Dupilumab in Patients with Atopic Dermatitis: A Multicentric, Long-Term, Real-World Portuguese Study.

INTRODUCTION: Several clinical trials have established the efficacy and safety of dupilumab for treating atopic dermatitis (AD). However, literature remains scarce in reporting the long-term effectiveness, safety, and drug survival of dupilumab in real-world settings. This study aimed to describe the latter outcomes of dupilumab in patients with AD. METHODS: This Portuguese, multicentric, observational, retrospective study included consecutive adult patients with AD who initiated dupilumab between January 2019 and September 2023, with a follow-up period up to 30 months. Drug discontinuation and adverse effects data were used to estimate drug survival. Clinical assessments included the Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), and Dermatology Life Quality Index (DLQI). RESULTS: A total of 312 patients were included in the study, with 56.4% being male (median age of 30 years, range 18-83). The 30-month drug survival rate was 82.0%. During the study period, 12.5% of the sample (n = 39 patients) discontinued treatment: 7.3% due to treatment failure, 2.9% due to safety concerns, 1.3% due to complete disease control, 0.6% due to pregnancy, and 0.3% due to lack of compliance. Adverse events not leading to drug discontinuation were noted in 25.6% of the sample (n = 80). Conjunctivitis was the most frequently reported adverse event (17%), followed by facial erythema (9%). At 30 months, the mean EASI decreased significantly from 27.30 ± 11.89 at baseline to 2.92 ± 3.96 (p < 0.001), reflecting an overall improvement of 89.3%. Similarly, pruritus NRS decreased from 7.36 ± 1.90 at baseline to 1.74 ± 2.16 at month 30 (p < 0.001), improving by 76.4%, and mean DLQI changed from 18.0 ± 7.09 at baseline to 2.67 ± 3.95 at month 30 (p < 0.001), decreasing by 85.2%. CONCLUSIONS: This study increases our current understanding of dupilumab in real-world settings, demonstrating its long-term effectiveness and safety in treating AD.

Accuracy of saliva for SARS-CoV-2 detection in outpatients and their household contacts during the circulation of the Omicron variant of concern.

BACKGROUND: While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening. METHODS: To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa coefficient were calculated to assess diagnostic performance. RESULTS: Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3-94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen's kappa value of 0.74 [95% confidence interval (CI): 0.67-0.81]. Sensitivity was 77% (95% CI: 70.9-82.2), specificity 95% (95% CI: 91.9-97), PPV 89.8% (95% CI: 83.1-94.4), NPV 87.9% (95% CI: 83.6-91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5-92)] with a Cohen's kappa value of 0.63 (95% CI: 0.35-0.91). CONCLUSIONS: Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant.

The use of the cap and underwater technique as an aid in endoscopic diagnosis and treatment of upper gastrointestinal bleeding: case series.

BACKGROUND AND AIMS: Upper GI bleeding (UGIB) is a medical emergency associated with elevated mortality and significant costs to the health care system. EGD is currently the method of choice for the diagnosis and management of these conditions. However, the location of bleeding lesions and technical difficulties in achieving endoscope stability may challenge even the most experienced endoscopists. Herein, we demonstrate the use of the cap and underwater technique as a helpful aid in these situations. METHODS: We present a case series of 4 patients with acute UGIB who underwent EGD with suboptimal endoscopic visualization or technical difficulties in identifying the source of bleeding. A transparent plastic cap was attached to the distal tip of the gastroscope, and the water immersion technique (underwater) was used for endoscopic re-evaluation of the bleeding site. RESULTS: Three patients presented with duodenal bleeding, and 1 was diagnosed with diffuse bleeding from the esophagus. The clear and accurate identification of the source of bleeding and effective hemostasis were possible after cap and underwater technique evaluation in all patients. CONCLUSION: The use of the cap and underwater technique is a simple, safe, and low-cost strategy that improves the identification and control of UGIB in locations with poor visibility and technical challenges during endoscopic evaluation.

Optical properties of organosilicon compounds containing sigma-electron delocalization by quasiparticle self-consistent GW calculations.

We investigate theoretically the electronic and optical absorption properties of two sub-classes of oligosilanes: (i) Si(CH3)4, Si4(CH3)8, and Si8(CH3)8 that contain Si dot, ring and cage, respectively, and exhibit typical SiC and SiSi bonds; and (ii) persilastaffanes Si7H6(CH3)6 and Si12H6(CH3)12, which contain extended delocalized σ-electrons in SiSi bonds over three-dimensional Si frameworks. Our modeling is performed within the GW approach up to the partially self-consistent GW0 approximation, which is more adequate for reliably predicting the optical band gaps of materials. We examine how the optical properties of these organosilicon compounds depend on their size, geometric features, and Si/C composition. Our results indicate that the present methodology offers a viable way of describing the optical excitations of tailored functional Si-C-based clusters and molecular optical tags with potential use as efficient light absorbers/emitters in molecular optical devices.

Evaluation of recurrence and surgical complementation rates after endoscopic resection of large colorectal non-pedunculated lesions

BACKGROUND AND AIM: the process that leads to the development of colorectal cancer takes many years and most tumors originate from polyps and non-polypoid lesions. Techniques of endoscopic resection are surgical treatment options, even in case of large lesions or with initial invasion. This study aimed to evaluate the recurrence and surgical complementation rates after endoscopic resection of large colorectal non-pedunculated lesions. METHODS: a retrospective, longitudinal and descriptive trial was performed via an analysis of colonoscopies with the resection of non-pedunculated lesions larger than 3 cm, performed between 2014 and 2017. RESULTS: sixty-two lesions were included from 61 patients and 32 (52.5 %) were female. The age ranged from 36 to 89 years, with a mean age of 60.5 years. Lesions had an average diameter of 40.08 mm, ranging from 30 to 80 mm. Regarding the location of the lesions, the most frequent colonic segments were the ascending and rectum, both accounting for 22.6 %. Considering the morphologic endoscopic classification, 67.7 % were granular laterally spreading tumors (LST), 38.8 % were homogeneous granular and 29 % were mixed granular. The most frequent histological types were tubulovillous adenoma (30.7 %) and intramucosal adenocarcinoma (29 %). The resection technique was piecemeal mucosectomy in 85.5 %. Five lesions were removed by en bloc mucosectomy, two (3.2 %) by endoscopic submucosal dissection (ESD) and two (3.2 %) by a hybrid technique. The recurrence rate was 25.8 %. Three patients needed complementary surgical treatment and the clinical success of endoscopic treatment was 95.1 %. CONCLUSION: recurrence rate after endoscopic resection of large colorectal lesions was 25.8 % and surgical complementation rate due to failure in the endoscopic treatment of recurrence was 4.8 %

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Evaluation of recurrence and surgical complementation rates after endoscopic resection of large colorectal non-pedunculated lesions.

BACKGROUND AND AIM: the process that leads to the development of colorectal cancer takes many years and most tumors originate from polyps and non-polypoid lesions. Techniques of endoscopic resection are surgical treatment options, even in case of large lesions or with initial invasion. This study aimed to evaluate the recurrence and surgical complementation rates after endoscopic resection of large colorectal non-pedunculated lesions. METHODS: a retrospective, longitudinal and descriptive trial was performed via an analysis of colonoscopies with the resection of non-pedunculated lesions larger than 3 cm, performed between 2014 and 2017. RESULTS: sixty-two lesions were included from 61 patients and 32 (52.5 %) were female. The age ranged from 36 to 89 years, with a mean age of 60.5 years. Lesions had an average diameter of 40.08 mm, ranging from 30 to 80 mm. Regarding the location of the lesions, the most frequent colonic segments were the ascending and rectum, both accounting for 22.6 %. Considering the morphologic endoscopic classification, 67.7 % were granular laterally spreading tumors (LST), 38.8 % were homogeneous granular and 29 % were mixed granular. The most frequent histological types were tubulovillous adenoma (30.7 %) and intramucosal adenocarcinoma (29 %). The resection technique was piecemeal mucosectomy in 85.5 %. Five lesions were removed by en bloc mucosectomy, two (3.2 %) by endoscopic submucosal dissection (ESD) and two (3.2 %) by a hybrid technique. The recurrence rate was 25.8 %. Three patients needed complementary surgical treatment and the clinical success of endoscopic treatment was 95.1 %. CONCLUSION: recurrence rate after endoscopic resection of large colorectal lesions was 25.8 % and surgical complementation rate due to failure in the endoscopic treatment of recurrence was 4.8 %.

Modeling the Field Emission Enhancement Factor for Capped Carbon Nanotubes Using the Induced Electron Density.

In many field electron emission experiments on single-walled carbon nanotubes (SWCNTs), the SWCNT stands on one of two well-separated parallel plane plates, with a macroscopic field FM applied between them. For any given location "L" on the SWCNT surface, a field enhancement factor (FEF) is defined as FL/FM, where FL is a local field defined at "L". The best emission measurements from small-radii capped SWCNTs exhibit characteristic FEFs that are constant (i.e., independent of FM). This paper discusses how to retrieve this result in quantum-mechanical (as opposed to classical electrostatic) calculations. Density functional theory (DFT) is used to analyze the properties of two short, floating SWCNTs, capped at both ends, namely, a (6,6) and a (10,0) structure. Both have effectively the same height (∼5.46 nm) and radius (∼0.42 nm). It is found that apex values of local induced FEF are similar for the two SWCNTs, are independent of FM, and are similar to FEF values found from classical conductor models. It is suggested that these induced-FEF values are related to the SWCNT longitudinal system polarizabilities, which are presumed similar. The DFT calculations also generate "real", as opposed to "induced", potential-energy (PE) barriers for the two SWCNTs, for FM values from 3 V/µm to 2 V/nm. PE profiles along the SWCNT axis and along a parallel "observation line" through one of the topmost atoms are similar. At low macroscopic fields, the details of barrier shape differ for the two SWCNT types. Even for FM = 0, there are distinct PE structures present at the emitter apex (different for the two SWCNTs); this suggests the presence of structure-specific chemically induced charge transfers and related patch-field distributions.

Adult blaschkolinear acquired inflammatory skin eruption (BLAISE) with simultaneous features of lichen striatus and blaschkitis.

Blaschkitis and lichen striatus are generally distinguished in the literature by the age of onset, lesion distribution, and histopathology. However, there is currently no clear consensus among authors about whether to consider blaschkitis and lichen striatus different clinical entities or a spectrum ofthe same disease. We present a case of adult BLAISE with features of both lichen striatus and blaschkitis, which seems to support the theory that these clinical entities may in fact represent a spectrum of the same pathological process.

Hidradenitis Suppurativa in Children Treated with Finasteride-A Case Series.

BACKGROUND: Hidradenitis suppurativa (HS) is rare in childhood, with only 2% of cases in patients younger than 11 years. It is a chronic, recurrent, debilitating condition for which no universally effective treatment has been developed. We present five cases of children with HS diagnosed between the ages of 6 and 11 years. METHODS: Patients were treated with oral finasteride 1 to 5 mg/day. All had entered puberty at the time of treatment initiation. All had normal laboratory results before starting treatment. The maximum duration of treatment was 24 months. RESULTS: Four patients were female. Two were overweight. Three had been previously treated with oral antibiotics, and two of these with oral isotretinoin, with partial or no improvement. Overall improvement of the disease was observed in all patients, with a reduction of the frequency and intensity of the flares. No adverse effects were observed or reported during treatment. CONCLUSION: Treatment of HS can be challenging. The options available include antimicrobials, immunosuppressants, hormonal therapies, lasers, and surgery. The authors report the largest series of children with HS treated with finasteride. The results support the use of finasteride as monotherapy for the treatment of this disease in children. Further studies are necessary to fully understand the role of this drug in the management of this disease.

Importance of immunogenicity testing for cost-effective management of psoriasis patients treated with adalimumab.

INTRODUCTION: Up to 30% of patients treated with anti-tumor necrosis factor drugs do not respond adequately, and up to 50% lose response over time. Immunogenicity is now known to be one of the main causes of this loss of response. METHODS: Serum levels of adalimumab and anti-drug antibodies (ADAs) were measured in 19 patients with psoriasis. RESULTS: Eighty-nine percent of the patients were responders (Psoriasis Area Severity Index (PASI) > 75) and 11% were partial responders (PASI 50-75). The serum levels of adalimumab were lower than the cutoff in both of the partial responders and the ADAs were high, whereas the other 17 patients had adalimumab levels above the cutoff and low ADA levels. Both partial responders were obese and none of them were taking methotrexate. Both patients switched to ustekinumab, and a PASI 90 response was observed after 16 weeks. CONCLUSION: Immunogenicity is a risk of biological drugs. In this work, the detection of low levels of adalimumab and high levels of ADAs using a sandwich ELISA correlated with loss of clinical response. Testing immunogenicity and the drug pharmacokinetics of biological drugs in psoriasis patients will probably be part of the daily management of these patients in the future.

Infantile myofibromatosis - a clinical and pathological diagnostic challenge.

Infantile myofibromatosis is a rare disorder of fibroblastic/myofibroblastic proliferation and represents the most frequent type of mesenchymal tumor in the neonatal period and primary infancy.Three clinical types have been described: solitary, multicentric, and generalized (with visceral involvement). A correct characterization of the histopathology is essential to diagnose these neoplasias in early infancy. We present a case of multicentric infantile myofibromatosis with regression over time.

Annular elastolytic giant cell granuloma: a "visible" diagnosis.

Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin disease of undetermined cause, characterized by annular plaques with raised erythematous borders in sun-exposed skin. The typical histologic features are dermal infiltration by multinucleated giant cells, elastin degeneration, and elastophagocytosis. The authors describe a clinical case of AEGCG, which exhibited an excellent response to hydroxycloroquine.