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.

Effectiveness and safety of brodalumab in the treatment of plaque, scalp and palmoplantar psoriasis: A multicentre retrospective study in a Spanish population.

BACKGROUND AND OBJECTIVE: The data in clinical practice regarding the effectiveness and safety of brodalumab in psoriasis are scarce, especially at scalp and palmoplantar locations. The main objective was the percentage of patients achieving absolute PASI ≤3/ ≤1/ =0 for plaque psoriasis and the percentage of patients achieving an IGA 0-1/IGA 0 for the special locations at Week 52 of treatment. PATIENTS AND METHODS: Observational retrospective multicentre study in 28 Spanish Hospitals that included adult patients with plaque psoriasis treated with brodalumab, from September 2018 until March 2021. RESULTS: A total of 200 patients were included. The mean baseline PASI was 10.97 (±6.28) with a mean basal scalp (n = 58) and palmoplantar (n = 40) IGA of 2.10 (±0.97) and 2.15 (±1.26), respectively. At Week 52, 93.98%/75.90%/68.67% of patients reached an absolute PASI ≤3/ ≤1/ =0 in plaque psoriasis (n = 83), with a percentage of patients achieving scalp (n = 27) and palmoplantar (n = 19) IGA 0-1/IGA 0 of 96.3%/88.9% and 100%/88.9%, respectively. Fifteen per cent of patients reported any adverse events with candidiasis being the most reported (6%), but only 6% of the adverse events required the withdrawal. CONCLUSIONS: Brodalumab demonstrated high PASI and IGA responses and was well tolerated in clinical practice in plaque, scalp and palmoplantar psoriasis.

Effects of tetracycline, sulfonamide, fluoroquinolone, and lincosamide load in pig slurry on lettuce: Agricultural and human health implications.

The application of pig slurry as fertilizer in agriculture provides nutrients, but it can also contain veterinary medicines, including antibiotic residues (ABs), which can have an ecotoxicological impact on agroecosystems. Furthermore, uptake, translocation, and accumulation of ABs in crops can mobilize them throughout the food chain. This greenhouse study aims to assess AB uptake from soil fertilized with pig slurry and its phenotypical effects on Lactuca sativa L. The plants were cropped in loamy clay soil dosed at 140 kg total N/ha and containing antibiotics (lincomycin, sulfadiazine, oxytetracycline, and enrofloxacin) at different concentration levels (0, 0.05, 0.5, 5, 50, and 500 mg/kg fresh weight, fw). Whereas sulfadiazine (11.8 ng/g fw) was detected in lettuce leaves at the intermediate doses (0.5 mg/kg), lincomycin and its transformation products (hydroxy/sulfate) were only detected at the 50 mg/kg fw dose. In addition, increased AB doses in the pig slurry resulted in decreased lettuce fresh weight and lipid and carbohydrate content and became lethal to lettuce at the highest AB concentrations (500 mg/kg fw). Nevertheless, even at higher doses, the AB content in lettuce following pig-slurry fertilization did not pose any direct significant human health risk (total hazard quotient<0.01). However, the promotion of antimicrobial resistance in humans due to the intake of these vegetables cannot be ruled out.

Different proteomic strategies to identify genuine Small Ubiquitin-like MOdifier targets and their modification sites in Trypanosoma brucei procyclic forms.

SUMOylation is an important post-translational modification conserved in eukaryotic organisms. In Trypanosoma brucei, SUMO (Small Ubiquitin-like MOdifier) is essential in procyclic and bloodstream forms. Furthermore, SUMO has been linked to the antigenic variation process, as a highly SUMOylated focus was recently identified within chromatin-associated proteins of the active variant surface glycoprotein expression site. We aimed to establish a reliable strategy to identify SUMO conjugates in T. brucei. We expressed various tagged variants of SUMO from the endogenous locus. His-HA-TbSUMO was useful to validate the tag functionality but SUMO conjugates were not enriched enough over contaminants after affinity purification. A Lys-deficient SUMO version, created to reduce contaminants by Lys-C digestion, was able to overcome this issue but did not allow mapping many SUMOylation sites. This cell line was in turn useful to demonstrate that polySUMO chains are not essential for parasite viability. Finally, a His-HA-TbSUMO(T106K) version allowed the purification of SUMO conjugates and, after digestion with Lys-C, the enrichment for diGly-Lys peptides using specific antibodies. This site-specific proteomic strategy led us to identify 45 SUMOylated proteins and 53 acceptor sites unambiguously. SUMOylated proteins belong mainly to nuclear processes, such as DNA replication and repair, transcription, rRNA biogenesis and chromatin remodelling, among others.

Occurrence of antibiotics in Lettuce (Lactuca sativa L.) and Radish (Raphanus sativus L.) following organic soil fertilisation under plot-scale conditions: Crop and human health implications.

Recent studies have demonstrated the crop uptake of antibiotics (ABs) from soils treated with AB-carrying fertilisers. However, there is a lack of plot-scale studies linking their effects at the agronomic and metabolomic/transcriptomic level to their impact on human health. This paper assesses the plant uptake of 23 ABs following two productive cycles of lettuce and radish cropped with sewage sludge, pig slurry, the organic fraction of municipal solid waste, or chemical fertilisation under plot-scale conditions (32 plots spanning 3-10 m2 each). AB uptake by plants depended on both the vegetable and the AB class and was higher in radish than in lettuce edible parts. Levels ranged from undetectable to up to 76 ng/g (fresh weight). Repetitive organic fertilisation resulted in an increase in the concentration of ABs in lettuce leaves, but not in radish roots. Significant metabolomic and transcriptomic changes were observed following soil fertilisation. Nevertheless, a human health risk assessment indicates that the occurrence of ABs in lettuce or radish edible parts does not pose any risk. To our knowledge, this is the first holistic plot-scale study demonstrating that the use of organic fertilisers containing ABs is safe for crop security and human health.

[Diagnostic keys for disseminated eczema: experience of a Dermatitis Contact unit (2003-2019)].

The aim of this study was to establish the diagnoses of patients with disseminated eczema and analyze the allergens involved in disseminated eczema due to allergic contact dermatitis. We analyzed the data from patients with a diagnosis of disseminated / generalized eczema who had undergone anamnesis, physical examination and patch tests in a Contact Dermatitis consultation from 2003 to 2019. Allergic contact dermatitis was the most frequent diagnosis, folowed by atopic dermatitis, asteatotic eczema, and gravitational eczema. The allergens most frequently involved in allergic contact dermatitis were isothiazolinones, topical medications, paraphenylenediamine, and fragrances. Allergic contact dermatitis caused almost half of the cases of disseminated eczema. It would be therefore advisable for patients with disseminated eczema to be assessed at a Contact Dermatitis unit and undergo patch tests.

Imaging manifestations of pulmonary melioidosis: A case series.

Melioidosis is an endemic disease in Southeast Asia and Oceania caused by the gram-negative bacillus Burkholderia pseudomallei. We studied 15 adult patients from Colombia with microbiologically diagnosed pulmonary melioidosis. We reviewed 15 chest X-rays and 10 chest computed tomography (CT) studies. Of the 15 patients, 87% met the criteria for acute infection and 13% met the criteria for chronic infection. The most common findings on chest X-rays were consolidation (86%), nodules (26%), and cavitation (20%). On CT studies, consolidation and nodules were observed in 90% of cases; the areas of consolidation were predominantly located in the basal and central zones in 60%. Areas of cavitation were observed in 50%, pleural effusion in 60%, and mediastinal lymph nodes in 30%. In patients with acute pulmonary melioidosis (n=8), the findings observed were nodules (100%), mixed pattern with nodules and consolidation (87%), pleural effusion (88%), and mediastinal lymph nodes (25%). The two patients with chronic pulmonary melioidosis both had cavitation. Acute lung infection with B. Pseudomallei has radiologic manifestations similar to those of pneumonia due to other causes. In areas where the disease is endemic, it is essential to include acute melioidosis in the differential diagnosis of pulmonary nodules and chronic melioidosis in the differential diagnosis of cavitated chronic lung lesions.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Assessing spatiotemporal patterns of multidrug-resistant and drug-sensitive tuberculosis in a South American setting.

We examined the spatiotemporal distribution of laboratory-confirmed multidrug-resistant tuberculosis (MDR TB) cases and that of other TB cases in Lima, Peru with the aim of identifying mechanisms responsible for the rise of MDR TB in an urban setting. All incident cases of TB in two districts of Lima, Peru during 2005-2007 were included. The spatiotemporal distributions of MDR cases and other TB cases were compared with Ripley's K statistic. Of 11,711 notified cases, 1187 received drug susceptibility testing and 376 were found to be MDR. Spatial aggregation of patients with confirmed MDR disease appeared similar to that of other patients in 2005 and 2006; however, in 2007, cases with confirmed MDR disease were found to be more tightly grouped. Subgroup analysis suggests the appearance of resistance may be driven by increased transmission. Interventions should aim to reduce the infectious duration for those with drug-resistant disease and improve infection control.

Influence of design, physico-chemical and environmental parameters on pharmaceuticals and fragrances removal by constructed wetlands.

The ability of several mesocosm-scale and full-scale constructed wetlands (CWs) to remove pharmaceuticals and personal care products (PPCPs) from urban wastewater was assessed. The results of three previous works were considered as a whole to find common patterns in PPCP removal. The experiment took place outdoors under winter and summer conditions. The mesocosm-scale CWs differed in some design parameters, namely the presence of plants, the vegetal species chosen (Typha angustifolia versus Phragmites australis), the flow configuration (surface flow versus subsurface flow), the primary treatment (sedimentation tank versus HUSB), the feeding regime (batch flow versus continuous saturation) and the presence of gravel bed. The full-scale CWs consisted of a combination of various subsystems (ponds, surface flow CWs and subsurface flow CWs). The studied PPCPs were ketoprofen, naproxen, ibuprofen, diclofenac, salicylic acid, carbamazepine, caffeine, methyl dihydrojasmonate, galaxolide and tonalide. The performance of the evaluated treatment systems was compound dependent and varied as a function of the CW-configuration. In addition, PPCP removal efficiencies were lower during winter. The presence of plants favoured naproxen, ibuprofen, diclofenac, salicylic acid, caffeine, methyl dihydrojasmonate, galaxolide and tonalide removal. Significant positive correlations were observed between the removal of most PPCPs and temperature or redox potential. Accordingly, microbiological pathways appear to be the most likely degradation route for the target PPCPs in the CWs studied.

[Cutaneous leiomyomas: a clinicpathological and epidemiological review].

BACKGROUND: Cutaneous, superficial and or suprafascial leiomyoma are divided into three variants: piloleiomyomas (PL), angioleiomyomas (AL) and genital leiomyomas (GL) that include the vulvar, scrotal and areolar forms. This study set out to establish the clinical and histological characteristics and incidence of each variant, and any likely associations with internal neoplasms. METHODS: A review was carried out of 255 cases of cutaneous leiomyomas diagnosed between 1982 and 2018 at the Pathology departments of three hospitals (Navarra and Alicante). Demographic, clinical, histological and immunohistochemical variables were described and compared. RESULTS: The incidence of PL in Navarra was 4.3 cases per million inhabitants a year, with another 20 cases of AL and 1.4 cases of GL. Cutaneous forms make up approximately 3.5% of the total leiomyomas. The population with PL suffered more frequently from breast cancer (OR?=?4.8; CI 95%: 1.3-17.4; p?=?0.006). Nipple leiomyomas are small, accompanied by localised pain, and are predominantly fascicular or solid, with very infrequent effect on the subcutaneous cellular tissue and scarce atypia. This makes for a contrast with the other GLs, which are medium sized and infrequently painful, predominantly nodular, and frequent effect on the subcutaneous tissue and atypia. CONCLUSIONS: The information provided here about the clinical and histological characteristics of the different varieties of leiomyomas indicate that there is a need to reconsider the classification of nipple leiomyomas outside the group of GLs. An association between PL and breast carcinoma was detected, which needs to be confirmed in future studies so as to determine if this leiomyoma is a risk marker for breast cancer.

Metabolomic and phenotypic implications of the application of fertilization products containing microcontaminants in lettuce (Lactuca sativa).

Cultivation practice using organic amendments is plausible to ensure global food security. However, plant abiotic stress due to the presence of metals and organic microcontaminants (OMCs) in fertilization products cannot be overlooked. In this study, we monitored lettuce metabolism and phenotypic response following the application of either sewage sludge (SS), the organic fraction of municipal solid waste, swine manure (SM), chemical fertilizers (CF), or no amendment (C) in a greenhouse facility. The experimental set-up consisted of five treatments with five replicates (25 experimental units randomly distributed). All fertilizers were supplied at the equivalent agronomic total nitrogen dose, but the occurrence of trace metals and/or OMCs was greater in the SS and SM than the rest. Non-target metabolomic analysis (high-resolution mass spectrometry coupled with partial least squares regression) identified more than 300 plant metabolites (amino acids, organic acids, sugar alcohols, and sugars), 55 of which showed significant changes in their relative abundances depending on the type of amendment. Functional analysis indicated that the use of CF or SS increased the levels of metabolites involved in carbohydrate and nitrogen metabolism. Therefore, although SS and SM fertilizers had a greater presence of heavy metals and/or OMCs, our results indicate that they did not induce measurable adverse effects in the lettuce phenotype or metabolism. Metabolic changes between fertilizers (CF and SS vs. C and SM) were mainly due to nitrogen availability.

Imaging manifestations of pulmonary melioidosis: a case series. / Manifestaciones radiológicas de la melioidosis pulmonar. Serie de casos.

Melioidosis is an endemic disease in Southeast Asia and Oceania caused by the gram-negative bacillus Burkholderia pseudomallei. We studied 15 adult patients from Colombia with microbiologically diagnosed pulmonary melioidosis. We reviewed 15 chest X-rays and 10 chest computed tomography (CT) studies. Of the 15 patients, 87% met the criteria for acute infection and 13% met the criteria for chronic infection. The most common findings on chest X-rays were consolidation (86%), nodules (26%), and cavitation (20%). On CT studies, consolidation and nodules were observed in 90% of cases; the areas of consolidation were predominantly located in the basal and central zones in 60%. Areas of cavitation were observed in 50%, pleural effusion in 60%, and mediastinal lymph nodes in 30%. In patients with acute pulmonary melioidosis (n=8), the findings observed were nodules (100%), mixed pattern with nodules and consolidation (87%), pleural effusion (88%), and mediastinal lymph nodes (25%). The two patients with chronic pulmonary melioidosis both had cavitation. Acute lung infection with B. Pseudomallei has radiologic manifestations similar to those of pneumonia due to other causes. In areas where the disease is endemic, it is essential to include acute melioidosis in the differential diagnosis of pulmonary nodules and chronic melioidosis in the differential diagnosis of cavitated chronic lung lesions.