Parental Assessment of Infantile Hemangioma Cosmetic Clinical Outcomes: Results of the Spanish Hemangioma Nationwide Prospective Cohort.

BACKGROUND: Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. OBJECTIVE: To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. PATIENTS AND METHODS: The Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016-2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores - both before and after treatment - as well as the outcomes percent considered excellent (>9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents' assessments. RESULTS: The median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p<0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p>0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. CONCLUSION: This is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.

Understanding limb necrotizing infections: A comprehensive approach.

INTRODUCTION: Necrotizing soft tissue infections (NSTI) are increasing, posing a significant risk of morbidity and mortality. Due to nonspecific symptoms, a high index of suspicion is crucial. Treatment involves a multidisciplinary approach, with broad-spectrum antibiotics, early surgical debridement, and life support. This study analyzes the characteristics, demographics, complications, and treatment of NSTI in a hospital in Madrid, Spain. METHODS: A retrospective observational study was conducted, including all surgically treated NSTI patients at our center from January 2016 to December 2022, examining epidemiological and clinical data. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) was prospectively calculated for all patients. RESULTS: Twenty-two patients (16 men, 6 women, mean age 54.8) were included. Median time from symptom onset to emergency room visit was 3.5 days. All reported severe treatment-resistant pain; sixteen had fever exceeding 37.8°C (72.7%). Skin lesions occurred in twelve (54.5%), and thirteen had hypotension and tachycardia (59.1%). Treatment involved resuscitative support, antibiotherapy, and radical debridement. Median time to surgery was 8.25h. Intraoperative cultures were positive in twenty patients: twelve Streptococcus pyogenes, four Staphylococcus aureus, one Escherichia coli, and four polymicrobial infection. In-hospital mortality rate was 22.73%. CONCLUSIONS: We examined the correlation between our results, amputation rates and mortality with LRINEC score and time to surgery. However, we found no significant relationship unlike some other studies. Nevertheless, a multidisciplinary approach with radical debridement and antibiotic therapy remains the treatment cornerstone. Our hospital stays, outcomes and mortality rates align with our literature review, confirming high morbimortality despite early and appropriate intervention.

External fixation in intra-articular fractures of the calcaneus: Is it a valid option as definitive treatment?

INTRODUCTION: The therapeutic management of calcaneal fractures is currently a major source of controversy in the literature. There is no consensus on the need to treat these injuries conservatively or surgically, nor on the criteria for deciding one option or the other. Although the gold standard has classically been the open approach and osteosynthesis, there are currently minimally invasive techniques that also report good results. Our objective is to present our results and experience with the MBA® Orthofix external fixator in a series of cases of calcaneal fractures. METHODS: We performed a retrospective observational study in our center, between the years 2019 and 2021, of Sanders types II-IV calcaneal fractures operated with MBA® Orthofix external fixator. We recorded a total of 38 patients, 42 fractures. We registered demographic information, intraoperative, postoperative, radiological and functional parameters, using the American Orthopedic Foot and Ankle Society (AOFAS), Manchester-Oxford Foot Questionnaire (MOXFQ), EQ-5D and VAS scales. RESULTS: A total of 26 men and 12 women were included, and the median age was 38 years. Mean follow-up was 24,4 months (6, 8-40, 1). The average time to surgery was 7 days and partial loading was started at 2.5 weeks after external fixation, which was removed at 9.2 weeks. The average Böhler angle correction was 7, 4°, Gissane - 12,2°, length 2 mm and calcaneal width was reduced by 5 mm. We recorded two superficial infections, one peroneal entrapment and three subtalar arthrodesis due to post-traumatic osteoarthritis. The AOFAS obtained was 79.1 + / - 15.7 points, MOXFQ 20.1 + / - 16.1 points, EQ-5D 0.84 + / - 0.2 and VAS 3.3 + / - 1.9. CONCLUSION: The external fixator is an excellent surgical alternative for complex articular fractures of the calcaneus, obtaining clinical and radiological results comparable to other osteosynthesis techniques and significantly reducing soft tissue complications.

Smokers and risk of hospital death by COVID calculated with SAVANA's natural language processing in the Castilla-La Mancha area.

INTRODUCTION: During the COVID pandemic, it was speculated that patients with the virus who were smoking-related might have a lower likelihood of disease exacerbation or death. To assess whether there is an association between smoking and risk of in-hospital mortality, SAVANA's big data and Natural Language Processing (NLP) technology is used. METHOD: A retrospective, observational, non-interventional cohort study was conducted based on real-life data extracted from medical records throughout Castilla La Mancha using Natural Language Processing and Artificial Intelligence techniques developed by SAVANA. The study covered the entire population of this region with Electronic Medical Records in SESCAM presenting with a diagnosis of COVID from March 1, 2020 to February 28, 2021. RESULTS: Smokers had a significantly higher percentage of cardiovascular risk factors (hypertension, dyslipidemia and diabetes), COPD, asthma, IDP, IC, CVD, PTE, cancer in general and lung cancer in particular, bronchiectasis, heart failure and a history of pneumonia (p < 0.0001).Former smokers, current smokers and non-smokers have a significant age difference. As for in-hospital deaths, they were more frequent in the case of ex-smokers, followed by smokers and then non-smokers (p < 0.0001). CONCLUSION: There is an increased risk of dying in hospital in SARS-COV2-infected patients who are active smokers or have smoked in the past.

Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings / Aplicação exógena de ácido salicílico induz tolerância à salinidade em mudas de berinjela

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

The REWRITE Study - REal-WoRld effectIveness of TrifluridinE/tipiracil in Patients with Previously Treated Metastatic Colorectal Cancer.

AIMS: In the pivotal RECOURSE trial, trifluridine/tipiracil improved survival outcomes in refractory metastatic colorectal cancer (mCRC), while demonstrating an acceptable toxicity profile. Routine clinical practice evidence is important to support the ongoing value of recently approved medicines. Our objective was to assess the utilisation patterns and real-world effectiveness of trifluridine/tipiracil in previously treated mCRC patients. MATERIALS AND METHODS: This was a retrospective observational study including consecutive patients who started trifluridine/tipiracil between 1 April 2018 and 30 September 2019 in the medical oncology departments of three major public hospitals in Portugal. The primary outcome measure was overall survival. Associations between overall survival and patient and tumour characteristics were assessed using multivariate Cox regression analyses. RESULTS: In total, 111 patients were included in the study, with a mean age of 64 years. From these, 45.9% received two prior lines of treatment, 47.8% had three or more previous lines of treatment and 83.6% had Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at baseline. The median duration of trifluridine/tipiracil treatment was 3.7 cycles (95% confidence interval 3.4-4.1). Most patients (80.4%) remained on their planned dose throughout the trifluridine/tipiracil treatment period, fulfilling 100% relative dose intensity. The median overall survival in the total study cohort was 7.9 months (95% confidence interval 6.4-9.8) and the median progression-free survival was 3.4 months (95% confidence interval 3.2-3.9). The median overall survival was significantly higher in patients with a normal serum lactate dehydrogenase (LDH) level (median overall survival 11.2 months for [135, 205] IU/l LDH [95% confidence interval 8.2-NR] and 13.6 months for [205, 251] IU/l LDH [95% confidence interval 8.2-NR]) and in better fitted (ECOG = 0-1) patients (median overall survival 8.0 months; 95% confidence interval 6.7-10.0). The median time to worsening performance status was 6.2 months (95% confidence interval 5.0-8.0). Treatment discontinuation due to adverse events was low (3.1%). CONCLUSION: Our study confirms the effectiveness of trifluridine/tipiracil in real-life mCRC patients. Overall survival and progression-free survival outcomes are consistent with the efficacy profile reported in the earlier randomised RECOURSE clinical trial. Like other real-world studies, we found no additional safety concerns in the use of trifluridine/tipiracil.

Large-scale real-life analysis of survival and usage of therapies in multiple myeloma.

Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Ovarian cancer prevention by opportunistic salpingectomy is a new de facto standard in Germany.

PURPOSE: The most prevalent and aggressive subtype of epithelial ovarian carcinoma (EOC), high-grade serous carcinoma (HGSC), originates in many cases from the fallopian tubes. Because of poor prognosis and lack of effective screening for early detection, opportunistic salpingectomy (OS) for prevention of EOC is being implemented into clinical routine in several countries worldwide. Taking the opportunity of a gynecological surgery in women at average cancer risk, extramural fallopian tubes are completely resected preserving the ovaries with their infundibulopelvic blood supply. Until recently, only 13 of the 130 national partner societies of the International Federation of Obstetrics and Gynecology (FIGO) have published a statement on OS. This study aimed to analyze the acceptance of OS in Germany. METHODS: (1) Survey of German gynecologists in 2015 and 2022 by the Department of Gynecology of the Jena University Hospital in co-operation with the Department of Gynecology at Charité-University Medicine Berlin with support of NOGGO e. V. and AGO e. V. (2) Salpingectomy numbers in Germany for years 2005-2020 as retrieved from the Federal Statistical Office of Germany (Destatis). RESULTS: (1) Survey: Number of participants was 203 in 2015 and 166 in 2022, respectively. Nearly all respondents (2015: 92%, 2022: 98%) have already performed bilateral salpingectomy without oophorectomy in combination with benign hysterectomy with the intention to reduce the risk for malignant (2015: 96%, 2022: 97%) and benign (2015: 47%, 2022: 38%) disorders. Compared to 2015 (56.6%), considerably more survey participants performed OS in > 50% or in all cases in 2022 (89.0%). Recommendation of OS for all women with completed family planning at benign pelvic surgery was approved by 68% in 2015 and 74% in 2022. (2) Case number analysis: In 2020, four times more cases of salpingectomy were reported by German public hospitals compared to 2005 (n = 50,398 vs. n = 12,286). Of all inpatient hysterectomies in German hospitals in 2020, 45% were combined with salpingectomy, and more than 65% in women at the age of 35 to 49 years. CONCLUSION: Mounting scientific plausibility regarding involvement of fallopian tubes in the pathogenesis of EOC led to change of clinical acceptance of OS in many countries including in Germany. Case number data and widespread expert judgment demonstrate that OS has become a routine procedure in Germany and a de facto standard for primary prevention of EOC.

Selection of Quality Indicators for the Certification of Dermato-Oncology Units: The CUDERMA Project Delphi Consensus Study. / Proyecto CUDERMA: Consenso Delphi de los indicadores de calidad para la certificación de las unidades de dermatología de atención en dermato-oncología.

Quality indicators are crucial for standardizing and guaranteeing the quality of health care practices. The Spanish Academy of Dermatology and Venereology (AEDV) launched the CUDERMA Project to define quality indicators for the certification of specialized units in dermatology; the first 2areas selected were psoriasis and dermato-oncology. The aim of this study was to achieve consensus on what should be evaluated by these indicators using a structured process comprising a literature review and selection of an initial list of indicators to be evaluated in a Delphi consensus study following review by a multidisciplinary group of experts. The selected indicators were evaluated by a panel of 28 dermatologists and classified as either «essential¼ or «of excellence¼. The panel agreed on 84 indicators, which will be standardized and used to develop the certification standard for dermato-oncology units.

Comparación de las características epidemiológicas, clínicas y quirúrgicas de pacientes con y sin recidiva de hernias inguinales operados en el Centro Médico Naval.

BACKGROUND: Recurrent inguinal hernia is currently considered a complex hernia of the abdominal wall after it has been managed with a primary procedure, which represents a more technically challenging hernia. OBJECTIVE: To determine the difference in epidemiological, clinical and surgical characteristics of patients with recurrent inguinal hernia and patients without recurrence. METHOD: Analytical cross-sectional study, in people over 18 years of age after surgery for inguinal hernia at the Naval Medical Center during the period from July 1, 2016 to June 30, 2019, integrating two study groups. RESULTS: 106 patients were included, 29 surgeries for recurrence, predominance of men and older than 60 years. Differences was found between the group of surgery for recurrence and the group of primary surgery in surgical time in minutes, with medians of 115 (p25 75 and p75 154) and 72 (p25 58 and p75 110), respectively (p = 0.001); type of open approach, 62.1% and 88.3% (p = 0.005), and type of regional anesthesia, 48.3% and 75.3% (p = 0.008). Correlation between body mass index and size of the hernial defect was explored, obtaining r of -0.099 and p = 0.652, with a null correlation between them. CONCLUSIONS: With the findings obtained in this study, it is possible to hypothesize the behavior of the naval population which may differ from the general population and thus establish follow-up protocols to give magnitude to already known factors.

ANTECEDENTES: La hernia inguinal recidivante es considerada actualmente como una hernia compleja de la pared abdominal después de que se haya manejado con un procedimiento primario, lo que representa una hernia con un mayor desafío técnico. OBJETIVO: Determinar las diferencias en las características epidemiológicas, clínicas y quirúrgicas de pacientes con hernia inguinal recidivante y sin recidiva. MÉTODO: Estudio transversal analítico en mayores de 18 años operados por hernia inguinal en el Centro Médico Naval durante el periodo del 1 de julio de 2016 al 30 de junio de 2019, integrando dos grupos de estudio. RESULTADOS: Se incluyeron 106 pacientes, 29 cirugías por recidiva, predominio de hombres y mayores de 60 años. Se encontraron diferencias entre el grupo de cirugía por recidiva y el grupo de cirugia primaria en tiempo quirúrgico, con medianas de 115 (p25 75 y p75 154) y 72 (p25 58 y p75 110) minutos, respectivamente (p = 0.001); tipo de abordaje, abierto 62.1% y 88.3% (p = 0.005); y tipo de anestesia, regional 48.3% y 75.3% (p = 0.008). Se exploró la correlación entre el índice de masa corporal y el tamaño del defecto herniario, obteniendo r de −0.099 y p = 0.652, con una correlación nula entre ambas. CONCLUSIONES: Con los hallazgos obtenidos en este estudio es posible plantear hipótesis del comportamiento de la población naval que pueda diferir de la población general, y con esto establecer protocolos de seguimiento para dar magnitud a factores ya conocidos.

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Amphiphilic silicones to mitigate lens epithelial cell growth on intraocular lenses.

Silicone intraocular lenses (IOLs) that resist lens epithelial cell (LEC) growth would greatly improve patient outcomes. Herein, amphiphilic surface modifying additives (SMAs) were incorporated into an IOL-type diphenyl silicone to reduce LEC growth without compromising opto-mechanical properties. The SMAs were poly(ethylene oxide)-silane amphiphiles (PEO-SAs) [H-Si-ODMSm-block-PEO8-OCH3], comprised of a PEO segment and siloxane tether of varying lengths (m = 0, 13, and 30). These three SMAs were each blended into the addition cure diphenyl silicone at varying concentrations (5, 10, 15, 20, and 25 µmol g-1) wherein the wt% of PEO was maintained for all SMAs at a given molar concentration. The chemical crosslinking and subsequent retention of SMAs in modified silicones was confirmed. Key material properties were assessed following equilibration in both air and aqueous environments. Silicones modified with SMAs having longer tethers (m = 13 and 30) underwent rapid and substantial water-driven restructuring of PEO to the surface to form highly hydrophilic surfaces, especially as SMA concentration increased. The % transmittance was also maintained for silicones modified with these particular SMAs. The moduli of the modified silicones were largely unchanged by the SMA and remained in the typical range for silicone IOLs. When the three SMAs were introduced at the highest concentration, modified silicones remained non-cytotoxic and LEC count and associated alpha-smooth muscle actin (α-SMA) expression decreased with increasing tether length. These results demonstrate the potential of silicones modified with PEO-SA SMAs to produce LEC-resistant IOLs.

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

OBJECTIVE: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. METHODS: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. RESULTS: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. CONCLUSION: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of COVID-19 in patients with multiple myeloma based on a global data network.

The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Multiple myeloma (MM) patients show an increased risk for infections and they are expected to be particularly vulnerable to SARS-CoV-2 infection. Here we have obtained a comprehensive picture of the impact of COVID-19 in MM patients on a local and a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCO) all over the world. Through propensity score matched analyses we found that the number of new diagnoses of MM was reduced in 2020 compared to 2019 (RR 0.86, 95%CI 0.76-0.96) and the survival of newly diagnosed MM cases decreased similarly (HR 0.61, 0.38-0.81). MM patients showed higher risk of SARS-CoV-2 infection (RR 2.09, 1.58-2.76) and a higher excess mortality in 2020 (difference in excess mortality 9%, 4.4-13.2) than non-MM patients. By interrogating large EMR datasets from HCO in Europe and globally, we confirmed that MM patients have been more severely impacted by COVID-19 pandemic than non-MM patients. This study highlights the necessity of extending preventive measures worlwide to protect vulnerable patients from SARS-CoV-2 infection by promoting social distancing and an intensive vaccination strategies.