The Hospital of the Future in 10 points. / El hospital del futuro en 10 puntos.

Over the course of 2018 and 2019, the Spanish Society of Internal Medicine carried out a project called "The Future Hospital." Based on cumulative knowledge on the Spanish National Health System, this project seeks to transfer the observations on the organization of healthcare in future hospitals made by the Royal College of Physicians in the United Kingdom to the context of the Spanish healthcare system. The project's participants included numerous scientific and medical societies, professional associations in the health sector, and patient associations. This aim of this article is to highlight, in 10 points, predictions that arose from this project that we consider to be the most relevant, reserving the last point for the challenges for the field of internal medicine that can be surmised from these proposals.

First month prednisone dose predicts prednisone burden during the following 11†months: an observational study from the RELES cohort.

AIM: To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2-12). METHODS: 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2-12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2-12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2-12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). RESULTS: Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2-12 dose categories (p<0.001). The cumulative prednisone-1 dose was directly associated with the cumulative prednisone-2-12 dose (p<0.001). Compared with patients on no prednisone, patients taking medium (adjusted OR 5.27, 95% CI 2.18 to 12.73) or high-dose prednisone-1 (adjusted OR 10.5, 95% CI 3.8 to 29.17) were more likely to receive prednisone-2-12 doses of >7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of ≥6, the model did not change. CONCLUSION: The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months.

Identification of miRNAs as potential modulators of tissue factor expression in patients with systemic lupus erythematosus and antiphospholipid syndrome.

BACKGROUND: Tissue factor (TF) is the main initiator of the coagulation cascade and elements that may upregulate its expression might provoke thrombotic events. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are autoimmune diseases characterized by a high TF expression in monocytes. OBJECTIVES: To examine the role of microRNAs (miRNAs) in TF expression and to evaluate their levels in SLE and APS patients. METHODS: An in silico search was performed to find potential putative binding sites of miRNAs in TF mRNA. In vitro validation was performed transfecting cells expressing TF (THP-1 and MDA-MB-231) with oligonucleotide miRNA precursors and inhibitors. Additionally, reporter assays were performed to test for the binding of miR-20a to TF mRNA. Levels of miRNAs and TF were measured by quantitative (qRT-PCR) in patients with APS and SLE. RESULTS: Overexpression of miRNA precursors, but not inhibitors, of two of the members of cluster miR-17∼92, for example miR-19b and miR-20a, in cells expressing TF decreased TF mRNA, protein levels, and procoagulant activity between 30% and 60%. Reporter assays showed that miR-20a binds to TF mRNA. Finally, we measured levels of miR-19b and miR-20a in monocytes from patients with APS and SLE and observed significantly lower miRNAs levels in comparison with healthy subjects inversely correlated with the levels of TF. CONCLUSIONS: Down-regulation of miR-19b and miR-20a observed in patients with SLE and APS could contribute to increased TF expression and thus provoke the hypercoagulable state characteristic of these patients.

The naevus count on the arms as a predictor of the number of melanocytic naevi on the whole body.

A study of melanocytic naevi was carried out in southern Spain to examine the relationship between numbers of naevi at different body sites as predictors of whole-body naevus count and to determine whether the naevus count on the arms is valid for identifying the risk factors for total naevi. Subjects were the control group from a case-control study on risk factors for cutaneous melanoma. They were selected from visitors to the University of Granada Hospital (southern Spain) between 1989 and 1993. Of 200 people invited to participate, 146 accepted (73%). Data were collected by personal interview, and melanocytic naevi were counted over the entire body surface by clinical skin examination performed by one dermatologist. Partial correlation coefficients (R) estimated by multiple linear regression were calculated. Comparisons between whole-body naevi and naevi on the arms, and their relationship with risk factors, were assessed by analysis of variance and covariance. Arms in men (adjusted R = 0.88) and thighs in women (adjusted R = 0.82) were the best predictors of total naevi after adjusting for age and sun exposure. Age, occupational and leisure sun exposure, and sunburns showed significant correlations with the total number of naevi. Similar results were found for the naevus count on the arms. In conclusion, the prediction of whole-body numbers of naevi by a naevus count on specific sites differs between men and women: arms in men and thighs in women are the best predictors. Nevertheless, naevus counts on the arms allowed us to study the risk factors for total naevi as well as whole-body naevus count: age and occupational sun exposure were the strongest determinants.

Autoimmune progesterone dermatitis: treatment with oophorectomy.

Autoimmune progesterone dermatitis is a rare manifestation of hypersensitivity to endogenous hormones with polymorphic clinical manifestations. We report a 28-year-old woman with a 5-year history of mucocutaneous erythema multiforme occurring cyclically in the premenstrual period. Progesterone sensitivity was demonstrated by challenge test with medroxyprogesterone acetate. Treatments with oestrogens, tamoxifen and triptorelin had to be withdrawn because of intolerable adverse effects. Oophorectomy finally cured the disease.

Melanocytic nevi and risk of cutaneous malignant melanoma in southern Spain.

The main objective of this study was to assess whether cutaneous malignant melanoma (CMM) shows a stronger relation with the melanocytic nevi count at the site where CMM was diagnosed than with the melanocytic nevi count at other sites, stratifying by histologic CMM type, in a southern Mediterranean population. Cases and controls were selected from a population in southern Spain in 1988-1993. The study population included 116 incident cases with non-familial CMM (International Classification of Diseases 9th Revision (ICD-9) code 172), and 116 controls matched 1:1 for sex and age (+/- 4 years). Data were collected by personal interview, and melanocytic nevi were counted over the entire body surface by clinical skin examination performed by a dermatologist. Crude and multiple risk factor-adjusted odds ratios and 95% confidence intervals were computed by conditional logistic regression analysis. After adjustment by skin type, unexposed skin color, and sun exposure, CMM was found to occur significantly more frequently in individuals with a high number of melanocytic nevi at the same site where CMM originated (odds ratio (OR) for >8 nevi = 12.0, 95% confidence interval (CI) 1.3-108.2). The ability to predict the number of melanocytic nevi on different anatomic sites on CMM, but excluding the CMM cases on each corresponding site, was also examined. A significant trend with the number of nevi on the anterior surface of thighs was found (OR for >4 nevi = 4.5, 95% CI 1.4-14.9). Melanocytic nevi count on the melanoma site was the variable most closely related to superficial spreading melanoma subtype (SSM) (OR for >8 nevi = 82.19, 95% CI 2.72-2,454). On the other hand, the number of melanocytic nevi on the melanoma site was unrelated to risk of CMM subtypes other than SSM. These results support the hypothesis that nevi are an important risk factor for melanoma, especially SSM, in populations with a darker ethnic background.

Linear IgA disease in a patient with bladder carcinoma.

We report a patient with a transitional bladder carcinoma who developed a widespread blistering eruption. The lesions showed immunopathological findings characteristic of linear IgA disease with a good response to sulphapyridine. The relationship between linear IgA disease and neoplasia has been the subject of several reports suggesting that this association is not due to chance.

Sun exposure, pigmentary traits, and risk of cutaneous malignant melanoma: a case-control study in a Mediterranean population.

The main objective of this study was to assess the influence of sun exposure and pigmentary traits on the risk of cutaneous malignant melanoma (CMM) in a Mediterranean population (Andalusia, southern Spain). Cases and controls were selected from 1988 to 1993. The study population included 105 incident cases with non-familial CMM (ICD-9 code 172) and 138 controls aged 20 to 79 years. Data were collected by personal interview, and melanocytic nevi were counted over the entire body surface. Crude, and multiple-risk factor adjusted, odds ratios (OR) and their 95 percent confidence intervals (CI) were computed. After adjustment, the major constitutional risk factor was skin type I-II (OR = 29.8, CI = 8.9-100) compared with skin type V. Statistically significant and positive trends were observed between the risk of CMM and occupational sun exposure of the skin (P = 0.003), recreational exposure (P < 0.001), and cumulative lifetime sun exposure (P < 0.001). Several characteristics related to sun exposure during summer increased the CMM risk, e.g., episodes of blistering sunburns and the number of sunbaths in childhood. Use of sunscreens and spending summer holidays in places other than beach were associated with a lower risk of CMM. Regarding pigmentary traits, CMM significantly occurred with more frequency in individuals with a high degree of freckling and quoted numbers of melanocytic nevi. In conclusion, the results support sun exposure and pigmentary traits (skin type, melanocytic nevi, and freckles) as main risk factors for CMM in this population.

Thrombosis and antiphospholipid syndrome: a preliminary assessment of three antithrombotic treatments.

To assess retrospectively three antithrombotic treatments in the secondary prevention of thrombosis in the antiphospholipid syndrome (APS), 23 patients (six systemic lupus erythematosus, seven lupus-like disease and 10 primary antiphospholipid syndrome) were included in this study. Treatments assessed were: (1) aspirin 75 mg daily, (2) warfarin (international normalised ratios (INRs) 2.0-2.9) +/- aspirin 75 mg daily, and (3) warfarin (INRs > 2.9) +/- aspirin 75 mg daily. Where patients had received two or three of these treatments successively, the periods of time on each treatment were added and the number of patients with recurrence(s) on each treatment were compared by Fisher's exact probability test. 'High' anticoagulation (INRs > 2.9) +/- aspirin 75 mg daily was more effective than aspirin 75 mg daily, there was a trend in favour of 'high' anticoagulation (P = 0.066). No statistically significant difference could be demonstrated when comparing 'low' anticoagulation +/- aspirin 75 mg daily with aspirin 75 mg daily (P = 0.092). These results suggest that aggressive anticoagulation with or without low-dose aspirin is effective in preventing further thromboembolic events in APS.

Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether the occurrence of seizures is correlated with the presence of serum antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE) patients. METHODS: The study included 221 unselected patients with SLE. Of these, 21 patients with epileptic seizures not attributed to any cause other than SLE were identified. Epilepsy was diagnosed by clinical history and electroencephalography. Blood samples were tested for the presence of antibodies to cardiolipin (aCL, IgG and IgM isotypes) and lupus anticoagulant (LAC). RESULTS: LAC was detected in 43.8% of the patients with epilepsy and in 20.8% of controls (P = 0.057). A statistically significant association was found between moderate-to-high titers of IgG aCL and the presence of seizures (P = 0.02). Brain computed tomography and/or magnetic resonance imaging scanning was performed in 14 patients. All patients with abnormal features found on these tests had positive aPL (P = 0.03). Nine patients (42.9%) had at least 1 of the classic features associated with the aPL syndrome. CONCLUSION: We confirmed that epilepsy as a primary neuropsychiatric event is significantly associated with moderate-to-high titers of IgG aCL in SLE patients. Our results suggest that aPL could have a role in the etiopathogenesis of epilepsy in SLE.

[Thyroid lymphoma in a 51-year-old woman]. / Linfoma de tiroides en una mujer de 51 años.

Thyroid gland is an uncommon site for involvement by lymphoma. Because of the lack of specific histopathologic criteria for diagnosis, thyroid lymphomas are not usually diagnosed until a thyroidectomy is done, even when a fine-needle aspiration biopsy is performed before surgery. We report the case of a woman with a non-Hodgkin lymphoma presenting as thyroid enlargement with systemic manifestations of the disease. The preoperative histologic diagnosis was poorly differentiated thyroid carcinoma. If the lymphoma was primarily thyroid or the involvement of thyroid was a part of the generalized dissemination of a nodal non-Hodgkin lymphoma is difficult to establish. She was treated with a combination of surgery and chemotherapy with excellent outcome. We comment the problems in the diagnosis of this disease.

Muir-Torre syndrome associated with a family history of hyperlipidemia.

The Muir-Torre syndrome is a rare disorder characterized by sebaceous neoplasms of the skin and multiple visceral malignancies. The syndrome appears to be a familial, autosomal dominant condition. We diagnosed this syndrome in a previously unreported patient and found a personal and family history of malignancies and hyperlipidemia. The association of Muir-Torre syndrome with a family history of hyperlipidemia, another autosomal dominant condition, has not been previously reported. The possible genetic relationship between the two disorders is discussed.