Identification of bacteriophages in the vagina of pregnant women: a descriptive study.

OBJECTIVE: To determine the presence and identity of extracellular bacteriophage (phage) families, genera and species in the vagina of pregnant women. DESIGN: Descriptive, observational cohort study. SETTING: São Paulo, Brazil. POPULATION: Pregnant women at 21-24 weeks' gestation. METHODS: Vaginal samples from 107 women whose vaginal microbiome and pregnancy outcomes were previously determined were analysed for phages by metagenomic sequencing. MAIN OUTCOME MEASURES: Identification of phage families, genera and species. RESULTS: Phages were detected in 96 (89.7%) of the samples. Six different phage families were identified: Siphoviridae in 69.2%, Myoviridae in 49.5%, Microviridae in 37.4%, Podoviridae in 20.6%, Herelleviridae in 10.3% and Inviridae in 1.9% of the women. Four different phage families were present in 14 women (13.1%), three families in 20 women (18.7%), two families in 31 women (29.1%) and one family in 31 women (29.1%). The most common phage species detected were Bacillus phages in 48 (43.6%), Escherichia phages in 45 (40.9%), Staphylococcus phages in 40 (36.4%), Gokushovirus in 33 (30.0%) and Lactobacillus phages in 29 (26.4%) women. In a preliminary exploratory analysis, there were no associations between a particular phage family, the number of phage families present in the vagina or any particular phage species and either gestational age at delivery or the bacterial community state type present in the vagina. CONCLUSIONS: Multiple phages are present in the vagina of most mid-trimester pregnant women. TWEETABLE ABSTRACT: Bacteriophages are present in the vagina of most pregnant women.

Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.

OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Renal function at admission as a prognostic marker for patients hospitalised for a first episode of heart failure. Results of the PREDICE study. / Función renal al ingreso como marcador pronóstico en pacientes hospitalizados por un primer episodio de insuficiencia cardíaca. Resultados del estudio PREDICE.

BACKGROUND AND OBJECTIVE: Heart failure (HF) is a frequent condition that deteriorates quality of life and results in high morbidity and mortality. A considerable number of studies have been implemented in recent years to determine the factors that affect the prognosis of HF; however, few studies have assessed the prognosis of patients hospitalised for their first episode of HF. The aim of our study was to analyse the prognostic impact of renal function on patients hospitalised for a first episode of HF. MATERIAL AND METHODS: We recruited 600 patients hospitalised for a first episode of HF in 3 tertiary Spanish hospitals. We analysed the mortality risk during the first year of follow-up according to renal function at the time of admission. RESULTS: The patients with the highest degree of kidney failure at admission were older (P<.001), were more often women (p=.01) and presented a higher degree of dependence (P<.05), as well as a higher prevalence of arterial hypertension (P<.001), chronic renal failure (P<.001) and anaemia (P<.001). In the multivariate analysis, the degree of kidney failure at admission remained an independent predictor of increased mortality risk during the first year of follow-up. CONCLUSIONS: The presence of kidney failure at admission was a marker of poor prognosis in our cohort of patients hospitalised for a first episode of HF.

Amniotic fluid lactic acid and matrix metalloproteinase-8 levels at the time of fetal surgery for a spine defect: association with subsequent preterm prelabour rupture of membranes.

OBJECTIVE: In utero fetal surgery to correct incomplete closure of the spinal cord lessens the extent of permanent damage but is associated with preterm prelabour rupture of membranes (PPROM). We determined whether compounds in amniotic fluid collected at the time of surgery predicted subsequent development of PPROM. DESIGN: Prospective study. SETTING: Hospitals in Sao Paulo, Brazil. POPULATION: Twenty-four consecutive pregnant women at 24-26 weeks of gestation seen between February and October 2017 with a singleton pregnancy underwent in utero surgery to correct an open spinal defect in their fetus. METHODS: Amniotic fluid was tested for lactic acid, matrix metalloproteinase 2 (MMP-2), MMP-8, MMP-9 and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. Clinical data were collected after completion of all laboratory studies. MAIN OUTCOME MEASURE: Amniotic fluid concentration of compounds in women with or without PPROM. RESULTS: Preterm prelabour rupture of membranes occurred in seven (29.2%) women. There were no differences in maternal age, gravidity, parity, race, history of caesarean sections or fetal gender between women with or without PPROM. Length of surgery, days of wound healing and length of hospital stay were also indistinguishable. The median concentrations of MMP-8 (1.7 versus 0.6 ng/ml; P = 0.0041) and lactic acid (7.1 versus 5.9 mm; P = 0.0181) were higher in women with PPROM. The amniotic fluid MMP-8 level was also negatively correlated with gestational age at delivery (Spearman r = -0.4217, P = 0.0319). CONCLUSION: Differences in susceptibility to develop PPROM are present before fetal surgery. An increase in anaerobic glycolysis, evidenced by the intra-amniotic lactic acid level, may enhance MMP-8 production and weaken maternal and fetal membranes. TWEETABLE ABSTRACT: Matrix metalloproteinase-8 and lactic acid in amniotic fluid predict preterm prelabour rupture of membranes.

Perinatal outcomes after open fetal surgery for myelomeningocele repair: a retrospective cohort study.

OBJECTIVE: Describe outcomes of open fetal surgery for myelomeningocele (MMC) repair in two Brazilian hospitals and the impact of surgical experience on outcome. DESIGN: Retrospective cohort study. SETTING: Sao Paulo, Brazil. POPULATION: 237 pregnant women carrying a fetus with an open spinal defect. METHODS: Surgical details, and maternal and fetal outcomes collected from all patients. MAIN OUTCOME MEASURES: Analysis of surgical and perinatal outcome parameters. RESULTS: Total surgical time was 119 ± 7.6 minutes. Preterm labour occurred in 24.2%, premature rupture of membranes in 26.7%, placental abruption in 0.8%, need for a blood transfusion at delivery in 2.1%, and dehiscence at the repair site in 2.5%. Reversal of hindbrain herniation at birth occurred in 71.4%. There were no maternal deaths or severe maternal morbidities. The failure rate with the patient anaesthetised was 0.42% and perinatal mortality was 2.1% (three intrauterine demises and two neonatal deaths). Comparing results from our study in the first 3 years with the last 3 years demonstrated improvement in the total surgical time (121.2 ± 6.4 versus 118.5 ± 8.2 minutes, P = 0.005) and an increase in reversal of hindbrain herniation at birth (64.0 versus 77.1%, P = 0.042). CONCLUSION: Our open fetal surgical approach for MMC was effective and results were comparable to past studies. Improvements in surgical performance and perinatal outcome increased as the surgical team became more familiar with the procedure. FUNDING: The study was funded solely by institutional funds. TWEETABLE ABSTRACT: Brazilian experience of in utero open surgery for myelomeningocele repair.

Effects of cervical cerclage on cervical length and the impact of changes in cervical length on pregnancy prognosis.

OBJECTIVE: To identify any cervix-related morphological and functional marker that can be correlated with pregnancy prognosis in patients who have undergone cerclage for cervical incompetence. DESIGN: An observational and prospective study. SETTING: Department of Obstetrics, Paulista School of Medicine - Federal University of São Paulo (UNIFESP-EPM). METHODS: Patients with cervical incompetence who underwent cervical cerclage using a modified version of the McDonald procedure during or before the 22nd week of pregnancy. The patients were examined by transvaginal ultrasound in the preoperative period, the immediate postoperative period, and between 20 and 24 weeks, 24 weeks + 1 day and 28 weeks, and 28 weeks + 1 day and 32 weeks. Cervical length and the presence of funneling were evaluated during all examinations. Changes in cervical length, presence or absence of funneling, percent increase or decrease in cervical length, and cervical length of less than established values (.

Application of fluorescence in situ hybridization (FISH) as a tool to aid cytogenetics in 1,409 fetal samples.

AIM: To evaluate the technical application of fluorescence in situ hybridization (FISH) as a support to classical cytogenetic in numerical chromosomal aneuploidies studies in samples of amniotic fluid, chorionic villus, and fetal loss. MATERIALS AND METHODS: The authois performed cytogenetic analyses in 1,409 patients (678 amniocentesis, 512 chorionic villus samples, and 219 spontaneous abortions) during one year. FISH molecular study aided traditional cytogenetic in 90 cases. These cases were indicated based on the diagnostic hypothesis of each patient or when no cellular growth was obtained. The authors standardized the FISH in discoloured slides. RESULTS: They had 85% positive FISH in amniotic fluid, 70% in chorionic villus, and 90% in abortion material using 13, 18, 21 X and Y centromeric probes. It showed 12% of altered FISH in amniotic fluid (100% trisomies), 10% in chorionic'villus (50% trisomy and 50% X - monosomy), and 22% in abortion material (50% trisomy, 25% X-monosomy, and 25% triploidy). FISH and cytogenetic analysis confirmed the results. CONCLUSION: This technique revolutionized clinical and research applications of cytogenetics. In this particular paper, FISH was a valuable and reliable technique to promptly identify rapid detection of aneuploidies in interphase cells, metaphase spread and paraffin-embedded samples. It is hoped that, in the future, the economic viability of array CGH and FISH, with the decreasing cost of testing and their genomics advantages can be incorporated as routine and customized in the approach of prenatal diagnosis.

Early implementation of MAK robotic device in total knee arthroplasty rehabilitation: A proof-of-concept study.

BACKGROUND: Effective rehabilitation following total knee arthroplasty (TKA) is crucial for enhancing both range of motion (ROM) and functional outcomes. While robotics has demonstrated its potential in various medical contexts, the evidence on its application in TKA rehabilitation is still scarce. The marsi active knee (MAK), a robotic device that has already proven to be safe and beneficial in people with neurological disease, has been tested to facilitate the rehabilitation of TKA patients. OBJECTIVE: This study aims to evaluate the safety, patient satisfaction, and clinical impact of integrating the MAK into an early rehabilitation regimen for TKA patients. METHODS: The intervention comprised 14 one-hour sessions administered thrice a week, utilizing the MAK within 48 h post-TKA surgery. The rehabilitation sessions incorporated exercises involving passive mobilizations, sit-to-stand transitions, and gait training. Comprehensive data encompassing safety parameters, patient satisfaction, and clinical outcomes were meticulously collected and analyzed. RESULTS: Six participants successfully completed the rehabilitation protocol with the MAK device. Notably, no significant adverse events were documented. Application of the device corresponded to perceptible reductions in self-reported pain levels. Vital signs remained within minimal variance pre- and post-rehabilitation. Participants proficiently engaged in all assisted exercises facilitated by the device, culminating in a high overall satisfaction rating of 4.6 ± 0.5 out of 5. CONCLUSION: The findings indicate that the MAK device exhibits a commendable level of safety while obtaining considerable patient satisfaction during the early rehabilitation phase following TKA, suggesting this device may be a reliable adjunct to TKA protocols.

Safety and usability of the MAK exoskeleton in patients with stroke.

BACKGROUND AND PURPOSE: Stroke is one of the leading causes of disability in adults worldwide, and one of the main objectives in the rehabilitation of these patients is to recover the gait. New technologies have emerged to cope with this issue, complementing conventional therapy with the use of devices such as exoskeletons. The Marsi Active Knee (MAK) exoskeleton (Marsi Bionics SL, Madrid, Spain) has already been tested, but an updated version was improved to allow the patients to perform functional exercises. The aim of this study was to assess the safety and usability of the MAK in the stroke population as well as its potential clinical effects. METHODS: A single-group open label intervention trial was conducted. The device was used twice a week for 5 weeks during 1 h per visit. During the visits, sit-to-stand transitions, walking, stair climbing, trunk rotations, and weight-transfer exercises were performed using the device. Adverse events were collected from participants and therapists to assess safety. The Quebec User Evaluation of the Satisfaction with assistive Technology (QUEST 2.0) was used by both therapists and participants to assess usability. To evaluate its clinical effects, active range of motion (ROM) and muscle strength were assessed in the lower limb. RESULTS: Six participants with stroke were recruited. The device was shown to be safe since no serious adverse events were reported neither by patients nor by therapists. Every proposed exercise was performed. Regarding clinical effects, overall muscle strength showed an increase after the treatment, although ROM measurements did not show any difference. DISCUSSION: Our results suggest that the MAK device is safe for stroke patients. Nevertheless, further changes to enhance usability are recommended, such as an improvement of the attachment system and an adaptation for the drop foot. Beneficial effects regarding increases in muscle strength were obtained. Further trials with a larger sample size, longer intervention periods, and a control group are needed to verify these results. Also, future research should focus on the usability of the MAK as an assistive technology.

Association of serum levels of vascular endothelial growth factor and early ectopic pregnancy.

BACKGROUND: This study evaluated serum vascular endothelial growth factor (VEGF) concentrations in women with ectopic pregnancy (EP), miscarriage, and normal pregnancy (NP). MATERIALS AND METHODS: This was a case-control study comparing serum VEGF concentrations among 72 women with ectopic pregnancy (n = 35), miscarriage (n = 15), and normal pregnancy (n = 22) matched for gestational age. For the determination of serum VEGF concentration a solid phase sandwich enzyme-linked immunosorbent assay (ELISA) was used. Patients were stratified according to serum VEGF above or below 200 pg/ml. RESULTS: The serum level of VEGF was significantly higher in women with EP (median 211.1 pg/ml; range 5-1,017.0 pg/ml) than in women with normal pregnancy (median 5 pg/ml; range 5-310.6 pg/ml) p < 0.0001. Serum VEGF concentrations did not show any statistically significant difference between women with miscarriage (median 231.9 pg/ml; range 5-813.7 pg/ml) and EP (median 211.1 pg/ml; range 5-1,017.0 pg/ml). When threshold concentrations of serum VEGF level > 200 pg/ml were used, an EP could be distinguished from a normal pregnancy with a sensitivity of 51.4%, a specificity of 90.9%, and a positive predictive value of 90%. Between EP and miscarriage, the sensitivity was 51.4%, specificity 42.8%, and a positive predictive value of 69.2%. CONCLUSIONS: Serum VEGF could not distinguish an EP from a miscarriage. However, serum VEGF concentrations could discriminate a normal intrauterine pregnancy (IUP) from an unviable pregnancy (EP or miscarriage).

Assessment of fetomaternal hemorrhage by Kleihauer-Betke test, flow cytometry and α-fetoprotein after invasive obstetric procedures.

PURPOSE: The aim of this study was to evaluate the passage of fetal red blood cells to the maternal circulation, after invasive obstetric procedures, through the Kleihauer-Betke test, flow cytometry and by measurement of maternal serum alpha-fetoprotein level. METHODS: This prospective descriptive study with patients submitted to amniocentesis, cordocentesis, chorionic villus sampling (CVS), amnioreduction and ventriculoamniotic shunt was performed for karyotype analysis, treatment of hydrocephalus and polyhydramnios and to assess fetal lung maturity. Maternal blood samples were collected before and 60 minutes after the invasive obstetric procedure to search for fetal erythrocytes using the Kleihauer-Betke test, flow cytometry and serum alpha-fetoprotein measurement. RESULTS: Ten invasive obstetric procedures were performed. The mean age of the patients was 29.2 years and the mean gestational age was 29.6 weeks. The procedures were: five amniocenteses, two cordocenteses, one CVS, one ventriculo-amniotic shunt and one amnioreduction with cephalocentesis. The indications for the procedures were: karyotype analysis in five patients, fetal lung maturity assessment in two patients, amnioreduction in one patient, fetal hydrocephalus shunt in one patient and polyhydramnios related to hydranencephaly in one patient. Regarding the path of puncture, three procedures were accomplished through the placenta and seven apart from it. All punctures were successful at the first attempt. There was no significant increase of fetal erythrocyte quantity in maternal blood samples using the Kleihauer-Betke test. After cordocentesis, a significant increase of fetal erythrocytes was detected by flow cytometry and serum alpha-fetoprotein measurement. CONCLUSION: Invasive obstetric procedures during prenatal care are safe when performed by experienced professionals using adequate techniques, with minimal chance of passage of fetal erythrocytes from the fetal compartment.

Interruption of a study of cervical ripening with isosorbide mononitrate due to adverse effects.

PURPOSE OF INVESTIGATION: The objective of this study was to evaluate cervix length and the presence of cervical gland area (CGA) in ultrasounds performed before and after the administration of vaginal isosorbide mononitrate (IMN) for cervical ripening. METHODS: We performed an observational, descriptive, and longitudinal study of pregnant patients indicated for labor induction and with a Modified Bishop Score (MBS) lower than six. For cervical ripening, 40 mg of vaginal IMN was administered at 0, 16, and 24 hours after the initiation of cervix preparation. RESULTS: After enrolling 11 patients, the study had to be discontinued due to adverse effects. Three patients requested that they be withdrawn. Headaches were reported by all patients. Nausea, dizziness, dyspnea, and vomiting were also reported. The average cervical lengths at 0, 16, 24 and 36 hours were 27.6, 27.7, 25.9, and 23.0 mm, respectively. CGA disappeared in one of seven patients. CONCLUSIONS: The use of IMN appears to increase the MBS, slightly reducing cervical length without altering the appearance of CGA. Considering the importance of maternal wellbeing during labor, the routine use of IMN cannot be recommended for cervical ripening in the third trimester due to the frequency and intensity of side-effects.

Three-dimensional power Doppler placental vascularisation indices in early pregnancy: a pilot study.

The objective of our study was to assess 1st trimester placental vascularisation using three-dimensional (3D) power Doppler vascular indices. A cross-sectional study was used involving 41 normal pregnancies from 7 to 10 + 6 weeks. Placental volume was obtained using the 30° virtual organ computer-aided analysis (VOCAL) method. The mean, median, standard deviation (SD), minimum and maximum values were calculated for three vascular indices: the VI, vascularisation index; the FI, flow index and the VFI, vascularisation and flow index. Pearson's correlation coefficient (r) was used to assess the correlation between vascular indices and crown-rump length (CRL). Our results showed mean (± SD) values ranged from 8.66 ± 12.04 to 15.34 ± 13.89 for the VI, from 63.83 ± 43.61 to 109.22 ± 33.87 for the FI and from 9.52 ± 13.86 to 20.59 ± 22.97 for the VFI. There was no correlation between CRL and VI (r = 0.073, p = 0.630) nor VFI (r = 0.147 and p = 0.037); there was a weak correlation between CRL and FI (r = 0.332, p = 0.037). It was concluded that the FI was the only 3D power Doppler vascular index that was correlated with CRL between 7 and 10 + 6 weeks' gestation.

Corticosteroids and tocilizumab reduce in-hospital mortality in severe COVID-19 pneumonia: a retrospective study in a Spanish hospital.

BACKGROUND: There is an urgent need to reduce mortality of COVID-19. We examined if corticosteroids and tocilizumab reduce risk for death in patients with severe pneumonia caused by SARS-CoV-2. METHODS: A retrospective cohort study was performed in a single university hospital. All adult patients admitted with confirmed severe COVID-19 pneumonia from 9 March to 9 April 2020 were included. Severe pneumonia was defined as multi-lobar or bilateral pneumonia and a ratio of oxygen saturation by pulse oximetry to the fraction of inspired oxygen (SpFi)<315. All patients received antiviral and antibiotic treatment. From March 26, patients also received immunomodulatory treatment with corticosteroids (methylprednisolone 250 mg/day for 3 days), or tocilizumab or both. In-hospital mortality in the entire cohort and in a 1:1 matched cohort sub-analysis was evaluated. RESULTS: 255 patients were included, 118 received only antiviral and antibiotic treatment while 137, admitted after March 26, also received immunomodulators. In-hospital mortality of patients on immunomodulatory treatment was significantly lower than in those without [47/137(34.3%) vs. 69/118(58.5%), (p < .001)]. The risk of death was 0.44 (CI, 0.26-0.76) in patients receiving corticosteroids alone and 0.292 (CI, 0.18-0.47) in those treated with corticosteroids and tocilizumab. In the sub-analysis with 202 matched patients, the risk of death was 0.356 (CI 0.179-0.707) in patients receiving corticosteroids alone and 0.233 (0.124-0.436) in those treated with the combination. CONCLUSIONS: Combined treatment with corticosteroids and tocilizumab reduced mortality with about 25% in patients with severe COVID-19 pneumonia. Corticosteroids alone also resulted in lower in-hospital mortality rate compared to patients receiving only antiviral and antibiotic treatment. Corticosteroids alone or combined with tocilizumab may be considered in patients with severe COVID-19 pneumonia.