Prevalence of Potentially Pathogenic Germline Variants Among Adult Patients in the Philippines With Solid Malignancies Who Underwent Tumor Genomic Profiling.

PURPOSE: In high-income countries, 2%-10% of tumor genomic profiling (TGP) reports reveal incidental pathogenic germline variants. A third of these patients would not qualify for genetic testing on the basis of current guidelines. Our study determined the prevalence of potentially pathogenic germline variants (PPGVs) in TGP results of adult patients with solid malignancies in the Philippines. METHODS: Annotated reports of patients with solid cancers who underwent TGP using FoundationOne or FoundationOne Heme between January 2021 and July 2023 were reviewed. PPGV criteria include having a variant allele frequency of >30% and were categorized as (1) high penetrance gene (HP), founder variant (FV), or variant associated with clinical presentation (VA). Pathogenicity was crosschecked through the ClinVar database. RESULTS: Of 446 patients, 13 PPGV variants were found in 50 (11.2%) patients at a median age of 60.5 years. Of them, 28 (56%) had HP (BRCA1, BRCA2, MSH2, MSH6, MLH1, RAD51C, RAD51D), 25 (50%) patients had VA (APC, SMAD4, CDH1, CDKN2A, PTEN), and two patients with lung cancer had a FV (EGFR p.Thr790Met). Six patients had more than one PPGV. PPGVs were primarily found in patients with colorectal (42% of 50 patients with PPGVs), breast (16%), ovarian (6%), and lung (6%) cancer (P < .001). HP genes were mostly found in female patients (71.4%; P = .03). CONCLUSION: With a PPGV prevalence of 11% in this study, it is important to recognize PPGVs as it can prompt genetic counseling and confirmatory germline testing.

Injectable Thermoresponsive Microparticle/Hydrogel System with Superparamagnetic Nanoparticles for Drug Release and Magnetic Hyperthermia Applications.

Cancer is a disease that continues to greatly impact our society. Developing new and more personalized treatment options is crucial to decreasing the cancer burden. In this study, we combined magnetic polysaccharide microparticles with a Pluronic thermoresponsive hydrogel to develop a multifunctional, injectable drug delivery system (DDS) for magnetic hyperthermia applications. Gellan gum and alginate microparticles were loaded with superparamagnetic iron oxide nanoparticles (SPIONs) with and without coating. The magnetic microparticles' registered temperature increases up to 4 °C upon the application of an alternating magnetic field. These magnetic microparticles were mixed with drug-loaded microparticles, and, subsequently, this mixture was embedded within a Pluronic thermoresponsive hydrogel that is capable of being in the gel state at 37 °C. The proposed DDS was capable of slowly releasing methylene blue, used as a model drug, for up to 9 days. The developed hydrogel/microparticle system had a smaller rate of drug release compared with microparticles alone. This system proved to be a potential thermoresponsive DDS suitable for magnetic hyperthermia applications, thus enabling a synergistic treatment for cancer.

The parotid gland, an unusual site of colorectal cancer metastasis.

Colorectal cancer commonly metastasises to the liver, peritoneum and lungs. With disseminated disease, it can spread to more unusual sites. Parotid gland metastasis usually originates from head and neck malignancies. We present a case of stage IV sigmoid colon adenocarcinoma with metastases to the left parotid. The patient was a 53-year-old Filipino man diagnosed with stage IV sigmoid adenocarcinoma with liver metastases in June 2021. He underwent laparoscopic sigmoidectomy and received eight cycles of chemotherapy with capecitabine and oxaliplatin with partial response of his liver lesions. Capecitabine monotherapy was then maintained. On September 2022, he experienced persistent left facial pain, with no relief after dental tooth extraction and antibiotics. A computed tomography (CT) scan revealed a 5 × 7 × 6 cm inhomogenous mass in the left parotid with destruction of the mandible. A fine needle biopsy was consistent with a high-grade carcinoma. After multidisciplinary discussions, a repeat core needle biopsy was deemed necessary to proceed with immunohistochemistry. With strong positivity for cytokeratin 20 (CK20), carcinoembryonic antigen, special AT-rich sequence-binding protein 2 and CAM 5.2, and weak positivity for CK7, the parotid mass was diagnosed as metastatic adenocarcinoma from the colon. He then received palliative radiation to the parotid mass for pain control. A gastrostomy tube was also inserted for nutritional support. Treatment with next-line chemotherapy (FOLFIRI regimen) was planned. Unfortunately, he contracted COVID-19 pneumonia and succumbed to respiratory failure. Pursuing the histologic diagnosis of this uncommon area of metastasis was necessary for appropriate treatment planning. Fostering multidisciplinary collaboration throughout the complex aspects of cancer care requires patient advocacy, leadership and effective communication. For our patient, it was essential to coordinate with surgery and pathology to maximise the diagnostic yield of a repeat biopsy while minimising complications and treatment delays.

Prophylactic strategies for hand-foot syndrome/skin reaction associated with systemic cancer treatment: a meta-analysis of randomized controlled trials.

PURPOSE: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are common toxicities of several systemic cancer treatments. Multikinase inhibitor-induced HFSR is distinguished from chemotherapy-induced HFS in terms of pathogenesis, symptomatology, and treatment. Multiple trials have investigated the efficacy of preventive strategies such as COX-inhibitors, pyridoxine, and urea cream; however, no consensus has been made. This meta-analysis evaluated data from high-quality trials to provide strong evidence in forming recommendations to prevent systemic cancer therapy-induced HFS/HFSR. METHODS: A systematic search of PubMed, Embase, Cochrane, clinical trials databases, and hand searching were utilized to identify randomized trials (RCTs) investigating prophylactic strategies for HFS/HFSR in cancer patients receiving systemic treatment. Trials published until August 2021 were included. Using the random effects model, pooled odds ratios were calculated for rates of all-grade and severe HFS/HFSR. Subgroup analysis based on type of cancer treatment given was done. RESULTS: Sixteen RCTs were included (N=2814). For all-grade HFS/HFSR, celecoxib (OR 0.52, 95% CI 0.32-0.85, p=0.009) and urea cream (OR 0.48, 95% CI 0.39-0.60, p<0.00001) both showed statistically significant risk reduction. Celecoxib was effective in preventing HFS in patients who received capecitabine (50.5% vs 65%, p=0.05), while urea cream was effective in both capecitabine HFS (22.3% vs 39.5%, p=0.02) and sorafenib-induced HFSR (54.9% vs 71.4%, p<0.00001). Pyridoxine at higher doses showed a trend towards benefit in preventing all grade HFS (69.6% vs 74.1%, p=0.23). CONCLUSIONS: Urea cream and celecoxib are both effective in preventing HFS/HFSR in patients receiving systemic cancer treatment. Particularly, celecoxib is more effective in preventing all-grade capecitabine-induced HFS, while urea cream shows more benefit in preventing moderate to severe sorafenib-induced HFSR. Studies investigating optimal dosing for celecoxib and urea cream are recommended. There is inadequate evidence to make recommendations regarding pyridoxine.

Bioethanol production from Chlorella vulgaris ESP-31 grown in unsterilized swine wastewater.

The potential of microalgae to remove nutrients from swine wastewater and accumulate carbohydrates was examined. Chlorella sorokiniana AK-1 and Chlorella vulgaris ESP-31 were grown in 10% unsterilized swine wastewater and obtained a maximum carbohydrate content and productivity of 42.5% and 189 mg L-1d-1, respectively. At 25% wastewater and 25% BG-11 concentration, the maximum carbohydrate productivity and total nitrogen removal efficiency of C. vulgaris ESP-31 were improved to 266 mg L-1d-1 and 54.2%, respectively. Further modifications in light intensity, inoculum size, and harvesting period enhanced the biomass growth, carbohydrate concentration, and total nitrogen assimilation to 3.6 gL-1, 1.8 gL-1, and 92.2%, respectively. Ethanol fermentation of the biomass resulted in bioethanol yield and concentration of 84.2% and 4.2 gL-1, respectively. Overall, unsterilized swine wastewater was demonstrated as a cost-effective nutrient source for microalgal cultivation which further increases the economic feasibility and environmental compatibility of bioethanol production with concomitant swine wastewater treatment.

On the single and multiple associations of COVID-19 post-acute sequelae: 6-month prospective cohort study.

Medical research is progressing to clarify the full spectrum of sub-acute and long-term effects of the post-COVID-19 syndrome. However, most manuscripts published to date only analyze the effects of post-COVID-19 in patients discharged from hospital, which may induce significant bias. Here, we propose a pioneering study to analyze the single and multiple associations between post-COVID-19 characteristics with up to 6-months of follow-up in hospitalized and non-hospitalized COVID-19 patients. The cohort study was conducted from May to October 2020 at the University Hospital Virgen de la Nieves, the leading hospital assigned for patients with COVID-19 in Granada, Spain. A total of 372 and 217 patients-with 217 and 207 included in the first and second follow-up visits-were referred 2 and 6 months after diagnosing COVID-19, respectively. We find out that post-COVID-19 clinical and mental health impairment symptoms are correlated with patient gender. Logistic adjustments showed strong statistically robust single and multiple associations of demographic, clinical, mental health, X-ray, laboratory indices, and pulmonary function variables. The functional lung tests are good predictors of chest CT imaging abnormalities in elderly patients. Bilateral lung involvement, subpleural reticulum, ground-glass opacity, peripheral lung lesions, and bronchiectasis were the most common findings of the high-resolution computed tomography images. Non-hospitalized patients suffer more severe thromboembolic events and fatigue than those hospitalized.

Predictors of adverse perinatal outcome up to 34 weeks, a multivariable analysis study.

The objective was to evaluate the best predictors of adverse perinatal outcome (APO) in foetuses examined up to 34 weeks and delivered by spontaneous or induced labour. This was a retrospective study of 129 pregnancies that underwent an ultrasound Doppler examination at 23-34 weeks and entered into labour within 30 days. Cerebroplacental ratio (CPR) and mean uterine artery pulsatility index (mUtA PI) were converted into multiples of the median (MoM) and estimated foetal weight (EFW) into centiles to adjust for gestational age (GA). Sonographic and clinical parameters were evaluated using logistic regression analysis.The multivariable model for the prediction of APO presented a notable accuracy: Detection rate (DR) was 39.5% for a false positive rate (FPR) of 5% and 56.8% for a FPR of 10%, AUC 0.82, p < .0001. Significant predictors were GA, EFW centile, and CPR MoM, but not mUtA PI MoM. Moreover, the type of labour onset did not exert any influence on APO. In conclusion, up to 34 weeks, prediction of APO after spontaneous or induced labour may be done measuring CPR and EFW.IMPACT STATEMENTWhat is already known on this subject? Earlier in pregnancy, foetal growth restriction is caused by placental disease causing progressive hemodynamic changes. These changes have been exhaustively described. Conversely, information about the best predictors of adverse outcome is scarce.What do the results of this study add? The findings of this study show that prior to 34 weeks and up to 1 month before labour, labour outcome might be predicted by gestational age, foetal cerebroplacental ratio (CPR) and estimated foetal weight (EFW).What are the implications of these findings for clinical practice and/or further research? If CPR behaves as a good marker of outcome not only at the end of pregnancy but also earlier in gestation, it might be interrogated along with EFW in foetuses attempting vaginal delivery to determine the risk of adverse outcome.

Retina and Brain Display Early and Differential Molecular and Cellular Changes in the 3xTg-AD Mouse Model of Alzheimer's Disease.

The concept 'the retina as a window to the brain' has been increasingly explored in Alzheimer´s disease (AD) in recent years, since some patients present visual alterations before the first symptoms of dementia. The retina is an extension of the brain and can be assessed by noninvasive methods. However, assessing the retina for AD diagnosis is still a matter of debate. Using the triple transgenic mouse model of AD (3xTg-AD; males), this study was undertaken to investigate whether the retina and brain (hippocampus and cortex) undergo similar molecular and cellular changes during the early stages (4 and 8 months) of the pathology, and if the retina can anticipate the alterations occurring in the brain. We assessed amyloid-beta (Aß) and hyperphosphorylated tau (p-tau) levels, barrier integrity, cell death, neurotransmitter levels, and glial changes. Overall, the retina, hippocampus, and cortex of 3xTg-AD are not significantly affected at these early stages. However, we detected a few differential changes in the retina and brain regions, and particularly a different profile in microglia branching in the retina and hippocampus, only at 4 months, where the number and length of the processes decreased in the retina and increased in the hippocampus. In summary, at the early stages of pathology, the retina, hippocampus, and cortex are not significantly affected but already present some molecular and cellular alterations. The retina did not mirror the changes detected in the brain, and these observations should be taking into account when using the retina as a potential diagnostic tool for AD.

Burnout and resilience of internal medicine physician trainees in a tertiary government hospital in the Philippines during the COVID-19 pandemic: A Mixed-method study

@#<p style="text-align: justify;"><strong>Objectives:</strong> Internal Medicine physician trainees faced unique challenges as the primary frontline physicians at a tertiary COVID-19 government referral center during the COVID-19 pandemic. This study examined the prevalence of burnout and resilience of these physician trainees during the early period of the pandemic, the determinants of burnout, and their sources of anxiety and coping mechanisms.</p><p style="text-align: justify;"><strong>Methods:</strong> Using a mixed-methods approach, we conducted an online cross-sectional survey to measure burnout and resilience among 196 Internal Medicine physician trainees using the Maslach Burnout Index Human Services Survey for Medical Personnel and the Connor-Davidson Resiliency questionnaires, respectively. We then conducted virtual focus group discussions and in-depth key informant interviews to explore the trainees' sources of anxiety and coping mechanisms until thematic saturation was satisfied.</p><p style="text-align: justify;"><strong>Results:</strong> Out of 146 respondents (from 196 eligible participants, 74% response rate), four percent of physician trainees fit the frank burnout profile, 40% were engaged, while the majority had intermediate profiles (23% ineffective, 28% overextended, and 4% disengaged). The mean resilience score was 72.9 (SD 12.4). Resilience was a significant negative predictor for burnout (Beta Coefficient = -0.73, p<0.001). Its protective effect decreases in those with more exposure to patient deaths (Beta Coefficient = 6.767, p<0.05). Significant sources of anxiety included changes in the practice of medicine (changes in workflow, working in full personal protective equipment, telemedicine and zoom fatigue, constant threat of acquiring the infection) and having competing demands between service and training. Coping mechanisms included preserving a haven, maintaining social relationships, and self-care.</p><p style="text-align: justify;"><strong>Conclusion:</strong> In the largest government hospital in the Philippines, four percent of Internal Medicine physician trainees had burnout, 40% were engaged, and the majority were at-risk for burnout a few months into the COVID-19 pandemic in 2020. Resilience reduces the risk for burnout. However, its protective effect decreased with exposure to a higher number of patient deaths per week.</p>

Absence of relevant QT interval prolongation in not critically ill COVID-19 patients.

SARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients. We evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 h after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors. We included 219 patients (mean age of 63.6 ± 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404-433), and after treatment QTc was prolonged to 423 ms (405-438) (P < 0.001), with an average increase of 1.8%. Most of the patients presented a normal QTc under treatment, with only 31 cases (14.1%) showing a QTc interval > 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation. Ambulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.

Use of systemic lidocaine for postoperative acute pain management in single-lung transplantation: Case report / Lidocaína sistêmica para el tratamiento del dolor agudo posoperatorio en trasplante unipulmonar. Reporte de caso

Abstract Introduction: Lung transplantation is associated with severe pain, which can delay recovery. Systemic lidocaine has useful analgesic properties for managing acute pain; however, little is known on its use after lung transplantation. Due to pharmacological alterations during the postoperative period, the use of analgesics implies a demanding process to avoid toxicity, so lidocaine may play a role in this scenario. In this sense, the purpose of this case report is to present the use of systemic lidocaine as an option for acute pain management when other analgesics fail. Case presentation: The following is the case of a male patient with acute pain in the postoperative period of single-lung transplantation. Opioids and non-opioid analgesics showed limited efficacy, so systematic lidocaine was administered. Systemic administration of lidocaine was effective for pain control, functional recovery, and opioid decrease during the postoperative period. Conclusions: Systemic administration of lidocaine was a useful alternative for achieving optimal postoperative pain management in lung transplantation, since it allowed adequate analgesia and lung function recovery with decreased use of opioids. This drug may be a component of multimodal analgesia in selected patients when other options fail however, its routine use is not recommended.

Resumen Introducción. El trasplante pulmonar se asocia con dolor severo, lo que puede retrasar la recuperación del paciente. La lidocaína sistémica tiene propiedades analgésicas útiles para el manejo del dolor agudo; sin embargo, su uso después del trasplante pulmonar es poco conocido. Debido a las alteraciones farmacológicas durante el período posoperatorio, el uso de analgésicos es un proceso exigente para evitar toxicidad, por lo que la lidocaína puede tener un rol en ese contexto. En este sentido, el objetivo del presente reporte es describir el uso de lidocaína sistémica como una opción para el manejo del dolor cuando otros analgésicos han fallado. Presentación del caso. Paciente masculino con dolor severo en el posoperatorio de un trasplante unipulmonar. El uso de opioides y de analgésicos no opioides mostró una eficacia limitada, por lo que se decidió aplicar lidocaína sistémica, la cual fue efectiva para el control del dolor, la recuperación funcional y la disminución de opioides durante el período posoperatorio. Conclusiones. La lidocaína sistémica fue un fármaco útil para el manejo del dolor posoperatorio del trasplante de pulmón, ya que permitió una analgesia adecuada y una recuperación funcional pulmonar con menor uso de opioides. Este fármaco puede ser parte de la analgesia multimodal en pacientes seleccionados cuando otras opciones analgésicas han fallado; sin embargo, no se recomienda su uso rutinario.

Correlation of Kryptor and Elecsys® immunoassay sFlt-1/PlGF ratio on early diagnosis of preeclampsia and fetal growth restriction: A case-control study.

OBJECTIVES: The measurement of the soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio on automated platforms has improved the detection of preeclampsia and fetal growth restriction (PE/FGR). The cut-off points of >38 and ≥85 has been defined for "rule in" and "aid in diagnosis", respectively, using the Elecsys® platform. We aimed to compare the performance of these cut-offs between the Elecsys® and Kryptor platforms at 24-28 weeks. STUDY DESIGN: Observational case-control study of singleton pregnancies at high risk for PE/FGR and sFlt-1/PlGF measurement at 24-28 weeks' gestation: 21 cases (9 early PE/FGR with delivery <32 weeks) were 1:1 matched for body mass index and parity with 21 controls. Correlations of the sFlt-1, PlGF and sFlt-1/PlGF values and diagnostic accuracy of the >38 and ≥85 cutoffs for early and late PE/FGR using Elecsys® and Kryptor assays were evaluated. MAIN OUTCOME MEASURES: PE/FGR cases showed significantly higher median (IQR) sFlt-1/PlGF values at 24-28 weeks vs. controls, using both Elecsys® and Kryptor platforms: 55 (13-254) and 97 (13-530) vs. 4.1 (2.0-6.5) and 3.9 (1.8-7.7), respectively. The sFlt-1/PlGF correlation between both methods was excellent (r2 = 0.95) although lower PlGF and higher sFlt-1/PlGF values were observed with Kryptor. The higher diagnostic accuracy was obtained for early PE/FGR with the ≥85 cutoff (95.2%; 95%CI: 83.8-99.4%) in both platforms. CONCLUSION: sFlt-1/PlGF measurements correlates well between Elecsys® and Kryptor platforms, and the cutoffs of >38 and ≥85 exhibit high diagnostic accuracy for assessing early PE/FGR at 24-28 weeks with both methods.

[From autism spectrum to autism constellation]. / Del espectro autista a la constelación autista.

Research on autism and mental disorders has been unsuccessful over the past few decades, as can be inferred from the poor results related to advances in other diseases. It is concerning that, after more than a half century of research based on the Diagnostic and Statistical Manual of Mental Disorders (DSM), no biological markers have been found to prove the validity of the DSM mental disorders. Criticisms to DSM have been focused mainly on the categorical conceptualization, false comorbidity and the polythetic nature of diagnostic criteria. The lack of validity of the DSM model requests for a change in research designs, in order to overcome the problems derived from a paradigm that has stopped to be productive. In the field of clinical practice, it is even more pressing a change of mindset in order to incorporate the heterogeneity of endophenotypes that overflows the classification of the DSM, to adopt a dimensional perspective of mental problems and to develop an alternative interpretation for comorbidity. Related to research are suggested designs based on Domain Research Criteria and a multifactorial analysis with very large samples (big data). For clinical practice it is suggested a dimensional approach based on the specificities of each person with autism.

La investigación sobre el autismo, y sobre los trastornos mentales en general, ha sido poco fructífera durante las últimas décadas, como se desprende de los escasos resultados obtenidos en comparación con los avances en otras enfermedades. Preocupa que, tras más de medio siglo de investigación basada en el Diagnostic and Statistical Manual of Mental Disorders (DSM), no se hayan encontrado marcadores biológicos que acrediten la validez de los trastornos mentales que lo configuran. Las críticas al DSM, todas ellas aplicables al autismo, se han centrado principalmente en la conceptualización categórica, en la falsa comorbilidad y en el carácter politético de los criterios diagnósticos. La falta de validez del modelo del DSM insta a un cambio en los diseños de investigación, con el fin de superar el bloqueo derivado de un paradigma que ha dejado de ser productivo. En el terreno de la práctica clínica resulta, incluso más apremiante, un cambio de mentalidad que permita: incorporar la heterogeneidad de endofenotipos que desbordan la clasificación del DSM, adoptar una perspectiva dimensional de los problemas mentales y desarrollar una interpretación alternativa de la comorbilidad Con referencia a la investigación, se proponen diseños basados en criterios de investigación por dominios (Research Domain Criteria) y en análisis multifactoriales con muestras muy grandes (big data). Por lo que respecta a práctica clínica se sugiere un enfoque dimensional basado en las especificidades de cada persona con autismo, lo cual desborda el patrón clínico del espectro.

Del espectro autista a la constelación autista / From autism spectrum to autism constellation

La investigación sobre el autismo, y sobre los trastornos mentales en general, ha sido poco fructífera durante las últimas décadas, como se desprende de los escasos resultados obtenidos en comparación con los avances en otras enfermedades. Preocupa que, tras más de medio siglo de investigación basada en el Diagnostic and Statistical Manual of Mental Disorders (DSM), no se hayan encontrado marcadores biológicos que acrediten la validez de los trastornos mentales que lo configuran. Las críticas al DSM, todas ellas aplicables al autismo, se han centrado principalmente en la conceptualización categórica, en la falsa comorbilidad y en el carácter politético de los criterios diagnósticos. La falta de validez del modelo del DSM insta a un cambio en los diseños de investigación, con el fin de superar el bloqueo derivado de un paradigma que ha dejado de ser productivo. En el terreno de la práctica clínica resulta, incluso más apremiante, un cambio de mentalidad que permita: incorporar la heterogeneidad de endofenotipos que desbordan la clasificación del DSM, adoptar una perspectiva dimensional de los problemas mentales y desarrollar una interpretación alternativa de la comorbilidad Con referencia a la investigación, se proponen diseños basados en criterios de investigación por dominios (Research Domain Criteria) y en análisis multifactoriales con muestras muy grandes (big data). Por lo que respecta a práctica clínica se sugiere un enfoque dimensional basado en las especificidades de cada persona con autismo, lo cual desborda el patrón clínico del espectro.

Research on autism and mental disorders has been unsuccessful over the past few decades, as can be inferred from the poor results related to advances in other diseases. It is concerning that, after more than a half century of research based on the Diagnostic and Statistical Manual of Mental Disorders (DSM), no biological markers have been found to prove the validity of the DSM mental disorders. Criticisms to DSM have been focused mainly on the categorical conceptualization, false comorbidity and the polythetic nature of diagnostic criteria. The lack of validity of the DSM model requests for a change in research designs, in order to overcome the problems derived from a paradigm that has stopped to be productive. In the field of clinical practice, it is even more pressing a change of mindset in order to incorporate the heterogeneity of endophenotypes that overflows the classification of the DSM, to adopt a dimensional perspective of mental problems and to develop an alternative interpretation for comorbidity. Related to research are suggested designs based on Domain Research Criteria and a multifactorial analysis with very large samples (big data). For clinical practice it is suggested a dimensional approach based on the specificities of each person with autism.

Edema agudo de pulmón por altura tras 48 horas de estancia en una estación de esquí / High-Altitude Acute Pulmonary Edema after 48 Hours in a Ski Station

No disponible

Ventana aortopulmonar, ductus ausente y arteria subclavia izquierda aislada / Aortopulmonary window, absent ductus, and left subclavian artery isolation

No disponiblel

Fetal Biometry and Doppler Study for the Assessment of Perinatal Outcome in Stage I Late-Onset Fetal Growth Restriction.

OBJECTIVE: To compare perinatal outcomes on fetuses classified as stage I late-onset fetal growth restriction (FGR) depending on the estimated fetal weight (EFW) centile category and the fetal and maternal Doppler study. MATERIAL AND METHODS: Retrospective cohort study on 131 cases of stage I late-onset FGR (diagnosis ≥32+0 weeks), defined as: EFW < 3rd centile and normal Doppler (G1) or EFW < 10th centile and mean uterine artery pulsatility index (PI) > 95th centile (G2) or EFW < 10th centile and mild fetal Doppler alteration: umbilical artery PI > 95th centile, middle cerebral artery PI < 5th centile, or cerebroplacental ratio < 5th centile (G3). All groups were compared to their perinatal results. RESULTS: There were 37, 30, and 64 cases in G1, G2, and G3, respectively. G1 and G2 showed lower percentages of cesarean section when compared with G3 (18.4, 22.5, and 45.3% (p < 0.01), respectively), being attributable to an excess of cesarean sections for non-reassuring fetal status. These differences remained when definitive birth weight centile was above that considered to define FGR, being 5.9, 12.5, and 41.8% (p < 0.01), respectively. DISCUSSION: In stage I late-onset FGR fetuses, abnormal fetal Doppler is associated with a poorer tolerance to vaginal delivery, even when the birth weight is > 10th centile.