Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.

OBJECTIVE: Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. METHODS: Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, ß = 80%, one sided. RESULTS: 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. CONCLUSION: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

Experiences of water immersion during childbirth: a qualitative thematic synthesis.

BACKGROUND: The increasing demand for childbirth care based on physiological principles has led official bodies to encourage health centers to provide evidence-based care aimed at promoting women's participation in informed decision-making and avoiding excessive medical intervention during childbirth. One of the goals is to reduce pain and find alternative measures to epidural anesthesia to enhance women's autonomy and well-being during childbirth. Currently, water immersion is used as a non-pharmacological method for pain relief. This review aimed to identify and synthesize evidence on women's and midwives' experiences, values, and preferences regarding water immersion during childbirth. METHODS: A systematic review and thematic synthesis of qualitative evidence were conducted. Databases were searched and references were checked according to specific criteria. Studies that used qualitative data collection and analysis methods to examine the opinions of women or midwives in the hospital setting were included. Non-qualitative studies, mixed-methods studies that did not separately report qualitative results, and studies in languages other than English or Spanish were excluded. The Critical Appraisal Skills Program Qualitative Research Checklist was used to assess study quality, and results were synthesized using thematic synthesis. RESULTS: Thirteen studies met the inclusion criteria and were included in this review. The qualitative studies yielded three key themes: 1) reasons identified by women and midwives for choosing a water birth, 2) benefits experienced in water births, and 3) barriers and facilitators of water immersion during childbirth. CONCLUSIONS: The evidence from qualitative studies indicates that women report benefits associated with water birth. From the perspective of midwives, ensuring safe water births requires adequate resources, midwives training, and rigorous standardized protocols to ensure that all pregnant women can safely opt for water immersion during childbirth with satisfactory results.

A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients.

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Preliminary study of elastic-tension digital neoprene orthoses for proximal interphalangeal joint flexion contracture.

Flexion contracture of the proximal interphalangeal joint (PIPJ) is one of the most frequent complications in finger trauma. Orthoses are the most widely used method to optimize total end-range time (TERT). No previous studies showed that an elastic tension orthosis could be applied for longer than 12 h. We aimed to demonstrate that the elastic-tension digital neoprene orthosis (ETDNO) can achieve higher TERT and therefore better range of motion than other elastic-tension orthoses (ETO) described in the literature. A prospective study of treatment of PIPJ flexion contracture included 10 PIP joints in 8 patients who met the selection criteria. They were instructed to use the ETDNO for around 23 h per day as far as possible, during a period of 3 weeks. Patients reported a mean TERT of 20.6 h a day. PIPJ contracture improved by a mean Torque Range of Motion (TROM) of 23.5° at 500 g and 22.9° at 800 g of passive extension force during the 3-week treatment. Based on the results of this study, the ETDNO appears to offer a highly effective approach for improving PIPJ flexion contracture, increasing range of motion in extension. ETDNO's efficacy probably lies in the significantly improved comfort and low-profile design, enabling excellent compliance and thus optimizing TERT. LEVEL OF EVIDENCE: Level III.

Characterization and comparison of commercial oils used for human embryo culture.

STUDY QUESTION: Are there significant differences between the available commercial oil brands used for human IVF? SUMMARY ANSWER: Important differences have been detected among the tested oil brands in their potential to stabilize culture conditions and, more importantly, in their direct effect on embryo development and viability. WHAT IS KNOWN ALREADY: Mineral oil is a critical component of the human culture system due to its protective and stabilizing roles during in vitro embryo development. Many different oils are available on the market, with differences in their viscosity, density and overall quality. STUDY DESIGN, SIZE, DURATION: Thirteen different commercial oil brands were compared. PARTICIPANTS/MATERIALS, SETTING, METHODS: Each oil was firstly analyzed to assess its viscosity, density, peroxide value and potential oxidation. Secondly, the capacity of each oil to reduce pH, osmolality and temperature fluctuations during embryo culture and manipulation was compared. Lastly, a sensitive mouse embryo assay (MEA) protocol, previously optimized to detect toxicity in oils samples, was used to compare the overall quality of the different brands in terms of embryo developmental rates up to the blastocyst stage. At the end of the MEAs, a triple labeling protocol was applied to analyze Oct4+ cells, apoptotic cells and total cell counts in the blastocysts obtained by fluorescence microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: Significant divergences were detected in the rise of osmolality and the equilibration and stability of pH between different oils, which could be correlated to their physico-chemical characteristics. In particular, oil samples with a higher viscosity tended to offer an additional protection against fluctuations in the culture conditions, however, the differences in temperature stability between oils were minor. Two out of the 13 oil samples, which were commercially available, were identified as embryo-toxic by applying the MEA protocol with increased sensitivity for toxicity detection. Additionally, substantial differences in the total number of cells and the number of cells in the inner cell mass of the obtained blastocysts were also detected between oil groups. LIMITATIONS, REASONS FOR CAUTION: A single lot of oil was used for each brand and, thus, lot-to-lot variations in oil quality could not be determined. However, several bottles from the same oil were included to account for potential intra-lot variability. WIDER IMPLICATIONS OF THE FINDINGS: Commercial oils differ in both their physical characteristics and their performance in maintaining the stability of the culture conditions during in vitro embryo culture. Oil selection is important for embryo culture success. Additionally, the detection of embryo-toxic oils which had already been released to the human IVF market showcases the importance of applying sensitive MEA protocols for a better detection of toxicity in this type of samples. STUDY FUNDING/COMPETING INTEREST(S): This study was privately funded. TRIAL REGISTRATION NUMBER: N/A.

Clinical outcomes of FOLFIRINOX and gemcitabine–nab paclitaxel for metastatic pancreatic cancer in the real world setting

Background/objectives The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. Methods This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival—OS) and toxicity. Results A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil–lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. Conclusions In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates (AU)

Clinical outcomes of FOLFIRINOX and gemcitabine-nab paclitaxel for metastatic pancreatic cancer in the real world setting.

BACKGROUND/OBJECTIVES: The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. METHODS: This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival-OS) and toxicity. RESULTS: A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil-lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. CONCLUSIONS: In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates.

Obstrucción venosa retiniana en receptores de trasplante de órgano sólido. Estudio de 4 casos y revisión de la literatura / Retinal vein occlusion in solid organ transplant recipients. Study of 4 cases and literature review

La obstrucción venosa retiniana (OVR) se ha relacionado fundamentalmente con los factores de riesgo vascular y con el glaucoma; sin embargo, existen pocos estudios de la OVR en pacientes con trasplante de órgano sólido. Se analizó una serie de 331 pacientes que presentaron OVR (de rama en 226 casos y central en 105 casos) a lo largo de 10 años y se compararon las características entre los 4 pacientes con antecedente de trasplante de órgano sólido (hepático, renal o bipulmonar) que presentaron una OVR y el resto. En nuestra serie la OVR en los trasplantados comenzó a edades más tempranas que en el resto de pacientes con OVR (58 vs. 68 años, respectivamente), afectó a la vena central de la retina (100% vs. 32%) y se asoció con la diabetes mellitus (75% vs. 25%) y con los tratamientos esteroideo (100% vs. 1%) e inmunosupresor (tacrolimus 75% vs. 0%)

Although retinal venous obstruction (RVO) has been primarily related to vascular risk factors and glaucoma, there are a few studies of RVO in patients with solid organ transplants. An analysis was performed on total of 331 patients who presented with RVO (branch RVO in 226 cases and central RVO in 105 cases) over a 10 year period, and the characteristics were compared with the 4 patients with a history of solid organ transplant (liver, renal, or bipulmonary) who presented with RVO. In this series, the onset of RVO in transplant patients occurred at earlier ages than in other patients with RVO (58 vs. 68 years, respectively), affected the central vein of the retina (100% vs. 32%), and was associated with diabetes mellitus (75% vs. 25%), as well as with steroidal (100% vs. 1%) and immunosuppressive (tacrolimus 75% vs. 0%) treatments

Anisocoria como manifestación inicial de esclerosis múltiple. Utilidad de la resonancia magnética nuclear de 3 teslas / Anisocoria as initial manifestation of multiple sclerosis. Use of 3 tesla magnetic resonance imaging

Mujer de 21 años que presenta midriasis arreactiva en ojo derecho que contrae con el test de pilocarpina al 1%. La angio-TC craneal y la resonancia magnética nuclear (RMN) de 1,5 T no detectaron anomalías. Ante una posterior limitación de la aducción, supraducción e infraducción de dicho ojo, se solicitó una RMN de 3 T, que evidenció una lesión del mesencéfalo en la salida del tercer par craneal. Tras mejoría, no tuvo nuevos episodios hasta 18 meses después, cuando acudió con una probable neuritis óptica y síntomas sistémicos. En este momento la RMN de 1,5 T detectó placas desmielinizantes infratentoriales y supratentoriales. La punción lumbar posterior y la evolución clínica confirmaron el diagnóstico de esclerosis múltiple recurrente-remitente

A 21-year-old woman seen in this clinic with non-reactive mydriasis in the right eye that contracted with 1% pilocarpine. Cranial angio-CT and 1.5 T magnetic resonance imaging (MRI) did not detect any disease. Given a subsequent limitation of adduction, supraduction, and infarction of the right eye, a 3 T MRI was requested. This showed a lesion of the midbrain at the exit of the 3rd cranial nerve. After improvement, no new episodes were observed until 18 months later, when the patient presented with probable optic neuritis and systemic symptoms. At this time the 1.5 T MRI detected infratentorial and supratentorial demyelinating plaques. A subsequent lumbar puncture and clinic outcome confirmed the diagnosis of relapsing-remitting multiple sclerosis

Retinal vein occlusion in solid organ transplant recipients. Study of 4 cases and literature review. / Obstrucción venosa retiniana en receptores de trasplante de órgano sólido. Estudio de 4 casos y revisión de la literatura.

Although retinal venous obstruction (RVO) has been primarily related to vascular risk factors and glaucoma, there are a few studies of RVO in patients with solid organ transplants. An analysis was performed on total of 331 patients who presented with RVO (branch RVO in 226 cases and central RVO in 105 cases) over a 10 year period, and the characteristics were compared with the 4 patients with a history of solid organ transplant (liver, renal, or bipulmonary) who presented with RVO. In this series, the onset of RVO in transplant patients occurred at earlier ages than in other patients with RVO (58 vs. 68 years, respectively), affected the central vein of the retina (100% vs. 32%), and was associated with diabetes mellitus (75% vs. 25%), as well as with steroidal (100% vs. 1%) and immunosuppressive (tacrolimus 75% vs. 0%) treatments.

Anisocoria as initial manifestation of multiple sclerosis. Use of 3 tesla magnetic resonance imaging. / Anisocoria como manifestación inicial de esclerosis múltiple. Utilidad de la resonancia magnética nuclear de 3 teslas.

A 21-year-old woman seen in this clinic with non-reactive mydriasis in the right eye that contracted with 1% pilocarpine. Cranial angio-CT and 1.5 T magnetic resonance imaging (MRI) did not detect any disease. Given a subsequent limitation of adduction, supraduction, and infarction of the right eye, a 3 T MRI was requested. This showed a lesion of the midbrain at the exit of the 3rd cranial nerve. After improvement, no new episodes were observed until 18 months later, when the patient presented with probable optic neuritis and systemic symptoms. At this time the 1.5 T MRI detected infratentorial and supratentorial demyelinating plaques. A subsequent lumbar puncture and clinic outcome confirmed the diagnosis of relapsing-remitting multiple sclerosis.

A real world analysis of recurrence risk factors for early colorectal cancer T1 treated with standard endoscopic resection.

BACKGROUND AND STUDY AIM: Currently, endoscopic resection of early colorectal cancer defined as carcinoma with limited invasion of the mucosa (Tis) and submucosa (T1) is possible. However, lymph node spreading increases to 16.2% of cases when tumor invades the submucosa. We analyzed the previously identified factors for lymph node dissemination and recurrence, in our population. PATIENTS AND METHODS: We analyzed retrospectively all patients with T1 tumors, treated at our center with endoscopic resection and some with additional surgery between January 2006 and January 2018. Statistical analysis was performed using IBM SPSS Statistics 25.0. RESULTS: One hundred fifty-nine patients were treated with endoscopic resection, 56.6% with additional surgery. The mean age was 68.74 years and 69. 9% were male. All patients who underwent additional surgery presented negative margins and 8.8% presented positive lymph nodes. In a mean follow-up of 23.36 months, 13 patients had relapsed. The risk of relapse did not differ between patients treated with additional surgery from those who only underwent endoscopic resection (p = 0.506). On the other hand, lymph node dissemination (p = 0.007) and a positive endoscopic margin (p = 0.01) were independent risk factors for relapse. There was a positive association between lymph node dissemination and lymphatic (p = 0.07), vascular (p = 0.007), and perineural (p = 0.001) invasion and also with degree of histological differentiation (p = 0.001). CONCLUSION: In our study, lymphatic, vascular, and perineural invasion and also the degree of histological differentiation were associated with lymph node dissemination. However, the only independent risk factors for long-term recurrence were a positive margin and lymph node dissemination.

Uso del análisis de la capa de células ganglionares para el diagnóstico en la neuromielitis óptica anti-glucoproteína de la mielina del oligodendrocito / Use of ganglion cell layer analysis for diagnosing anti-glycoprotein neuromyelitis optica of oligodendrocyte myelin

Paciente de 26 años con episodios de neuritis óptica recurrentes en contexto de diagnóstico de sospecha de neuromielitis óptica. En el primer brote la paciente presentó gran afectación de la agudeza visual del ojo izquierdo; se objetivó en la tomografía de coherencia óptica afectación de la capa de células ganglionares en ambos ojos, que evidenciaba posible lesión extensa del nervio, que llegaba hasta el quiasma óptico. Así mismo, en la RMN con contraste se objetivó afectación del nervio óptico izquierdo de gran longitud que comprometía el quiasma y que permitía la sospecha etiológica de neuromielitis. A pesar de que los anticuerpos anti-MOG y anti-AQP4 fueron negativos en un primer momento, la afectación bilateral de las células ganglionares hizo sospechar una lesión extensa, que es más característica de las neuromielitis anti-MOG seropositivas

The case concerns a 26-year-old patient with bilateral recurrent optic neuritis episodes in the context of suspected neuromyelitis optica. In the first outbreak, she had greatly impaired visual acuity of the left eye, as well as seeing ganglion cell layer damage in both eyes in the optic coherence tomography, with evidence of a possible extensive lesion in the optic chiasma. Likewise, MRI with contrast showed a great involvement of the left optic nerve that compromises the chiasma increasing the suspicion of a neuromyelitis origin. Althogh the anti-myelin oligodendrocyte glycoprotein (MOG) and anti-AQP4 (aquaporin-4) antibodies were negative at first, bilateral involvement of the ganglion cells suggested an extensive lesion that is more characteristic of seropositive anti-MOG neuromyelitis

Use of ganglion cell layer analysis for diagnosing anti-glycoprotein neuromyelitis optica of oligodendrocyte myelin. / Uso del análisis de la capa de células ganglionares para el diagnóstico en la neuromielitis óptica anti-glucoproteína de la mielina del oligodendrocito.

The case concerns a 26-year-old patient with bilateral recurrent optic neuritis episodes in the context of suspected neuromyelitis optica. In the first outbreak, she had greatly impaired visual acuity of the left eye, as well as seeing ganglion cell layer damage in both eyes in the optic coherence tomography, with evidence of a possible extensive lesion in the optic chiasma. Likewise, MRI with contrast showed a great involvement of the left optic nerve that compromises the chiasma increasing the suspicion of a neuromyelitis origin. Althogh the anti-myelin oligodendrocyte glycoprotein (MOG) and anti-AQP4 (aquaporin-4) antibodies were negative at first, bilateral involvement of the ganglion cells suggested an extensive lesion that is more characteristic of seropositive anti-MOG neuromyelitis.

Enteritis inducida por quimioterapia: experiencia institucional y revisión bibliográfica / Chemotherapy-induced enteritis: Institutional experience and review of the literature

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