Biallelic germline mutations in MAD1L1 induce a syndrome of aneuploidy with high tumor susceptibility.

Germline mutations leading to aneuploidy are rare, and their tumor-promoting properties are mostly unknown at the molecular level. We report here novel germline biallelic mutations in MAD1L1, encoding the spindle assembly checkpoint (SAC) protein MAD1, in a 36-year-old female with a dozen of neoplasias. Functional studies demonstrated lack of full-length protein and deficient SAC response, resulting in ~30 to 40% of aneuploid blood cells. Single-cell RNA analysis identified mitochondrial stress accompanied by systemic inflammation with enhanced interferon and NFκB signaling both in aneuploid and euploid cells, suggesting a non-cell autonomous response. MAD1L1 mutations resulted in specific clonal expansions of γδ T cells with chromosome 18 gains and enhanced cytotoxic profile as well as intermediate B cells with chromosome 12 gains and transcriptomic signatures characteristic of leukemia cells. These data point to MAD1L1 mutations as the cause of a new variant of mosaic variegated aneuploidy with systemic inflammation and unprecedented tumor susceptibility.

Nutritional Predictors of Mortality after 10 Years of Follow-Up in Patients with Chronic Kidney Disease at a Multidisciplinary Unit of Advanced Chronic Kidney Disease.

Nutritional monitoring in advanced chronic kidney disease (ACKD) units provides personalized care and improves clinical outcomes. This study aimed to identify mortality risk factors in chronic kidney disease (CKD) patients on nutritional follow-up in the multidisciplinary ACKD unit. A retrospective cross-sectional observational study was conducted in 307 CKD patients' stage 3b, 4−5 followed-up for 10 years. Clinical and nutritional monitoring was performed by malnutrition-inflammation score (MIS), biochemical parameters (s-albumin, s-prealbumin, and serum C-reactive protein (s-CRP), body composition measured by bioelectrical impedance analysis (BIA), anthropometry, and handgrip strength measurements. The sample was classified into non-survivors, survivors, and censored groups. Of the 307 CKD patients, the prevalence of protein-energy wasting (PEW) was 27.0% using MIS > 5 points, s-CRP > 1 mg/dL was 19.20%, and 27.18% died. Survivors had higher significant body cell mass (BCM%) and phase angle (PA). Survival analyses significantly showed that age > 72 years, MIS > 5 points, s-prealbumin ≤ 30 mg/dL, PA ≤ 4°, and gender-adjusted handgrip strength (HGS) were associated with an increased risk of mortality. By univariate and multivariate Cox regression, time on follow-up (HR:0.97), s-prealbumin (HR:0.94), and right handgrip strength (HR:0.96) were independent predictors of mortality risk at 10 years of follow-up in the ACKD unit. Nutritional monitoring in patients with stage 3b, 4−5 CKD helps to identify and treat nutritional risk early and improve adverse mortality prognosis.

Dynamic assessment of interleukin-6 during hemodialysis and mortality in coronavirus disease-19.

The impact of the newly discovered severe acute respiratory syndrome coronavirus 2 causing coronavirus disease-19 (COVID-19) in hemodialysis patients remains poorly characterized. Some hemodialysis techniques reduce systemic inflammation but their impact on COVID-19 has not been addressed. The aim of this prospective study was to evaluate factors associated with mortality in COVID-19 hemodialysis patients, including the impact of reducing interleukin-6 using a cytokine adsorbent filter. This is a prospective single-center study including 16 hemodialysis patients with COVID-19. All were dialyzed using a polymethyl methacrylate (PMMA) filter. Interleukin-6 levels were obtained before and after the first admission hemodialysis session and at 1 week. Baseline comorbidities, laboratory values, chest X-ray, and treatments were recorded and compared between survivors and non-survivors. Out of 16 patients (13 males, mean age 72 ± 15 years), 4 (25%) died. Factors associated with mortality were dialysis vintage (P = 0.01), chest X-ray infiltrates (P = 0.032), serum C-reactive protein (P = 0.05), and lactate dehydrogenase (P = 0.02) at 1 week, oxygen therapy requirement (P = 0.02) and anticoagulation (P < 0.01). At admission, non-survivors had higher predialysis and postdialysis interleukin-6 levels (P = 0.02 for both) and did not present the reduction of interleukin-6 levels during the dialysis session with PMMA filter that was observed in survivors (survivors vs. non-survivors: 25.0 [17.5-53.2]% vs. -2.8 [-109.4-12.8]% reduction, P = 0.04). A positive balance of interleukin-6 during the admission dialysis was associated with mortality (P = 0.008). In conclusion, in hemodialysis COVID-19 patients, a positive interleukin-6 balance during the admission hemodialysis session was associated with higher mortality.

Treatment of Bowen's disease with photodynamic therapy. Observational study in 171 patients with 5-aminolaevulinic acid (BF-200 ALA) and methyl aminolaevulinate (MAL).

An observational study was carried out in the photodynamic therapy (PDT) section of Fuenlabrada's hospital (Madrid, Spain). Our goal was to investigate the efficacy and safety of PDT in Bowen's disease (BD). Between June 2011-June 2017 171 patients (191 lesions) with diagnosis of BD were enrolled in the study (95 women and 76 men; average age of 74.31 years). Lesions were treated with one 5-aminolaevulinic acid (BF-200 ALA)-PDT or methyl-5-aminolaevulinate (MAL)-PDT cycle of two sessions in one week. A second treatment cycle was performed in cases of clinical persistence at 12 weeks. Our results showed that 47/55 lesions were resolved (84.75%) after one or two ALA-PDT cycle and 75/136 lesions (55.15%) after one or two MAL-PDT cycles, in the 12-month follow-up. In conclusion PDT is a safe and non-invasive treatment option in BD. In addition, our results suggest a better response with ALA-PDT over MAL-PDT. Limits: observational study with a limited number of patients.

Treatment of superficial basal cell carcinoma with photodynamic therapy. Observational study in 22 patients with 5-aminolaevulinic acid and methyl aminolaevulinate.

BACKGROUND: There is limited literature on efficacy in 5-aminolaevulinic acid (BF-200 ALA) and methyl-5-aminolaevulinate (MAL) for superficial basal cell carcinoma (sBCC). AIMS: To investigate the efficacy and safety of PDT in sBCC. METHODS: Analytical observational study between January 2014 and January 2017. Follow-up at 12, 24 and 52 weeks. Lesions were treated with one BF-200 ALA-PDT or MAL-PDT cycle of two sessions in one week. A second treatment cycle, with the same photosensitizer precursor, was performed in cases of clinical persistence at 12 weeks. RESULTS: A total of 22 patients (30 lesions) were enrolled in the study. By sex, 13 men and 9 women. Average age of 72,14 years. In the 12-month follow-up 15/16 lesions were resolved (93,75%) after one or two BF-200 ALA-PDT cycle and 7/14 lesions (50%) after one or two MAL-PDT cycles. In most patients, tolerance to the therapy was good or regular, with no differences between the two groups. No long-term adverse effects were reported. LIMITATIONS: The observational nature and the low number of patients. CONCLUSION: PDT is a safe and non-invasive treatment option in sBCC. Our results suggest a better response with BF-200 ALA-PDT over MAL-PDT, at 12 months of follow-up.

Successful treatment of recalcitrant discoid lupus erythematosus with ustekinumab.

We report a 52-year old woman with a 28-year historyof disfiguring facial discoid lupus erythematosus(DLE), persistent despite both classical therapiesand rituximab. Ustekinumab 45 mg was started incombination with methotrexate and intralesionalcorticosteroids. Methotrexate and intralesionalcorticosteroids were withdrawn 30 months later andustekinumab maintained as monotherapy. Fortyeight months later stable improvement was achievedwithout side effects. Only nine patients with cutaneouslupus erythematosus (CLE) treated with ustekinumabhave been reported to date. Ustekinumab could be apromising alternative in severe and recalcitrant casesof CLE. Possibly, the Th17-inflammation pathway isplaying a role in these patients.

Ectima gangrenoso en paciente portadora de trasplante renal / Ecthyma gangrenosum in a renal transplant recipient

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Angioma serpiginosum: report of an unusual acral case and review of the literature.

We report the case of a 35-year-old woman with deep-red asymptomatic macules on the plantar and dorsal skin of the right great toe. Histopathologic findings were compatible with Angioma serpiginosum. Immunohistochemical stains for estrogens and progesterone receptors were negative. Dermoscopy showed an erythematous parallel ridge pattern with double rows of irregular dots and globules. We report an unusual case of angioma serpiginosum with acral volar skin involvement. The dermoscopic features described may aid in the diagnosis of AS in this specific skin area. Acral volar skin involvement must be included in the clinical spectrum of Angioma serpiginosum and in the differential diagnosis of acral vascular lesions.

Angioma serpiginosum: report of an unusual acral case and review of the literature

We report the case of a 35-year-old woman with deep-red asymptomatic macules on the plantar and dorsal skin of the right great toe. Histopathologic fi ndings were compatible with Angioma serpiginosum. Immunohistochemical stains for estrogens and progesterone receptors were negative. Dermoscopy showed an erythematous parallel ridge pattern with double rows of irregular dots and globules. We report an unusual case of angioma serpiginosum with acral volar skin involvement. The dermoscopic features described may aid in the diagnosis of AS in this specifi c skin area. Acral volar skin involvement must be included in the clinical spectrum of Angioma serpiginosum and in the differential diagnosis of acral vascular lesions.

Validation of dermoscopy as a real-time noninvasive diagnostic imaging technique for actinic keratosis.

OBJECTIVE: To validate dermoscopy as a real-time noninvasive diagnostic imaging technique for actinic keratosis (AK). DESIGN: Prospective study to validate a diagnostic test. SETTING: Dermatology department of a tertiary university hospital in Fuenlabrada, Madrid, Spain. PATIENTS: A total of 178 patients with a clinical diagnosis of AK participated in the study. MAIN OUTCOME MEASURES: An independent blinded comparison was performed between dermoscopy results and histopathological findings, the gold standard for the diagnosis of AK. All the patients underwent both diagnostic tests. RESULTS: One hundred seventy-eight lesions were evaluated. The concordance between dermoscopy results and histopathological findings was 0.917. The sensitivity of dermoscopy for the diagnosis of AK was 98.7%, with a specificity of 95.0%, a positive likelihood ratio of 19.74, and a negative likelihood ratio of 0.01. A diagnostic algorithm that combined follicular openings and erythematous pseudonetwork demonstrated a sensitivity of 95.6% and a specificity of 95.0% for the diagnosis of AK. CONCLUSIONS: The sensitivity and specificity of dermoscopy for the diagnosis of AK were high, as was the concordance between dermoscopy results and histopathological findings. As a real-time noninvasive diagnostic imaging technique for AK, dermoscopy may be incorporated in the management of patients with these lesions.

Dermatomyofibromas presenting in pediatric patients: clinicopathologic characteristics and differential diagnosis.

Dermatomyofibroma represents a rare benign fibroblastic/ myofibroblastic cutaneous tumor that mostly occurs in young adult women. It has been seldom reported in pediatric patients. In this analysis, the clinical, histopathological and immunohistochemical findings of 12 dermatomyofibromas occurring in patients up to 16 years of age are compared with those reported in adults. Six patients were male and six were female. Nine lesions were located on the neck, two on the back and one involved the chest. The usual presentation was as an asymptomatic plaque composed of bland spindled cells arranged in dermal fascicles that were oriented parallel to the epidermis. Immunohistochemically, the lesional cells expressed calponin in 11 cases, smooth muscle actin in six and muscle-specific actin in three. In contrast to prior reports from adults, dermatomyofibromas in pediatric patients do not show a female predilection. In addition, they are mostly located on the neck (56%), while in adults the most frequent location is the shoulder (35%). Dermatomyofibromas seem to stabilize after an initial period of enlargement. Punch biopsy and clinical follow up could be an alternative approach to the surgical excision in some cases of dermatomyofibroma, particularly in instances in which surgery might inflict cosmetic defects.

Long-term management of erythrodermic psoriasis with anti-TNF agents.

Erythrodermic psoriasis is a chronic condition that is difficult to treat. Biological agents offer a new alternative, but there are no controlled trials to support their use; there are a few reports of patients treated with these agents, but often only with short term results. We report a 68-year-old man with erythrodermic psoriasis and ankylosing spondylitis, treated with infliximab for 48 weeks and then low-dose etanercept monotherapy for 34 additional months. Excellent results were obtained for both conditions without significant side effects. We think etanercept can be a good therapeutic option for long-term control of erythrodermic psoriasis.