMA recommendations. Only controlled clinical trials with patients with diabetes were included. Results: Six studies, involving 418 patients with diabetes, were included. Two studies used only aerobic exercise; two studies combined aerobic, resistance and balance exercise; and two studies combined aerobic and balance exercise by Thai Chin Chuan methods. Physical activity and exercise significantly improved nerve velocity conduction, peripheral sensory function and foot peak pressure distribution. Moreover, the ulcers incidence rate per year was lower in the intervention groups, compared with the controls [0.02 vs. 0.12]. Conclusion: This review suggests evidence that physical activity and exercise is an effective non-pharmacological intervention to improve diabetic foot related outcomes. Combined multi-disciplinary treatments are more effective in the prevention of foot complications in patients with diabetes.This work was funded within the scope of project NANOSTIMA – Macro–to–Nano Human Sensing: Towards Integrated Multimodal Health Monitoring and Analytics from operation NORTE 01 0145 FEDER000016, co–funded by the European Regional Development Fund [ERDF] through NORTE 2020 [Programa Operacional Regional do Norte 2014/2020]

Arthritis and X-linked agammaglobulinemia

Primary immunodeficiencies are defined as genetically determined functional and/or quantitative abnormalities in one or more of the components of the immune system. Immunodeficiency and arthritis can be related, although the mechanisms are not always clear. Different causes for immunodeficiency can secondarily be found in patients with arthritis; on the other hand, arthritis can be a manifestation of primary immunodeficiency. Arthritis occurs chiefly in humoral primary immunodeficiencies, namely in X-linked agammaglobulinemia and common variable immunodeficiency, and may be one of the warning signs for primary immunodeficiency. We report a case of arthritis as the presenting feature of X-linked agammaglobulinemia. In X-linked agammaglobulinemia, arthritis may be a consequence of infection, most notably by Mycoplasma, or of immune dysfunction itself. In children, and occasionally in young adults, a combination of arthritis and hypogammaglobulinemia should suggest primary immunodeficiency, although other causes of hypogammaglobulinemia must be excluded. Physicians evaluating patients with arthritis should be aware of this fact so that an early diagnosis can be pursued as it is of extreme importance in the optimal management and prognosis of these patients

Physico-chemical characterizations of sawdust-derived biochar as potential solid fuels

Characterization Malaysian rubber-wood sawdust derived biochar (MRWSB) produced in the fixed bed pyrolysis under different temperatures (450 to 850°C) were studied for its applicability as a solid fuel. A range of analyses were carried out, including biochar oxidation reactivity , inorganic species, oxygen and hydrogen contents in the biochars, release of heteroatoms in biochar as the gaseous product, and biochar structural evolution during pyrolysis process. The results show that the optimum temperature for carbonization to obtain a char having moderately high yield was found as 450 °C. Thermogravimetric analyses (TG) shows that temperatures induces a progressively more ordered carbonaceous structure and leads to a significant changes in the biochar reactivity. The process is coupled with the loss of heteroatoms, released as dominantly carbon dioxide (C02) and carbon dioxide (CO). In addition, the elemental study of wood-derived biochar shows the higher carbon content but with low H/C and 0/C ratio suggested this material was dominated by highly aromatic structures and this were revealed in the Fourier transform infra-red (FTIR). More importantly, insignificant amount of inorganic species is evidenced in the samples

Exuberant calcinosis and acroosteolysis. A diagnostic challenge

A case of exuberant acroosteolysis and subcutaneous tissue calcinosis in the absence of skin involvement is presented. Different hypotheses are discussed following the clinical unfolding of the case in practice

A case of infliximab-induced lupus in a patient with ankylosing spondylitis: is it safe switch to another anti-TNF-α agent?

Anti-TNF-α therapies are the latest class of medications found to be associated with drug-induced lupus, a distinctive entity known as anti-TNF-α-induced lupus (ATIL) (Williams et al., Rheumatology (Oxford) 48:716-20, 2009; De Rycke et al., Lupus 14:931-7, 2005; De Bandt et al., Clin Rheumatol 22:56-61, 2003). With the widespread use of these agents, it is likely that the incidence of ATIL will increase. The onset of ATIL in patients with rheumatoid arthritis and Crohn's disease has been described, but the literature regarding the occurrence of this entity in patients with ankylosing spondylitis (AS) is scarce (De Bandt et al., Clin Rheumatol 22:56-61, 2003; Ramos-Casals et al., Autoimmun Rev 9:188-93, 2010; Perez-Garcia et al., Rheumatology 45:114-116, 2006). To our knowledge, few reports of switching anti-TNF-α therapy after ATIL in AS have been reported (Akgül et al., Rheumatol Int, 2012). Therefore, it is not clear whether the development of ATIL should prohibit switch to another therapy, since patients may respond to another anti-TNF-α agent (Akgül et al., Rheumatol Int, 2012; Bodur et al., Rheumatol Int 29:451-454, 2009; Mounach et al., Clin Exp Rheumatol 26:1116-8, 2008; Williams and Cohen, Int J Dermatol 50:619-625, 2011; Ye et al., J Rheumatol 38:1216, 2011; Wetter and Davis, Mayo Clin Proc 84:979-984, 2009; Cush, Clin Exp Rheumatol 22:S141-147, 2004; Kocharla and Mongey, Lupus 18:169-7, 2009). A lack of published experience of successful anti-TNF-α switching is a cause of concern for rheumatologists faced with this challenging clinical scenario. We report the case of a 69-year-old woman with AS who developed infliximab-induced lupus, which did not recur despite the subsequent institution of etanercept. The authors review and discuss ATIL and the possible implications for subsequent treatment with alternative anti-TNF-α agents