Open-label Prospective Cohort Study Research Articles

Off-label letrozole for tubal pregnancy monotherapy is not an alternative to methotrexate: a prospective cohort study.

Inhibition of estradiol production by letrozole may interfere with physiological effects of progesterone necessary to maintain the pregnancy. Treatment of tubal pregnancy (TP) with letrozole would allow to avoid the disadvantages of methotrexate (MTX). The aim was to compare the effectiveness of letrozole with MTX in the management of TP. A prospective open-label cohort study was conducted among women with TP and increasing B-human chorionic gonadotropin (B-hCG) concentrations. MTX was administered in a single dose of 100 mg intravenously, while letrozole in a dose of 5 mg orally for 10 days. Blood parameters (B-hCG, hemoglobin, creatinine, urea, transaminases, bilirubin) were tested on days 0, 4 and 7. Out of 22 eligible women, 14 received MTX and received 8 letrozole. Mean age, lesion diameter, gestation age in the MTX vs letrozole arm were: 31 vs 32 years (p = 0.3), 13.2 vs 16.3 mm (p = 0.1), 7 + 1 vs 7 + 0 weeks (p = 0.6), respectively. In case of 4 women treated with letrozole and in 2 treated with MTX (4/8, 50% vs 2/14, 14.3%, p = 0.07) the treatment was unsuccessful. There were no significant differences in blood parameters on days 0, 4 and 7 between both arms, except for the increasing urea concentration in the letrozole arm (p = 0.01). Even though the results did not reach statistical significance, it is likely that a larger study sample would confirm the trend of letrozole being less effective. The results did not support the use of letrozole in the studied regimen as an alternative to MTX.

Treatment of neuropsychiatric symptoms in Alzheimer’s disease with a cannabis-based magistral formulation: An open-label prospective cohort study

Treatment of neuropsychiatric symptoms in Alzheimer’s disease with a cannabis-based magistral formulation: An open-label prospective cohort study

P-302 Oral ofloxacin combined with vaginal metronidazole for chronic endometritis: a prospective open-label cohort study

Abstract Study question Does oral ofloxacin 2x200 mg for 10 days combined with vaginal metronidazole 1x500 mg for 10 days reduce the activity of chronic endometritis? Summary answer The investigated antibiotics may be beneficial in some cases of chronic endometritis, except in cases of concomitant endometrial polyp, where they adversely affect treatment outcome. What is known already Chronic endometritis (CE) is characterized by the presence of atypical plasma cell infiltrates (CD138 positive) in the endometrial stroma. CE may adversely affects fertility by reducing endometrial receptivity, impairing decidualization and uterine contractility, thus increasing the risk of recurrent pregnancy loss and implantation failure. Some idiopathic infertility cases are attributed to CE. The diagnostics of CE is challenging because the clinical evaluation is nonspecific and the immunohistochemical criteria are not consistent between research centers. Literature data suggested that successful treatment of CE with antibiotics could improve live birth rates, but a preferred treatment regimen has not been identified. Study design, size, duration A prospective cohort study included women undergoing office hysteroscopy (OH) at a tertiary referral center in 2021-2023. Women diagnosed with CE were assigned, based on their preference, to the intervention arm of ofloxacin 2x200 mg orally for 10 days + metronidazole 500 mg vaginally for 10 days or to the control arm (no antibiotics). 100 women underwent repeated hysteroscopy after 3 cycles, of which 77 received antibiotics and 23 were controls. Participants/materials, setting, methods Women aged 18-45 who met eligibility criteria for OH were included. Karl Storz 5.0 mm Bettocchi® operating sheath with a 2.9 mm 30° telescope and a 5Fr working channel was used. Endometrial lesions or biopsy specimens were collected with grasping forceps, blunt scissors or bipolar needle electrode. Saline was used as the dilating medium. Tissue samples were subjected to histopathological examination. Plasma cells were detected by immunohistochemical staining with Monoclonal Mouse Anti-Human CD138 antibodies. Main results and the role of chance The most common findings identified at hysteroscopy were endometrial polyps (43%), polypoid endometrium (38%), micropolyps (23%), focal (27%) and diffuse hyperemia (18%) and cesarean scar defect (14%). CE was defined as the presence of > 2 plasma cells/mm2. The Mann-Whitney U test showed a significantly higher plasma cell count (PCC) in the presence of a cesarean scar defect than in other cases (23 vs. 18/mm2, p = 0.031) and a tendency towards a lower PCC in micropolyps (9 vs. 21/mm2, p = 0.063). The correlation of hysteroscopic findings with CE activity was weaker than expected. Using repeated measures ANOVA, no difference in PCC between primary and follow-up hysteroscopy was found in either arm (p = 0.8), while post-hoc tests showed that the mean PCC decreased from 12 to 5/mm2 (p = 0.02) in the intervention arm, and from 14 to 6 (p = 0.23) in the control arm. On follow-up hysteroscopy, polyp remission was observed significantly more often in the control arm than in the intervention arm (61% vs. 27%, pChi2=0.02), in which de novo polyp was observed in 4%. In polypoid endometrium, the remission rate was similar in both arms (19% vs. 22%), and the rate of de novo lesions was significantly lower in interventional arm (16% vs. 39%, pChi2=0.035). Limitations, reasons for caution The limitations include the small sample size, the CE definition based on the number of plasma cells calculated using the Receiver Operating Characteristic curve for the purposes of the study, and the empirical selection of antibiotic therapy. Wider implications of the findings Due to the weak correlation of hysteroscopic findings with CE activity, the diagnostics and treatment of CE based on clinical evaluation of the uterine cavity is not justified. Poorly selected antibiotic therapy may adversely affect the outcomes of treatment. Trial registration number 1072.6120.322.2020

Distinct Lipidomic Profiles between People Living with HIV Treated with E/C/F/TAF or B/F/TAF: An Open-Label Prospective Cohort Study.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug-drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17-6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. ClinicalTrials.gov; identifier, NCT06019273.

Residual upper airway obstruction during nocturnal noninvasive ventilation despite high positive expiratory pressure. Impact of oronasal mask to nasal mask switch

BackgroundNasal mask (NM) and oronasal masks (OM) can be used to provide noninvasive ventilation (NIV). Recent studies suggested that OM is the most used interface and that there is no difference in efficacy or in tolerance between OM and NM for chronic use. However, studies focusing on video laryngoscopy underlined the impact of OM in residual upper airway obstruction (UAO) under NIV. We sought to assess the real-life practice of switching from OM to NM when UAO events persist despite high EPAP levels. MethodsIn an open-label single center prospective cohort study, data from files and full night polysomnography on NM and OM were collected for patients wearing OM and presenting an UAO index ≥15/h despite an EPAP level ≥ 10 cmH20. ResultsForty-four patients were included in the study. In 31 patients (74 %), switching to a NM reduced UAOi to ≥10/h. Interestingly, 92 % of these patients still had NM at 3 to 12 months of follow-up. Switching to a NM was also associated with a trend in paCO2 reduction and significant improvements in Epworth, sleep quality and NIV compliance. Successful interface switching was significantly associated with female gender, and a trend was observed in non-smokers. ConclusionAs for CPAP, switching to a NM improved NIV efficacy in a selected group of patients presenting residual UAO events despite high EPAP levels. Additionally, this switch has an impact on compliance and subjective sleepiness. Thus, in patients with persisting UAO on OM, switching to a NM could be a first-line intervention before considering further investigation such as polygraphy or video laryngoscopy. We also derive an algorithm for mask allocation and adaptation in acute and chronic NIV use.

Preoperative respiratory strength training is feasible and safe and improves pulmonary physiologic capacity in individuals undergoing cardiovascular surgery

ObjectiveTo determine the safety, feasibility, and physiologic impact of a preoperative respiratory strength training (RST) program in individuals undergoing elective cardiac surgery (CS). MethodsTwenty-five adults undergoing an elective CS at an academic hospital setting enrolled and completed RST 5 days/week (50 repetitions, 50% training load, ≥3 weeks) at home via telehealth in this open-label prospective cohort study. RST adherence, telehealth attendance, and adverse events were tracked. Pre- and post-RST outcomes of maximum expiratory pressure (MEP), maximum inspiratory pressure (MIP), voluntary cough spirometry, and patient-reported dyspnea were collected. Descriptive analyses and Wilcoxon signed rank-tests were performed. ResultsTwo participants (9%) did not complete the prescribed RST program. No significant RST-related adverse events occurred. Treatment adherence for all enrolled participants was 90%, and telehealth attendance was 99%. Of the CS patients who completed the prescribed program (n = 23; 91%), treatment adherence and telehealth attendance were excellent (98% and 100%, respectively). Significant increases in primary outcomes were observed: MEP mean change, +15.4 (95% confidence interval [CI], +3.4 to +27.3, P < .007); MIP mean change, +14.9 (95% CI, +9.4 to +20.4, P < .0001). No statistically significant differences in voluntary cough or perceived dyspnea outcomes were observed (P > .05). ConclusionsThese preliminary data demonstrate that a preoperative RST program is safe and feasible and can improve short-term respiratory physiologic capacity (MEP and MIP) in CS patients. Future research is warranted to validate the current findings in a larger cohort of CS patients and to determine whether RST improves postoperative extubation outcomes, airway clearance capacity, and aspiration following cardiac surgery.

Nd:YAG 1064-nm laser for residual infantile hemangioma after propranolol treatment

Infantile hemangiomas (IH) are common benign tumors of infancy. Most IH involute, either spontaneously, or secondary to pharmacological treatment with systemic propranolol. Propranolol treatment mostly leads to regression of hemangiomas with satisfactory aesthetic results, but unfortunately not in all cases. To assess the safety and efficacy of long pulsed Nd:YAG 1064 nm laser in treating patients with residual infantile hemangioma after systemic propranolol treatment. This is an open-label prospective cohort study. 30 patients with focal residual IH that had sub-optimal responses to systemic propranolol treatment were enrolled in the study. The patients were treated with 1 to 3 sessions with long pulsed Nd:YAG 1064 nm laser. The maximal response of the IH was assessed using a 4-point scale evaluation scale system. Of the 30 patients enrolled, 18 patients exhibited a great response (> 76% improvement), 10 patients had a good response (> 51–75% improvement), while only 2 patients showed a moderate response (< 50% improvement) to the treatment. No patients had an unsatisfactory response. No serious side effects were observed, and only minor side effects were reported. The treatment with long pulsed Nd:YAG 1064 nm laser for residual IH, which were resistant to systemic propranolol treatment, is safe and effective. Thus, we suggest its use as a second-line treatment for patients with sub-optimal aesthetic results following systemic propranolol.

The Relationship Between Esophageal Pressure and Diaphragm Thickening Fraction in Spontaneously Breathing Sedated Children: A Feasibility Study.

Diaphragm ultrasound is a novel alternative to esophageal pressure measurements in the evaluation of diaphragm function and activity, but data about its reliability in a pediatric setting are lacking. We aimed to compare the esophageal pressure swing (∆Pes, gold standard) with the diaphragmatic thickening fraction (DTF) as a measure of inspiratory effort in sedated children. Additionally, we studied the effect of positive end-expiratory pressure (PEEP) on the end-expiratory thickness of the diaphragm (DTee). Prospective open-label non-randomized interventional physiological cohort study. Operating room in tertiary academic hospital. Children 28 days to 13 years old scheduled for elective surgery with general anesthesia, spontaneously breathing through a laryngeal mask airway, were eligible for inclusion. Exclusion criteria were disorders or previous surgery of the diaphragm, anticipated difficult airway or acute cardiopulmonary disease. All measurements were performed prior to surgery. Patients were subjected to different levels of respiratory load, PEEP and anesthetic depth in a total of seven respiratory conditions. The esophageal pressure and diaphragm thickening fraction were simultaneously recorded for five breaths at each respiratory condition. The relation between ∆Pes and DTF was studied in a mixed model. We analyzed 407 breaths in 13 patients. Both DTF (p = 0.03) and ∆Pes (p = 0.002) could detect respiratory activity, and ∆Pes and DTF were associated across respiratory conditions (p < 0.001; R2 = 31%). With increasing inspiratory load, ∆Pes increased significantly, while DTF did not (p = 0.08). Additionally, DTee did not differ significantly between 10, 5, and 0 cm H2O PEEP (p = 0.08). In spontaneously breathing sedated children and across different respiratory conditions, DTF could differentiate minimal or no inspiratory effort from substantial inspiratory effort and was associated with ∆Pes. Increased efforts resulted in higher ∆Pes but not larger DTF.

Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study

Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.

The results of systemic thrombolytic therapy for acute ischemic stroke in women and men depending on the stroke risk factors

Background: Systemic thrombolytic therapy (STLT) with alteplase is the method of choice in all patients with acute ischemic stroke (IS) within the first 4.5 hours after the symptom onset. There is a noticeable difference between men and women in the clinical characteristics and results of stroke treatment; however, results of studies have been contradictory.&#x0D; Aim: To evaluate the efficacy of STLT with alteplase in women compared to men, depending on the presence of some risk factors for stroke.&#x0D; Materials and methods: This open-label prospective observational non-interventional cohort study of STLT in IS included 209 patients (102 women, the main group, and 107 men, or the comparison group) aged 32 to 86 years. All patients received STLT with alteplase within 4.5 hours from the onset of IS symptoms. The primary endpoint of the study was 28-day survival, and the secondary endpoint was the achievement of mobility independence (0 to 2 points by the modified Rankin Scale (mRS)).&#x0D; Results: The demographic and clinical patient characteristics of both groups were comparable, but women were on average 5 years older than men (p = 0.003). The index IS was not the first one in 31.4% of women and 23.4% of men (p 0.05). There were no significant differences in the severity of stroke and the timing of STLT. Men had a high mortality rate in the acute period of IS, but the difference was non-significant. PST-STLT hemorrhagic transformation was more common in men, with the difference being non-significant (2 0.743, p = 0.389). Women were more likely to have type 2 diabetes mellitus (DM2) (37.3% and 20.6%, respectively, 2 7.111, p = 0.008). In women, there was a trend towards better symptom regression by about 1 point (p = 0.129). The women with DM2 had a 13% higher survival than men (p = 0.038). The numbers of patients achieving independence (02 points on the mRS scale) by Day 28 was not different (56 women and 52 men). No between-groups differences were found in the numbers of patients with arterial hypertension and atrial fibrillation. Only 13 women (12.75%) and 21 men (20%) had a normal body mass index, while 56.3% of women and 46.7% of men had obesity 2 or 3 grades, with the gender differences being non-significant.&#x0D; Conclusion: In women, who have received STLT in the acute period of IS, the death rates and the functional outcomes were non-inferior to those in men, despite their older age, hyperglycemia in the acute period and past history of DM2. The risk factors for stroke in women, compared to men, could be the potential cause of more frequent IS recurrence (every third case in women and every fourth in men was recurrent). Despite a number of negative factors (age, obesity, metabolic syndrome, hyperglycemia, DM2, atrial fibrillation), there was a trend towards better outcomes of STLT in women.

Cannabis-based magistral formulation is highly effective as an adjuvant treatment in drug-resistant focal epilepsy in adult patients: an open-label prospective cohort study.

The safety and efficacy of a formulation high in cannabidiol (CBD) and low in ∆9-tetrahydrocannabinol (THC) to treat drug-resistant epilepsy have been examined previously in children, but not in adult population. The aim of this study was to evaluate whether CBD-rich oil, as an add-on treatment to conventional antiepileptic drugs, was effective, safe, and well-tolerated in adults with drug-resistant focal epilepsy (DRFE). An open-label, prospective cohort, single-center in adult patients with DRFE, were receiving stable doses of antiepileptic drugs (AEDs). A cannabis based-magistral formulation (CBMF) (100 mg/ml CBD and THC <1.9 mg/ml) was administrated 0.1 ml sublingually every 12 hours, up-titrated weekly. The primary outcome was to establish a reduction in seizures frequency >50% at 12 weeks. Adverse-drug reactions monitoring was done. p-value <0.05 was statistically significant. Between August 2020 and July 2022, 44 (38.6%) patients completed >3 months of follow-up. The median daily dose of CBD was 200 mg, that of THC was 4 mg, and that of CBD per kilogram of weight was 3.7 mg. The median number of seizures per month before CBD treatment was 11, and after CBD treatment was 2.5 (p<0.001). A reduction in seizures >50% at 12 week was achieved in 79.5% of the patients. The median percentage change in seizure frequency per month was 84.1% at 12 weeks. Five patients reported any adverse-drug reactions. The CBMF is a highly effective and safety therapy to treat adult patients with DRFE. The reduction in seizures frequency is maintained over time.

Assessment of xenon-induced depth of hypnosis according to Kugler’s scale in elderly and senile patients undergoing knee replacement surgery: a prospective open-label cohort study

INTRODUCTION. Anesthesia with xenon is characterized by stable hemodynamic parameters, cardio- and neuroprotection preferable in elderly. Assessment of the depth of hypnosis remains challenging. The Kugler classification based on electroencephalogram has been suggested for such assessment. OBJECTIVES. To assess the feasibility of Kugler scale for objective assessment of the depth of hypnosis induced by xenon alone or in combination with narcotics and regional anesthesia during knee arthroplasty in elderly. MATERIALS AND METHODS. The study included 57 patients divided into 2 groups. In group 1, general anesthesia with xenon was performed, fentanyl and femoral nerve block were used for pain control. In group 2, xenon anesthesia was performed in combination with femoral and sciatic nerve block. The depth of hypnosis was monitored using EEG and matched with the Kugler scale. Also, the bispectral index (BIS) was recorded. RESULTS. At xenon concentration of 40 %, the depth of hypnosis reached D2 stage in group 1 and D1 in group 2 patients, while at 55 % and above it was D2 in both groups. Fentanyl increased the δ-rhythm by 19.08 %, which corresponded to reduction in the effective xenon concentration by 20 %. A correlation between δ-rhythm decrease and BIS was seen in groups 1 (r = –0.78; R2 = 60 %) and 2 (r = –0.61; R2 = 37 %). The differences could be related to the use of fentanyl in group 1. The intergroup difference between the reduction of BIS was not significant. CONCLUSIONS. In elderly patients undergoing knee arthroplasty under combined anesthesia, stage D2 according to Kugler scale (proportion of δ-rhythm more than 50 %) is achieved at xenon concentration of 55 % without narcotics and at concentration of 40 % with fentanyl. The diminished correlation between δ-rhythm and BIS in group 2 and no difference in decrease of BIS suggests that BIS is less accurate for determining the depth of hypnosis during xenon monoanesthesia.

Effect of bisoprolol on central aortic systolic pressure in Chinese hypertensive patients after the initial dose and long-term treatment.

We conducted a prospective open-label cohort study with the aim of examining the effects of the highly β1-selective agent bisoprolol on central aortic systolic pressure (CASP) after the first dose and after 6 weeks’ treatment and whether the CASP response could be predicted from the early response. Chinese patients with primary hypertension (BP ≥140/90 mmHg) on no therapy or background amlodipine were treated with bisoprolol 2.5 mg daily for 6 weeks. Brachial systolic BP (Br-SBP), resting heart rate (HR), and CASP were determined at baseline, 24 hours after the first dose, and pre-dose after treatment for 6 weeks using the BPro® device. In 42 patients (age 54 ± 9 years), the mean reductions in CASP and Br-SBP after 6 weeks of treatment were not significantly different from each other at −14.5 ± 12.7 and −15.4 ± 12.9 mmHg (both p < 0.01), respectively. Changes in CASP and Br-SBP were highly correlated after the first dose (r = 0.964, p < 0.01) and after 6 weeks (r = 0.963, p < 0.01) and the reductions in CASP after 6 weeks were also associated with the reduction in CASP after the first dose (r = 0.577, p < 0.01). Bisoprolol was shown to effectively reduce CASP and this effect was directly proportional to the reduction in Br-SBP and of a similar magnitude. More favorable CASP responses to long-term therapy may be predicted by greater reductions in CASP after the first dose.

Fecal Microbiota Transplantation Commonly Failed in Children With Co-Morbidities.

Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here, we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources. Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and four pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared fecal donor were examined as controls for microbiome restoration using 16S rRNA gene sequencing of longitudinal fecal specimens. FMT was significantly more effective in rCDI recipients without underlying chronic co-morbidities where fecal microbiome composition in post-transplant responders was restored to levels of healthy children. Microbiome reconstitution was not associated with symptomatic resolution in some rCDI patients who had co-morbidities. Significant elevation in Bacteroidaceae, Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, and Erysipelotrichaceae was consistently observed in pediatric rCDI responders, while Enterobacteriaceae decreased, correlating with augmented complex carbohydrate degradation capacity. Recipient background disease was a significant risk factor influencing FMT outcomes. Special attention should be taken when considering FMT for pediatric rCDI patients with underlying co-morbidities.

Effects of methylene blue on microcirculatory alterations following cardiac surgery: A prospective cohort study.

Methylene blue is used as rescue therapy to treat catecholamine-refractory vasoplegic syndrome after cardiac surgery. However, its microcirculatory effects remain poorly documented. We aimed to study microcirculatory abnormalities in refractory vasoplegic syndrome following cardiac surgery with cardiopulmonary bypass and assess the effects of methylene blue. A prospective open-label cohort study. 20-Bed ICU of a tertiary care hospital. 25 Adult patients receiving 1.5 mg kg-1 of methylene blue intravenously for refractory vasoplegic syndrome (defined as norepinephrine requirement more than 0.5 μg kg-1 min-1) to maintain mean arterial pressure (MAP) more than 65 mmHg and cardiac index (CI) more than 2.0 l min-1 m-2. Complete haemodynamic set of measurements at baseline and 1 h after the administration of methylene blue. Sublingual microcirculation was investigated by sidestream dark field imaging to obtain microvascular flow index (MFI), total vessel density, perfused vessel density and heterogeneity index. Microvascular reactivity was assessed by peripheral near-infrared (IR) spectroscopy combined with a vascular occlusion test. We also performed a standardised measurement of capillary refill time. Despite normalised CI (2.6 [2.0 to 3.8] l min-1 m-2) and MAP (66 [55 to 76] mmHg), patients with refractory vasoplegic syndrome showed severe microcirculatory alterations (MFI < 2.6). After methylene blue infusion, MFI significantly increased from 2.0 [0.1 to 2.5] to 2.2 [0.2 to 2.8] (P = 0.008), as did total vessel density from 13.5 [8.3 to 18.5] to 14.9 [10.1 to 14.7] mm mm-2 (P = 0.02) and perfused vessel density density from 7.4 [0.1 to 11.5] to 9.1 [0 to 20.1] mm mm-2 (P = 0.02), but with wide individual variation. Microvascular reactivity assessed by tissue oxygen resaturation speed also increased from 0.5 [0.1 to 1.8] to 0.7 [0.1 to 2.7]% s-1 (P = 0.002). Capillary refill time remained unchanged throughout the study. In refractory vasoplegic syndrome following cardiac surgery, we found microcirculatory alterations despite normalised CI and MAP. The administration of methylene blue could improve microvascular perfusion and reactivity, and partially restore the loss of haemodynamic coherence. ClinicalTrials.gov identifier: NCT04250389.

1108 Balloon tamponade versus a novel vacuum-induced hemorrhage control device for treatment of postpartum uterine bleeding

Intrauterine devices are an important tool in postpartum hemorrhage (PPH) management. Uterine balloon tamponade (UBT) has been available for decades. A recent, large open-label prospective cohort study of a novel device using vacuum-induced hemorrhage control (VHC) (Jada System®, Figure 1) has been published (D’Alton 2020). The objective of this analysis was to retrospectively review UBT cases at 2 of the 12 participating sites in the VHC study, to provide context for VHC outcomes. A retrospective multi-center chart review of UBT cases was conducted. UBT chart review included a maximum of 30 cases per site in a sequential review from August 2017 to August 2020. Estimated blood loss (EBL) at initiation had no upper limit for UBT cases. VHC data was collected in an open-label prospective cohort study from February 2018 to January 2020, and participant characteristics were previously published. Treatment success was defined as avoidance of escalation of treatment for ongoing bleeding for both UBT and VHC interventions. Sixty UBT and 106 VHC cases were included. PPH was successfully treated in 80% of UBT patients and 94% of VHC patients. Prior treatment with uterotonics and uterine massage was administered before all UBT and VHC cases. Median EBL at device insertion and rates of RBC transfusion was greater for patients with UBT. The median device treatment time was longer for UBT versus VHC patients (15.9 hours and 3.2 hours). For UBT, it was not possible to determine timing of PPH control until device removal, as observation post-tamponade is required to verify uterine contraction and control of bleeding (Table 1). Both UBT and VHC are effective tools for management of PPH. VHC was associated with shorter duration of treatment with direct monitoring of bleeding. VHC was initiated at a lower EBL than UBT, which may account for apparent differences in transfusion rates. Further study is needed to assess comparative effectiveness of treatments for PPH.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Efficacy and safety of rituximab biosimilar (CT-P10) in IgG4-related disease: an observational prospective open-label cohort study

ObjectiveRituximab is increasingly used in IgG4-related disease (IgG4-RD) but high costs limit its wide off-label administration. European and US regulatory agencies have recently approved rituximab biosimilars for the treatment of different rheumatologic and hematological conditions. No data are available, yet, on the efficacy and safety of rituximab biosimilars for the treatment of IgG4-RD. Scope of the present work is to evaluate the efficacy and safety of the rituximab biosimilar CT-P10 (RTX-B) in patients with IgG4-RD. MethodsPatients with active IgG4-RD, naïve to rituximab or switched from the originator (RTX-O) to the biosimilar were treated with RTX-B and prospectively followed-up for 18 months. Safety and efficacy were assessed at six months. Relapse rate was assessed at 18 months. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). ResultsThirty-eight patients were included in this study. Thirty-three patients (87%) were naïve to RTX. Five patients (13%) relapsed after RTX-O and were switched to RTX-B. After six months, 21 patients (60%) achieved disease remission. The median serum IgG4 concentration decreased from 1344 to 575 mg/L (p < 0.01), and the median IgG4-RD RI decreased from 7.5 to 0 (p < 0.01). B-cell depletion was observed in all patients. Eight patients (36%) relapsed within 18 months. Side effects related to RTX-B administration were observed in 14 patients (37%). These results are in line with our previous experience with RTX-O. ConclusionsThe (TruximaTM) rituximab biosimilar CT-P10 represents a safe and effective alternative to rituximab originator for the treatment of IgG4-RD.

Chemical Ablation of Genicular Nerve with Phenol for Pain Relief in Patients with Knee Osteoarthritis: A Prospective Study.

Radiofrequency ablation of the genicular nerve is performed for knee osteoarthritis (KOA) when conservative treatment is not effective. Chemical ablation may be an alternative, but its effectiveness and safety have not been examined. The objective of this prospective open-label cohort study is to evaluate the effectiveness and safety of ultrasound-guided chemical neurolysis for genicular nerves with phenol to treat patients with chronic pain from KOA. Forty-three patients with KOA with pain intensity score (Numeric Rating Scale, NRS) ≥4, and duration of pain of more than 6months were considered for enrollment. Ultrasound-guided diagnostic blocks of genicular nerves (superomedial, inferomedial, and superolateral) with 1.5mL of 0.25% bupivacaine at each site were performed. Those who reported more than 50% reduction in NRS went on to undergo chemical neurolysis, using 1.5mL 7% glycerated phenol in each genicular nerve. NRS and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were assessed before intervention and at 2weeks and 1, 2, 3, and 6months following the intervention. NRS and WOMAC scores improved at all time points. Mean pain intensity improved from 7.2 (95% confidence interval [CI]: 6.8 to 7.7) at baseline to 4.2 (95%CI: 3.5 to 5.0) at 6-month follow-up (P<0.001). Composite WOMAC score improved from 48.7 (95%CI: 43.3 to 54.2) at baseline to 20.7 (95%CI: 16.6 to 24.7) at 6-month follow-up (P<0.001). Adverse events did not persist beyond 1month and included local pain, hypoesthesia, swelling, and bruise. Chemical neurolysis of genicular nerves with phenol provided efficacious analgesia and functional improvement for at least 6months in most patients with a low incidence of adverse effects.

Optic Nerve Sheath Diameter in Acute Liver Failure: A Prospective Cohort Study

Introduction: Acute liver failure (ALF) is a rare disease that may lead to cerebral edema and death. An increased optic nerve sheath diameter (ONSD) may reflect an early increase in intracranial pressure. We assessed the feasibility and safety of the ONSD measurement and its association with outcomes in patients with ALF. Methods: This was an open-label prospective cohort study including adult patients with ALF admitted to a liver-specialized intensive care unit (ICU) in an academic center between October 2018 and February 2020 (among 24): 20 as intention-to-treat and 17 as per-protocol analyses. The ONSD measurement (primary exposure) used an ultrasound transducer (3 determinations on each eye per patient). The primary outcome was hospital mortality. Results: Among the 20 patients, 11 (55.0%) were females and the mean age was 45 ± 16 years. On the day of ONSD measurement (median 32.4 h post-ICU admission; IQR 19.8–59.8): 8 patients (40.0%) were in a coma, the mean international normalized ratio (INR) was 3.3 ± 1.4, median bilirubin was 12.3 mg/dL (IQR 4.7–24.5), mean ammonia was 163 ± 101 µmol/L, and mean SOFA score was 11 ± 5. The mean bilateral ONSD was 5.6 ± 0.7 mm, with a very good correlation between right and left eyes (Pearson’s r = 0.90). Ten (50.0%) patients were transplanted and 13 (65.0%) patients survived the hospital stay (all with a 2-month extended Glasgow Outcome Scale of 8). The mean ONSD was significantly higher for hospital non-survivors than survivors both in the intention-to-treat (6.2 vs. 5.3 mm; p = 0.004) and per-protocol (6.2 vs. 5.2 mm; p = 0.004) analyses. No adverse effects from ONSD measurements were reported. Conclusions: In patients with ALF, a higher ONSD was associated with higher hospital mortality. ONSD measurement is feasible and safe and may have prognostic value.

Long-term echocardiography results in patients with ST-segment elevation myocardial infarction after pharmaco-invasive reperfusion therapy, depending on the choice of thrombolytic drug

Objectives: to analyze the results of echocardiography 1 year after STEMI in patients undergoing pharmaco-invasive reperfusion using various thrombolytic drugs.Materials and Methods: 240 patients with STEMI after pharmaco-invasive reperfusion were included in an open-label prospective cohort study. Depending on the thrombolytic agent used, the patients were divided into 4 groups: in the 1st (n = 73) — lysis was performed with alteplase; in the 2nd (n = 40) — tenecteplase; in the 3rd (n = 95) — forteplase; in the 4th (n = 32) — streptokinase. Depending on the fibrin-specificity of the thrombolytic, all patients were presented with 2 groups: the group of fibrin-specific thrombolytics (FST, n = 208) and the group of fibrin-nonspecific streptokinase (FNST, n = 32). Echocardiography was assessed 1 year after reperfusion.Results: after 1 year, there was a slight violation of the global LV systolic function, while the EF between the groups did not differ (p = 0.420). A higher EF was recorded in the FST group compared with FNST (49.8 ± 7.4 % versus 47.4 ± 6.8 %; p = 0.048). After 1 year, violations and local LV contractility persisted in each of the four groups (p = 0.161). At the same time, lower WMSI were recorded in the FST group compared to FNST (1.19 [1.06; 1.38] versus 1.25 [1.175; 1.5]; p = 0.029). In the FST group, significantly lower iEDV were recorded (p = 0.048), and iESV (p = 0.022) and LA size (p = 0.007) compared with FNST. In dynamics, 1 year after reperfusion in the FST group, there was a significant increase in EF by 5.5 % (p = 0.000) and a decrease in LV WMSI by 5 % (p = 0.000) compared with the FNST group.Conclusions: pharmaco-invasive treatment of STEMI with the use of thrombolytic drugs after 1 year of follow-up is characterized by comparable echocardiography parameters. After 1 year of follow-up, patients undergoing pharmaco-invasive treatment with fibrin-specific drugs had significantly higher EF, as well as lower WMSI, iEDV, iESV, and LA size compared to fibrin-nonspecific streptokinase.