Efficacy of omalizumab for the treatment of bullous pemphigoid: Spanish multicentre real-world experience.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are older and have associated multiple comorbidities. Topical and systemic corticosteroids are considered the first-line treatment for BP, and immunosuppressants are used as steroid-sparing treatments. However, both have side-effects and contraindications, which are even more common in this older population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease these side-effects while achieving equal or better effectiveness and response rates. Omalizumab is a monoclonal antibody that targets IgE and has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES: To assess the efficacy and safety of omalizumab for the treatment of BP. METHODS: We carried out a multicentre, retrospective, observational study including patients diagnosed with BP who received omalizumab for ≥ 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment were measured, and we evaluated the possible correlation with clinical response. We excluded patients treated with omalizumab for < 3 months, as we consider this duration to be insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment, we used the percentage of body surface area improvement. RESULTS: We included 36 patients. The vast majority had associated multiple comorbidities, and all patients had used other systemic therapies apart from corticosteroids before omalizumab. In total, 83% experienced some kind of treatment response and 42% of all patients treated achieved complete response. We did not find any correlation between higher IgE levels and a better response (P = 0.2). All patients tolerated omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it provided clinical response in most patients, and nearly one-half of the cases achieved complete response. It showed no side-effects, which is crucial in older patients with BP.

Assessment of potential predictive factors of dupilumab response in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab has shown to be an effective and safe treatment for patients with moderate-to-severe atopic dermatitis (AD). OBJECTIVE: To evaluate the predictive factors of response (PRF) in patients with moderate-to-severe AD treated with dupilumab. METHODS: Observational, retrospective and multicentre study conducted on adult patients diagnosed with moderate-to-severe AD treated with dupilumab, with a post-treatment follow-up of at least 16 weeks. The primary endpoints were EASI-75 and the IGA scale at week 52. RESULTS: A total of 198 patients were included in the analysis. Mean age was 38 ± 15.1 years and 116 (58.6%) were men. The most prevalent AD-predominant phenotypes were flexural eczema (45.3%), head-and-neck eczema (18.2%) and erythroderma (17.7%). At week 52, 140 (86.4%) patients achieved EASI-75 and 119 (93.0%) achieved an improvement in ≥2 points from baseline in IGA score. Women were 3.6 times more likely to achieve EASI-75 response than men (Odds ratio: 3.58; p = 0.020). While increased body mass index significantly reduced the probability of obtaining an improvement of ≥2 points in the IGA scale at week 52 (odds ratio: 0.88; p = 0.049). CONCLUSIONS: Dupilumab was an effective treatment in patients with moderate-to-severe AD. Additionally, sex and body mass index were significantly associated with achieving EASI-75 and an improvement of ≥2 points in the IGA scale, respectively, at week 52.

Hidradenitis Suppurativa from a Multi-Omic Scope.

Hidradenitis suppurativa (HS) is recognized as a systemic immune-mediated disease (IMID), sharing genetic and environmental risk factors with other IMIDs such as inflammatory bowel disease and psoriasis. Over time, correlating clinical findings with genetic, proteomic, and metabolomic results has been challenging due to diverse sampling methods, analysis techniques, and the use of variable clinical phenotype descriptions across studies. This review aims to summarize the results from various omics fields to explore the etiopathology of HS. Genetic studies highlight defects in Notch and γ-secretase signaling and inflammasome function. Syndromic HS involves specific mutations in autoinflammatory syndromes such as pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) and pyoderma gangrenosum, acne, and HS (PASH). Proteomic analyses reveal key inflammatory pathways indicating activation of both innate and adaptive immunity. Additionally, microbiome studies show an increased presence of anaerobes like Prevotella in HS lesions and a decreased presence of commensals such as Staphylococcus epidermidis. Gut microbiota dysbiosis, particularly involving Ruminococcus gnavus and Clostridium ramosum, is associated with HS. Moreover, metabolomic profiling indicates dysregulated tryptophan catabolism and lipid metabolism, with increased 5-lipoxygenase-derived metabolites and odd-chain fatty acids suggesting bacterial involvement. In summary, despite advances, robust associations between genetics, proteomics, microbiome, and metabolomics in HS are still lacking. Integrating these datasets could identify new clinical phenotypes, genetic predispositions, microbial signatures, and therapeutic targets, enhancing personalized treatment strategies and biomarker discovery for HS classification, prognosis, and treatment response.

Treatment of severe atopic dermatitis with tralokinumab in clinical practice: short-term effectiveness and safety results.

BACKGROUND: Tralokinumab was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) and is the first selective interleukin (IL)-13 inhibitor that specifically neutralizes IL-13 with high affinity. OBJECTIVES: To determine the real-life short-term effectiveness and safety of tralokinumab treatment in patients with moderate-to-severe AD. METHODS: A multicentre retrospective study was conducted including adult patients with moderate-to-severe AD who started tralokinumab treatment from 1 April to 30 June 2022 in 16 Spanish hospitals. Demographic and disease characteristics, severity and quality of life scales were collected at the baseline visit and at weeks 4 and 16. RESULTS: Eighty-five patients were included. Twenty-seven patients (32%) were non-naive to advanced therapy (biological or Janus kinase inhibitors inhibitors). All included patients had severe disease with baseline Eczema Area and Severity Index (EASI) scores of 25.4 (SD 8.1), Dermatology Life Quality Index (DLQI) 15.8 (5.4) and peak pruritus numerical rating scale (PP-NRS) 8.1 (1.8) and 65% had an Investigator's Global Assessment (IGA) of 4. At week 16, there was improvement on all scales. The mean EASI decreased to 7.5 (SD 6.9, 70% improvement), SCORing Atopic Dermatitis improved 64% and PP-NRS, 57%. Also, 82%, 58% and 21% of the patients achieved EASI 50, 75 and 90, respectively. The percentage of EASI 75 responders was significantly higher among the naive vs. non-naive groups (67% vs. 41%). The safety profile was acceptable. CONCLUSIONS: Patients, with a long history of disease and prior multidrug failure, showed a good response to tralokinumab, confirming clinical trial results.

Retinal Neurodegeneration Measured With Optical Coherence Tomography and Neuroimaging in Alzheimer Disease: A Systematic Review.

BACKGROUND: Optical coherence tomography (OCT) has enabled several retinal alterations to be detected in patients with Alzheimer disease (AD), alterations that could be potential biomarkers. However, the relationship between the retina and other biomarkers of AD has been underresearched. We gathered and analyzed the literature about the relationship between retinal and cerebral alterations detected via neuroimaging in patients with AD, mild cognitive impairment (MCI), and preclinical AD. METHODS: This systematic review followed the PRISMA Statement guidelines through the 27 items on its checklist. We searched in PubMed, BVS, Scopus, and the Cochrane Library, using the keywords: Alzheimer's disease, optical coherence tomography, white matter, cortex, atrophy, cortical thickness, neuroimaging, magnetic resonance imaging, and positron emission tomography. We included articles that studied the retina in relation to neuroimaging in patients with AD, MCI, and preclinical AD. We excluded studies without OCT, without neuroimaging, clinical cases, opinion articles, systematic reviews, and animal studies. RESULTS: Of a total of 35 articles found, 23 were finally included. Although mixed results were found, most of these corroborate the relationship between retinal and brain disorders. CONCLUSIONS: More rigorous research is needed in the field, including homogenized, longitudinal, and prolonged follow-up studies, as well as studies that include all stages of AD. This will enable better understanding of the retina and its implications in AD, leading to the discovery of retinal biomarkers that reflect brain alterations in AD patients in an accessible and noninvasive manner.

Pleomorphic mastocytoma in an adult.

Cutaneous mastocytoma (CM) is a localized variant of mastocytosis, characterized by an over-accumulation of mast cells in the skin, without extra-cutaneous organ involvement. It is defined as the presence of up to 3 isolated mast-cell skin lesions and commonly develops in newborns and children. We report the case of a 35-year-old healthy Caucasian woman presenting with a 4-year history of a pruritic brown plaque on her left breast. Hematoxylin-eosin staining showed a dense dermal infiltrate of atypical mast cells extending to the subcutis. The cells presented a marked nuclear pleomorphism with bilobed and multilobed nuclei. Immunohistochemical studies revealed strongly expressed KIT (CD117) and CD25 proteins. Serum tryptase levels and bone marrow biopsy were normal. The diagnosis was a solitary cutaneous pleomorphic mastocytoma. This case can be added to 17 other cases of adult mastocytoma documented in the literature, although, unlike other reported cases, and as far as we are aware, this is the first case of pleomorphic mastocytoma in an adult.

Adalimumab-related alopecia in a patient affected by psoriasis.

Alopecia induced by biological therapy is a rare side effect of this type of drugs. A total of 23 patients of psoriasiform eruptions with severe scalp involvement that induced alopecia during anti-tumor necrosis factor (anti-TNF) treatment of non-dermatological conditions have been previously reported. We present a 50-year-old man affected by plaque psoriasis that developed psoriasiform patches with alopecia over his scalp 10 months after initiating treatment with adalimumab. Punch biopsy of the alopecic area on the scalp revealed psoriasiform epidermal changes and alopecia areata-like dermal changes. Along with these findings, there was a dermal inflammatory infiltrate made up of eosinophils and plasma cells. In conclusion, scalp psoriasiform lesions with alopecia in patients treated with anti-TNF agents have been rarely reported. We describe a patient with anti-TNF therapy-related alopecia affected by psoriasis. Our patient has a peculiar histology with features of psoriasis and alopecia areata in addition to eosinophils and plasma cells. This entity may respond to topical treatment. However in patients of severe scalp involvement anti-TNF suspension should be considered.

Preparation of high-quality activated carbon from polyethyleneterephthalate (PET) bottle waste. Its use in the removal of pollutants in aqueous solution.

A waste-treats-waste approach has been used for the removal of two common pollutants, namely p-nitrophenol and/or Fe(III) from aqueous solution. Polyethyleneterephthalate (PET) from bottle waste has been used as the precursor for the preparation of activated carbons (ACs) by physical activation with steam and chemical activation with potassium hydroxide under controlled heating conditions and atmospheres. The resulting ACs were characterized in terms of chemical composition, porous texture and surface chemistry, and morphology. Selected ACs were tested as adsorbents for the removal of the aforementioned pollutants in aqueous solution. For comparison purposes, a commercial AC was also used. In general, the yield of the process of preparation of ACs is lower than 10% with steam and between 24.62 and 32.07% with potassium hydroxide. ACs possess a very high carbon content and a very low ash content. The BET surface areas reach 1235 m(2) g(-1) with steam and 1002 m(2) g(-1) with potassium hydroxide at most. Also, the degrees of development of micro- and mesoporosity are markedly larger with steam. Conversely, the development of macroporosity is much larger with potassium hydroxide. The PET-derived ACs exhibit a better adsorption behavior towards p-nitrophenol than the commercial AC, both in terms of adsorption rate and adsorption capacity. On the contrary, the commercial AC acts as a better adsorbent of Fe(III) ions. As compared to separately, the simultaneous presence of both solutes in the adsorptive solution scarcely affects the adsorption process except for equilibrium for Fe(III).

Structural and Functional Retinal Changes in Patients with Mild Cognitive Impairment with and without Diabetes.

Our objective is to analyze retinal changes using optical coherence tomography angiography (OCT-A) in patients with mild cognitive impairment (MCI) to characterize structural and vascular alterations. This cross-sectional study involved 117 eyes: 39 eyes from patients with MCI plus diabetes (DM-MCI), 39 eyes from patients with MCI but no diabetes (MCI); and 39 healthy control eyes (C). All patients underwent a visual acuity measurement, a structural OCT, an OCT-A, and a neuropsychological examination. Our study showed a thinning of retinal nerve fiber layer thickness (RNFL) and a decrease in macular thickness when comparing the MCI-DM group to the C group (p = 0.008 and p = 0.016, respectively). In addition, an increase in arteriolar thickness (p = 0.016), a reduction in superficial capillary plexus density (p = 0.002), and a decrease in ganglion cell thickness (p = 0.027) were found when comparing the MCI-DM group with the MCI group. Diabetes may exacerbate retinal vascular changes when combined with mild cognitive impairment.

PERCIST and Hopkins criteria and PET/CT metabolic parameters as prognostic factors in squamous head and neck cancer.

AIM: To assess the clinical utility of PERCIST and Hopkins criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with head and neck squamous cell carcinoma treated by chemoradiotherapy. MATERIAL AND METHODS: Forty patients (34 men) diagnosed with head and neck squamous cell carcinoma were retrospectively assessed over an interval of 8 years. PERCIST and Hopkins criteria were used to assess response to treatment. Variations in the metabolic parameters maximum SUV (ΔSUVmax), metabolic tumor volume (ΔMTV) and total lesion glycolysis (ΔTLG) between pre- and post-treatment PET/CT studies were also determined. The Cox regression model, ROC curves and the Kaplan-Meier method were used for the analysis of prognostic factors and survival curves. RESULTS: The mean follow-up was 39.4 months, with 24 progressions and 22 deaths. Both PERCIST and Hopkins criteria and the three metabolic parameters were predictive factors in the univariate analysis and only ΔSUVmax was in the multivariate analysis. Survival analysis showed statistically significant differences in PFS and CSS curves for the five parameters considered. CONCLUSION: Application of PERCIST and Hopkins criteria as well as ΔSUVmax, ΔMTV and ΔTLG from PET/CT studies proved to be prognostic factors for survival in patients in our setting for treating head and neck cancer. The results may help to personalize treatment.

Completion of the informed consent in radioguided surgery by the General Surgery and Nuclear Medicine services of a radioguided surgery unit.

OBJECTIVE: To identify the frequency of errors in informed consent documents in radioguided surgery in a third level hospital and to detect possible causes or factors associated with a greater risk of error. MATERIAL AND METHODS: Informed consent forms of a total of 369 radioguided surgery interventions, completed by the Nuclear Medicine and General Surgery services, were analyzed, and the degree of completion of the forms and its correlation with the physicians responsible, type of pathology, intervention, and waiting time were compared with the completion of consent by another specialty. RESULTS: Errors were identified in 22 consent forms from Nuclear Medicine and 71 from General Surgery. The most common error was the absence of identification of the physician responsible (17 in Nuclear Medicine, 51 in General Surgery), and the second most common was the absence of a document (2 in Nuclear Medicine, 20 in General Surgery). There were significant differences in the errors made depending on the doctor in charge, with no significant correlation with the other variables. CONCLUSIONS: The physicians responsible were the main factor associated with a greater risk of error in the completion of informed consent forms. Further studies are needed to analyze the causal factors and possible interventions to minimize errors.

Are antihistamines still used during omalizumab treatment for chronic spontaneous urticaria?

Background: The guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend adding omalizumab to the treatment of patients with uncontrolled disease despite four-fold doses of second-generation antihistamines (AH). On the contrary, some studies revealed that omalizumab was effective without concomitant AH and several authors suggest tapering off AH when CSU is controlled with omalizumab. Objectives: The aim of our study was to evaluate the use of AH during treatment with omalizumab in patients with CSU in real clinical practice. Materials & Methods: This was a multicentre cross-sectional and observational study conducted by the Catalan and Balearic Chronic Urticaria Network (XUrCB) based on a cohort of 298 CSU patients treated with omalizumab. Results: In total, 23.5% of our patients decided themselves to stop taking AH during omalizumab treatment. The ratio of patients with CSU without concomitant inducible urticaria and the percentage of patients with a good response to omalizumab (UAS7≤6 and/or UCT ≥12) were higher in those who stopped taking AH. Conclusion: More studies are required to identify the phenotypic characteristics of patients responding to omalizumab as monotherapy in order to avoid overtreating with AH. Our study suggests that patients with CSU without concomitant inducible urticaria and those who achieve a good response to omalizumab tend to be controlled by omalizumab without AH. In order to establish guidelines on how to stop AH, further evidenced-based studies are required.

Adsorption of cadmium on carbonaceous adsorbents developed from used tire rubber.

Carbonaceous adsorbents (CAs) are developed from used tire rubber (UTR) and tested as adsorbents of Cd(2+) in aqueous solution. In the preparation of the CAs, UTR was treated thermally at 400-900 °C for 2 h in N(2) and at 850 °C for 2 h in steam. Concentrated NaOH, HCl, H(2)SO(4), HNO(3) and H(2)O(2) solutions were also used. UTR and H900 (i.e. UTR pyrolyzed at 900 °C) were treated with O(3) at 25 °C for 1 h and with air at 250 °C for 1 and 24 h. CAs were characterized texturally by N(2) adsorption at -196 °C, mercury porosimetry, and density measurements. The surface groups were analyzed by FT-IR spectroscopy. Using the batch method, the adsorption process of Cd(2+) was studied mainly from the kinetic standpoint at various pH values of the adsorptive solution. Significant porosity developments are achieved only when UTR is heat-treated, in particular in steam. However, the variety and concentration of surface groups are low in CAs. This is so even for CAs prepared using oxidizing agents as strong as O(3) and H(2)O(2), which has been associated with a lack of available or accessible surface active sites for oxidation in UTR and H900, respectively. Thermal and thermal-chemical treatments are usually more effective than chemical treatments to increase the adsorption of Cd(2+) in aqueous solution. The adsorption process of Cd(2+) is first fast and then much slower. Adsorption-time data fit better to a pseudo-second order kinetic equation than to a pseudo-first order kinetic equation. The extent to which the adsorption process occurs is strongly dependent on the pH of the Cd(2+) solution, being larger at pH 4.6 or 7.0 according to the adsorbent.

Adsorption of bisphenol A by activated carbon developed from PET waste by KOH activation.

This study deals with the preparation of activated carbon (AC) from poly(ethylene terephthalate) (PET) waste and with the physicochemical characterization of AC and its use as adsorbent of bisphenol A (BPA) in aqueous solution. AC was prepared by chemical activation with KOH and by physical activation in steam. The activation with KOH was carried out by impregnation first of PET by wet and dry routes at the PET/KOH weight ratios of 1:1, 1:3, and 1:5 and by carbonization then of the resulting products at 850 °C for 2 h in N2 atmosphere. The activation in steam was performed by heating at 900 °C for 1 h. The ACs were characterized by N2 adsorption at - 196 °C, mercury porosity, mercury density measurements, FT-IR spectroscopy, and measurement of pH of the point of zero charge (pHpzc). The activation yield is 58.4-49.4% with KOH in aqueous solution, 75.8-23.9% with solid KOH, and 5.9% with steam. Using solid KOH, greater developments of a more heterogeneous porosity with increasing impregnation PET/KOH ratio are achieved. For SK1:5, SBET is 1990 m2 g-1 and the pore volumes are 0.71 cm3 g-1, micropores; 0.81 cm3 g-1, mesopores; and 1.77 cm3 g-1, macropores. The data of BPA adsorption fit better to the Ho and Mckay second order kinetic model than to the Lagergren first-order kinetic model and to the Langmuir equation than to the Freundlich equation. From the kinetic and thermodynamic standpoints, the adsorption process of BPA is more favorable for SK1:5.

A Stable High-Capacity Lithium-Ion Battery Using a Biomass-Derived Sulfur-Carbon Cathode and Lithiated Silicon Anode.

A full lithium-ion-sulfur cell with a remarkable cycle life was achieved by combining an environmentally sustainable biomass-derived sulfur-carbon cathode and a pre-lithiated silicon oxide anode. X-ray diffraction, Raman spectroscopy, energy dispersive spectroscopy, and thermogravimetry of the cathode evidenced the disordered nature of the carbon matrix in which sulfur was uniformly distributed with a weight content as high as 75 %, while scanning and transmission electron microscopy revealed the micrometric morphology of the composite. The sulfur-carbon electrode in the lithium half-cell exhibited a maximum capacity higher than 1200 mAh gS -1 , reversible electrochemical process, limited electrode/electrolyte interphase resistance, and a rate capability up to C/2. The material showed a capacity decay of about 40 % with respect to the steady-state value over 100 cycles, likely due to the reaction with the lithium metal of dissolved polysulfides or impurities including P detected in the carbon precursor. Therefore, the replacement of the lithium metal with a less challenging anode was suggested, and the sulfur-carbon composite was subsequently investigated in the full lithium-ion-sulfur battery employing a Li-alloying silicon oxide anode. The full-cell revealed an initial capacity as high as 1200 mAh gS -1 , a retention increased to more than 79 % for 100 galvanostatic cycles, and 56 % over 500 cycles. The data reported herein well indicated the reliability of energy storage devices with extended cycle life employing high-energy, green, and safe electrode materials.

[Radioguided surgery of intestinal carcinoid tumor relapse. Role of SPECT-CT]. / Cirugía radiodirigida de metástasis de tumor carcinoide intestinal. Importancia de la realización de SPECT-TAC.

We present a patient with clinical suspicion of intestinal carcinoid relapse confirmed by a somatostatin receptor scintigraphy. A very intense somatostatin avid abdominal lesion was located and radioguided surgery was proposed. Prior to the procedure, we performed a SPECT-CT that made it possible to detect and localize the lesion anatomically, thus facilitating the performance of the radioguided procedure. Furthermore, it modified the planning of the intervention with the adequate physical and human resources to prevent the possible surgical complications.

[Optimization of sentinel lymph node biopsy in breast cancer by intraoperative axillary palpation]. / Optimización de la biopsia selectiva de ganglio centinela en el cáncer de mama mediante palpación axilar intraoperatoria.

INTRODUCTION: Sentinel node biopsy (SNB) by radioisotopes is a widely accepted and reliable surgical method for staging breast cancer in patients with unknown positive axillary lymph nodes involvement. The main limitation of this method is due to the appearance of false negatives that may be caused by tumor lymph node blockage of the sentinel lymph node and uptake in the neighboring lymph nodes. Infiltered sentinel nodes are generally increased in size and firm. Thus, they can be detected by intraoperative palpation, even when there is no uptake by the radiotracer. AIM: To reduce the false negative rates by applying intraoperative axillary palpation after SNB. METHOD: Over a two-year period, we complemented the SNB in 168 patients with careful intraoperative axillary palpation, detecting and removing all the palpable suspicious lymph nodes (SLN) that were analyzed as sentinel nodes RESULTS: In 32 out of 168 patients, 50 palpable SLN were found. In 3 out of 32 patients, 4 infiltrated SLNs were demonstrated with negative SNB and positive axillary lymphadenectomy. Thus, intraoperative palpation avoided false negative results. In one patient, one palpable SLN with tumor involvement was observed and SNB was also positive. In the remaining 28 patients, the histological analysis of 45 SLN was negative for tumor but SNB was positive in 3 patients. CONCLUSION: Intraoperative axillary palpation, once the SNB was done, reduced the false negative rate. Thus, we consider that it should be included as one more part of this procedure.