Evaluation of the Knowledge of Primary Care Physicians About Important Nail Diseases Before and After a Short Online Training.

INTRODUCTION: Nail diseases are often diagnosed late with a potential prognostic and functional impact. This could be partly due to knowledge gaps among primary care physicians (PCPs). OBJECTIVES: To evaluate the knowledge about diagnosis and management of ten common/important nail conditions in a population of French PCPs and its improvement after a 31-minute online training session. METHODS: We submitted 10 pre-test and post-test clinical cases and an educative online course on the diagnosis and the management of nail diseases to 138 volunteer PCPs; 73 completed the whole training path. RESULTS: Compared to pre-test, more PCPs in the post-test required an urgent second opinion to dermatologist for pigmented melanoma (100% versus 80.3%; P <0.05) and use of inappropriate/dangerous systemic treatment for trauma-induced nail changes was reduced after the training program (0% versus 6.8%; P <0.05). A lack of knowledge remained after training for amelanotic melanoma with an increase of mycological/bacteriological tests (9.6% versus 0%; P <0.05). CONCLUSIONS: Management of nail diseases by our panel of PCPs was suboptimal and was improved after a short online training.

Significance of Primary Melanoma Regression on Local Infiltrate and Outcome.

INTRODUCTION: The characteristics and the prognostic value of regression in primary melanomas are controversial. OBJECTIVES: To further characterize "hot" and "cold" tumor's stromas and to investigate the association between dermoscopy, pathology, and the prognostic implications of regression. METHODS: A 14-year-collection-based retrospective analysis was carried out on 40 patients with confirmed regressive melanomas. RESULTS: The extent of regression in dermoscopy was associated with the stage of the regression (P = 0.05) and with the MelanA patterns in histology (P = 0.02). Blue-gray and gray-brown color of the peppering (P = 0.01), and the eccentric, multifocal character of the dermoscopic regression (P = 0.05) were associated with "hot" stromas (CD8+, Granzym B+). Focal histologic regression (regressing melanomas) was associated with a good outcome (P < 0.001), while a complete regression (regressed melanomas) was associated with melanoma-related death (P < 0.001). "Hot" stromas (CD8+ were significantly associated with survival at 10 years (P = 0.044), while "hot" stromas (Granzyme B+) were associated with the locoregional extension (P = 0.016), and the initial distant metastasis (P = 0.016). CONCLUSIONS: Dermoscopic features of regression in primary melanomas were associated with the stage of regression, its extent, and the "hot" or "cold" nature of the tumor stroma, with prognostic implications.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

Addition of azathioprine to the switch of anti-TNF in patients with IBD in clinical relapse with undetectable anti-TNF trough levels and antidrug antibodies: a prospective randomised trial.

OBJECTIVES: In patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumour necrosis factor (anti-TNF), algorithms recommend a switch of anti-TNF without immunosuppressive drug. The aim of our study was to compare in these patients two strategies: either switch to a second anti-TNF alone or with addition of azathioprine (AZA). After randomisation outcomes (time to clinical and pharmacokinetic failure) were compared between the two groups during a 2-year follow-up period. DESIGN: Consecutive IBD patients in immune-mediated LOR to a first optimised anti-TNF given in monotherapy were randomised to receive either AZA or nothing with induction by a second anti-TNF in both arms. Clinical failure was defined for Crohn's disease (CD) as a Harvey-Bradshaw index ≥5 associated with a faecal calprotectin level >250 µg/g stool and for UC as a Mayo score >5 with endoscopic subscore >1 or as the occurrence of adverse events requiring to stop treatment. Unfavourable pharmacokinetics of the second anti-TNF were defined by the appearance of undetectable trough levels of anti-TNF with high antibodies (drug-sensitive assay) or by that of antibodies (drug-tolerant assay). RESULTS: Ninety patients (48 CDs) were included, and 45 of them received AZA after randomisation. The second anti-TNF was adalimumab or infliximab in 40 and 50 patients, respectively. Rates of clinical failure and occurrence of unfavourable pharmacokinetics were higher in monotherapy compared with combination therapy (p<0.001; median time of clinical failure since randomisation 18 vs >24 months). At 24 months, survival rates without clinical failure and without appearance of unfavourable pharmacokinetics were respectively 22 versus 77% and 22% versus 78% (p<0.001 for both) in monotherapy versus combination therapy. Only the use of combination therapy was associated with favourable outcomes after anti-TNF switch. CONCLUSION: In case of immune-mediated LOR to a first anti-TNF, AZA should be associated with the second anti-TNF. TRIAL REGISTRATION NUMBER: 03580876.

Comparison of Immunoassays for Measuring Serum Levels of Golimumab and Antibodies Against Golimumab in Ulcerative Colitis: A Retrospective Observational Study.

BACKGROUND: Golimumab is a monoclonal anti-tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure-response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels). METHODS: This study was based on samples from 78 ulcerative colitis patients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen R&D, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen R&D, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen R&D), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody. RESULTS: Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen R&D assay, respectively (P < 0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen R&D assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen R&D assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven R&D), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen R&D and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen R&D drug-tolerant assay and in the same 2 patients by the 3 other assays. CONCLUSIONS: Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.

Cost savings using a test-based de-escalation strategy for patients with Crohn's disease in remission on optimized infliximab: A discrete event model study.

BACKGROUND: Drug de-escalation is considered in Crohn's disease patients in sustained remission on optimized infliximab treatment. AIM: We built a model to evaluate the magnitude of cost savings in patients' disease course with or without drug de-escalation guided by infliximab trough levels. METHODS: We designed 4 virtual cohorts (P1-P4) of 10,000 patients in clinical remission on optimized infliximab treatment followed for 2 years. P1: no drug de-escalation - 10 mg/kg/8 weeks; P2: drug de-escalation from 10 mg/kg/8 weeks to 5 mg/kg/8 weeks according to trough levels; P3: no drug de-escalation - 10 mg/kg/6 weeks; and P4: drug de-escalation from 10 mg/kg/6 weeks to 10 mg/kg/8 weeks according to trough levels. For P2 and P4 cohorts, drug de-escalation was decided if trough levels were ≥7 µg/mL and no de-escalation if trough levels were <7 µg/mL. Only costs related to drug administration were considered. RESULTS: The cost differences when comparing P1 versus P2 and P3 versus P4 were 7.6% and 4.6%, respectively, corresponding to costs savings of €30.5 millions and €20.3 million for 10,000 patients. CONCLUSION: Over a 2-year period, infliximab de-escalation according to trough levels led to cost saving of about 6%, corresponding to around €25.4 million.

Is the Pharmacokinetic Profile of a First Anti-TNF Predictive of the Clinical Outcome and Pharmacokinetics of a Second Anti-TNF?

AIM: The aim of this study was to evaluate prospectively the clinical outcomes and pharmacokinetics of a second anti-TNF according to the pharmacokinetics of the first anti-TNF in patients with inflammatory bowel disease (IBD). METHODS: In patients in loss of response (LOR) to a first optimized anti-TNF and switched to a second anti-TNF, pharmacokinetics of anti-TNF were measured at the switch time, 30 weeks later, at the time of LOR, or at the end of the study (102 weeks). RESULTS: At the switch time, patients (n = 59) belonged to 4 groups according to the pharmacokinetics of the first anti-TNF: group 1 (n = 18), therapeutic trough levels; group 2 (n = 13) undetectable trough levels with antibodies against anti-TNF; group 3 (n = 13) without antibodies against anti-TNF; and group 4 (n = 15) subtherapeutic trough levels. After switching, the failure rates at week 30 and during the follow-up were as follows, respectively: in group 1 with therapeutic levels, 50% and 78%, despite therapeutic levels of the second anti-TNF in 83% of cases; in group 2 with undetectable levels and antibodies, 15% and 69% with undetectable levels of the second anti-TNF and antibodies in 85% of cases; in group 3 with undetectable levels without antibodies, 0% and 31% with therapeutic levels in 77% of cases; in group 4 with subtherapeutic levels, 13% and 33% with therapeutic levels in 73% of cases. Clinical remission rates were significantly lower (P ≤ 0.05) in groups 1 and 2 with therapeutic or undetectable levels with antibodies than in the 2 other groups. CONCLUSION: In the case of LOR with therapeutic levels of the first anti-TNF or undetectable levels with antibodies, the switch to a second anti-TNF results in pharmacokinetic profile similar to the first one and again in LOR in most of the patients.

Improvement of Genetic Testing for Cutaneous Melanoma in Countries With Low to Moderate Incidence: The Rule of 2 vs the Rule of 3.

Importance: Genetic testing for melanoma-prone mutation in France, a country with low to moderate incidence of melanoma, is proposed in cases with 2 invasive cutaneous melanomas and/or related cancers in the same patient, or in first- or second-degree relatives (rule of 2). In preclinical studies, these rules led to disclosure of mutation(s) in more than 10% of these families, the threshold widely accepted to justify genetic testing for cancers. Objective: To reconsider these criteria in a general population testing of patients. Design, Setting, and Participants: This was a retrospective study, performed from 2004 to 2015 at Angers and Lyons University Hospitals, of a cohort of 1032 patients who underwent genetic testing. Main Outcomes and Measures: Frequency of mutation in high (CDKN2A, CDK4, and BAP1) and intermediate (MITF) susceptibility genes; statistical effect of histologic subtype, age, dysplastic nevi syndrome, and associated cancers on mutation rate; and evaluation of cases with anamnestic uncertainty. Results: The mutation rate was 67 of 1032 patients (6.5%). Their mean (SD) age was 54.5 (14.2) years [range, 18-89 years], and 543 (52.6%) were men. It increased to 38 of 408 patients (9.3%) when applying a rule of 3 (those with ≥3 primary melanomas or genetically related cancers) (P = .68) and to 27 of 150 patients (18.0%) with a rule of 4 (4 primary melanomas or related cancer) (P < .001). The impact of age at first melanoma was observed only in those younger than 40 years, with a rate of 32 of 263 (12.1%) (P = .12) for the rule of 2 and 22 of 121 (18.2%) (P = .001) for the rule of 3. Use of the rule of 2 in patients younger than 40 years reduced the number of missed CDKN2A-mutated-families when applying the rule of 3 from 14 of 43 to 7 of 43. Anamnestic uncertainty, found in 88 families (8.5%), if excluded, would have led us to withdraw of only 21 cases (23.8%), and only 1 mutation would have been missed. Conclusions and Relevance: We propose using the rule of 3 to recommend genetic testing in France and countries with low to moderate incidence of melanoma, except in families and patients with a first melanoma occurrence before age 40 years in whom the rule of 2 could be maintained.

Dermoscopic Features of Subungual Squamous Cell Carcinoma: A Study of 44 Cases.

BACKGROUND: Subungual squamous cell carcinoma (SSCC) is the most frequent tumor of the nail apparatus. Its diagnosis is often missed or delayed because the clinical presentation is atypical and can mimic other conditions. Accurate diagnosis can only be made by performing an appropriate surgical biopsy, but biopsy is painful and often leaves definitive dystrophic scars. The use of dermoscopy, a noninvasive technique, has been described to be useful for the preoperative evaluation of nail diseases. OBJECTIVES: To define the different clinical and dermoscopic presentations of SSCC and to compare them with onychomatricoma-associated clinical and dermoscopic features published in our previous study. METHODS: A retrospective review of 44 cases of SSCC seen in our institution over an 8-year period. Six observers scored 19 clinical criteria and 14 dermoscopic criteria as present or absent. Then, we compared those data to a previously published study about the preoperative diagnosis of onychomatricoma. RESULTS: Only 1 dermoscopic criterion was significantly associated with SSCC compared to onychomatricoma: localized hyperkeratosis (odds ratio, OR = 6.25, p = 0.012, 95% confidence interval CI = 1.50-26.01). In contrast, parallel edges (OR = 0.03, p < 0,001, 95% CI = 0.003-0.20) and sharp demarcation of the lesion (OR = 0.24, p = 0.004, 95% CI = 0.09-0.63) can statistically significantly be considered as in favor of onychomatricoma. By contrast, we believe that the presence of unparalleled lateral edges of the nail lesion or of fuzzy edges are more in favor of SSCC. CONCLUSIONS: Dermoscopy of the nail plate and of the nail free edge in SSCC provides useful information in order to better select cases to be submitted to biopsy.

Surgical Treatment of Subungual Squamous Cell Carcinoma by Wide Excision of the Nail Unit and Skin Graft Reconstruction: An Evaluation of Treatment Efficiency and Outcomes.

Importance: The best surgical treatment modalities for subungual squamous cell carcinoma (SUSCC) without bone invasion need to be determined. The limited available data on Mohs micrographic surgery do not demonstrate its use as a standard procedure. A previous study in a limited series of patients has shown that wide surgical excision of the nail unit was associated with a low rate of recurrence. Objectives: To confirm the efficiency of wide surgical excision of the nail unit with full-thickness skin graft reconstruction on a series of patients with SUSCC with an extended follow-up and to evaluate short- and long-term postoperative morbidity and patient satisfaction. Design, Setting, and Participants: A consecutive series of 55 patients with biopsy-proven SUSCC without bone invasion treated by wide surgical excision of the nail unit followed by full-thickness skin graft reconstruction from January 1, 2000, to August 31, 2012 were included. After a minimum follow-up of 5 years, the recurrences were collected from the referring physicians. Statistical analysis was conducted from January 1 to June 30, 2016. Main Outcomes and Measures: Demographic data, pathologic characteristics of tumors, postoperative follow-up, and recurrences were collected from medical records. Patients' satisfaction with surgery, quality of life, and delayed postoperative morbidity (functional outcome and sensory disorders) were assessed from a questionnaire mailed to patients and physicians. Results: Among the 55 patients (23 women and 32 men; mean age, 64 years), the mean follow-up was 6.6 years (range, 5.0-11.2 years), with a minimum follow-up of 5 years. Fifty-two questionnaires (95%) were returned. Two recurrences were observed. Minor early postoperative complications, such as graft infection and delayed wound healing, were seen in 6 patients; 8 patients experienced severe pain. Late postoperative complications included hypersensitivity to mechanical shocks (39 of 51 patients [76%]), mildly increased sensitivity to cold (38 of 51 patients [75%]), loss of fine touch sensation (17 of 35 patients [49%]), and epidermal inclusion cysts (9 of 51 patients [18%]). Most patients were very satisfied with cosmetic and global outcomes of the surgery. Conclusions and Relevance: Total excision of the nail unit followed by a full-thickness skin graft is a safe and efficient treatment for SUSCC without bone involvement, with satisfying cosmetic and functional outcomes.

Development and Internal Validation of a Model Using Fecal Calprotectin in Combination with Infliximab Trough Levels to Predict Clinical Relapse in Crohn's Disease.

BACKGROUND: The best noninvasive method predicting clinical relapse remains undetermined in infliximab (IFX)-treated patients with Crohn's disease. METHODS: All patients with CD on IFX maintenance treatment and in clinical remission for at least 16 weeks, between 2011 and 2014, were enrolled in a prospective single-center study. The Crohn's Disease Activity Index (CDAI), fecal calprotectin, C-reactive protein levels, antibodies (ATI), and trough level (TLI) of IFX were measured at every IFX infusion. The best thresholds of TLI (2 versus 3 µg/mL) and calprotectin (50 versus 250 µg/g stools) were identified across four logistic regression models. RESULTS: One hundred nineteen patients (mean age: 34 ± 12 yrs, mean disease duration: 7.8 yrs) were included. Mean follow-up was 20.4 months, and 17% of the patients were on IFX and azathioprine at inclusion. During follow-up, 37 patients (31.1%) relapsed, 78% within the first 6 months. The clinical characteristics of the relapsed and nonrelapsed patients were similar. After logistic regression, fecal calprotectin >250 µg/g stools (OR: 4.09; 95% CI, 1.01-16.21; P = 0.049) and TLI <2 µg/mL (OR: 14.85; 95% CI, 3.67-60; P < 0.0001) were associated with loss of response. A training cohort of 55 patients was isolated randomly to implement prediction rules for loss of response. The best predictive rules were the combination of a TLI <2 µg/mL and a fecal calprotectin level >250 µg/g stools (78.3%). These rules were validated on a test cohort of 64 patients with an accuracy of 87%, (sensitivity = 0.94, specificity = 0.84, positive predictive value = 0.73, and negative predictive value = 0.97). CONCLUSIONS: In IFX-treated patients with CD in clinical remission, a combination of TLI (<2 µg/mL) and fecal calprotectin (>250 µg/g of stools) is a good model for predicting loss of response. In contrast with previous data, low TLIs ranging from 2 to 3 µg/mL should neither systematically lead to the optimization of IFX use nor a switch in the treatment.

Motivations of patients seeking supportive care for cancer from physicians prescribing homeopathic or conventional medicines: results of an observational cross-sectional study.

BACKGROUND & AIMS: The motivations of patients who consult a homeopathic (GP-Ho) or conventional (GP-CM) general practitioner for supportive care during cancer treatment have not been widely studied. We investigated the reasons why cancer patients consult a GP-Ho versus a GP-CM for supportive care and the GPs' motivations for their prescriptions. METHODS: This observational survey was carried out in France between October 2008 and October 2011. GPs across France were randomly selected and asked to recruit four cancer patients each. At inclusion, the sociodemographic and clinical (including psychological) characteristics and medical history of the patients were recorded by the GPs and the patients noted their quality of life (QoL) and anxiety/depression using the Quality of Life Questionnaire-C30 (QLQ-C30) and Hospital Anxiety and Depression Scale (HADS) self-questionnaires. The main motivations of the patients regarding the type of GP consultation and the main reasons for the GPs' prescriptions were recorded. RESULTS: Six hundred and forty four patients were included in the analysis: 399 consulted a GP-CM (n = 112) and 245 a GP-Ho (n = 73). Patients consulting a GP-Ho were more often female [OR = 1.93; 95%CI: 1.11-3.35; p = 0.02], employed in a professional capacity [OR = 6.57; 95%CI: 1.96-21.99; p = 0.002], have a shorter time since cancer diagnosis [OR = 2.19; 95%CI: 1.24-3.87; p = 0.007], have received targeted anticancer therapy [OR = 3.70; 95%CI: 1.67-8.18; p = 0.001] and have a high QLQ-C30 score for constipation [OR = 1.01; 95%CI: 1.00-1.02; p = 0.001]. Patients mainly consulted a GP-Ho to receive overall care (73.5% vs. 64.9%; p = 0.024) and medicines to prevent anticancer treatment-related side-effects (63.7% vs. 41.4%; p < 0.0001). In contrast, patients consulted a GP-CM to receive psychological care (50.1% vs. 40.8%; p = 0.021) and more information regarding the oncologists' strategic decisions (p < 0.0001). There was a significantly greater prescription of psychotropic drugs by GP-CM (53.7% vs. 22.4%, p < 0.0001). CONCLUSIONS: Patients consulting a GP-Ho or GP-CM had different motivations for seeking supportive care. There was a significantly greater prescription of psychotropic drugs by GP-CM.

New insights into renal toxicity of the B-RAF inhibitor, vemurafenib, in patients with metastatic melanoma.

PURPOSE: Vemurafenib (VMF) is a B-RAF inhibitor used in the treatment of B-RAF-V600-mutant metastatic melanomas. Reports of acute kidney injury (AKI) in patients treated with VMF are scarce. METHODS: To investigate the incidence and severity of AKI, we conducted a retrospective, observational, monocentric study in the Lyon Sud Hospital University, France, which included 74 patients with metastatic B-RAF-mutated melanomas treated with VMF, between June 2011 and August 2014. According to the Kidney Disease Improving Global Outcomes Guidelines, AKI is defined as an increase in serum creatinine concentration exceeding the baseline concentration by 1.5 fold. Serum creatinine was thus determined before treatment, on a monthly basis during treatment, and 3 months after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-) and further subdivided into three groups according to AKI severity (stage 1, 2 or 3). To visualize the tissue damage caused by VMF, kidney biopsies were performed for two stage 1 AKI+ patients. RESULTS: Of the 74 patients, 30 (40.5 %) were AKI-, and of the 44 AKI+ patients (59.5 %), 29 (66 %) were diagnosed within the first three months of treatment. There were significantly more men in the AKI+ group: n = 33 (75 %) versus n = 12 (40 %) women, p = 0.004 with an odds ratio for developing AKI of 4.6 (95 % CI 1.48-14.23). Most AKI + cases were considered as stage 1 (n = 40; 91 %) and the remaining four (9 %) as stage 2 AKI. Kidney biopsies revealed interstitial fibrosis and acute focal tubular damage. However, renal failure was reversible in 80 % of patients within 3 months of VMF discontinuation. CONCLUSIONS: We observed frequent, reversible, moderately severe AKI with some histological evidence of tubular and interstitial damage in VMF-treated patients, suggesting that renal function should be carefully monitored in male patients, especially during the first 3 months.

Hidradenitis suppurativa (HS): An unrecognized paradoxical effect of biologic agents (BA) used in chronic inflammatory diseases.

BACKGROUND: Paradoxical hidradenitis suppurativa (HS) induced by biologic agents (BA) is scarcely reported. OBJECTIVE: We sought to describe the clinical characteristics and outcome of patients developing paradoxical HS under BA. METHODS: This was a multicenter nationwide retrospective study asking physicians to report all cases of HS, confirmed by a dermatologist, occurring during treatment of an inflammatory disease by a BA. RESULTS: We included 25 patients (15 inflammatory rheumatism, 9 Crohn's disease, 1 psoriasis) treated by 5 BA (adalimumab = 12, infliximab = 6, etanercept = 4, rituximab = 2, tocilizumab = 1). Median duration of BA exposure before HS onset was 12 (range 1-120) months. Patients were mostly Hurley stage I (n = 13) or II (n = 11). Simultaneously to HS or within 1 year, 11 patients developed additional inflammatory diseases, including paradoxical reactions (psoriasis = 9, Crohn's disease = 3, alopecia areata = 1, erythema elevatum diutinum = 1). Complete improvement of HS was more frequently obtained after BA discontinuation or switch (n = 6/10, 60%) rather than maintenance (n = 1/14, 7%). Reintroducing the same BA resulted in HS relapse in 3 of 3 patients. LIMITATIONS: Retrospective nature and lack of complete follow-up for some patients are limitations. CONCLUSION: HS is a rare paradoxical adverse effect of BA, but fortuitous association cannot be excluded in some cases. We observed a trend toward better outcome when the BA was discontinued or switched.

Dermoscopic Features of Onychomatricoma: A Study of 34 Cases.

BACKGROUND: Onychomatricoma is a benign tumor of the nail matrix with a precise histopathological definition but many different clinical features and differential diagnoses. OBJECTIVES: The diagnosis of onychomatricoma is based on the pathological examination of a surgical specimen. The objective of this study was to define preoperative diagnostic criteria using noninvasive investigations: observation and dermoscopy. METHODS: A total of 34 cases of onychomatricoma were studied. In detail, 6 observers evaluated 12 clinical and 12 dermoscopical criteria as present or absent. RESULTS: For clinical criteria, the highest mean values were leuconychia (3.21), splinter hemorrhages (3.45), and thickening of the plate (3.0). Dermoscopical criteria were more often found present, such as longitudinal parallel white lines (4.33), parallel lesion edges (4.61), splinter hemorrhages (4.48), dark dots (3.96), free-edge nail pitting (4.5), and thickening of the free edge (5.27). CONCLUSION: Dermoscopical criteria for onychomatricoma are more frequently present and less subject to divergent interpretation. This offers new and original preoperative reliable diagnostic criteria and should be used in the evaluation of nail tumors.

Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn's disease patients who lose response to infliximab.

BACKGROUND: The use of pharmacokinetics is associated with cost savings in anti-tumor necrosis factor (anti-TNF) therapy, but the long-term cost savings in a large cohort of Crohn's disease (CD) patients are unknown. AIM: The goal of this study was to compare the cost of anti-TNF therapy in two cohorts of CD patients losing response to infliximab, one using a test-based strategy and one an empirical dose escalation. METHODS: We used a selected mathematical model to describe the trajectories of CD patients based on a discrete event system. This design allowed us to track over a given period a double cohort of patients who moved randomly and asynchronously from one state to another, while keeping all the information on their entire trajectory. Both cohorts were modeled using state diagram parameters where transition probabilities from one state to another are derived from literature data. Costs were estimated based on the French health care system. RESULTS: Cost savings among the 10,000 CD patients using a test-based strategy were €131,300,293 at 5 years. At 5 years the mean cost saving was €13,130 per patient. The direct cost of the test had no impact on the results until the cost per test reached €2,000. CONCLUSIONS: A test-based strategy leads to major cost savings related to anti-TNF therapy in CD.

Blastic plasmacytoid dendritic cell neoplasms: clinico-immunohistochemical correlations in a series of 91 patients.

Blastic plasmacytoid dendritic cell neoplasm is a rare clinicopathologic entity, characterized by strong skin tropism and a poor prognosis. The diagnosis is generally made by skin biopsy with appropriate immunohistochemical studies. To identify potential biological prognostic factors for blastic plasmacytoid dendritic cell neoplasm, we performed an extended clinico-immunohistochemical study on a series of 91 well-documented cases collected since 1995 by the French Study Group on Cutaneous Lymphomas. Skin biopsies were analyzed using a panel of 12 immunohistochemical markers (CD4, CD56, CD123, CD303, TCL1, CD68, CD2, CD7, TdT, Ki-67, S100, and MX-1). The results were correlated with survival. The 5 most characteristic markers of this entity (CD4, CD56, CD123, CD303, and TCL1) were expressed simultaneously in only 46% of patients. However, when 4 markers were expressed the diagnosis could still be reliably made without resorting to any additional stains. Expression of TdT and/or S100 correlated with varying degrees of maturation. Statistical survival analyses showed that CD303 expression and high proliferative index (Ki-67) were significantly associated with longer survival.

Melanoma patients under vemurafenib: prospective follow-up of melanocytic lesions by digital dermoscopy.

Second primary melanomas (SPMs) induced by vemurafenib have been recently described. The aim of this study was to define the dermoscopical signs of melanoma in this context. Patients underwent a total body examination before receiving vemurafenib. Each single melanocytic lesion was registered before therapy by digital dermoscopy (DD), and then repeated monthly until therapy disruption. Forty-two patients were included, the mean duration of follow-up was 6.7 months, and a mean number of 51 lesions per patients were captured and followed. A total number of 2,155 lesions were recorded, of which 56.1% presented at least one change during the study. More common changes concerned the color of the lesions (up to 15%) and appearance or disappearance of globules (14.6%). Thirty-six of the melanocytic lesions were surgically excised, 21 were classified as a nevus, 1 was a lentigo, and 14 as a second new primary melanoma (occurring in 21% of our patients). DD allowed us to excise only 36/2,155 (1.6%) of the lesions and permitted us to detect 14 SPM in the 42 patients with a highly efficient malignant/benign ratio of 63.6%. Although vemurafenib is now tested in an adjuvant setting DD should be systematically used in order to accurately detect SPM and reduce the number of unnecessary excisions.

Relationships between black tea consumption and key health indicators in the world: an ecological study.

OBJECTIVES: The aim of this study was to investigate potential statistical relationships between black tea consumption and key health indicators in the world. The research question is: Does tea consumption is correlated with one or more epidemiological indicators? DESIGN: Ecological study using a systematic data-mining approach in which the unit of the analysis is a population of one country. SETTING: Six variables, black tea consumption data and prevalence data of respiratory diseases, infectious diseases, cancer, cardiovascular diseases and diabetes, have been studied at a global level. PARTICIPANTS: Data from 50 participating countries in the World Health Survey were investigated. PRIMARY AND SECONDARY OUTCOMES MEASURES: Level of statistical relationships between variables. RESULTS: Principal component analysis established a very high contribution of the black tea consumption parameter on the third axis (81%). The correlation circle confirmed that the 'black tea' vector was negatively correlated with the diabetes vector and was not correlated with any of the other four health indicators. A linear correlation model then confirmed a significant statistical correlation between high black tea consumption and low diabetes prevalence. CONCLUSIONS: This innovative study establishes a linear statistical correlation between high black tea consumption and low diabetes prevalence in the world. These results are consistent with biological and physiological studies conducted on the effect of black tea on diabetes and confirm the results of a previous ecological study in Europe. Further epidemiological research and randomised studies are necessary to investigate the causality.

Clinical and economic impact of malnutrition per se on the postoperative course of colorectal cancer patients.

BACKGROUND & AIMS: To assess the medico-economic impact of malnutrition in patients who underwent surgery for colorectal cancer. METHODS: We performed post-hoc analyses of data from the Alves et al. prospective study. Using standard criteria of malnutrition, 2 groups were created a posteriori: Well-nourished (WN) and Mal-nourished (MN) patients. The 2 groups were statistically adjusted for age, cancer status, and scheduled surgery. Individual costs were valued using the French National Cost Study. Postoperative morbidity, mortality, hospital length-of-stay (LOS), and discharge setting were compared. We defined 3 scenarios, the most accurate estimate and its upper and lower limits, to assess the economic impact of malnutrition. RESULTS: 453 patients were included in the analyses. Complication and mortality rates were not significantly different between the 2 groups. MN patients had a mean LOS 3.41 days significantly longer than WN patients (p = 0.017). In MN patients, the cost of hospital stay was increased by around 3360 €, creating an annual impact of 10,159,436 € for French non-profit hospitals. CONCLUSIONS: Malnutrition in colorectal cancer surgical patients is associated with an increased LOS resulting in significant budget impact. Further studies are needed to investigate this impact and the related cost-benefit of perioperative specialized nutritional support and implementation of the ERAS protocol in this homogeneous category of patients.