In silico identification of drug candidates against COVID-19.

The COVID-19 pandemic has caused unprecedented health and economic crisis throughout the world. However, there is no effective medication or therapeutic strategy for treatment of this disease currently. Here, to elucidate the inhibitory effects, we first tested binding affinities of 11 HIV-1 protease inhibitors or their pharmacoenhancers docked onto SARS-CoV-2 main protease (M pro ), and 12 nucleotide-analog inhibitors docked onto RNA dependent RNA polymerase (RdRp). To further obtain the effective drug candidates, we screened 728 approved drugs via virtual screening on SARS-CoV-2 M pro . Our results demonstrate that remdesivir shows the best binding energy on RdRp and saquinvir is the best inhibitor of M pro . Based on the binding energies, we also list 10 top-ranked approved drugs which can be potential inhibitors for M pro . Overall, our results do not only propose drug candidates for further experiments and clinical trials but also pave the way for future lead optimization and drug design.

Correction to: Hormonal receptors in cutaneous vascular malformations: 51 cases.

The original version of this article contained error. Table 2 was shown in the wrong version, thus corrected table is shown in this article.

Hormonal receptors in cutaneous vascular malformations: 51 cases.

Vascular malformations (VMs) are rare congenital anomalies that develop during embryogenesis in different types of vessels. Several triggering factors of cutaneous VMs include trauma, infections, or hormonal changes. We investigated the expression of hormonal receptors (androgen, estrogen, progesterone) in tissue samples of well-characterized VMs. A secondary objective was to identify self-reported triggering factors for these VMs, including hormonal changes, in the cohort of patients. We included patients with VM samples obtained in the tertiary center for vascular anomalies of the University Hospital Center of Tours, France, from January 1, 2007, to August 1, 2018. Immunohistochemistry was used to detect the expression of hormonal receptors (estrogen, progesterone, androgens). We obtained 51 samples from 51 patients: 13 cystic lymphatic malformations (CLMs), 16 venous malformations (VeMs), 11 arteriovenous malformations (AVMs), 4 combined VMs, 4 PIK3CA-related overgrowth spectrum, 1 Parkes-Weber syndrome, 1 Gorham syndrome, and 1 multiple lymphangioendotheliomatosis with thrombopenia. In total, 38 (74.5%) samples were positive for androgen receptor: 11 (84.6%) CLMs, 12 (75.0%) VeMs, 8 (72.2%) AVMs, and 7/11 (63.5%) other samples. All samples were negative for estrogen and progesterone receptors. Triggering factors were self-reported in 7 cases and were most frequently hormonal changes (n = 6, 18.2%). Hormonal triggers were frequent in AVMs (n = 4). Among patients with identified hormonal triggers, VM samples were positive for androgen receptor in 3 and negative in 3. Three-quarters of our VM samples expressed androgen receptor, and most CLM, VeM, and AVM samples were positive. Hormonal triggers were identified in 6/33 patients, mostly with AVMs.

Clinical and haemodynamic risk factors associated with discrepancies in lower limb length with capillary malformations: data from the national paediatric French cohort CONAPE.

BACKGROUND: Genetics discoveries have allowed for a better understanding of capillary malformations (CMs) associated with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed. OBJECTIVES: To identify clinical and haemodynamic factors associated with leg length discrepancy (LLD) in children with CMs of the lower limbs. METHODS: Data were obtained from the multicentre French national cohort CONAPE (COhorte Nationale d'enfants atteints d'Angiome Plan de membrE inférieur), from children aged 2-12 years old with CMs of the lower limbs. Clinical characteristics were prospectively collected. Haemodynamic factors were measured by an sonographer who calculated the arterial blood flow (ABF) in both lower limbs. An ABF difference ≥ 50% between the two lower limbs was considered relevant. LLD ≥ 2% was determined by the same radiologist on centralized radiographs. RESULTS: We analysed data at baseline for 96 children. The mean ± SD age was 5·6 ± 3·1 years; 49 (51%) were male; and 14 (15%) showed LLD. In total, 32 patients (33%) had venous anomalies, 13 (14%) lymphatic anomalies and in one child a diagnosis of Parkes Weber syndrome was made. Only an increased circumference above the knee was more frequent with than without LLD (43% vs. 13%, P = 0·02). In all, 10/79 patients (13%) showed a difference in ABF ≥ 50%: four had LLD. The frequency of differences in ABF ≥ 50% was greater with than without LLD [33% (n = 4/12) vs. 9% (n = 6/67), P = 0·04]. CONCLUSIONS: ABF measured by Duplex ultrasonography is a simple, low-cost and noninvasive complementary examination for help in detecting LLD, with a difference of ≥ 50% possibly associated.

Nail features in healthy term newborns: a single-centre observational study of 52 cases.

INTRODUCTION: The anatomy and embryology of the nail are well known, and nail abnormalities are a feature of many genodermatoses. However, the physiological aspect is not well described. We aimed to analyse the physiological features of nails in healthy newborns. METHODS: We performed an observational, prospective study at University Hospital Center of Tours between July and October 2015. Newborns were included by a dermatologist assistant during the systematic examination on release of the mother from the hospital. The medical history of the mother and infant were recorded by using a standardized questionnaire. Finger- and toenails were systematically photographed for a second interpretation by a dermatologist with blinding to the first photograph. RESULTS: Fifty-eight patients were eligible, and 52 were included. Half of the newborns were males, and the mean age at inclusion was 3.6 ± 1.2 days. Fingernails had an oval shape (71.1%) or a flat curvature (63.5%), and half had a lunula. Toenails showed an apparent hypertrophy of the proximal nail fold (38.4%) and lateral nail fold (73.1%). The shape of the nails was triangular (50.0%) or round (21.1%). We noted koilonychia in 32.7% of infants and lunula in 7.7%. Distal parts showed onychoschizia (28.8%) and onycholysis (26.9%). CONCLUSION: Koilonychia, onychoschizia of toenails or absence of lunula are physiological features of nails in newborns.

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.

[Frequency of lymphoscintigraphic anomalies in the contralateral limb and progression of unilateral primary lymphedema in children]. / Fréquence des anomalies lymphoscintigraphiques infracliniques controlatérales et évolution des lymphœdèmes primaires unilatéraux de l'enfant.

BACKGROUND: Primary lymphoedema (LE) is the consequence of lymphatic insufficiency, usually associated with hypoplasia of the lymph vessels and/or nodes. Lymphoscintigraphy allows early diagnosis. OBJECTIVES: To assess the frequency of contralateral LE by lymphoscintigraphy in children with unilateral primary LE of one limb; to assess facets of clinical bilateralization of LE. METHODS: This retrospective single-centre study included children with unilateral LE followed up at the Tours university hospital centre between 2004 and 2014. Parents were contacted by phone to obtain follow-up data. RESULTS: Of the 13 children included, 6 (46%) displayed bilateral lymphatic anomalies on lymphoscintigraphy. Within a median follow-up period of 6 years, clinical bilateralization was observed in one girl after progression of her LE for 7 years; in her case, bilateral lymphatic insufficiency was detected at the initial lymphoscintigraphy. CONCLUSION: While contralateral subclinical lymphatic insufficiency is frequent in children with unilateral primary LE of the limbs, clinical bilateralization appears only rarely.

Serial lymphoscintigraphic findings in a patient with Gorham's disease with lymphedema.

Gorham's disease is a rare disorder characterized by vascular, "lymphangio- matous" and/or "hemangiomatous" lesions in bone and surrounding soft tissues. Associated lymphedema has not been reported and clinical evolution is unpredictable. Plain radiographs, CT, MRI, and occasionally bone scintigraphy, are used to detect the bone and soft tissues changes. Biopsy is a major component of the diagnostic process. We report the findings of serial lymphoscintigraphy in a young boy with a polyostotic Gorham's disease associated with lymphangioma of the thigh and lower limb lymphedema. In this patient, lymphoscintigraphy was useful for diagnosis and follow-up of primary lymphedema. It provided valuable information concerning the occurrence, location, and progression of lymphatic lesions in both bone and soft tissues.

Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients.

BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.

[Thigh root reconstruction with a pedicled DIEP flap]. / Reconstruction d'une perte de substance de racine de cuisse sur membre lymphœdèmateux par un lambeau DIEP pédiculé

Root thigh extensive loss of substance requires surgical coverage. The presence of chronic lymphedema (LC) makes random with the postoperative healing time longer. We report an original case of reconstruction of extensive loss of substance from the root of the thigh using a pedicled deep inferior epigastric flap perforator (DIEP) flap. A 22-year-old woman with angiosarcoma occurring in hemi-body lymphedema. The defect generated by the oncologic resection was 16×24cm. She was reconstructed by a pedicled DIEP flap. Skin wound healing was obtained within 30 days. Donor site healing was obtained within 15 days. The pedicled DIEP flap seems to be effective for root thigh reconstruction.

[The CONSORT statement (CONsolidated Standards Of Reporting Trials)]. / Les recommandations CONSORT (CONsolidated Standards Of Reporting Trials).

The CONSORT group, made up in particular of methodologists and journal editors, has created a tool in the form of a list. This tool, known as the "CONSORT statement", sets out all items that must be reported when preparing for publication in medical journals with regard to methods, results and discussion of randomised controlled trials (RCT). The aim of this group and of the CONSORT statement is to help authors prepare a standard presentation of the methodology and results of their studies. The desired effect is to ensure greater transparency and optimal rigor in such presentations, and thus in study design. This will make it easier for readers to verify such studies and to assess any potential sources of study bias.

Patients' acceptance of medical photography in a French adult and paediatric dermatology department: a questionnaire survey.

BACKGROUND: Despite the increasing use of medical photography by dermatologists, no study on patients' perceptions of photography in dermatology has been performed to date. OBJECTIVES: Firstly, to evaluate patients' perceptions of medical photography. Secondly, to assess whether perceptions differed between patients in our adult department and parents accompanying a child in our paediatric department. METHODS: An opinion survey was conducted at the Hospital of Tours (France) among adult patients (adult department) and accompanying parents (paediatric department) by completion of a questionnaire after any medical photography had been performed. RESULTS: We collected 272 questionnaires regarding 158 adults and 114 children. A camera used only in the department, and storage of the images in the department's records were the most accepted modalities (> 90%), especially in the paediatric survey. Respondents agreed with the sharing of the images with other practitioners and in medical meetings (> 85%) rather than distribution via publications (58·3%), e-mails (45·5%), health magazines (44·3%) and websites (32·0%). Most (78·8%) considered that the consent form should list all the possible uses of the images. Need for renewed consent for each use of the images was significantly more often expressed in the paediatric than the adult survey (44·5% vs. 24·5%, P = 0·001). More than 95% of respondents considered medical photography to be useful for improving diagnosis, monitoring of skin disease and aiding teaching. CONCLUSIONS: These findings could be used to improve practice, to increase the acceptability of medical photography and for devising a standardized consent form for medical practitioners performing medical photography.