Prongs or Mask for Nasal Continuous Positive Airway Pressure in Neonates: Which One Is More Comfortable?

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is a common mode of respiratory support in neonatal intensive care units. Our objective was to compare whether NCPAP given with nasal prongs compared with a nasal mask reduces the pain scores in preterm infants with respiratory distress. METHODS: Preterm infants on NCPAP due to respiratory distress were included in the study. All infants received NCPAP via the Infant Flow SiPAP. The COVERS pain scale was used to score the infants' pain. Each infant was studied alternating between nasal prongs and a nasal mask. Heart rate, respiratory rate, oxygen saturation, and transcutaneous CO2 (tcCO2) were monitored. Blood pressure and the infants' pain scores were determined every 30 minutes and the average of measurements was taken. RESULTS: The median (interquartile range) values of pain scores, respiratory rates, oxygen saturations, tcCO2 levels, and systolic blood pressures differed significantly and favored the nasal mask. CONCLUSIONS: This study demonstrates that continuous positive airway pressure via a nasal mask leads to a significant reduction in pain scores without altering the respiratory parameters of babies. On the basis of this study, it is possible to conclude that NCPAP applied via nasal mask may be a good alternative to NCPAP applied via nasal prongs.

Prevalence of Comorbid Factors in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Randomized Trial of an Oral Microbiota-Based Therapeutic.

BACKGROUND: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. METHODS: Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1-2, 3-4, ≥5); (ii) baseline creatinine clearance (<30, 30-50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. RESULTS: Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. CONCLUSIONS: In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.

Importance: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. Objectives: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. Design, Setting, and Participants: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. Interventions: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. Main Outcomes and Measures: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. Results: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). Conclusions and Relevance: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. Trial Registration: ClinicalTrials.gov identifier: NCT03183141.

Effect of video camera monitoring feedback on hand hygiene compliance in neonatal intensive care unit, an interventional study.

BACKGROUND: The purpose of this study was to determine whether use of a video camera surveillance system for hand hygiene (HH) monitoring, video-based education, and feedback could improve the HH compliance in a neonatal intensive care unit (NICU). METHODS AND MATERIALS: This was an interventional before-after trial conducted in a level-III NICU between July 2019 and June 2020. HH compliance was measured using randomly selected video-camera footage in the baseline, intervention, and maintenance periods. After the baseline, an intervention consisting of feedback and education with video scenarios was implemented. The primary outcome was change in HH compliance. The compliance rates were analyzed as an interrupted time series (ITS) with a segmented regression model adjusted for autocorrelation for each study period. RESULTS: We identified a total of 8335 HH indications. There were non significant increases in the total compliance rate (9.0%, 95% CI -2% to 20%) at the time of intervention and in the compliance rate after intervention (0.26%, 95% CI -0.31% to 0.84%) per day. The hand hygiene compliance before patient contact significantly increased (19.8%, 95% CI, 4.8%-34.8%). Incorrect glove use improved non-significantly with the intervention (-3.4%, 95% CI -13.4% to 6.7%). CONCLUSION: In this study of HH monitoring using video-camera footage combined with an intervention including feedback and education, there were inconsistent improvements in HH compliance. However, these improvements were not sustained in the long term. Frequent feedback and education may be required to sustain high compliance.

Intestinal perforation after intravitreal low dose ranibizumab injection for the treatment of type 1 retinopathy of prematurity: A case report.

PURPOSE: To report a newborn patient with gastrointestinal (GIS) perforation after intravitreal ranibizumab (RBZ) treatment. CASE REPORT: The patient was born at 31 gestational week and hospitalized with the diagnosis of small for gestational age and prematurity. In the follow up he underwent GIS surgery due to necrotizing enterocolitis (NEC) and was diagnosed with retinopathy of prematurity (ROP). At 43 weeks of postmenstrual age, he developed intestinal perforation after 12 h of the second low-dose RBZ injection. According to our knowledge, this is the first report of GIS perforation due to low-dose intravitreal RBZ treatment in an infant with severe ROP. CONCLUSION: The risk of GIS perforation should be taken into consideration during the application of intravitreal vascular endothelial growth factor antagonist agents, especially in newborns with previous GIS surgery and a history of NEC, and these patients should be carefully monitored for GIS complications.

Extended Follow-up of Microbiome Therapeutic SER-109 Through 24 Weeks for Recurrent Clostridioides difficile Infection in a Randomized Clinical Trial.

This study examines adverse events and durability of response of SER-109, an investigational microbiome therapeutic comprised of purified Firmicutes spores, compared with placebo for Clostridioides difficile infection.

The outcome of two SMA cases treated with nusinersen at seven hours and at three days of life: the earliest ever.

New molecular therapies are available for the treatment of spinal muscular atrophy (SMA) but early intervention is required. We report two cases that were diagnosed prenatally, where treatment with nusinersen was initiated within 7 h and three days respectively. The children were followed up for 13 months and almost six years respectively. Both children have developed within entirely normal centiles, indicating that initiating treatment immediately after birth, as in these cases, is essential for a good outcome.

COVID-19 disease characteristics in different pediatric age groups.

INTRODUCTION: Little is known about the COVID-19 disease characteristics and differences between different pediatric age groups. This study aimed to investigate the disease characteristics according to age groups. METHODOLOGY: We conducted a retrospective, single-center study of pediatric COVID-19 in a tertiary care hospital in Turkey. The patients were divided into three groups: 15 days-24 months old (Group 1), 25-144 months old (Group 2), and 145-210 months old (Group 3) according to age. RESULTS: A total of 139 pediatric patients with COVID-19 were examined. Twenty-nine patients (20.9%) were in Group 1, 52 (37.4%) were in Group 2, 58 (41.7%) were in Group 3. Thirty-nine patients (28.1%) were hospitalized. The most common symptoms were cough (55.4%) and fever (51.8%). The median chest X-ray (CXR) score of hospitalized patients was 1 (min 0-max 7), and the median CXR score of outpatients was 1 (min 0-max 6). Fever was significantly more frequent in Group 1, and chest pain was more frequent in Group 3. Group 1 had significantly higher WBC, lymphocyte, thrombocyte counts, AST, LDH, D-dimer, and Troponin T levels but lower hemoglobin, total protein, and albumin levels. The treatment included antibiotics, oseltamivir, hydroxychloroquine, and supportive therapy. Only one patient (0.7%) received non-invasive mechanical ventilatory support. CONCLUSIONS: As we know the clinical course of COVID-19 in children is less severe than in adults. We also found significant differences in both clinical and laboratory findings between different pediatric age groups which supports the theory that disease pathogenesis is highly variable according to age.

Computed Tomography-guided Percutaneous Drainage of Pneumomediastinum in a Newborn: A Case Report.

BACKGROUND: Neonatal pneumomediastinum is seen in 2.5 per 1000 live births and is mostly managed conservatively. An intervention is essential in cases with tension pneumomediastinum. Ultrasonography-guided (USG-guided) relief of pneumomediastinum has been reported in newborns. There are no reported cases of computed tomography-guided (CT-guided) drainage of pneumomediastinum in neonates. CASE PRESENTATION: A newborn girl born at 34 weeks of gestation was intubated due to respiratory distress and received intratracheal surfactant treatment. Pneumomediastinum was detected at the chest X-ray on the 6th postnatal hour. On the second postnatal day, the patient's oxygen needs increased, tachypnea and subcostal retractions recurred, so it was decided to intervene. USG-guided drainage of the pneumomediastinum was attempted twice but was unsuccessful. Percutaneous drainage with CT guidance was performed successfully. CONCLUSION: This report aims to emphasize that CT-guided intervention of pneumomediastinum can be an effective alternative in a newborn if USG-guided intervention fails.

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown.

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (-6.6%, 95% CI -18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601.

Acute lung injury after exchange transfusion in two newborns with Glucose-6-phosphate dehydrogenase deficiency.

Transfusion-related lung injury (TRALI) is a condition that develops suddenly within the first six hours after a blood transfusion and it is one of the most important causes of blood transfusion-related mortality. There are few data in the literature about TRALI in the neonatal period. We present two newborn patients who developed TRALI after exchange transfusion due to high bilirubin levels. Our first case was a late preterm LGA baby and was on CPAP. The baby was intubated due to sudden deterioration after the exchange transfusion. Our second case was born at term and, an exchange transfusion was performed on the 5th day of life. He developed respiratory distress unexpectedly soon after the exchange transfusion and was intubated. Glucose-6- phosphate dehydrogenase (G6PD) deficiency was detected in both of our cases. We wanted to emphasize that TRALI should be considered in the differential diagnosis of respiratory distress that develops soon after a transfusion in the newborn period and to draw attention to that TRALI may develop more frequently in patients with G6PD deficiency.

A multicenter study on epidemiological and clinical characteristics of 125 newborns born to women infected with COVID-19 by Turkish Neonatal Society.

Limited data are available on pregnant women with COVID-19 and their neonates. We aimed to evaluate the epidemiological and clinical characteristics of newborns born to women infected with COVID-19. A multicenter cohort study was conducted among newborns born to mothers with COVID-19 in 34 neonatal intensive care units (NICUs) in Turkey. Pregnant women (n = 125) who had a positive RT-PCR test and their newborns were enrolled. Cesarean section, prematurity, and low-birthweight infant rates were 71.2%, 26.4%, and 12.8%, respectively. Eight of 125 mothers (6.4%) were admitted to an intensive care unit for mechanical ventilation, among whom six died (4.8%). Majority of the newborns (86.4%) were followed in isolation rooms in the NICU. Four of 120 newborns (3.3%) had a positive RT-PCR test result. Although samples taken on the first day were negative, one neonate became positive on the second day and the other two on the fifth day. Sample from deep tracheal aspirate was positive on the first day in an intubated case.Conclusion: COVID-19 in pregnant women has important impacts on perinatal and neonatal outcomes. Maternal mortality, higher rates of preterm birth and cesarean section, suspected risk of vertical transmission, and low rate of breastfeeding show that family support should be a part of the care in the NICU.Trial registration: ClinicalTrials.gov identifier: NCT04401540 What is Known: • The common property of previous reports was the conclusions on maternal outcomes, rather than neonatal outcomes. • Published data showed similar outcomes between COVID-19 pregnant women and others. What is New: • Higher maternal mortality, higher rates of preterm birth and cesarean section, suspected risk of vertical transmission especially in a case with deep tracheal aspiration during the intubation, and the possible role of maternal disease severity on the outcomes are remarkable findings of this study. • In contrast to recommendation for breastfeeding, parents' preference to formula and expressed breast milk due to anxiety and lack of information shows that family support should be a part of the care in the NICU.

A rare case of gastric cancer with bilateral breast metastasis during pregnancy.

BACKGROUND: Gastric cancer is rare during pregnancy and often diagnosed at a later stage due to overlapping symptoms of pregnancy. Breast metastasis of gastric cancer is another uncommon entity. We present a rare case of breast metastasis of gastric cancer during pregnancy. CASE REPORT: A 26-year-old female was diagnosed with gastric cancer at 14 weeks of gestation and underwent total gastrectomy. She rejected adjuvant chemotherapy and continued pregnancy without any follow-up. Cancer recurred in bilateral breasts at 34th week of gestation mimicking primary inflammatory breast cancer. MANAGEMENT AND OUTCOME: It was difficult to diagnose breast metastasis during pregnancy because of overlapping pregnancy symptoms. Following an unresponsive period to antibiotherapy, a fine needle biopsy on breast was performed and signet cell adenocarcinoma metastasis was determined. We started chemotherapy after delivery. There was a near complete response after first line of chemotherapy. Unfortunately, cancer was relapsed within three months and we started second-line chemotherapy. DISCUSSION: To our knowledge, this is the fourth case reported in medical literature of gastric cancer presented with breast metastasis during pregnancy. We will try to draw attention to diagnosis, treatment and different presentation of gastric cancer during pregnancy with review of the literature.

A Multicentered Study on Epidemiologic and Clinical Characteristics of 37 Neonates With Community-acquired COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) primarily affects adults and spares children, whereas very little is known about neonates. We tried to define the clinical characteristics, risk factors, laboratory, and imagining results of neonates with community-acquired COVID-19. METHODS: This prospective multicentered cohort study included 24 neonatal intensive care units around Turkey, wherein outpatient neonates with COVID-19 were registered in an online national database. Full-term and premature neonates diagnosed with COVID-19 were included in the study, whether hospitalized or followed up as ambulatory patients. Neonates without severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) via reverse transcriptase-polymerase chain reaction testing or whose mothers had been diagnosed with COVID-19 during pregnancy were excluded. RESULTS: Thirty-seven symptomatic neonates were included. The most frequent findings were fever, hypoxemia, and cough (49%, 41%, 27%, respectively). Oxygen administration (41%) and noninvasive ventilation (16%) were frequently required; however, mechanical ventilation (3%) was rarely needed. Median hospitalization was 11 days (1-35 days). One patient with Down syndrome and congenital cardiovascular disorders died in the study period. C-reactive protein (CRP) and prothrombin time (PT) levels were found to be higher in patients who needed supplemental oxygen (0.9 [0.1-8.6] vs. 5.8 [0.3-69.2] p = 0.002, 11.9 [10.1-17.2] vs. 15.2 [11.7-18.0] p = 0.01, respectively) or who were severe/critical (1.0 [0.01-8.6] vs. 4.5 [0.1-69.2] p = 0.01, 11.7 [10.1-13.9] vs. 15.0 [11.7-18.0] p = 0.001, respectively). CONCLUSIONS: Symptomatic neonates with COVID-19 had high rates of respiratory support requirements. High CRP levels or a greater PT should alert the physician to more severe disease.

Clinical and laboratory awareness for an under recognized pathogen in newborn meningitis: Mycoplasma Hominis: a case report.

BACKGROUND: Mycoplasma hominis is a well-known bacterium colonizing the genito-urinary tract. It may cause pneumonia, bacteremia, abscesses, chronic lung disease, and rarely meningitis during the newborn period. CASE: A preterm infant with a birth weight of 885 grams was born at 27 weeks of gestation and had respiratory distress syndrome needing mechanical ventilation. Spontaneous intestinal perforation and grade four intraventricular hemorrhage was diagnosed on day three. CONCLUSION: M. hominis was accepted as the causative agent of meningitis in this case report.

Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder: two randomized controlled studies.

The endogenous opioid system is thought to play an important role in the regulation of mood. Buprenorphine/samidorphan (BUP/SAM) combination is an investigational opioid system modulator for adjunctive treatment of major depressive disorder (MDD). To confirm results from early studies, we report the efficacy and safety of BUP/SAM as adjunctive treatment in patients with MDD and an inadequate response to antidepressant therapy (ADT) in FORWARD-4 and FORWARD-5: two phase 3, randomized, double-blind, placebo-controlled studies that utilized the same sequential parallel-comparison design. Efficacy was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). FORWARD-5 achieved the primary endpoint and demonstrated that adjunctive BUP/SAM 2 mg/2 mg was superior to placebo (average difference change from baseline to week 3 through end of treatment [EOT] in MADRS-6 and -10 versus placebo: -1.5, P = 0.018; -1.9, P = 0.026, respectively). FORWARD-4 did not achieve the primary endpoint (change from baseline in MADRS-10 at week 5 versus placebo: -1.8, P = 0.109), although separate analyses showed significant treatment differences at other timepoints using traditional, regulatory-accepted endpoints such as reduction in MADRS-10 at EOT. The pooled analysis of the two studies demonstrated consistently greater reduction in MADRS-10 scores from baseline for BUP/SAM 2 mg/2 mg versus placebo at multiple timepoints including EOT and average change from baseline to week 3 through EOT (-1.8, P = 0.010; -1.8, P = 0.004, respectively). The overall effect size (Hedges' g) in the pooled analyses for MADRS-10 change from baseline to EOT was 0.22. Overall, BUP/SAM was generally well tolerated, with most adverse events (AEs) being mild or moderate in severity. The most common AEs, occurring in ≥5% of patients in the BUP/SAM 2 mg/2 mg treatment group, which was more frequently than the placebo group, included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, and no evidence of dependence or opioid withdrawal by AEs or objective measures. This report describes adjunctive BUP/SAM 2 mg/2 mg combination, a therapy with a novel opioidergic mechanism of action, as a potential new treatment option for patients with MDD who have an inadequate response to currently available ADT.