Association of the Kynurenine Pathway of Tryptophan Metabolism With Human Immunodeficiency Virus-Related Gut Microbiota Alterations and Visceral Adipose Tissue Accumulation.

BACKGROUND: The aim of the study was to investigate the association between human immunodeficiency virus (HIV)-related gut microbiota changes, alterations in the kynurenine (Kyn) pathway of tryptophan (Trp) metabolism, and visceral adipose tissue in the context of HIV infection. METHODS: Three hundred eighty-three people with HIV (PWH) were included from the Copenhagen comorbidity in HIV infection (COCOMO) study. Gut microbiota composition was analyzed by 16S ribosomal ribonucleic acid sequencing. Plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured by single-slice computed tomography (CT) scan (4th lumbar vertebra). RESULTS: The HIV-related gut microbiota alterations were associated with lower Trp (ß -.01; 95% confidence interval [CI], -0.03 to -0.00) and higher Kyn-to-Trp ratio (ß 0.03; 95% CI, 0.01-0.05), which in turn was associated with higher VAT-to-SAT ratio (ß 0.50; 95% CI, 0.10-0.90) and larger VAT area (ß 30.85; 95% CI, 4.43-57.28). In mediation analysis, the Kyn-to-Trp ratio mediated 10% (P = .023) of the association between the VAT-to-SAT ratio and HIV-related gut microbiota. CONCLUSIONS: Our data suggest HIV-related gut microbiota compositional changes and gut microbial translocation as potential drivers of high Kyn-to-Trp ratio in PWH. In turn, increased activity in the Kyn pathway of Trp metabolism was associated with larger visceral adipose tissue area. Taken together, our findings suggest a possible role for this pathway in the gut-adipose tissue axis in the context of HIV infection.

Hand eczema and stratum corneum ceramides.

BACKGROUND: Hand eczema (HE) is a multifactorial disease, comprising different aetiological conditions and different morphologies. There are two aetiologically distinct groups of HE recognised: exogenous, such as contact dermatitis (allergic and/or irritant HE) and endogenous, such as the classic hyperkeratotic HE. Differences in the skin barrier properties of these two conditions could theoretically be expected. AIM: To examine whether differences exist in the lipid profile and the susceptibility of the stratum corneum (SC) in patients with allergic/irritant HE and those with hyperkeratotic HE. METHODS: Using cyanoacrylate, SC samples were taken from 23 patients with allergic/irritant HE and 15 with hyperkeratotic HE for lipid analysis by high-performance thin-layer chromatography (HPTLC). Samples were also taken from adjacent, unaffected skin. Severity of HE was assessed by the Hand Eczema Severity Index (HECSI), and skin barrier susceptibility was assessed by measuring transepidermal water loss (TEWL) after a 24-hour patch test with sodium lauryl sulfate (SLS). RESULTS: No statistically significant difference was found between groups for the lipid analysis or for skin susceptibility to SLS. We found a significantly higher HECSI score for hyperkeratotic HE compared with irritant or allergic HE (P = 0.02). CONCLUSIONS: There appears to be no difference in skin barrier between allergic/irritant HE (exogenous eczema) and hyperkeratotic HE (endogenous eczema) with regard to SC lipids or susceptibility to SLS.

Ceramide profile in hypohidrotic ectodermal dysplasia.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disease. The clinical presentation includes lack of sweating ability, and an often widely spread dermatitis resembling atopic dermatitis (AD). In AD, the skin-barrier defect is partly ascribed to the altered lipid profile in the stratum corneum and partly to mutations of the filaggrin genes. To our knowledge, no data are available about the epidermal lipid profile of HED. AIM: To compare the ceramide profile for patients with HED and AD. METHODS: The ceramide profile and ceramide/cholesterol ratio were compared between patients with HED (n = 7) and patients with AD (n = 21), using cyanoacrylate to take biopsy samples from the stratum corneum. Lipids were extracted from the biopsies and analysed using high-performance thin-layer chromatography. RESULTS: The lipid profiles of HED and AD were similar in distribution, apart from ceramide 1, which was significantly higher in HED (P = 0.04). CONCLUSIONS: The increased ceramide 1 level found in HED compared with AD is known to play a role in the structure of the lipid bilayers. However, further studies are needed to identify the functional significance of these observations and thereby elucidate differences in the skin barrier between HED and AD.

Histopathological grading of soft tissue tumours. Prognostic significance in a prospective study of 278 consecutive cases.

A consecutive 10-year series of 278 soft tissue sarcomas was prospectively graded, using a system based on the number of mitoses and taking into account parameters such as cellularity, anaplasia, necrosis, and histogenetic type and subtype of tumour. Prognostic factors in relation to metastasis-free survival were studied by uni- and multivariate analysis. Fifty-seven (20.5 per cent) were low-grade tumours, 43 (15.5 per cent) were intermediate, and 178 (64 per cent) were high grade. High-grade tumours were divided into two groups; 80 (29 per cent) grade 3A (= 5-20 mitoses per 10 high power fields (HPF)) and 78 grade 3B (28 per cent) (= more than 20 mitoses/10 HPF); 10 HPF corresponds to 2.5 mm2. Twenty (7.2 per cent) high-grade tumours could not be further subdivided. Grading was found to be the prognostic factor associated with the strongest predictive value. Five-year survival in low-grade and intermediate tumours (95 and 86 percent, respectively) differed significantly (P less than 0.0001) from high grade (50 per cent) and (p = 0.0018) between grade 3A (64 per cent) and grade 3B (41 per cent). Other prognostic indicators of importance in high-grade tumours were age, local recurrence at presentation (primary operation outside the Centre), and localization (superficial vs. deep).

[Delayed diagnosis of epiphysiolysis capitis femoris]. / Forsinket diagnose af epiphysiolysis capitis femoris.

The prognosis in epiphysiolysis of the head of the femur (ECF) depends on immediate treatment in the earliest stage of the disease. The reasons for and the extent of delayed diagnosis of slipping of the epiphysis in the hip were analysed in 56 children (72 hips) with ECF. The median total delay was six months with a delay of one month due to the patient and delay of three months due to the doctor. Pain in the lower limbs not related to the hip, including pain in the knee, occurred in 1/3 of the patients and resulted in more extensive delays due to the doctor (median four months). Other reasons for delay due to the doctor were erroneous interpretation of the x-ray films (14 patients). The most characteristic clinical finding was limited internal rotation of the affected hip. Comparison with the literature revealed that delay in the diagnosis of ECF has not been reduced during the past 35 years. Clinical examination of the hips should be undertaken in any child who complains of pain in the knee or thigh. If internal rotation is limited, x-ray examination including Lauenstein's projection should be carried out or the child should be referred to a department of orthopaedic surgery on account of suspected hip disease.

Amputation of the little finger.

We review 17 patients who had 21 amputations of the little finger. Transmetacarpal amputations gave satisfactory results in older patients, but in young patients loss of breadth of the palm caused significant disability. Disarticulation through the metacarpophalangeal joint is recommended in younger patients.

Benign cystic lesions of peripheral nerves.

A patient with multiple cystic changes of the sural nerve, and another with a tarsal tunnel syndrome caused by invasion of the median plantar nerve by a ganglion in the tarsal tunnel, are presented. It is believed that there are three different kinds of benign cystic involvement of the peripheral nerves, multiple cystic degeneration of the nerve itself, invasion of nerves from outside by a ganglion and formation of simple cysts within the nerve proper, presumably as a result of trauma.

The Chiari pelvic osteotomy. A long-term review of clinical and radiographic results.

We have reviewed a series of 94 Chiari pelvic osteotomies carried out from 1966 to 1982. In 83 hips the indication for surgery had been pain, and of these patients 73 (88%) had appreciable relief within one year of operation. The other 11 hips were all in children and were painless; in them the osteotomy had successfully stabilised progressive subluxation of the hip. At review after a mean follow-up of 10 years (range, 2 to 18 years) 68 previously painful hips were reassessed. Although function of the hips had deteriorated slowly with time, four of the seven cases with 18 years' follow-up had good function and only minor symptoms. A detailed analysis of the radiographic changes produced by the Chiari osteotomy was made, using computerised analysis of variance. The beneficial effects of the osteotomy resulted from complex changes, among which the provision of a stable fulcrum for the hip seemed to be the most important.

Dislocated femoral neck fractures. A follow-up study of 98 cases treated by multiple AO (ASIF) cancellous bone screws.

A series of 98 dislocated femoral neck fractures were treated by closed reduction and osteosynthesis with multiple AO (ASIF) cancellous bone screws. The patients were followed up for 2 years (or until death). The degree of dislocation did not have a statistically significant influence on the failure rate, which was, however, significantly correlated with poor reduction. Thirty-nine percent of the fractures were complicated by non-union or late segmental collapse. Forty-three of the patients participated in the 2 year follow-up examination. Of these patients, 38 had achieved excellent or good hip function. It was concluded that the reduction was the most important single factor in treatment of these factors.

Trochanteric and subtrochanteric fractures. The operative results in a prospective and comparative study of Ender nailing and McLaughlin Osteosynthesis.

A comparative and prospective study was performed in order to evaluate the advantages or disadvantages of the Ender operation in comparison with the McLaughlin technique. The series included 145 patients, 72 operated by the Ender method, and 73 by the McLaughlin method. There were no differences between the two groups as regards anaesthesia time, operation time, mean stay in hospital, morbidity and mortality. Technical problems were encountered in 40 of the Ender operated fractures (56 per cent), whereas the figure for the patients treated with the McLaughlin method was 17 (23 per cent). Ten (14 per cent) patients in the Ender group but only 2 (3 per cent) in the McLaughlin group needed re-operation. Three deep infections occurred in the McLaughlin group, but non in the Ender group. It was concluded that the only advantage which could be demonstrated in the Ender group was a low infection rate. Many disadvantages were revealed, the most outstanding being the many technical problems encountered and the great number of re-operations required.