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.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience. / [Artículo traducido] Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Clinical and histological characterization of vesicular COVID-19 rashes: a prospective study in a tertiary care hospital.

COVID-19 is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). Vesicular skin rashes have been reported as associated with COVID-19, but there is little information about this cutaneous manifestation. We designed a prospective observational study of patients diagnosed with COVID-19 who had vesicular lesions. Clinical characterization of skin findings was conducted by dermatologists. When possible, histological analysis and detection of SARS-CoV-2 in the content of the vesicles was performed. In total, 24 patients were included. A disseminated pattern was found in 18 patients (75%), and a localized pattern was found in 6 (25%). Median duration of the skin rash was 10 days. Of the 24 patients, 19 (79.2%) developed the skin rash after the onset of COVID-19 symptoms. Histological examination in two patients was consistent with viral infection, SARS-CoV-2 was not detected in four patients. This single-centre study shows the clinical characteristics of vesicular skin rashes in patients with COVID-19.

Split-face study comparing conventional MAL photodynamic therapy in multiple actinic keratosis with complete time vs. half-time red light LED conventional illumination.

BACKGROUND: Conventional photodynamic therapy (PDT) with methylaminolevulinic acid (MAL) and daylight PDT have demonstrated similar efficacy in the treatment of actinic keratosis (AK). The reason for the use of daylight is to reduce pain during illumination but daylight has the limitation of the weather conditions. The difference in the doses of red light applied between these two methods suggests that an intermediate dose with red light conventional illumination could be effective in PDT of AK. OBJECTIVE: To compare the efficiency of conventional MAL-PDT with half-time conventional red light illumination in patients with multiple AK. MATERIAL AND METHODS: Adult patients with more than five symmetrically distributed AK were selected. After randomization, one area was treated with conventional PDT (Aktilite® , 630 nm, 37 J/cm2 , 8 min), while the contralateral was illuminated half time (Aktilite® , 630 nm, 37 J/cm2 , 4 min). Patients evaluated pain in each different side. Patients were evaluated at baseline, 3 and 6 months after PDT treatment by a blinded dermatologist. A questionnaire to be done at home 24 h after completing treatment was deliver to the patients to evaluate any side-effects. RESULTS: A total of 774 lesions were treated, 385 with conventional PDT and 389 with half-time PDT (P > 0.05). Conventional PDT was 85% of complete response of AK (327/385) at 3 months, and half-time PDT was 82% (319/389). At 6 months, conventional PDT was 70% (268/385) of complete response and half-time PDT was 65% (252/389). Pain during illumination was significantly lower in the VAS with the half-time protocol with a mean of 5.59 (SD 1.48) vs. 6.41 (SD 1.66) in conventional PDT. No difference in adverse effects was found between protocols. CONCLUSION: Conventional PDT with half-time illumination in multiple actinic keratosis is as effective as complete time illumination and decreased pain significantly.

New platelet functional method for identification of pathogenic antibodies in HIT patients.

Heparin-induced thrombocytopenia (HIT) is a thrombotic complication of heparin therapy. The most used functional method for HIT diagnosis is serotonin release assay (SRA). A different functional method based on ATP release with luciferin/luciferase long-life and stable luminescent signal is used here, which is shown to be comparable for accuracy with SRA in both negative (patients 4Ts ≤3, and negative for both anti-PF4/heparin immunoassay and SRA) and positive (4Ts >3, and positive for both PF4/heparin antibodies and SRA) patients. Our results show that ATP release is higher in washed platelets activated by sera from positive patients than in platelets activated by sera from negative patients. In conclusion, we demonstrate that ATP release assay is a valid alternative method to SRA for the identification of pathogenic anti-PF4/heparin antibodies.

Treatment of adult diffuse pityriasis lichenoides chronica with narrowband ultraviolet B: experience and literature review.

Pityriasis lichenoides chronica (PLC) is an infrequent dermatosis of unknown aetiology, wholse evolution and response to treatment differs between children and adults. When PLC is recalcitrant or unresponsive to topical treatment, phototherapy is one of the main treatments used. We carried out a prospective study of adult diffuse PLC treated with narrowband ultraviolet B (NB-UVB). We treated eight patients whose disease showed no response to topical therapy, and obtained a complete response rate of 88% in a mean of 23 sessions (cumulative dose 16.99 J/cm2 ). However, the relapse rate was 43% in the first 6 months. Our results are similar to those of other published studies but there is much variability between them in the doses applied and the number of sessions needed. Further studies are necessary to devise a protocol for NB-UVB treatment of PLC.

Osteoporosis across chronic liver disease.

Osteoporosis is a complication of chronic liver disease, with impact on morbidity, quality of life, and survival. The progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with liver disease. So, it is fundamental to make better the quality of life and to prevent complications. Metabolic bone disorders are common complications of chronic liver disease (CLD). Patients with CLD have an increased risk of bone fractures, with significant impact on morbidity, quality of life, and even on survival. Bone diseases, including osteomalacia, osteoporosis, and osteopenia, are frequently observed in many types of liver disease. The pathogenesis of damage and the mechanisms of bone loss are different in relation to the specific liver disease. The relevance of these conditions induced many authors to create a new nosographic entity known as "hepatic osteodystrophy", although this term is rarely used anymore and it is now commonly referred to as osteopenia or osteoporosis associated with chronic liver disease. This review is based on the personal experiences of the authors and upon research done of the available literature on this subject matter. The authors searched the PubMed database for publications containing the term "liver disease" in combination with "bone disease", "hepatic osteodistrophy", "osteoporosis", "osteopenia", "osteomalacia", and "fractures". They selected publications from the past 10 years but did not exclude older seminal publications, especially for colestatic liver diseases. This review of literature shows that osteoporosis crosses all CLD. It is important to underline that the progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with CLD. It is fundamental to make better the quality of life and it is mandatory to prevent complications and in particular the osteoporotic ones, especially fractures.

Technical note: Validation of a commercial system for the continuous and automated monitoring of dairy cow activity.

Current farm sizes do not allow the precise identification and tracking of individual cows and their health and behavioral records. Currently, the application of information technology within intensive dairy farming takes a key role in proper routine management to improve animal welfare and to enhance the comfort of dairy cows. An existing application based on information technology is represented by the GEA CowView system (GEA Farm Technologies, Bönen, Germany). This system is able to detect and monitor animal behavioral activities based on positioning, through the creation of a virtual map of the barn that outlines all the areas where cows have access. The aim of this study was to validate the accuracy, sensitivity, and specificity of data provided by the CowView system. The validation was performed by comparing data automatically obtained from the CowView system with those obtained by a manual labeling procedure performed on video recordings. Data used for the comparisons were represented by the zone-related activities performed by the selected dairy cows and were classified into 2 categories: activity and localization. The duration in seconds of each of the activities/localizations detected both with the manual labeling and with the automated system were used to evaluate the correlation coefficients among data; and subsequently the accuracy, sensitivity, specificity, and positive and negative predictive values of the automated monitoring system were calculated. The results of this validation study showed that the CowView automated monitoring system is able to identify the cow localization/position (alley, trough, cubicles) with high reliability in relation to the zone-related activities performed by dairy cows (accuracy higher than 95%). The results obtained support the CowView system as an innovative potential solution for the easier management of dairy cows.

Hyperbaric Oxygen Therapy Improves Glucose Homeostasis in Type 2 Diabetes Patients: A Likely Involvement of the Carotid Bodies.

The carotid bodies (CBs) are peripheral chemoreceptors that respond to hypoxia increasing minute ventilation and activating the sympathetic nervous system. Besides its role in ventilation we recently described that CB regulate peripheral insulin sensitivity. Knowing that the CB is functionally blocked by hyperoxia and that hyperbaric oxygen therapy (HBOT) improves fasting blood glucose in diabetes patients, we have investigated the effect of HBOT on glucose tolerance in type 2 diabetes patients. Volunteers with indication for HBOT were recruited at the Subaquatic and Hyperbaric Medicine Center of Portuguese Navy and divided into two groups: type 2 diabetes patients and controls. Groups were submitted to 20 sessions of HBOT. OGTT were done before the first and after the last HBOT session. Sixteen diabetic patients and 16 control individual were included. Fasting glycemia was143.5 ± 12.62 mg/dl in diabetic patients and 92.06 ± 2.99 mg/dl in controls. In diabetic patients glycemia post-OGTT was 280.25 ± 22.29 mg/dl before the first HBOT session. After 20 sessions, fasting and 2 h post-OGTT glycemia decreased significantly. In control group HBOT did not modify fasting glycemia and post-OGTT glycemia. Our results showed that HBOT ameliorates glucose tolerance in diabetic patients and suggest that HBOT could be used as a therapeutic intervention for type 2 diabetes.

Experimental evidence and mathematical modeling of thermal effects on human colonic smooth muscle contractility.

It has been shown, in animal models, that gastrointestinal tract (GIT) motility is influenced by temperature; nevertheless, the basic mechanism governing thermal GIT smooth muscle responses has not been fully investigated. Studies based on physiologically tuned mathematical models have predicted that thermal inhomogeneity may induce an electrochemical destabilization of peristaltic activity. In the present study, the effect of thermal cooling on human colonic muscle strip (HCMS) contractility was studied. HCMSs were obtained from disease-free margins of resected segments for cancer. After removal of the mucosa and serosa layers, strips were mounted in separate chambers. After 30 min, spontaneous contractions developed, which were measured using force displacement transducers. Temperature was changed every hour (37, 34, and 31°C). The effect of cooling was analyzed on mean contractile activity, oscillation amplitude, frequency, and contraction to ACh (10(-5) M). At 37°C, HCMSs developed a stable phasic contraction (~0.02 Hz) with a significant ACh-elicited mean contractile response (31% and 22% compared with baseline in the circular and longitudinal axis, respectively). At a lower bath temperature, higher mean contractile amplitude was observed, and it increased in the presence of ACh (78% and 43% higher than the basal tone in the circular and longitudinal axis, respectively, at 31°C). A simplified thermochemomechanical model was tuned on experimental data characterizing the stress state coupling the intracellular Ca(2+) concentration to tissue temperature. In conclusion, acute thermal cooling affects colonic muscular function. Further studies are needed to establish the exact mechanisms involved to better understand clinical consequences of hypothermia on intestinal contractile activity.

Restoration of peripheral blood natural killer and B cell levels in patients affected by rheumatoid and psoriatic arthritis during etanercept treatment.

Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-α agent used in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on the effects of anti-TNF-α on peripheral blood cells. We aimed to evaluate peripheral blood cells in RA and PsA patients during ETN treatment and to explore their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients who started ETN were included into the study and evaluated prospectively before the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were studied in terms of disease activity score on 28 joints (DAS28), clinical response and laboratory findings. Natural killer (NK) cells, B cells and T cells were characterized by immunophenotyping. Both the RA and the PsA patients showed reduced NK and B cell count before ETN treatment compared with controls. A negative correlation was demonstrated between DAS28 and B cell count in RA patients at baseline. Sustained significant increase of NK and B cells up to normal levels was observed in RA and PsA patients along ETN treatment. Increase of NK cell count was associated with a good-moderate clinical response to ETN in both RA and PsA patients. During ETN treatment peripheral blood NK and B cells levels were restored in RA and PsA patients. Correlations between NK and B cells with disease activity were observed, suggesting that those effects could be mediated by ETN treatment.

Fluorescence diagnosis and photodynamic therapy for Bowen's disease treatment.

INTRODUCTION: It has already been demonstrated the high efficacy of photodynamic therapy (PDT) for Bowen's disease (BD) treatment. Fluorescence diagnosis consists on registration of the fluorescence emitted by tissue after application of a photosensitizer, indicating presence of tumoral cells. It has been described as a useful tool for actinic keratosis. Different results have been published about fluorescence diagnosis for basal cell carcinomas. Very few reports about the role of fluorescence diagnosis for this entity exist and this is the first one which correlates the fluorescence image after PDT with the histopathological response. OBJECTIVES: To assess the role of fluorescence diagnosis during BD follow-up. METHODS: We carried out an observational, retrospective and descriptive study. A total of 29 BD biopsy proven lesions were included. All the lesions had been treated with the standard protocol (Topical methyl- aminolaevulinic acid under occlusion for 3 hours and followed by illumination with red-light (630 nm, 38 J/cm(2), 7.5 minutes. Two sessions one week apart). Clinical and fluorescence photographs were taken before treatment and one month after the 2(nd) one. At that moment a post-treatment biopsy was performed. Clinical response was classified as partial, complete or no response. Fluorescence response was classified as negative, intermediate or intense. The follow-up period and the adverse events observed including pain were also collected. RESULTS: We found statistical association between fluorescence and the clinical and histopathological evaluations performed after treatment. Fluorescence diagnosis obtained a 100% sensitivity (higher than clinical evaluation alone) and a specificity of 85.7% (CI: 70.8-100). CONCLUSIONS: Fluorescence diagnosis seems a valid diagnostic tool, useful during the follow up of Bowen disease lesions with the advantage of avoiding unnecessary post-treatment biopsies.