Antithymocyte globulin induction therapy improves survival in lung transplantation for cystic fibrosis

Cystic fibrosis (CF) is an inherited condition that leads to respiratory failure and is the third most common indication for adult bilateral lung transplantation (LuTX). In contrast to other lung diseases, the immune system of CF patients is up‐regulated and we therefore hypothesized that these patients would benefit from induction therapy. In the current study, we investigated the impact of antithymocyte globulin (ATG) induction therapy in CF patients after LuTX. One hundred and forty six patients who underwent LuTX for CF at our centre between January 1999 and December 2010 were included in the study and retrospectively analysed. They were divided into two groups according to the immunosuppressive protocol: group‐A (n = 103) with and group‐B (n = 43) without induction therapy on top of the basic calcineurin inhibitor based triple immunosuppression with mycophenolate mofetil and steroids. Perioperative survival was significantly better in the ATG group, a benefit sustained for the entire follow‐up. ATG induction resulted in a significantly lower incidence of acute rejections without an increase in infectious complications. Taken together, our results indicate that ATG induction therapy confers a significant survival benefit in CF patients undergoing LuTX and reduces rejection. We advocate the use of induction therapy in this patient cohort.     

The influence of clinical course after lung transplantation on rehabilitation success

Pulmonary rehabilitation (PR) is a cornerstone of treatment following lung transplantation (LTx). The aim of this study was to observe the influence of a prolonged postsurgical clinical course on success of a 3‐week inpatient PR. LTx recipients were divided according to their clinical course defined by their individual length of stay (LOS) in the transplant center (cohort 1: LOS >; cohort 2: ≤42 days). Peak work rate (PWR), maximum oxygen uptake (VO_2max), 6‐min walk distance (6‐MWD), vital capacity (VC), forced expiratory volume in one second (FEV1), physical activity of daily life (ADL), and health‐related quality of life (HRQoL) measured using Short Form 36 questionnaire (SF36) were assessed at beginning and completion of PR. A total of 138 patients were included (LOS >42 days: 30; LOS ≤42 days: 108). At completion, physical functioning (VC, FEV1, PWR, VO_2max, 6‐MWD, ADL), and HRQoL (all SF36 domains) improved in each cohort (P < 0.05). No differences were found in between both cohorts in VC, FEV1, and ADL (n.s.), but in PWR, 6‐MWD, and the SF36 domain ‘physical functioning’ (P < 0.05). A 3‐week inpatient PR improves physical functioning despite prolonged hospitalization. HRQoL is close to normal. (ClinicalTrials.gov. identifier: NCT00759538)     

Phase 3 Study of Adjuvant Radiotherapy Versus Wait and See in pT3 Prostate Cancer: Impact of Pathology Review on Analysis

Background

In a randomised trial, radical prostatectomy (RP) followed by adjuvant radiotherapy (aRT) was compared with RP alone in patients with pT3 pN0 prostate cancer with or without positive margin at local pathology (German Cancer Society trial numbers ARO 96-02/AUO AP 09/95).

Objective

A pathology review was performed on 85% of RP specimens of patients to investigate the influence of pathology review on the analysis.

Design, setting, and participants

Patients post-RP (n = 385) were randomised before achieving an undetectable prostate-specific antigen (PSA) level to either wait and see (n = 192) or 60 Gy aRT (n = 193). Of 307 patients with undetectable PSA after RP, 262 had pathology review. These results were included prospectively into the analysis.

Outcome measurements and statistical analysis

Agreement between local and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic reliability for the different parameters was analysed by Cox regression model. Event-free rates were determined by Kaplan-Meier analysis with a median follow-up of 40 mo for the wait-and-see arm and 38.5 mo for the aRT arm.

Results and limitations

There was fair concordance between pathology review and local pathologists for seminal vesicle invasion (pT3c: 91%; κ = 0.76), surgical margin status (84%; κ = 0.65), and for extraprostatic extension (pT3a/b: 75%; κ = 0.74). Agreement was much less for Gleason score (47%; κ = 0.42), whereby the review pathology resulted in a shift to Gleason score 7. In contrast to the analysis of progression-free survival with local pathology, the multivariate analysis including review pathology revealed PSMs and Gleason score >6 as significant prognostic factors.

Conclusions

Phase 3 studies of postoperative treatment of prostate cancer should be accomplished in the future with a pathology review. In daily practice, a second opinion by a pathologist experienced in urogenital pathology would be desirable, in particular, for high-risk patients after RP.     

Bone Mass,Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro–finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = −0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = −1.23, p = .02). HOA was associated with lower failure load (−514 N; 95%CI, −1018 to −9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Management of vitiligo. Results of a questionnaire among dermatologists in The Netherlands

BACKGROUND: Several therapeutic options are available for the treatment of vitiligo. Concern exists that there is no uniform approach towards the management of vitiligo among Dutch dermatologists. METHODS: A written survey concerning the management of vitiligo was sent to 332 dermatologists in The Netherlands. RESULTS: The response rate was 86%. "Giving information and reassurance concerning the nature of disease" was regarded by most dermatologists (68%) as being the most important goal in the management of vitiligo. Only 16% of the dermatologists aimed for active treatment in vitiligo. The reported therapy choices in children resembled those of adults, except that slightly more dermatologists did not prescribe active therapy in children. Nine different therapeutic modalities were mentioned as first choice therapies. Topical corticosteroids were indicated by most dermatologists as first choice therapy (241 out of 266, i.e. 91%); however, only 2% indicated that 50% or more of the patients achieved a successful treatment; 66% found that less than 25% of the patients were successfully treated with topical corticosteroids. Only 15% of the respondents reported that 50% or more of the patients were treated successfully with narrow-band UVB. The observed response profile to broad-band UVB therapy was found to be comparable with that of narrow-band UVB. The classical therapy with oral psoralen plus UVA (PUVA) was prescribed as first choice therapy by only 12% (32 out of 266) of the dermatologists. Only 6% of these respondents observed that 50% or more of the patients achieved successful therapy using oral PUVA. The recommended maximum treatment duration for topical corticosteroids, oral PUVA, and UVB therapy was found to vary from 3 to 12 months. CONCLUSIONS: Most dermatologists in The Netherlands do not offer active treatment in vitiligo, probably because the estimated effectiveness of (nonsurgical) repigmentation therapy is low. In cases where treatment is prescribed, there appears to be no consensus on the choice of therapies and treatment strategies. The development of practice guidelines may be helpful in reducing inappropriate care and improving treatment outcome.     

Do‐it‐yourself cement work: the main cause of severe irritant contact dermatitis requiring hospitalization

Background. There are myriads of potentially irritant agents causing acute irritant contact dermatitis. In the large majority of cases, dermatitis is mild to moderate, and patients do not need hospitalization. However, some agents or special circumstances may cause severe dermatitis requiring more intensive therapy. Objectives. The aim of this study was to evaluate causative agents of severe acute irritant contact dermatitis requiring hospitalization. Methods. In this single‐centre observational cohort study, we included 54 consecutive patients presenting with signs and symptoms of acute irritant contact dermatitis for which hospitalization was necessary. The severity of dermatitis was graded (grade I–IV) according to intensity, and details related to the skin irritation (irritant agent, area of exposure, time interval to onset of symptoms, and duration of hospitalization) were determined. Results. All cases with severe ulcerative dermatitis (grade IV) were caused by wet cement, owing to prolonged skin contact. These cement burns are clearly associated with amateur work, younger age, male preponderance, and leg localization. Conclusions. The study data provide clear‐cut evidence that wet cement is a severely irritant substance that regularly causes the most severe form of acute irritant contact dermatitis. The main causative prerequisite for these cement burns is do‐it‐yourself work with poor protective measures.     

Progressive differentiation of human sebocytes in vitro is characterized by increasing cell size and altering antigen expression and is regulated by culture duration and retinoids

Abstract Increasing cell size, lipid accumulation, and altered antigen expression are features of sebaceous differentiation in vivo. Enhanced lipid synthesis with progressive differentiation is also present in cultured human sebocytes. This study was conducted to investigate the evolution of cell size and antigen expression of human sebocyles with progressive differentiation in vitro. Subconlluent human sebocyte cultures were examined for sebocyte differentiation evaluated on cytocentrifuge preparations by light microscopy and classified in stages according to morphological criteria described for sebocytes in vivo. Rates of 5.1 ±2. 2% undifferentiated sebocytes. 29.2 ±4.9% early differentiated, 20.7 ±4.1% advanced differentiated, 37.6±6.4% fully differentiated, and 5.9± 1.9% mature sebocytes were calculated in secondary cultures. The size of cultured sebocytes measured by computer-assisted planimetry significantly increased with progressive differentiation up to 4-5.5 times. The low rates of mature sebocytes and the only moderate increase of their size with progressive differentiation indicate an incomplete terminal differentiation in vitro. Sebocytes were subsequently stained with a series of monoclonal antibodies (mAb) to determine antigen expression using the alkaline phosphatase anti-alkaline phosphatase technique. The number of sebocytes labeled with the anti-keratin mAb CK8.12 and KLI, and the mAb 34DII (82 kD protein) increased with progressive differentiation; significant differences were found after comparing early and advanced differentiated sebocytes. Sebocytes were positively stained with the anti-keratin mAb 6BIO (K 4). RPNI162 (K 7), CK.I3 (K 13), RPNI165 (K 19). CK.8.60, and the mAb 115F5 (MAM-6c). OM-I (sebaceous gland antigen), and 24F10 (basic polypeptides) only at late-stage differentiation. The expression of keratins 4, 7, 13, and 19 was confirmed by gel electrophoresis and immunoblotting. The data obtained were used to study the effects of the duration of cultivation and of the retinoids isotretinoin and tretinoin on sebocyte differentiation in vitro. Subcultivalion of sebocytes upregulaled, and treatment with isotretinoin but not with tretinoin downregulated labeling with mAb which recognize indicating progressive and late-stage differentiation.     

Successful treatment of basal cell carcinomas in a nevoid basal cell carcinoma syndrome with topical 5% imiquimod

Gorlin-Goltz syndrome, also referred to as naevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant skin disease with complete penetrance and inconstancy of the four major findings: multiple naevoid basal cell carcinomas (BCCs), pits on palms and soles, skeletal abnormalities (for example, jaw cysts), and ectopic calcification. The treatment of multiple BCCs is still a matter of debate. We report three cases of multiple BCCs in Gorlin-Goltz syndrome treated with topical 5% imiquimod cream, an immune response modifier. Patients were successfully cleared of BCCs after treatment for 6-8 weeks. Histologically no apparent signs of BCC-persistence could be detected and no recurrences were detected during the 12 month follow up period.