A new paradigm in the management of scalp pruritus: findings from the SCALP-PR trial.

PURPOSE: The "Impact of scalp pruritus in dermatological consultations in Spain: The SCALP-PR trial" was initiated to address the common yet often insufficiently examined issue of scalp pruritus in dermatology. This condition leads to an uncontrollable urge to scratch, affecting the patients' quality of life and potentially causing scalp damage. This study aimed to explore the prevalence, patient profile, underlying conditios, and therapeutic approaches for scalp pruritus in Spain, and to assess the safety and efficacy profile, as well as the tolerability of a non-pharmacologic treatment. METHODS: From 2021 through 2022, 75 dermatologists enrolled a total of 359 patients in a study on scalp pruritus, approved by the Bellvitge University Hospital Research Ethics Committee, Barcelona, Spain. This evidence-based research combined a meta-analysis with observational study techniques focused on real-world evidence to examine the therapeutic impact on quality of life (QoL). Utilizing the Dermatology Life Quality Index (DLQI) for QoL assessments, the study evaluated the effectiveness of the topical product over 15 days. Data collection was conducted via an eCRF and analyzed with statistical methods to provide reliable insights into the management of scalp pruritus. RESULTS: The prevalence of scalp pruritus in Spain was found to be 6.9%, predominantly among women with a mean age of 52.5 years. The leading causes identified were seborrheic dermatitis and pruritus of undetermined etiology or sensitive scalp. Stress was noted as a key factor, with corticosteroids and hygienic measures being common therapies. The topical product demonstrated significant reductions in pruritus and scratching in more than 90% of patients after 15 days. Improvements were also seen in dermatological quality of life, with 87.1% of patients showing enhancements in DLQI scores. The product was well-received thanksto its cosmetic properties, with high ratings in texture, ease of application, and fragrance. CONCLUSION: The topical product studied is a safe, effective, and cosmetically appealing treatment, improving scalp pruritus in various etiologies for most patients. The results highlight the need for patient-center treatments in dermatology, providing important insights for clinical practice and future research.

Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

Cuero cabelludo sensible: diagnóstico y manejo práctico / Sensitive Scalp: Diagnosis and Practical Management

El cuero cabelludo sensible es una piel sensible de localización especial. Puede ser primario, cuando se presenta sin enfermedad del cuero cabelludo, y secundario cuando es atribuible a procesos como psoriasis, dermatitis seborreica, dermatitis atópica y otros. Las manifestaciones clínicas de la forma primaria son subjetivas. El escozor, picor, tricodinia y sensaciones disestésicas son el motivo de consulta, muy a menudo coincidiendo con alopecia. Clínicamente la piel del cuero cabelludo puede ser normal o eritematosa. No hay datos de laboratorio o histológicos específicos para un diagnóstico objetivo. Los factores desencadenantes son endógenos como el estrés y alteraciones emocionales y psicopatológicas, o ambientales como los tópicos inadecuados y los cosméticos. El tratamiento debe ser personalizado, incluyendo pimecrólimus, la hidratación con ácido hialurónico, y la mesoterapia con plasma rico en factores de crecimiento (AU)

Sensitive scalp is sensitive skin located on the scalp. Sensitivity is considered primary in the absence of an associated scalp disorder and secondary when caused by conditions such as psoriasis, seborrheic dermatitis, and atopic dermatitis. The clinical manifestations of primary sensitive scalp are subjective. Common presenting symptoms are burning, itching, trichodynia, and dysesthesia, often coinciding with hair loss. Clinically, the skin appears normal or red. An objective diagnosis based on laboratory or histologic findings is not possible. Triggers may be endogenous (e.g., stress and emotional or psychopathological disturbances) or exogeneous (e.g., topical products and cosmetics). Treatment must be individualized. Options include pimecrolimus, hydration with hyaluronic acid, and mesotherapy with plasma rich in growth factors (AU)

[Translated article] Sensitive Scalp: Diagnosis and Practical Management / Cuero cabelludo sensible: diagnóstico y manejo práctico

Sensitive scalp is sensitive skin located on the scalp. Sensitivity is considered primary in the absence of an associated scalp disorder and secondary when caused by conditions such as psoriasis, seborrheic dermatitis, and atopic dermatitis. The clinical manifestations of primary sensitive scalp are subjective. Common presenting symptoms are burning, itching, trichodynia, and dysesthesia, often coinciding with hair loss. Clinically, the skin appears normal or red. An objective diagnosis based on laboratory or histologic findings is not possible. Triggers may be endogenous (e.g., stress and emotional or psychopathological disturbances) or exogeneous (e.g., topical products and cosmetics). Treatment must be individualized. Options include pimecrolimus, hydration with hyaluronic acid, and mesotherapy with plasma rich in growth factors (AU)

El cuero cabelludo sensible es una piel sensible de localización especial. Puede ser primario, cuando se presenta sin enfermedad del cuero cabelludo, y secundario cuando es atribuible a procesos como psoriasis, dermatitis seborreica, dermatitis atópica y otros. Las manifestaciones clínicas de la forma primaria son subjetivas. El escozor, picor, tricodinia y sensaciones disestésicas son el motivo de consulta, muy a menudo coincidiendo con alopecia. Clínicamente la piel del cuero cabelludo puede ser normal o eritematosa. No hay datos de laboratorio o histológicos específicos para un diagnóstico objetivo. Los factores desencadenantes son endógenos como el estrés y alteraciones emocionales y psicopatológicas, o ambientales como los tópicos inadecuados y los cosméticos. El tratamiento debe ser personalizado, incluyendo pimecrólimus, la hidratación con ácido hialurónico, y la mesoterapia con plasma rico en factores de crecimiento (AU)

Pharmacological PI3K inhibition in head and neck squamous cell carcinoma: A systematic review.

BACKGROUND: This systematic review aimed to investigate the in vitro and in vivo effects of phosphatidylinositol-3-kinase (PI3K) inhibitors on head and neck squamous cell carcinoma (HNSCC). Considering the role of PI3K and its downstream effectors in cell proliferation, invasion, and survival, it is reasonable to expect that treatment with PI3K inhibitors could control HNSCC onset and progression. Thus, the research question for our review was whether pharmacological inhibition of PI3K affects HNSCC progression. METHODS: In vitro and in vivo studies were selected from six databases. We collected data regarding cell viability, apoptosis, and the regulation of protein expression levels from in vitro studies. For the in vivo studies, we analyzed the reduction in tumor size or gene and protein expression. RESULTS: The included studies showed reduced cell proliferation and apoptosis after treatment with PI3K inhibitors. PI3K inhibitors in combination with other drugs had an enhanced anticancer effects compared to those of single-drug treatments. CONCLUSIONS: The results support the potential of PI3K inhibitors as candidates for clinical trials in HNSCC.

Fluidized or not fluidized? Biophysical characterization of biohybrid lipid/protein/polymer liposomes and their interaction with tetracaine.

BACKGROUND: Nanomedicine and the pharmaceutical industry demand the investigation of new biomaterials to improve drug therapies. Combinations of lipids, proteins, and polymers represent innovative platforms for drug delivery. However, little is known about the interactions between such compounds and this knowledge is key to prepare successful drug delivery systems. METHODS: Biophysical properties of biohybrid vesicles (BhVs) composed of phospholipids, proteins, and amphiphilic block copolymers, assembled without using organic solvents, were investigated by differential scanning calorimetry and dynamic light scattering. We studied four biohybrid systems; two of them included the effect of incorporating tetracaine. Thermal changes of phospholipids and proteins when interacting with the amphiphilic block copolymers and tetracaine were analyzed. RESULTS: Lysozyme and the copolymers adsorb onto the lipid bilayer modifying the phase transition temperature, enthalpy change, and cooperativity. Dynamic light scattering investigations revealed relevant changes in the size and zeta potential of the BhVs. Interestingly, tetracaine, a membrane-active drug, can fluidize or rigidize BhVs. CONCLUSIONS: We conclude that positively charged regions of lysozyme are necessary to incorporate the block copolymer chains into the lipid membrane, turning the bilayer into a more rigid system. Electrostatic properties and the hydrophilic-lipophilic balance are determinant for the stability of biohybrid membranes. GENERAL SIGNIFICANCE: This investigation provides fundamental information associated with the performance of biohybrid drug delivery systems and can be of practical significance for designing more efficient drug nanocarriers.

Sensitive Scalp: Diagnosis and Practical Management. / Cuero cabelludo sensible: diagnóstico y manejo práctico.

Sensitive scalp is sensitive skin located on the scalp. Sensitivity is considered primary in the absence of an associated scalp disorder and secondary when caused by conditions such as psoriasis, seborrheic dermatitis, and atopic dermatitis. The clinical manifestations of primary sensitive scalp are subjective. Common presenting symptoms are burning, itching, trichodynia, and dysesthesia, often coinciding with hair loss. Clinically, the skin appears normal or red. An objective diagnosis based on laboratory or histologic findings is not possible. Triggers may be endogenous (e.g., stress and emotional or psychopathological disturbances) or exogeneous (e.g., topical products and cosmetics). Treatment must be individualized. Options include pimecrolimus, hydration with hyaluronic acid, and mesotherapy with plasma rich in growth factors.

The lamartina square and severity index in surgery for high-grade lumbar listhesis / O quadrado de lamartina e índice de severidade na cirurgia para listese lombar de alto grau / El lamartina square y índice de severidad en la cirurgía de la listesis lumbar de alto grado

ABSTRACT Objective: evaluate the correlation between main sacropelvic alignment measurements and pelvic retroversion reduction and assessing Lamartina Square effectiveness in choosing the proximal instrumentation level. Methods: sample comprising 21 patients with high-grade L5 -S1 spondylolisthesis subjected to arthrodesis with instrumentation from January 2004 to December 2016. Patients' demographic data, surgery type, complications, sagittal alignment parameters, Severity Index and Lamartina Square were recorded before surgery and in the last follow-up. Data processed in SPSS 22.0, with different means were calculated through Student's t test, for paired data. Linear correlation analysis was performed based on Spearman's coefficient. P <0.05 was statically significant. Results: there was significant improvement in the slip and Dubousset's lumbosacral kyphosis angles (> 100° in the last postoperative follow-up). There was significant reduction of slip rate ( and in the L4 and L5 Severity Index, which highlighted strong correlation to pelvic tilt, mismatch and slip angle. Severity index also showed strong inverse correlation between Dubousset's lumbosacral kyphosis angle and sacral slope. Conclusion: L5 Severity Index and Lamartina Square are important variables for preoperative planning of patients with high-grade lumbar spondylolisthesis. Level of Evidence IV; Case Series.

Resumo: Objetivo: avaliar a correlação entre as principais medidas do alinhamento sacropélvico com a retroversão pélvica e avaliar a efetividade do Lamartina Square na escolha do nível proximal de intrumentação. Métodos: amostra com 21 pacientes com espondilolistese de alto grau L5-S1, submetidos à artrodese com instrumentação, de 01/2004 a 12/2016. Os dados demográficos dos pacientes, tipos de cirurgias, complicações, parâmetros do alinhamento sagital, Severity Index e Lamartina Square foram registrados antes da cirurgia e no último acompanhamento. Dados processados no SPSS 22.0 com as diferenças das médias calculadas utilizando-se o teste t de Student para dados emparelhados. A análise da correlação linear foi realizada pelo coeficiente de Spearman. Significantes as análises com p < 0,05. Resultados: melhora significativa do ângulo de deslizamento e de cifose lumbosacral de Dubousset´s (> 100° no ultimo seguimento pósoperatório). Redução significativa da porcentagem de deslizamento ( e do severity index em L4 e L5. Este teve uma forte correlação direta com: tilt pélvico, mismatch, ângulo de deslizamento, porcentagem de deslizamento e uma forte inversa com: ângulo de cifose lumbosacral de Dubousset´s e o slope sacral. Conclusão: O Severity Index de L5 e o Lamartina Square devem ser consideradas variáveis importantes no planejamento pré-operatório de pacientes com espondilolistese lombar de alto grau.

Resumen: Objetivo: evaluar la correlación entre las principales medidas de alineación sacropélvica y la reducción de la retroversión pélvica y evaluar la eficacia de Lamartina Square en la elección del nivel de instrumentación proximal. Métodos: muestra compuesta por 21 pacientes con espondilolistesis L5-S1 de alto grado sometidos a artrodesis con instrumentación desde enero de 2004 hasta diciembre de 2016. Se registraron datos demográficos de los pacientes, tipo de cirugía, complicaciones, parámetros de alineación sagital, Índice de Severidad y Cuadrado de Lamartina antes de la cirugía y en el último seguimiento. Los datos procesados en SPSS 22.0, con diferentes medias, se calcularon mediante la prueba t de Student, para datos pareados. Se realizó un análisis de correlación lineal basado en el coeficiente de Spearman. P <0,05 fue estadísticamente significativo. Resultados: hubo mejoría significativa en los ángulos de deslizamiento y cifosis lumbosacra de Dubousset (> 100° en el último control postoperatorio). Hubo una reducción significativa en la tasa de deslizamiento (<50 %) y en el índice de gravedad L4 y L5, que destacó una fuerte correlación con la inclinación pélvica, la falta de coincidencia y el ángulo de deslizamiento. El índice de gravedad también mostró una fuerte correlación inversa entre el ángulo de cifosis lumbosacra de Dubousset y la pendiente sacra. Conclusión: L5 Severity Index y Lamartina Square son variables importantes para la planificación preoperatoria de pacientes con espondilolistesis lumbar de alto grado. Nivel de Evidencia IV; Serie de Casos.

Sagittal misalignment in adolescent idiopathic scoliosis / Desalinhamento sagital na escoliose idiopática do adolescente / Mala alineación sagital en la escoliosis idiopática del adolescente

ABSTRACT: Introduction: The correlation between sagittal and coronal parameters in patients with adolescent idiopathic scoliosis (AIS) presents contradictory results and is not fully understood. Objective: To evaluate the sagittal vertical axis (SVA) and its correlation with sagittal parameters and the main curve in patients diagnosed with AIS. Methods: 109 patients with AIS and indications for surgical treatment were evaluated. The correlation of the SVA with sagittal parameters (thoracic kyphosis, lumbar lordosis, pelvic incidence, lumbar lordosis, pelvic version, and sacral inclination) and with the main curves (main thoracic and thoracolumbar/lumbar) was evaluated. Results: The SVA ranged from -208 to 66.30 mm (mean -19.64 ± 36.21), above 50 mm in two patients (1.83%). There was no correlation between the sagittal parameters and the magnitude of the main curve and the SVA. Conclusion: The SVA showed great variability in the group of patients with AIS; a small percentage of patients had an SVA greater than 50 mm. The low percentage of patients with sagittal misalignment showed the compensatory capacity of young patients with vertebral deformity. Level of Evidence: III; Observational and Retrospective Study.

RESUMO: Introdução: A correlação entre os parâmetros sagitais e coronais nos pacientes com escoliose idiopática do adolescente (EIA) apresenta resultados contraditórios e não está totalmente esclarecida. Objetivo: Avaliar o eixo sagital vertical (SVA) e sua correlação com parâmetros sagitais e a curva principal de pacientes com diagnóstico de EIA. Métodos: Foram avaliados 109 pacientes com EIA e indicação de tratamento cirúrgico. Foi avaliada a correlação do SVA com parâmetros sagitais (cifose torácica, lordose lombar, incidência pélvica, lordose lombar, versão pélvica e inclinação do sacro) e com as curvas principais (torácica principal e toracolombar/lombar). Resultados: O SVA variou de -208 a 66,30 mm (média -19,64 ± 36,21), ficando acima de 50 mm em dois pacientes (1,83%). Não foi observada correlação dos parâmetros sagitais e da magnitude da curva principal com o SVA. Conclusão: O SVA apresentou grande variabilidade no grupo de pacientes com EIA e pequena porcentagem dos pacientes apresentaram SVA maior que 50 mm. A baixa porcentagem de pacientes com desalinhamento sagital evidenciou a capacidade compensatória dos pacientes jovens e com deformidade vertebral. Nível de Evidência: III; Estudo Observacional e Retrospectivo.

RESUMEN: Introducción: La correlación entre los parámetros sagitales y coronales en pacientes con escoliosis idiopática del adolescente (EIA) presenta resultados contradictorios y no se comprende completamente. Objetivo: Evaluar el eje vertical sagital (SVA) y su correlación con los parámetros sagitales y la curva principal en pacientes diagnosticados de EIA. Métodos: Se evaluaron 109 pacientes con EIA e indicación de tratamiento quirúrgico. Se evaluó la correlación del SVA con parámetros sagitales (cifosis torácica, lordosis lumbar, incidencia pélvica, lordosis lumbar, versión pélvica e inclinación sacra) y con las curvas principales (torácica principal y toracolumbar/lumbar). Resultados: El SVA osciló entre -208 y 66,30 mm (media -19,64 ± 36,21), siendo superior a 50 mm en dos pacientes (1,83%). No hubo correlación entre los parámetros sagitales o la magnitud de la curva principal y el SVA. Conclusión: El SVA mostró una gran variabilidad en el grupo de pacientes con EIA y un pequeño porcentaje de pacientes presentó una SVA superior a 50 mm. El bajo porcentaje de pacientes con desalineación sagital mostró la capacidad compensatoria de los pacientes jóvenes con deformidad vertebral. Nivel de Evidencia: III; Estudio Observacional y Retrospectivo.

Evaluation of cervical lordosis in patients with adolescent idiopathic scoliosis / Avaliação da lordose cervical nos pacientes com escoliose idiopática do adolescente / Evaluación de lordosis cervical en pacientes con escoliosis idiopática del adolescente

ABSTRACT: Introduction: In healthy individuals and in patients with adolescent idiopathic scoliosis (AIS), the curvature of the cervical spine varies greatly, with approximately 36-40% of AIS patients having kyphosis of the cervical spine. Aim: To assess the curvature of the cervical spine in AIS patients and subgroups according to Lenke's classification (1 to 6). Methods: 107 patients with AIS were assessed for cervical lordosis (C2-C7) using the Cobb method, subdivided into lordosis and cervical kyphosis. The following parameters were assessed and compared between the subgroups: T5-T12 thoracic kyphosis (TK); L1-S1 lumbar lordosis (LL), pelvic incidence (PI), sagittal vertical axis (SVA), T1 pelvic angle (TPA), C2-C7 cervical lordosis, C1-C2 cervical lordosis, T1 slope (T1s), neck tilt, thoracic inlet angle (TIA) and cervical sagittal axis (CSVA). Results: Kyphosis of the cervical spine was observed in 48% of patients. The Lenke classification curves (1 to 6) showed no difference with regard to the curvature of the cervical spine. In the subgroup with cervical lordosis, thoracic kyphosis, and T1 slope were significantly higher. Neck tilt was significantly higher in the subgroup with kyphosis. Conclusions: Almost half of the patients have kyphosis of the cervical spine, and the curvature of the cervical spine in AIS patients varies widely. Thoracic kyphosis, T1 slope, and neck tilt are significantly different between the subgroups of patients with lordosis or kyphosis. Level of Evidence III; Observational and Retrospective Study.

RESUMO: Introdução: Nos indivíduos saudáveis e nos pacientes com escoliose idiopática do adolescente (EIA) a curvatura da coluna cervical apresenta grande variação, sendo que aproximadamente 36-40% dos pacientes com EIA apresentam cifose da coluna cervical. Objetivo: Avaliar a curvatura da coluna cervical nos pacientes com EIA e nos subgrupos, de acordo com a classificação de Lenke (1 a 6). Métodos: Foram avaliados 107 pacientes com EIA quanto a lordose cervical (C2-C7), pelo método de Cobb, subdivididos em dois grupos: lordose e cifose cervical. Foram avaliados e comparados entre os subgrupos os seguintes parâmetros: cifose torácica T5-T12 (TK); lordose lombar L1-S1 (LL), incidência pélvica (PI), eixo sagital vertical (SVA), ângulo T1 pélvico (TPA), lordose cervical C2-C7, lordose cervical C1-C2, inclinação T1 (T1s), inclinação cervical (neck tilt), ângulo entrada torácica (TIA) e eixo cervical sagital (CSVA). Resultados: A cifose da coluna cervical foi observada em 48% dos pacientes. As curvas de classificação de Lenke (1 a 6) não apresentaram diferença com relação à curvatura da coluna cervical. No subgrupo com lordose cervical a cifose torácica e a inclinação de T1 foram significativamente maiores. A inclinação cervical foi significativamente maior no subgrupo com cifose. Conclusões: Quase a metade dos pacientes apresenta cifose da coluna cervical, sendo amplamente variável a curvatura da coluna cervical nos pacientes com EIA. A cifose torácica, a inclinação de T1 e a inclinação cervical são significativamente diferentes entre os subgrupos de pacientes com lordose ou cifose. Nível de Evidência III; Estudo Observacional e Retrospectivo.

RESUMEN: Introducción: En individuos sanos y en pacientes con escoliosis idiopática del adolescente (EIA), la curvatura de la columna cervical varía enormemente, y aproximadamente el 36-40% de los pacientes con EIA presentan cifosis de la columna cervical. Objetivo: Evaluar la curvatura de la columna cervical en pacientes con EIA y subgrupos según la clasificación de Lenke (1 a 6). Métodos: Se evaluó la lordosis cervical (C2-C7) de 107 pacientes con EIA mediante el método de Cobb, subdivididos en dos grupos: lordosis y cifosis cervical. Se evaluaron y compararon los siguientes parámetros entre los subgrupos: Cifosis torácica (TK) T5-T12; lordosis lumbar (LL) L1-S1, incidencia pélvica (PI), eje vertical sagital (SVA), ángulo pélvico T1 (TPA), lordosis cervical C2-C7, lordosis cervical C1-C2, inclinación T1 (T1s), inclinación del cuello, ángulo de la entrada torácica (TIA) y eje sagital cervical (CSVA). Resultados: Se observó cifosis de la columna cervical en el 48% de los pacientes. Las curvas de clasificación de Lenke (1 a 6) no mostraron diferencias con respecto a la curvatura de la columna cervical. En el subgrupo con lordosis cervical, la cifosis torácica y la inclinación T1 eran significativamente mayores. La inclinación cervical fue significativamente mayor en el subgrupo con cifosis. Conclusiones: Casi la mitad de los pacientes presentan cifosis de la columna cervical, y la curvatura de la columna cervical en los pacientes con EIA varía ampliamente. La cifosis torácica, la inclinación T1 y la inclinación cervical son significativamente diferentes entre los subgrupos de pacientes con lordosis o cifosis. Nivel de Evidencia: III; Estudio Observacional y Retrospectivo.

Hartmann's procedure versus primary anastomosis for Hinchey stage III diverticulitis: a prospective case-control study.

INTRODUCTION: Hartmann's procedure (HP) is the conventional treatment in patients with complicated diverticulitis. Segmental resection with primary anastomosis (PA) is a treatment alternative for those patients. Our aim was to compare the postoperative results of HP and PA in patients with complicated diverticulitis (Hinchey stage III). METHODS: A case-control study was conducted on patients operated on for purulent Hinchey stage III diverticulitis, within the time frame of 2000 and 2019. RESULTS: Twenty-seven patients that underwent PA were compared with 27 that underwent HP. The patients that underwent HP had a greater probability of morbidity at 30 days (OR 3.5; 95% CI 1.13-11.25), as well as a greater probability of major complications (OR 10.9; 95% CI 1.26-95.05). CONCLUSION: The patients that underwent segmental resection and PA presented with lower morbidity rates and higher stoma reversal rates than the patients that underwent HP.

Quantitative and qualitative features of acute phase-adverse events following SARS-CoV-2 vaccination in a large sample of people with multiple sclerosis.

INTRODUCTION: Few data are available on adverse events (AE) associated to vaccines in persons with multiple sclerosis (pwMS). AIMS: to study the incidence of acute phase AE (AP-AE) related to SARS-CoV-2 mRNA vaccines in pwMS compared to a control group, and to analyze the association between AP-AE and disease modifying treatments (DMT). METHODS: This was a cross-sectional study on 438 PwMS and 481 age- and sex-matched subjects not affected by dysimmune diseases that underwent two doses of SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer/BioNtech). RESULTS: Two hundred and twenty five (51.4%) pwMS complained of ≥1 AP-AE after the first dose, 269 (61.4%) after the second dose. A logistic regression analysis revealed that only pwMS on Fingolimod and Ocrelizumab did not show a higher risk of developing AP-AE. The likelihood to present with ≥1 AP-AE, after correcting for age and sex, was significantly higher in pwMS than controls. CONCLUSIONS: This study reports qualitative and quantitative features of AP-AE associated with the first and second doses of SARS-CoV-2 vaccine in a large sample of pwMS. The only risk factor identified for developing AP-AE is female gender. AntiCD-20 monoclonal antibodies and S1P inhibitors are associated with a lower risk of AP-AE occurrence.

The gut microbiome variability of a butterflyfish increases on severely degraded Caribbean reefs.

Environmental degradation has the potential to alter key mutualisms that underlie the structure and function of ecological communities. How microbial communities associated with fishes vary across populations and in relation to habitat characteristics remains largely unknown despite their fundamental roles in host nutrition and immunity. We find significant differences in the gut microbiome composition of a facultative coral-feeding butterflyfish (Chaetodon capistratus) across Caribbean reefs that differ markedly in live coral cover (∼0-30%). Fish gut microbiomes were significantly more variable at degraded reefs, a pattern driven by changes in the relative abundance of the most common taxa potentially associated with stress. We also demonstrate that fish gut microbiomes on severely degraded reefs have a lower abundance of Endozoicomonas and a higher diversity of anaerobic fermentative bacteria, which may suggest a less coral dominated diet. The observed shifts in fish gut bacterial communities across the habitat gradient extend to a small set of potentially beneficial host associated bacteria (i.e., the core microbiome) suggesting essential fish-microbiome interactions may be vulnerable to severe coral degradation.

Toxicological effects of air settled particles from the Vitoria Metropolitan Area mediated by oxidative stress, pro-inflammatory mediators and NFΚB pathway.

Atmospheric pollution is a major environmental and public health risk due to its effect on global air quality and climate. Increase in pollutants concentrations, especially particulate matter (PM), are associated with increased respiratory diseases. The pathophysiology of respiratory diseases involves molecular and cellular mechanisms as inflammatory biomarkers and reactive oxygen species production. Thus, the present study aimed to investigate the in vitro cytotoxic and pro-inflammatory effects of particulate matter (PM) of six monitoring stations (1-6) from the Vitoria Metropolitan Area (VMA), Espirito Santo, Brazil in 2018. The PM was chemically characterized by inductively coupled plasma mass spectrometry. In vitro cytotoxic effects of PM (3.12-200.0 µg/mL) were analyzed in human lung epithelial cells (A549) and macrophage cells (RAW 264.7) by MTT assay (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide). To investigate the pro-inflammatory effects of PM in RAW 264.7 cells, the levels of proinflammatory mediators such as nitric oxide (NO), superoxide anion (O2•-), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and the activation of nuclear factor kappa B (NF- κB) were measured. The comet assay evaluated genotoxicity. Cell cycle, oxidative stress (DCF and DHE), and apoptosis were analyzed by flow cytometry. Chemical analysis of PM revealed aluminum (Al) and Iron (Fe) as the major chemical elements in all studied monitoring stations. In addition, worrying concentrations of mercury (Hg) were detected in the PM. The in vitro results showed that PM presents a dose-dependent cytotoxic effect in macrophage and pulmonary epithelial cell lines. The PM increased the production of NO, O2•-, and pro-inflammatory cytokines TNF-α and IL-6. PM also promoted alterations in the cell cycle, increased apoptosis frequency, and DNA damage. Moreover, PM increased the expression NF-κB. In addition, a positive correlation between Al and Fe and ROS production was observed. Based on the results obtained during the study period, it was concluded that the sedimented particles from the VMA might have deleterious effects on human health, which was evidenced by the increase in oxidative stress, an increase in pro-inflammatory mediators, and genotoxic effects partially mediated by the NF-κB pathway. These results add aspects to elucidate the molecular mechanisms involved in the effects of sedimented particles in vivo and in vitro.

Comparative analysis of origin and branches of phrenic nerve in the diaphragm of the crab-eating fox (Cerdocyon thous) and domestic dog (Canis lupus familiaris).

The crab-eating fox (Cerdocyon thous) is a canid widely distributed throughout South America, considered the only representative of the gender. There is a lack of information about anatomical aspects of the species, mainly regarded of nervous system anatomy. For clinical and surgical approaches of these animals, the domestic dog is adopted as anatomophysiological model. So, the aim of the present study was to analyse origin and branches of the phrenic nerve in the diaphragm of crab-eating fox compared to domestic dog. Four specimens of Cerdocyon thous and four of Canis lupus familiaris were used. The phrenic nerve originated from the ventral branches of the fifth (C5), sixth (C6) and seventh (C7) cervical spinal nerves. Phrenic nerves were distributed in the diaphragm as lumbocostal trunk and sternal branch (100%) in the crab-eating fox, and in costosternal trunk and lumbar branch (75%) and lumbocostal trunk and sternal branch (25%) in the domestic dog. In both species, the lumbar branch innervates the diaphragm pillars, the costal branch addresses all costal region, and the sternal branch distributes in the costal ventrolateral region and the sternal part of the diaphragm, to the left and to the right.

Oral Manifestations in Patients with COVID-19: A 6-Month Update.

This is the first update of the previously published living systematic review that summarized evidence on the prevalence of oral signs and symptoms in patients with COVID-19. Hitherto, 183 studies were included, reporting data from 64,876 patients with COVID-19 worldwide. The overall prevalence of taste disorders was 38% (95% CI = 22% to 56%, I2 = 98%). Hypogeusia, dysgeusia, and ageusia were also evaluated by a meta-analysis, and the pooled prevalence was 34% for hypogeusia, 33% for dysgeusia, and 26% for ageusia. Taste disorders were associated with a positive COVID-19 test (odds ratio [OR] = 7.54, 95% CI = 5.24 to 10.86, I2 = 93%, P < 0.00001), showing high certainty of evidence. However, the association between taste disorders and mild/moderate severity of COVID-19 (OR = 1.63, 95% CI = 1.33 to 1.99, I2 = 69%, P < 0.0001) and female patients with COVID-19 (OR = 1.77, 95% CI = 1.26 to 2.48, I2 = 79%, P = 0.001) presented low certainty of evidence. Xerostomia was a new feature of this update, and the pooled data demonstrated a prevalence of 43% (95% CI = 36% to 50%, I2 = 71%) in patients with COVID-19. Regarding oral mucosal lesions, the most common clinical pattern was aphthous like, followed by herpes-like lesions, candidiasis, glossitis/depapillation/geographic tongue, parotitis, and angular cheilitis. Oral lesions were more frequent in the tongue, lips, and palate, presenting miscellaneous clinical aspects that are more likely to represent coinfections. Therefore, the reanalysis of current evidence suggests the triad xerostomia, taste dysfunction, and oral mucosal lesions as common manifestations in patients with COVID-19. However, these outcomes are under discussion, and more studies will be necessary to confirm their association with direct SARS-CoV-2 infection in the oral cavity.

Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study).

BACKGROUND: There is limited evidence for the benefit of olaparib in platinum-resistant ovarian cancer (PROC) patients with BRCA wild-type tumors. This study investigated whether this combination of a DNA-damaging chemotherapy plus olaparib is effective in PROC regardless BRCA status. PATIENTS AND METHODS: Patients with high-grade serous or endometrioid ovarian carcinoma and one previous PROC recurrence were enrolled regardless of BRCA status. Patients with ≤4 previous lines (up to 5 in BRCA-mut) with at least one previous platinum-sensitive relapse were included; primary PROC was allowed only in case of BRCA-mut. Patients initially received six cycles of olaparib 300 mg b.i.d. (biduum) + intravenous pegylated liposomal doxorubicin (PLD) 40 mg/m2 (PLD40) every 28 days, followed by maintenance with olaparib 300 mg b.i.d. until progression or toxicity. The PLD dose was reduced to 30 mg/m2 (PLD30) due to toxicity. The primary endpoint was progression-free survival (PFS) at 6 months (6m-PFS) by RECIST version 1.1. A proportion of 40% 6m-PFS or more was considered of clinical interest. RESULTS: From 2017 to 2020, 31 PROC patients were included. BRCA mutations were present in 16%. The median of previous lines was 2 (range 1-5). The overall disease control rate was 77% (partial response rate of 29% and stable disease rate of 48%). After a median follow-up of 10 months, the 6m-PFS and median PFS were 47% and 5.8 months, respectively. Grade ≥3 treatment-related adverse events occurred in 74% of patients, with neutropenia/anemia being the most frequent. With PLD30 serious AEs were less frequent than with PLD40 (21% versus 47%, respectively); moreover, PLD30 was associated with less PLD delays (32% versus 38%) and reductions (16% versus 22%). CONCLUSIONS: The PLD-olaparib combination has shown significant activity in PROC regardless of BRCA status. PLD at 30 mg/m2 is better tolerated in the combination.