Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas.

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas. / [Artículo traducido] Experiencia con bexaroteno en linfoma cutáneo de células T: un estudio del Grupo Español de Linfomas Cutáneos (GELC).

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.

BACKGROUND: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE: To identify prognostic factors for specific survival in patients with PCALCL. METHODS: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011). CONCLUSION: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL.

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

Coexistence of marginal zone cutaneous B-cell lymphoma and classic Hodgkin disease: does a biological relationship exist?

The coexistence of non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) in the same patient, although previously reported, is very unusual. This situation is extremely rare when the first diagnosis is a cutaneous B NHL, and exceptional if there is no personal background of cytostatic treatment. We report a 44-year-old man who developed cutaneous nodules over a period of two years. A marginal zone cutaneous B-cell lymphoma was diagnosed. On staging investigation a mass in the lingual tonsil was found and excision biopsy showed a classical Hodgkin lymphoma.

[Imaging fractures: more than just delineating fracture lines]. / Radiología de las fracturas: algo más que un trazo.

Skeletal trauma accounts for a high percentage of cases in daily clinical practice, especially in emergency departments. It is important not to limit radiology reports to the fracture. Radiologists must be familiar with the principles of bone trauma and elaborate concise reports that describe the complete extent of each lesion.This article aims to describe some of the patterns with which fractures present on plain-film radiographs, taking into account bone displacement, types of associated fractures, associations of fractures with luxations, soft-tissue lesions, and indirect signs. Likewise, we emphasize the need to perform computed tomography or magnetic resonance imaging studies in certain cases.

Examining perceptions, selections, and products in undergraduates' learning from multiple resources.

BACKGROUND: When learning about complex topics using the Internet, students commonly encounter a multitude of textual, non-textual (e.g., images and graphs), and multimedia (e.g., videos) resources. Yet students' learning from multiple texts and multiple (non-textual) resources (MT-MR learning) has received insufficient consideration in the literature. AIMS: We examine the associations among (1) undergraduates' conceptions of reasons for multiple resource access, (2) log-data of resource use when completing a MT-MR task, and (3) writing performance. SAMPLE: Participants were 72 undergraduate students in the United States. METHODS: Undergraduates were provided with a library of five texts and one video, with the option of accessing supplemental data (e.g., graphs and maps) in association with each resource. Log-data (e.g., time and supplemental data access) of undergraduates' resource use were collected. Undergraduates were then asked to compose a research report and to describe what they considered the purpose of multiple resource access to be. RESULTS: Four types of conceptions were identified, reflecting a desire to (1) access a lot of information, (2) understand multiple perspectives, (3) corroborate and evaluate information, and (4) develop a personal understanding of a given topic. Undergraduates who considered corroboration and evaluation to be the purpose of multiple resource access were more likely to access more supplemental data sources and performed better on a multiple resource learning task. CONCLUSIONS: Undergraduates in our sample held conceptions largely similar to, but in some aspects distinct from, those identified by Barzilai and Zohar (Cognit Instruct, 30, 2012, 39). Conceptions were associated with resource access during task completion and with writing performance.

Cutaneous expression of systemic candidiasis.

Skin lesions associated with Candida septicaemia occur only in a minority of patients, who are usually immunocompromised, but they can help to establish a diagnosis rapidly. The lesions form a characteristic maculopapular or nodular rash at the onset of the infection. We report three cases of systemic candidiasis (SC) with cutaneous manifestations in immunocompromised patients. In these patients, the lesions started as asymptomatic or slightly pruriginous macules, papules or nodules localized on the trunk and extremities. The patients' general condition was very poor and they presented a high fever at the onset of the illness. Candida spp. were isolated from blood in all cases, and histology showed yeasts in two of them. Most of the lesions resolved with antifungal treatment. The diagnosis of SC is often delayed or missed because of the absence of useful diagnostic tools, the varying clinical manifestations and the frequent negativity (50-75%) of blood cultures for Candida. Fluconazole is the treatment of choice for Candida albicans, but treatment response is unknown for other Candida spp., which may require treatment with amphotericin B.

Stage IV cutaneous acute graft-versus-host disease. Clinical and histological study of 15 cases.

BACKGROUND: The most severe form of cutaneous acute graft-versus-host disease (aGVHD), stage IV, is characterized by the appearance of vesicles and blisters. OBJECTIVE: To describe the clinicopathological characteristics and evolution of stage IV cutaneous aGVHD presented in our hospital. METHOD: Retrospective study. The following criteria for inclusion were applied: (i) patients subjected to allogeneic stem cell transplantation between 1st January 1984 and 31st of December 2006; (ii) development of vesicles and/or blisters; (iii) extracutaneous coincidental aGVHD manifestations; and (iv) presence of histopathological features consistent with aGVHD. RESULTS: Fifteen cases (10 females and 5 males) were studied. The mean age was 38.1 years. The lesions appeared after a median interval of 19 days, always following a milder stage of GVHD. Two patterns of clinical evolution were found. Mucosal involvement was observed in nine patients. Nikolsky's sign was positive in eight patients. Nine of the patients had biopsies of the vesiculobullous stage which showed a subepidermal blister with epidermal necrosis and basal vacuolar degeneration. Only two patients survived. CONCLUSION: Stage IV cutaneous aGVHD is a severe and unusual complication after haematopoietic stem cell transplantation. Prognosis is poor with a very high mortality rate, although the cause of death is varied and not strictly linked to the cutaneous disease.

Definition of treatment-resistant depression - Asia Pacific perspectives.

BACKGROUND: The lack of uniformity in the definition of treatment resistant depression (TRD) within the Asia-Pacific (APAC) region may have implications for patient management. We aimed to characterize the most commonly used TRD definition in selected APAC countries. METHODS: A systematic literature review of TRD definitions in APAC countries was conducted in Medline and Embase (2010-2016) and conference proceedings (2014 and 2016). TRD guidelines (APAC, Europe regional, US, or international) were also searched. An expert-panel explored APAC nuances in TRD definitions to achieve consensus for a regional-level definition. RESULTS: Ten guidelines and 89 studies qualified for study inclusion. Among the studies, variations were observed in definitions regarding: number of antidepressants failed (range: ≥1 to ≥3), classes of antidepressants (same or different; 59% did not specify class), duration of previous treatments (range: 4-12 weeks), dosage adequacy, and consideration of adherence (yes/no; 88% of studies did not consider adherence). No TRD-specific guidelines were identified. The emerging consensus from the literature review and panel discussion was that TRD is most commonly defined as failure to ≥2 antidepressant therapies given at adequate doses, for 6-8 weeks during a major depressive episode. LIMITATIONS: Few studies provided definitions of TRD used in daily clinical practice, and a limited number of countries were represented in the included studies and expert panel. CONCLUSION: Attaining consensus on TRD definition may promote accurate, and possibly early detection of patients with TRD to enable appropriate intervention that may impact patient outcomes and quality of life.

Secondary alteration of the transferrin isoelectric focusing pattern in a case of bacterial meningitis.

Congenital disorders of glycosylation (CDG) are a group of inherited defects in the synthesis and processing of the linked glycans of glycoproteins and other glycoconjugates. The phenotypic spectrum presents wide variability, and clinical diagnosis is not reliable in most cases. Isoelectric focusing (IEF) of serum transferrin is widely used as a tool to detect CDG. We describe a paediatric patient presenting an altered serum transferrin pattern due to a secondary disorder of glycosylation caused by pneumococcal meningitis (Streptococcus pneumoniae, serotype 19A). During admission, brain CT scan and MRI showed acute ischaemic lesions in brain frontotemporal parenchyma, and enlarged subarachnoidal spaces in the frontal area resembling a chronic injury. This led us to screen for inborn errors of metabolism potentially associated with these findings (homocystinuria, glutaric aciduria, CDG syndromes). Biochemical studies for the screening of these inborn errors of metabolism were normal except for sialotransferrin isoelectric focusing, which showed a type 2 pattern. However, 16 days later, together with the remission of the meningitis process, the sialotransferrin pattern had normalized. The apolipoprotein C-III (an O-glycoprotein) profile was normal in all samples analysed. In conclusion, infectious events should be ruled out in the differential diagnosis of CDG syndromes. Furthermore, our findings highlight the possibility that the type 2 IEF pattern of serum sialotransferrin detected in some patients with neonatal death due to organ failure and septic events might be secondary to the infectious process.

[The role of natriuretic peptides in heart failure]. / Ruolo dei peptidi natriuretici nello scompenso cardiaco.

Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

Strain rate imaging: data acquisition and postrocessing.

Several studies already demonstrated the clinical relevance of strain rate imaging. Unfortunately, so far only few echolaboratories are using this technique in their clinical practice. This is mainly due to the lack of information on how to perform a standard strain rate imaging study. Thus, the aim of the present review is to provide the bases and methodology to perform a correct strain rate study.

Atenolol vs enalapril in young hypertensive patients after successful repair of aortic coarctation.

Late arterial hypertension has been identified as a major predictor for morbidity and mortality in aortic coarctation (AoC) patients. Few data are available about efficacy and tolerability of angiotensin converting enzyme inhibitors vs beta-blockers in young AoC patients. This study aimed to evaluate the tolerability and efficacy on 24-h blood pressure (BP) and left ventricular mass/height(2.7) (LVMI), of atenolol vs enalapril. We enrolled consecutive AoC hypertensive patients with (a) no history of BP treatment or after >48 h of withdrawn, (b) aged 6-20 years, (c) body mass index (BMI) <90th percentile for age and sex, (d) >12 months from a successful AoC repair and (e) no major associated cardiovascular abnormalities. All patient were evaluated with 24-h ambulatory BP monitoring, standard echocardiography, strain-strain rate imaging, at enrolment, 3, 6 and 12 months of treatment. We studied 51 AoC patients (13±3.9 years, BMI: 21.4±4.3 kg m(-2)). Patients were randomly assigned at atenolol treatment (n=26), or enalapril treatment (n=25). The mean follow-up duration was 11±2 months. Both drugs were able to significantly reduce 24-systolic BP (SBP; atenolol: 133±11 mm Hg vs 124±16 mm Hg, P=0.016; enalapril: 135±6 mm Hg vs 127±7 mm Hg, P=0.001). Only enalapril was able to significantly reduce LVMI (47±12 vs 39.6±10 g m(-)(2.7), P=0.016). Only in atenolol group in two cases (7.7%) drug withdrawal was needed because of adverse events. Enalapril and atenolol are similarly effective in reducing SBP. However, only enalapril demonstrated a significant reduction of LVMI. In no case, enalapril was stopped because of adverse events.