Quality of life and subjective donor-site morbidity in patients after a free fibula flap.

INTRODUCTION: We evaluated the subjective donor-site morbidity and quality of life in patients with a free fibula flap (FFF) reconstruction in terms of self-reported symptoms, function and quality of life, and we compared inclusion vs. exclusion of the flexor hallucis longus (FHL) muscle in the graft, primary wound closure vs. skin graft and the occurrence vs. absence of donor-site complications. METHODS: In this cross-sectional study, patients who underwent a mandibula or maxilla reconstruction with a FFF between 2011 and 2021, were included. Symptoms and function were measured with the Foot and Ankle Outcome Score (FAOS) and quality of life with both FAOS and a Visual Analogue Scale (VAS). RESULTS: Thirty-four patients were included in the analyses (mean age 59 years, 59% males). Most patients underwent a mandibular reconstruction for a malignancy. The median FAOS domain scores ranged between 92.9 (interquartile range (IQR) 77.7-100.0) and 100.0 (IQR 88.2-100.0) points, and the median VAS score was 86.5 points. No statistically significant differences were found between inclusion vs. exclusion of the FHL, primary wound closure vs. graft and occurrence vs. absence of donor-site complications. An unfavorable trend was seen for inclusion of the FHL in the flap on recreational functioning, and quality of life. CONCLUSION: Patients who underwent a FFF experience little donor-site morbidity and high quality of life, as measured by FAOS and VAS.

Untreated PKU patients without intellectual disability: SHANK gene family as a candidate modifier.

Phenylketonuria (PKU) is an inborn error of metabolism caused by variants in the phenylalanine hydroxylase (PAH) gene and it is characterized by excessively high levels of phenylalanine in body fluids. PKU is a paradigm for a genetic disease that can be treated and majority of developed countries have a population-based newborn screening. Thus, the combination of early diagnosis and immediate initiation of treatment has resulted in normal intelligence for treated PKU patients. Although PKU is a monogenic disease, decades of research and clinical practice have shown that the correlation between the genotype and corresponding phenotype is not simple at all. Attempts have been made to discover modifier genes for PKU cognitive phenotype but without any success so far. We conducted whole genome sequencing of 4 subjects from unrelated non-consanguineous families who presented with pathogenic mutations in the PAH gene, high blood phenylalanine concentrations and near-normal cognitive development despite no treatment. We used cross sample analysis to select genes common for more than one patient. Thus, the SHANK gene family emerged as the only relevant gene family with variants detected in 3 of 4 analyzed patients. We detected two novel variants, p.Pro1591Ala in SHANK1 and p.Asp18Asn in SHANK2, as well as SHANK2:p.Gly46Ser, SHANK2:p.Pro1388_Phe1389insLeuPro and SHANK3:p.Pro1716Thr variants that were previously described. Computational analysis indicated that the identified variants do not abolish the function of SHANK proteins. However, changes in posttranslational modifications of SHANK proteins could influence functioning of the glutamatergic synapses, cytoskeleton regulation and contribute to maintaining optimal synaptic density and number of dendritic spines. Our findings are linking SHANK gene family and brain plasticity in PKU for the first time. We hypothesize that variant SHANK proteins maintain optimal synaptic density and number of dendritic spines under high concentrations of phenylalanine and could have protective modifying effect on cognitive development of PKU patients.

Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants.

Glycogen storage disease (GSD) type I is inborn metabolic disease characterized by accumulation of glycogen in multiple organs. We analyzed 38 patients with clinical suspicion of GSD I using Sanger and next-generation sequencing (NGS). We identified 28 GSD Ib and 5 GSD Ia patients. In 5 patients, GSD III, VI, IX, cholesteryl-ester storage disease and Shwachman-Diamond syndrome diagnoses were set using NGS. Incidences for GSD Ia and GSD Ib were estimated at 1:172 746 and 1:60 461 live-births, respectively. Two variants were identified in G6PC gene: c.247C>T (p.Arg83Cys) and c.518T>C (p.Leu173Pro). In SLC37A4 gene, 6 variants were detected. Three previously reported variants c.81T>A (p.Asn27Lys), c.162C>A (p.Ser54Arg) and c.1042_1043delCT (p.Leu348Valfs*53) accounted for 87% of all analyzed alleles. Computational, transcription studies and/or clinical presentation in patients confirmed pathogenic effect of 3 novel variants: c.248G>A (p.Gly83Glu), c.404G>A (p.Gly135Asp) and c.785G>A (p.Ser263Glyfs*33 or p.Gly262Asp). In the cohort, hepatomegaly, hypoglycemia and failure to thrive were the most frequent presenting signs of GSD Ia, while hepatomegaly and recurrent bacterial infections were clinical hallmarks of GSD Ib. All GSD Ib patients developed neutropenia while 20.6% developed inflammatory bowel disease. Our study revealed the highest worldwide incidence of GSD Ib. Furthermore, description of 3 novel variants will facilitate medical genetic practice.

Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias.

Specific mitochondrial enzymatic deficiencies in the catabolism of branched-chain amino acids cause methylmalonic aciduria (MMA), propionic acidemia (PA) and maple syrup urine disease (MSUD). Disease-causing mutations were identified in nine unrelated branched-chain organic acidurias (BCOA) patients. We detected eight previously described mutations: p.Asn219Tyr, p.Arg369His p.Val553Glyfs*17 in MUT, p.Thr198Serfs*6 in MMAA, p.Ile144_Leu181del in PCCB, p.Gly288Valfs*11, p.Tyr438Asn in BCKDHA and p.Ala137Val in BCKDHB gene. Interestingly, we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants. Aberrant enzymes p.Leu549Pro MUT, p.Leu641Pro MUT and p.Tyr206Cys PCCB did not show residual activity in activity assays. In addition, activity of MUT enzymes was not rescued in the presence of vitamin B12 precursor in vitro which was in accordance with non-responsiveness or partial responsiveness of patients to vitamin B12 therapy. Our study brings the first molecular genetic data and detailed phenotypic characteristics for MMA, PA and MSUD patients for Serbia and the whole South-Eastern European region. Therefore, our study contributes to the better understanding of molecular landscape of BCOA in Europe and to general knowledge on genotype-phenotype correlation for these rare diseases.

Molecular genetic study of congenital adrenal hyperplasia in Serbia: novel p.Leu129Pro and p.Ser165Pro CYP21A2 gene mutations.

PURPOSE: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease characterized by impaired adrenal steroidogenesis and most often caused by CYP21A2 gene mutations. For the first time, we reported complete spectrum and frequency of CYP21A2 gene mutations in 61 unrelated patients with classical and non-classical CAH from Serbia. METHODS: Direct DNA sequencing of whole CYP21A2 gene and polymerase chain reaction with sequence-specific primers for detection of CYP21A1P/CYP21A2 chimeras were combined. RESULTS: We identified 18 different pathogenic alleles-two of them novel. Mutation detection rate was highest in patients with salt-wasting form of CAH (94.7%). The most prevalent mutation was intron 2 splice site mutation, c.290-13A/C>G (18.5%). Other mutation frequencies were: CYP21A1P/CYP21A2 chimeras (13%), p.P30L (13%), p.R356W (11.1%), p.G110fs (7.4%), p.Q318X (4.6%), p.V281L (4.6%), p.I172N (2.8%), p.L307fs (2.8%), p.P453S (1.9%), etc. Mainly, frequencies were similar to those in Slavic populations and bordering countries. However, we found 6.5% of alleles with multiple mutations, frequently including p.P453S. Effects of novel mutations, c.386T>C (p.Leu129Pro) and c.493T>C (p.Ser165Pro), were characterized in silico as deleterious. The effect of well-known mutations on Serbian patients' phenotype was as expected. CONCLUSIONS: The first comprehensive molecular genetic study of Serbian CAH patients revealed two novel CYP21A2 mutations. This study will enable genetic counseling in our population and contribute to better understanding of molecular landscape of CAH in Europe.

Nail Psoriasis, the unknown burden of disease.

BACKGROUND: Psoriasis can be found at several different localizations which may be of various impact on patients' quality of life (QoL). One of the easy visible, and difficult to conceal localizations are the nails. OBJECTIVE: To achieve more insight into the QoL of psoriatic patients with nail psoriasis, and to characterize the patients with nail involvement which are more prone to the impact of the nail alterations caused by psoriasis. METHOD: A self-administered questionnaire was distributed to all members (n = 5400) of the Dutch Psoriasis Association. The Dermatology Life Quality Index (DLQI) and the Nail Psoriasis Quality of life 10 (NPQ10) score were included as QoL measures. Severity of cutaneous lesions was determined using the self-administered psoriasis area and severity index (SAPASI). RESULTS: Patients with nail psoriasis scored significantly higher mean scores on the DLQI (4.9 vs. 3.7, P = <0.001) and showed more severe psoriasis (SAPASI, 6.6 vs. 5.3, P = <0.001). Patients with coexistence of nail bed and nail matrix features showed higher DLQI scores compared with patients with involvement of one of the two localizations exclusively (5.3 vs. 4.2 vs. 4.3, P = 0.003). Patients with only nail bed alterations scored significant higher NPQ10 scores when compared with patients with only nail matrix features. Patients with psoriatic arthritis (PsA) and nail psoriasis experiences more impairments compared with nail psoriasis patients without PsA (DLQI 5.5 vs. 4.3, NPQ10 13.3 vs. 7.0). Females scored higher mean scores on all QoL scores. CONCLUSION: Greater attention should be paid to the possible impact nail abnormalities have on patients with nail psoriasis, which can be identified by nail psoriasis specific questionnaires such as the NPQ10. As improving the severity of disease may have a positive influence on QoL, the outcome of QoL measurements should be taken into account when deciding on treatment strategies.

The prevalence of onychomycosis in psoriatic patients: a systematic review.

We systematically reviewed all available literature concerning the prevalence of onychomycosis in patients with nail psoriasis and the distribution of pathogens causing onychomycosis in this specific group of patients. Databases searched were Pubmed, EMBASE and the Cochrane Controlled Clinical Trial Register. All studies reporting on the prevalence of onychomycosis in nail psoriasis were obtained, and quality assessment was determined by the STrengthening the Reporting of OBservational studies in Epidemiology checklist. Literature search revealed 720 studies, of which 10 studies met the inclusion criteria. The major limitation of the review was the heterogeneity of the included studies, which prevented the possibility to conduct a meta analysis. However, the average prevalence of 18.0% of onychomycosis in psoriatic patients seems to be increased when compared with control groups and literature on healthy population, even though the ultimate evidence remains lacking. As in the literature hypothesized shift in causative agents from dermatophytes to yeasts and/or moulds could not be confirmed. The clinical consequence of the relatively high prevalence of onychomycosis in psoriasis may be a general advice to rule out onychomycosis or concomitant onychomycosis in these patients with (suspected) nail psoriasis. This advice is stressed by the relative simplicity of treating the contribution of onychomycosis in the nail dystrophy but also the fact that nail psoriasis mostly is treated by immunosuppressive drugs, like steroids, methotrexate or biologics which may aggravate mycotic nail infections.

Nail psoriasis: a questionnaire-based survey.

BACKGROUND: Skin manifestations are the most characteristic finding of psoriasis. However, nail involvement is also a clinical feature of disease although it is often overlooked. The documented prevalence of nail psoriasis varies between 10·0% and 81·1%. OBJECTIVES: The aim of this investigation is to gain knowledge about the prevalence and clinical manifestations of nail psoriasis and patient experiences of treatment of nail psoriasis. METHODS: A structured, self-administered questionnaire was distributed to all members (n = 5400) of the Dutch Psoriasis Association. The questionnaire enquired about sociodemographic patient characteristics, disease-related data and treatment of nail psoriasis. Patients reported their nail manifestations with photographs after instruction. Patients with nail psoriasis were compared with patients without nail psoriasis. RESULTS: A response rate of 27% was achieved. The prevalence of nail psoriasis was 66·0%. The most frequently observed psoriatic nail manifestation was pitting (65·4%), whereas red spots in the lunula were infrequently seen (6·5%). Patients with nail psoriasis more frequently stated psoriasis capitis (75·8% vs. 65·7%), genital psoriasis (32·7% vs. 20·3%) and psoriatic arthritis (46·4% vs. 30·6%) compared with patients with psoriasis without nail involvement. Only 16·0% of patients received treatment for nail psoriasis. Systemic therapies were most frequently stated as being effective for nail lesions. CONCLUSIONS: Nail manifestations seem to be more prevalent in patients with psoriasis than previously thought. In addition, nail psoriasis is shown to be associated with widespread and more severe forms of psoriasis, and different treatment options are experienced as being effective for nail psoriasis. Notwithstanding, nail psoriasis is still an often overlooked feature of the disease.

Effects of a nursing information system in 5 Dutch hospitals.

Two studies of the effects of components of the integrated Nursing Information System VISION, involving five Dutch hospitals, were concluded in 1996. This paper summarises these studies and their results. The studies assessed effects on workload, quality of co-ordination, job satisfaction, patient satisfaction and quality of information supply. In both studies a quasi-experimental approach was followed. The results show significant positive effects with respect to quality of co-ordination, nurses job satisfaction and patient satisfaction. Workload measurements revealed a shift in the nurses' activities, but no change in the amount of time spent on patient care. On the basis of the positive results, 4 of the 5 hospitals have decided to extend the use of the system.

Epidemic Coxsackie B virus infection in Johannesburg, South Africa.

A particularly extensive epidemic of Coxsackie B3 virus infection occurred in Johannesburg in the spring and summer of 1984. A total of 142 positive cases were diagnosed by isolation of the virus from stools and other specimens (60) or by serology (82). Coxsackie B3 accounted for 87% of the isolations and was also the dominant serotype on serology. The outbreak involved predominantly children and young adults, with no apparent sex differences being noted. The majority of specimens came from the white population and no significant difference in age or sex distribution could be observed between the two race groups. The major clinical presentation in the white group was Bornholm disease followed by cardiac involvement and then meningoencephalitis. In the black group, however, myocarditis was the major clinical presentation, which is of particular interest taking into account the extremely high incidence of acute rheumatic carditis in this population and the prevalence of chronic cardiomyopathy.

Poliomyelitis outbreak in South Africa, 1982. II. Laboratory and vaccine aspects.

Between May and September 1982 an extensive epidemic of poliomyelitis occurred in Gazankulu in the north-eastern region of South Africa, with a total of 260 paralysed cases and 42 deaths. A three-part study was instituted, the first of which established the aetiological agent of the epidemic to be poliovirus type 1. This was determined initially by serology and later by isolation of the virus, chiefly from stool specimens. The potency of the trivalent oral polio vaccine manufactured at the National Institute for Virology, was evaluated in the second study by in vitro potency testing of samples recalled from the epidemic areas and also in vivo by determining the serological response of seronegative children immunized with fresh vaccine. Nearly half of the vaccine samples withdrawn from the field had sub-optimal titres whereas fresh vaccine produced a very satisfactory serological response. In order to plan immunization rationally, the third study, namely the determination of the immune status of the various populations throughout the country was instituted. This involved both serology, using a neutralization test on randomly collected sera and also an analysis of patient history and health card documentation. With the exception of the urban black area (Soweto), which had high levels of immunity both serologically (75%) and on history, other areas examined had poorer levels of immunity of approximately 52% on serological testing and 57% on history. It is clear that the epidemic was multifactorial in origin, with fall-offs in the level of immunization and evidence of breaks in the cold chain being the major factors.