Melanoma and intellectual disability: do prognostic factors at diagnosis differ from general population?

BACKGROUND: Few melanoma cases are reported in individuals with intellectual disability (ID), and prognostic factors at diagnosis are unknown in this population. This work was designed to investigate whether prognostic factors at diagnostic are different in patients with ID compared with a general population. METHODS: Melanoma cases retrieved from Hérault's Tumour Registry (HTR) from 1995 to 2015 were cross-referenced against a list of adult patients with ID, living in Hérault. Major prognostic factors were compared with those in non-ID melanoma patients included in HTR and in patients followed by Montpellier University Hospital and included in the Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome (RIC-Mel) database. RESULTS: Ten melanoma cases in individuals with ID were identified and compared with 3804 non-ID melanoma cases in HTR and 1024 non-ID melanoma cases included in RIC-Mel. Mean Breslow thickness at diagnosis was 4.6 mm in melanoma cases among those with ID versus 1.89 mm in HTR (P = 0.109) and 2.36 mm in RIC-Mel (P = 0.156). Stage at diagnosis was superior to stage IIB in 42.9% of ID cases versus 11.4% of non-ID cases in HTR (P < 0.05) and 8.5% in RIC-Mel (P < 0.05). CONCLUSIONS: Melanomas in patients with ID had less favourable prognostic factors at diagnosis, including higher Breslow thickness and more advanced stage, than melanomas in non-ID patients. These adverse prognostic factors indicate a later diagnosis in this population, leading to a poorer prognosis. This work underlines the need to improve melanoma screening among individuals with ID.

[Management of immune-related toxicities associated with immune checkpoints inhibitors: Data from the multidisciplinary meeting « ToxImmun ¼ in Eastern Occitania]. / Gestion des toxicités induites par les inhibiteurs de checkpoint immunologique : données de la réunion de concertation pluridisciplinaire « ToxImmun ¼ en Occitanie Est.

Immune checkpoint inhibitors (ICIs) can cause numerous and complex immune-related adverse events whose management need a multidisciplinary approach. Herein, we investigated 114 requests, mostly concerning patients suffering from lung cancer, that were submitted to the « ToxImmun ¼ multidisciplinary meeting in Eastern Occitania between December the 17th 2018 and January the 20th 2020. The leading reasons for the request concerned the putative causal link between immunotherapy and immune-toxicity and its management, followed by possible retreatment after temporary withdrawn because of adverse event, and finally the possibility to initiate ICIs in patients with pre-existing autoimmunity. Colitis, hepatitis and myocarditis were the most frequent immune-related adverse events (IRAEs), both all grade and grade 3-4. Sicca syndrome (with or without Sjogren criteria) was also frequent (26% of cases) and seems to be associated with severe toxicity and multi-toxicity. The mean time to first IRAE was 3.8 months, a time shortened with the use of anti-PD-L1 agents or ICI combination. A majority of requests came from initial evaluation by the internist confirming the early and main role of this specialty in the management of immunotoxicity. Expansion of this regional multidisciplinary meeting, coordinated by internists and medical oncologists, could improve management of immune-related adverse events for the patients' benefits.

Can postoperative calcemia kinetics predict the risk of hypocalcemia for the management of parathyroid adenoma in ambulatory surgery?

INTRODUCTION: The goal of this study was to analyse the kinetics of corrected calcemia levels (Cac) after parathyroid excision and to determine the percentage of variation (ΔCa) in the initial hours after surgery, in order to entertain an early discharge. POPULATION AND METHODS: Were included in this study, patients undergoing operation for parathyroid adenoma responsible for primary hyperparathyroidism (PHP). The Cac was measure preoperatively and four hours after surgery, and then every day until patient discharge. Group A included patients for whom the Cac was inferior to 2.2mmol/L at least once postoperatively while group B included patients for whom the Cac was always equal or superior to 2.2mmol/L. The ΔCa represented the percentage of the fall in postoperative Cac with respect to preoperative Cac. RESULTS: Between 2010 and 2017, 156 patients fulfilled the inclusion criteria (women 80.8%, [sex ratio 1:4], median age 64 years old). Preoperative Cac was statistically significantly lower in group A compared to group B (2.67 vs. 2.82mmol/L; P<0.0001). In total, 9.6% of patients had calcium supplementation for hypocalcemia, symptomatic or not. Postoperative Cac reached its nadir value on postoperative day 2. At four hours postoperative, the risk of postoperative calcelmia falling below 2.2mmol/L appeared when the ΔCa was superior to 6% with a sensitivity of 92.9% and a negative predictive value of 97.4%. CONCLUSION: After excision of a parathyroid adenoma for PHP, the Cac falls rapidly and reaches its nadir value on day 2. If the fall in calcemia is less than 6% four hours after surgery (vs. preoperative level), early discharge within the framework of ambulatory surgery is possible.

[Frequency of contact sensitization to modern dressings used to treat chronic leg ulcer]. / Fréquence des sensibilisations de contact aux pansements modernes utilisés sur les ulcères de jambe.

INTRODUCTION: Allergic contact dermatitis around chronic leg ulcers (CLU) is a common complication in patients presenting CLU and prolongs healing times. The aim of this study was to describe the rate of sensitization to modern dressings (MD) used in these patients and to assess whether there is a relation between the number of sensitizations and ulcer type, the time from onset of the ulcer, and patient age and gender. PATIENTS AND METHODS: We conducted a retrospective study at Reims University Hospital between 2010 and 2014 that included all patients with CLU of vascular etiology surrounded by eczematous lesions, and who had one of the patch-tests in the following 3 series: European baseline±leg ulcers±corticosteroids. RESULTS: Among the 73 patients included, 43 % were polysensitized. Thirty-three patients (45 %) were sensitized to MD (38 % to hydrocolloids, 18 % to hydrogels, 7 % to hydrocellular dressings, 7 % to hydrofiber dressings, 5 % to contact layers and 3 % to alginates). Median age and sex did not differ between "polysensitized" patients and "non-polysensitized" patients (P=0.84 and P=0.25, respectively). Polysensitization was more frequent among patients presenting ulcers for more than 5 years (P=0.032). CONCLUSION: Practically half of all patients presenting CLU with surrounding contact dermatitis had sensitization to modern dressings (mostly hydrocolloids and hydrogels). The rate of sensitization increased with the length of presence of CLU.

Life history and ecology of the elusive European short-snouted seahorse Hippocampus hippocampus.

To improve the understanding of the life history and ecology of one of Europe's most elusive fishes, the short-snouted seahorse Hippocampus hippocampus, data from wild populations in a shallow coastal lagoon in southern Portugal were analysed. The data were collected from 17 tagged seahorses on a focal-study grid as well as from >350 seahorses encountered during underwater visual surveys and a fishery-independent study using beach seines. These populations of settled juveniles and adults had a mean population density of 0·009 m-2 . During the study period (2000-2004), reproduction peaked in July and August. Juveniles recruited to the lagoon at c. 66 mm standard length (LS ) and 0·5 years of age and established small home ranges (0·8 to 18·2 m2 ). First reproduction was estimated at 100 mm and 1 year of age. Based on a fitted von Bertalanffy model, H. hippocampus grew quickly (growth coefficient K = 0·93) to a maximum theoretical size L∞ = 150 mm and have a maximum lifespan of c. 3·2 years. Courtship behaviours were consistent with the maintenance of pair bonds and males brooded multiple batches of young per year. Estimated annual reproductive output averaged 871 young (±632). Together these analyses provide the first life-history parameters for this species and indicate that H. hippocampus bears characteristics of opportunist and intermediate strategists. Such populations are predicted to exhibit large fluctuations in abundance, making them vulnerable to extended periods of poor recruitment.

[Innovative therapies for metastatic melanoma in elderly patients]. / Place des traitements innovants du mélanome métastatique chez le sujet âgé.

The mortality rate for malignant melanoma is higher in elderly patients aged 75 years or more, with over 25% of melanomas being diagnosed in this population. This poorer prognosis might perhaps be improved by emerging targeted therapies and immunotherapy, although these agents must be prescribed with care in this rather fragile population. The purpose of our review of the literature concerning phase-2 and -3 published trials of these innovative molecules was to examine their optimal use in elderly patients presenting metastatic malignant melanoma. Most of the trials examined included elderly patients and some were analyzed by age sub-groups. In conclusion, elderly patients with ECOG 0/1 status can be given ipilimumab or vemurafenib as first-line therapy depending on tumoral BRaf mutation status. The benefit of combined targeted therapies does not seem to apply consistently in elderly patients and their use must be discussed. Further specific data must be collected in elderly patients concerning anti-PD1 molecules. For more fragile patients, risk scales or scores should enable more accurate use of innovative therapies in metastatic melanoma. Moreover, physicians must be aware of the common drug interactions with targeted therapies, since elderly patients are often taking several concomitant drugs.

Clinical and histological features of head and neck melanoma: a population-based study in France.

BACKGROUND: Head and neck melanomas (HNMs) account for an increasing proportion of melanomas and have a poor prognosis. OBJECTIVES: To compare the clinical and histological characteristics of HNMs with those of melanomas at other sites (MOS), and to identify pertinent clinicopathological subgroups of HNM. METHODS: A retrospective population-based study of incident in situ and invasive melanomas in the period 2004-2011 was performed. RESULTS: HNMs represented 26·7% of 1548 melanomas, corresponding to a density ratio of 3·7 between HNMs and MOS. HNMs occurred later than MOS (71·2 vs. 58·4 years; P < 0·01), included a higher proportion of in situ cases (49·6% vs. 13·5%; P < 0·01) and were mainly lentigo malignant melanomas (73·0% vs. 2·6%; P < 0·01). Invasive HNMs included a higher proportion of thick (> 2 mm) tumours [33·7% vs. 24·1% (P = 0·01); mean Breslow thickness: 2·18 vs. 1·77 mm (P = 0·03)] and nodular melanomas (20·1% vs. 12%; P < 0·01). HNMs in the peripheral area of the head and neck differed from those of central location by a younger age of onset (65·2 vs. 72·4 years; P < 0·01), male predominance (64·4% vs. 33·8%; P < 0·01), and higher proportions of invasive (67·2% vs. 42%; P < 0·01) and nodular (15·1% vs. 7·5%; P = 0·01) melanomas. CONCLUSIONS: HNMs highly differ from MOS, and are clinically and histologically heterogeneous, possibly as a consequence of different patterns of sun exposure. These data could help to improve primary and secondary prevention messages for patients and doctors.

[Post-traumatic acral melanoma: an underestimated reality?]. / Mélanome acral post-traumatique : une réalité sous-estimée ?

BACKGROUND: The role of trauma in the physiopathology of malignant melanoma remains controversial. We report a case of acral melanoma in which a characterized trauma seems implicated in tumour progression; we performed a review of the literature. PATIENTS AND METHODS: A 73-year-old male consulted for a lesion of his right big toe. Physical examination revealed a dystrophic and hyperkeratotic nail destroyed by a growing lesion. Histological study showed an ulcerated superficial spreading melanoma with a Breslow thickness of 4mm. He had previously had this same toe broken, leaving gradually worsening dystrophy of the nail; the toe was injured again spontaneously and by partial removal of the nail tablet. DISCUSSION: A number of cases of "post-traumatic" melanomas have been reported. This hypothesis, though widely admitted for other tumours, remains debated for melanomas mainly because of possible recall bias. In this patient, there was a clear continuum of the lesion as well as topographic correspondence between the initial trauma, the remaining dystrophy and the appearance of the melanoma. Case-control studies have identified trauma as an independent risk factor for acral melanoma with a high relative risk; such risk is multiplied for repeated trauma, suggesting a "dose-effect" relationship. Trauma could act as the promotional stage of melanoma mediated by cytokines released during wound healing or it could cause direct activation of micro-vascular tumour cell transport. CONCLUSION: Our observation and literature research provide convincing arguments for a role of trauma in the development of acral melanomas. Dermatologists must pay attention to any unusual changes in an old scar.

Outbreak of tularaemia in brown hares (Lepus europaeus) in France, January to March 2011.

We report an outbreak of tularaemia in brown hares (Lepus europaeus) in France, which occurred from January to March 2011 and was characterised by a high mortality rate in the local hare population. In France, hare tularaemia is usually sporadic and does not significantly affect hare populations. The epizootic form of the outbreak reported here led us to reconsider the potential associated risks for hare populations and public health.

Prospective X-ray densitometry and ultrasonography study of the hand bones of patients with rheumatoid arthritis of recent onset.

OBJECTIVE: Bone demineralization observed in early rheumatoid arthritis is not easily measured. To measure bone loss and to discriminate between rheumatoid arthritis and other rheumatic diseases, we used two methods: dual-energy X-ray absorptiometry and ultrasonography. METHODS: From a population-based recruitment, 32 patients with early peripheral polyarthritis (median disease duration: 4 months) were studied. Clinical, laboratory, functional, hand-bone assessments were made at the entry an at months 6 and 12. Bone X-ray densitometry measurements were made on 16 areas of the hand. Speed of sound was measured across the proximal phalanges of the four fingers. X-rays of both hands were scored according to the modified Sharp's score. At 12 months, patients were classified as rheumatoid arthritis (N = 15; 9 F) or as other rheumatic diseases. RESULTS: We found: 1) significantly decreased bone mineral density (BMD) of the whole hand, in the rheumatoid arthritis group versus the other rheumatic diseases group, at 6 and 12 months (P < 0.05); 2) no significant decrease of bone mineral density (BMD) in other areas in the rheumatoid arthritis group; 3) no significant change of ultrasounds in either group; and 4) no significant correlation between the decrease of BMD in the rheumatoid arthritis group and clinical, biological or radiologic parameters, except for IFNgamma, whose production in whole blood cell culture was lower at entry in the rheumatoid arthritis group. CONCLUSION: DEXA bone assessment in rheumatoid arthritis was able t detect bone loss in the whole hand at 6 months.

Keratectasia induced by laser in situ keratomileusis in keratoconus.

PURPOSE: Corneal thinning disorders weaken the mechanical strength of affected corneas, suggesting that photorefractive procedures may be contraindicated in keratoconus. Few cases have been reported to confirm this hypothesis. METHODS: A 45-year-old man had two laser in situ keratomileusis (LASIK) procedures and one photorefractive keratectomy (PRK) performed on his left eye, and three LASIK procedures on his right eye. After these surgeries, a dramatic corneal ectasia and grade III haze occurred in both eyes, with a clinical diagnosis of keratoconus. The changes in his corneas were followed with videokeratography and slit-lamp microscopy. RESULTS: Preoperative videokeratograph of both eyes suggested keratoconus. After multiple refractive procedures, the best spectacle-corrected visual acuity was as low as 20/1200 bilaterally. Both eyes displayed dramatic corneal protrusion with corneal scarring. CONCLUSIONS: This case emphasizes the need for preoperative corneal thickness measurement and detailed analysis of videokeratographs. Thinning corneal disorders such as keratoconus, keratoconus suspects, or pellucid marginal degeneration are a contraindication for excimer laser ablative refractive procedures.

[Primary hypothyroidism revealing pseudohypoparathyroidism without hypocalcemia and hyperphosphoremia]. / Hypothyroïdie compensée révélant une pseudohypoparathyroïdie en l'absence d'hypocalcémie et d'hyperphosphorémie.

BACKGROUND: Type la pseudohypoparathyroidism is due to a molecular defect causing Gs protein deficiency. It is responsible for multi-hormonal resistance and skeletal abnormalities. Parathyroid hormone resistance can be subtle so that the diagnosis can be difficult in patients with atypical manifestations. CASE REPORT: A 10-year-old boy was first referred for growth retardation (height standard deviation score: -2.8). He had short metacarpals, and scaphocephaly. Laboratory findings revealed an elevation of plasma TSH (8,8 microU/mL) with normal thyroid hormone levels. The investigations ruled out common causes of compensated hypothyroidism. Despite normal blood calcium and phosphate levels, parathyroid hormone was elevated to 358 pg/mL (normal values: 10-60) without renal failure, suggestive of hormonal resistance. The diagnosis of pseudohypoparathyroidism type la was confirmed by a 50% reduction of Gs activity. Melanodermia, associated with an elevation of ACTH was suggestive of ACTH resistance without MSH resistance. Moreover, skeletal radiography showed a narrow lumbar canal. CONCLUSION: Type la pseudoypoparathyroidism could be part of the etiological diagnosis of primary hypothyroidism, even in the absence of hypocalcemia and hyperphosphatemia. Similarly, skeletal abnormalities extend beyond the classical features of Albright's osteodystrophy.