Gestational Age-Specific Reference Ranges for the sFlt-1/PlGF Immunoassay Ratio in Twin Pregnancies.

OBJECTIVE: Establish reference ranges for the Elecsys® soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) immunoassay ratio in twin pregnancies. METHODS: Data analyzed were from 3 prospective studies: Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia (PE) (PROGNOSIS), Study of Early-onset PE in Spain (STEPS), and a multicenter case-control study. Median, 5th, and 95th percentiles for sFlt-1, PlGF, and the sFlt-1/PlGF ratios were determined for normal twin pregnancies for 7 gestational windows and compared with the previous data for singleton pregnancies. RESULTS: The reference range analysis included 269 women with normal twin pregnancies. Before 29 weeks' gestation, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios did not differ between twin and singleton pregnancies. From 29 weeks' gestation to delivery, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios were substantially higher in twin versus singleton pregnancies. sFlt-1 values were higher in women with twin pregnancies across all gestational windows. PlGF values were similar or higher in twin versus singleton pregnancies; PlGF concentrations increased from 10 weeks + 0 days to 28 weeks + 6 days' gestation. CONCLUSIONS: Reference ranges for the sFlt-1/PlGF ratio are similar in women with twin and singleton pregnancies until 29 weeks' gestation but appear higher in twin pregnancies thereafter.

The diagnosis of rupture of fetal membranes (ROM): a meta-analysis.

AIM: The aim of this study was to compare the performance of tests based on the detection of insulin-like growth factor binding protein 1 (IGFBP-1) and placental α-microglobulin-1 (PAMG-1) in diagnosing rupture of fetal membranes (ROM) across different patient populations. METHODS: A meta-analysis was conducted on prospective observational or cohort studies investigating ROM tests based on the detection of IGFBP-1 and PAMG-1 meeting the following criteria: (1) performance metrics calculated by comparing results to an adequate reference method; (2) sensitivity thresholds of the investigated tests matching those of the currently available tests; (3) study population, as a minimum, included patients between 25 and 37 weeks of gestation. Sensitivities, specificities, and diagnostic odds ratios were calculated. RESULTS: Across all patient populations, the analyzed performance measures of the PAMG-1 test were significantly superior compared with those of the IGFBP-1 test. Of particular clinical relevance, PAMG-1 outperformed IGFBP-1 in the equivocal group, which comprised patients with uncertain rupture of membranes (sensitivity, 96.0% vs. 73.9%; specificity, 98.9% vs. 77.8%; PAMG-1 vs. IGFBP-1 tests, respectively). CONCLUSIONS: Compared with its performance in women with known membrane status, the accuracy of the IGFBP-1 test decreases significantly when used on patients whose membrane status is unknown. In this latter clinically relevant population, the PAMG-1 test has higher accuracy than the IGFBP-1 test.

Implementation and outcomes of monoclonal antibody infusion for COVID-19 in an inner-city safety net hospital: A South-Bronx experience.

BACKGROUND: Monoclonal antibody therapy (MAT) is recommended in mild to moderate Coronavirus disease 2019 (COVID-19) patients who are at risk of progressing to severe disease. Due to limited data on its outcomes and the logistic challenges in administering the drug, MAT has not been widely used in the United States (US) despite of emergency use authorization (EUA) approval by the Food and Drug Administration (FDA). AIM: We aim to study the outcomes of MAT in patients predominantly from ethnic minority groups and the challenges we experienced in implementing the infusion therapy protocol in an inner-city safety-net-hospital in the South Bronx. METHODS AND RESULTS: We conducted a retrospective observational study of 49 patients who were offered MAT as per EUA protocol of FDA. Patient who met the criteria for MAT and received therapy were included in treatment group (n = 38) and the remaining (n = 11) who declined treatment were included in the control group. A majority of patients (76%) in the study group reported symptomatic improvement, the day after infusion. There was statistically significant reduction in COVID-19 related hospitalizations (7.8 vs 54.5%, P = < 0.001) mortality (0 vs 18.1%, P value = 0.008) in the treatment group. CONCLUSION: MAT reduced both hospitalization and mortality in this predominantly Hispanic patient population with mild to moderate COVID-19 with high risk factors for disease progression.

Myocarditis and Drug Rash With Eosinophilia and Systemic Symptoms Syndrome: A Deadly Combination.

DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is a severe delayed type IV hypersensitivity drug reaction by T helper cell 2 (Th2) and Interleukin 5 (IL-5) resulting in activation of eosinophils. It is mostly reported with antiepileptic drugs (AEDs), antibiotics, and allopurinol. Here, we present the second case of myocarditis secondary to DRESS syndrome caused by amoxicillin. Most of the case reports present with cross-reactivity among the anticonvulsants and beta-lactams, which is also rarely been reported. Amoxicillin could reactivate human herpesvirus 6 (HHV 6) and Epstein-Barr virus (EBV) with a presentation similar to DRESS syndrome, but our patient was neither taking the anticonvulsants nor have any viral infection in the recent past. His RegiSCAR score was 6, consistent with definite DRESS syndrome. Management includes identification and prompt withdrawal of the offending drug and supportive care for patients without severe organ involvement and systemic corticosteroids for patients with severe organ involvement.

Lupus-Mediated Kidney Damage: Lupus Nephritis or Collapsing Glomerulopathy?

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. It has a myriad of presentations and can involve almost every organ. Its effects on the kidney hold critical importance because patients can ultimately progress to end-stage renal disease (ESRD) if inadequately treated. There are many published cases of collapsing glomerulopathy (CG) in patients with SLE. However, there are not many cases reported of both SLE-related CG and lupus nephritis. Based on our review of the medical literature, fewer than 25 cases have been written about this finding. There are no guidelines to manage these types of patients. Lupus causing CG poses particular challenges in terms of management, particularly treatment options. We present a case of a 47-year-old female who was found to have biopsy findings of both CG and lupus nephritis.

[Hospital care of patients with A/H1N1 influenza: evaluation of the first 1000 reported cases in Spain]. / Demanda de atención hospitalaria por gripe A/H1N1: evaluación de los primeros 1.000 casos atendidos.

INTRODUCTION AND OBJECTIVES: Influenza A is expected to have a great impact in countries in the northern hemisphere yet little has been reported about how this outbreak can affect hospital care. The aim of this study is to assess patients who demand care for flu symptoms and their outcome. MATERIAL AND METHODS: From the beginning of the outbreak a specific protocol was established for the care of patients with potential influenza A in admission, emergency and hospitalization ward. A nominal registry was designed with clinical and epidemiological data. RESULTS: 1018 patients were evaluated for potential influenza A from the beginning of the outbreak until the 31(st) August, 2009. 77% of them fulfilled clinical criteria and were classified as suspected cases. Mean age was 31,7 years (SD17,2), 52% were women, 3,3% pregnant or puerperal. The admission rate was 23,4% with a global mean stay of 3,5 days, and 2,5 for the adults who were admitted to the short stay hospital unit. 2,8 % had pneumonia, two patients required admission to the intensive care unit and one of them died. CONCLUSIONS: Our data show an outbreak with mild illness, with a remarkable percentage of pneumonia but with good outcome. Despite of the high percentage of admissions, and in order to avoid the misleading attention to other patients, we believe that an assistance model based in specific units, short stay and post-discharge follow up could be suitable.

COVID-19 and renin-angiotensin system modulators: what do we know so far?

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory system-coronavirus-2 (SARS-CoV-2), is an important medical problem worldwide. Increased risk of mortality has been reported in patients with cardiovascular disease, such as hypertension (HTN). SARS-CoV-2 invades the pulmonary alveolar epithelial cells by binding to the surface receptor, angiotensin-converting enzyme 2 (ACE2). Renin-angiotensin system (RAS) modulators can increase levels of ACE2. Thus, concerns have been raised regarding an increased risk of severe COVID-19 infection in patients receiving RAS antagonists. AREAS COVERED: We reviewed current literature about the potential association between the utilization of RAS inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-inhibitors) and angiotensin-receptor blockers (ARBs) and likelihood of developing severe COVID-19 infection and whether or not continuation of these medications is appropriate in patients with active disease. EXPERT OPINION: The joint statement from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC) and Heart Failure Society of America (HFSA), strongly recommends that physicians should not initiate or withdraw their usual RAS-related treatments (ACE-inhibitor/ARB) to COVID-19 infected patients with cardiovascular disease. The decision should be made based upon each patient's clinical presentation and hemodynamic status.

Asystolic Cardiac Arrest of Unknown Duration in Profound Hypothermia and Polysubstance Overdose: A Case Report of Complete Recovery.

BACKGROUND: Opioid addiction and overdose is a serious problem worldwide. Fatal overdoses from opioids are responsible for numerous deaths and are increasing, especially if taken in combination with other psychoactive substances. Combined with environmental exposure, opioid overdose can cause profound hypothermia. Opioid abuse and other drugs of abuse impair thermoregulation, leading to severe hypothermia. Both drug overdose and severe hypothermia can cause cardiac arrest. CASE REPORT: We report a case of 20-year-old man with history of polysubstance abuse presenting with severe hypothermia and asystole of unknown duration with return of spontaneous circulation (ROSC) achieved after 28 minutes of cardiopulmonary resuscitation (CPR). Urine toxicology was positive for cocaine, heroin, and benzodiazepine, along with positive blood alcohol level. The patient was rewarmed using non-invasive techniques. Hospital course was complicated by acute renal failure (ARF), severe rhabdomyolysis, severe hyperkalemia, ST-elevation myocardial infarction (STEMI), shock liver, coagulopathy, and aspiration pneumonia. CONCLUSIONS: Survival with full cardiovascular and neurologic recovery after a cardiac arrest caused by drug overdose in the setting of severe hypothermia is still possible, even if the cardiac arrest is of unknown or prolonged duration. Patients with severe hypothermia experiencing cardiac arrest/hemodynamic instability can be rewarmed using non-invasive methods and may not necessarily need invasive rewarming techniques.

Experience in IVIg therapy for selected women with recurrent reproductive failure and NK cell expansion.

PROBLEM: Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells). METHOD OF STUDY: Observational study of RRF women with NK or NKT-like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation. RESULTS: By multivariant logistic regression analysis after adjusting for age, NK cells subsets and other therapies, IVIg significantly improved the live birth rate to 96.3% in women with recurrent miscarriage (RM) compared with 30.6% in case not receiving IVIg (P < 0.0001). In women with recurrent implantation failure (RIF), in comparison with women not receiving IVIg, treatment increased the pregnancy rate from 26.2 to 93.8% (P ≤ 0.0001) and the live birth rate from 17.9 to 80.0% in RIF (P ≤ 0.0001). CONCLUSIONS: Immunomodulation with IVIg in our selected group of RRF patients with immunologic alterations enhanced clinical pregnancy and live birth rates. Our results may facilitate the design of future clinical trials of IVIg in this pathology.

New method to visualize neurons with DAT in slices of rat VTA using fluorescent substrate for DAT, ASP+

The ventral tegmental area (VTA), and in particular dopamine (DA) neurons in this region of midbrain, has been shown to play an important role in motivation (goal-directed behavior), reward, and drug addiction. Most evidence that implicates VTA DA neurons in these functions are based on widely accepted but indirect electrophysiological characterization, including the hyperpolarization activated non-specific cation current (Ih), spike frequency, and inhibition by D2 receptor agonists. In this study, we used a known neuronal dopamine transporter (DAT) fluorescent substrate [4-(4- (dimethylamino) styryl)-N-methylpyridinium iodide] (ASP+) to visualize DAT-containing cell bodies of DA neurons in VTA region in rat brain slices. Uptake of 100 nM of ASP+ in brain slices of rat VTA region marked 38% of visible neurons, while other neurons from this region and 100% neurons from hippocampus slices were not fluorescent. Using patch-clamp techniques, we have found that pronounced Ih current was present in all fluorescent neurons from VTA area, also spike frequency was similar to the widely accepted values for DA neurons. Furthermore, additional study has shown that there are 84% coincidence of ASP+ fluorescence in neuronal cell bodies and Falck-Hillarp labeling of DA cells. Electrophysiological recordings during ASP+ application have confirmed that low concentrations (100 nM) of ASP+ have no visible effect on neuronal activity during 1-2 hours after staining. Thus, uptake of fluorescent monoamine analog ASP+ by DAT can be an additional criterion for identification of DAT-containing neurons in slices.

Selective termination in dichorionic twins discordant for congenital defect.

OBJECTIVE: To evaluate the perinatal outcome of selective termination in dichorionic twins discordant for congenital defect, performed at the Hospital General Universitario Gregorio Marañon. STUDY DESIGN: Twenty-eight dichorionic twins with an anomalous fetus were included from May 2008 to February 2011. Intracardiac KCl (1-2 ml; 15 mEq/ml) under ultrasonographic guidance was used in all procedures. Congenital defect, gestational age at the procedure, incidence and perinatal outcome were retrieved. RESULTS: Selective termination was performed in 14 (50%) cases of structural defects with normal karyotype and in 14 (50%) cases of chromosomal abnormality, 13 of them (92.8%) trisomy 21. Median gestational age at the procedure was 17.8 weeks (range 14.5-24; SD 2.3), and 12 (42.8%) were performed before 18 weeks. The presenting fetus was terminated in 11 cases (39.3%). Selective termination was followed by the subsequent delivery of a viable infant in 27 out of 28 cases (96.4%). Fetal loss before 24 weeks occurred in 1 case (3.6%). Median gestational age at delivery was 38 weeks (range 24.1-40.1; SD 3.8). Twenty-four (88.9%) were delivered >34 weeks and 1 (3.7%) before 28 weeks. CONCLUSION: Selective termination in dichorionic twins discordant for congenital defect is a safe procedure with low risk of unintended fetal loss. This option is a reasonable alternative to expectant management or termination of the whole pregnancy.

Disparities in obstructive sleep apnea and its management between a minority-serving institution and a voluntary hospital.

We assessed disparities in severity of obstructive sleep apnea (OSA) and associated comorbidities, as well as in provision of sleep medicine health care, between patients evaluated for OSA in a voluntary hospital (VH) primarily serving a middle-class population with health-care insurance and a city hospital-based minority-serving institution (MSI) largely treating lower income, uninsured, and indigent patients. A retrospective chart review of patients evaluated for OSA at the VH (n=200) and at the MSI (n=103) was performed. Despite similar age and apnea hypopnea index, MSI patients had a greater body mass index, higher daytime systemic blood pressure, more comorbid medical conditions, and a lower minimum sleep SaO2 than VH patients. Systemic hypertension, diabetes mellitus, asthma, and congestive heart failure were more prevalent in the MSI group. Forty-two percent of the MSI patients diagnosed with OSA failed to follow up for treatment compared with 7% in the VH group, p<0.001. Disparities in OSA-associated comorbid conditions, as well as in delivery of sleep medicine-related health care, were evident between the VH and MSI groups. These findings suggest that OSA may be an important factor contributing to socioeconomic-based differences in morbidity and mortality.

Demanda de atención hospitalaria por gripe A/H1N1: evaluación de los primeros 1.000 casos atendidos / Hospital care of patients with A/H1N1 influenza: Evaluation of the first 1000 reported cases in Spain

Introducción y objetivos: A pesar del enorme impacto que se prevé tenga la pandemia por gripe A/H1N1 en países del hemisferio norte, todavía son escasos los datos disponibles de su repercusión a nivel hospitalario. El objetivo de este trabajo es evaluar la asistencia prestada a los pacientes atendidos por posible gripe A y su evolución en un hospital de tercer nivel.Material y método: Desde la aparición de los primeros casos se estableció un circuito específico de atención a pacientes con posible gripe A en la unidad de admisión, urgencias y hospitalización. Se diseñó un registro nominal con variables epidemiológicas y variables clínicas.Resultados: A 31 de agosto de 2009 se habían evaluado 1.018 pacientes por posible gripe A, de los que el 77% cumplía criterios clínicos. Entre los pacientes con sospecha de gripe A, la edad media (desviación estándar) fue de 31,71 (17,2) años, el 52% eran mujeres, un 3,3% de ellas embarazadas o puérperas. Ingresó el 23,4%, y la estancia media global fue de 3,5 días y de 2,5 días para los adultos que ingresaron en la unidad de corta estancia. Un 2,8% presentó neumonía y 2 pacientes necesitaron atención en unidad de cuidados intensivos (uno de ellos falleció).Conclusiones: Nuestra serie muestra una epidemia de gripe que se comporta de forma benigna con un porcentaje considerable de neumonías, pero que evolucionan favorablemente. A pesar del alto porcentaje de ingresos, y para evitar el menoscabo de la atención a otros enfermos, consideramos que un modelo asistencial basado en unidades específicas, estancias cortas y seguimiento posthospitalario puede ser adecuado (AU)

Introduction and objectives: Influenza A is expected to have a great impact in countries in the northern hemisphere yet little has been reported about how this outbreak can affect hospital care. The aim of this study is to assess patients who demand care for flu symptoms and their outcome. Material and methods: From the beginning of the outbreak a specific protocol was established for the care of patients with potential influenza A in admission, emergency and hospitalization ward. A nominal registry was designed with clinical and epidemiological data.Results: 1018 patients were evaluated for potential influenza A from the beginning of the outbreak until the 31st August, 2009. 77% of them fulfilled clinical criteria and were classified as suspected cases. Mean age was 31,7 years (SD17,2), 52% were women, 3,3% pregnant or puerperal. The admission rate was 23,4% with a global mean stay of 3,5 days, and 2,5 for the adults who were admitted to the short stay hospital unit. 2,8 % had pneumonia, two patients required admission to the intensive care unit and one of them died.Conclusions: Our data show an outbreak with mild illness, with a remarkable percentage of pneumonia but with good outcome. Despite of the high percentage of admissions, and in order to avoid the misleading attention to other patients, we believe that an assistance model based in specific units, short stay and post-discharge follow up could be suitable (AU)

Gigantomastia durante el embarazo / Gigantomasty during pregnancy

La gigantomastia, o hipertrofia mamaria masiva, es una entidad muy rara de etiología desconocida, que quizás se deba a una estimulación hormonal excesiva o a una hipersensibilidad del órgano diana. El tratamiento durante el embarazo es de soporte y farmacológico. En el posparto la mayoría de las pacientes requiere una reducción mamaria y una reconstrucción quirúrgica. Presentamos el caso de una paciente con un rápido crecimiento mamario bilateral durante el embarazo, a la que se tuvo que realizar una cesárea en la semana 32 de gestación por el gran riesgo materno que suponía mantener el embarazo. En un segundo tiempo se realizó una reducción mamaria bilateral

Gigantomastia, or massive breast hypertrophy, is a rare condition of unknown etiology that may be due to hormonal overproduction or hypersensitivity of the target organ. Treatment during pregnancy is supportive and pharmacologic. Most patients require reduction mammoplasty. We present the case of a patient with rapid and massive bilateral breast enlargement during pregnancy. Premature labour at 32 weeks was followed by delivery of a normal infant by caesarean section. In a second intervention, a reduction mammoplasty was carried out