To compare the accuracy of pulse oximetry oxygen saturation (SpO(2)) measured on the wrist compared with the ipsilateral palm, and SpO(2) measured on the ankle compared with the ipsilateral sole.
In ...this prospective observational study, neonates admitted to the neonatal intensive care unit were enrolled. We recorded SpO(2) (Masimo Radical-7 pulse oximeter) detected at the palm and ipsilateral wrist initially, then at 30 s, and at 1 min, and we repeated the same procedure over the sole and ipsilateral ankle. We recorded the time to obtain the SpO(2) readings from all these sites. Regression analysis was performed to determine the relationship between paired SpO(2) measurements. The mean difference (bias) and standard deviation of the paired SpO(2) differences (precision) were calculated (Bland-Altman plots).
A total of 150 patients (birth weight 2381±1020 g, gestational age 34.3±4.3 weeks, median postnatal age 3.5 days (25th-75th percentile 1-16 days)) were enrolled. There was a good correlation between SpO(2) measured at the palm versus the wrist (r=0.95, P<0.001 (right); r=0.97, P< 0.001 (left)) and between SpO(2) measured at the sole versus the ankle (r=0.92, P<0.001 (right); r=0.91, P<0.001 (left)). There was also a good agreement between paired SpO(2) measurements from these sites. The bias and precision for SpO(2) at the right palm and right wrist was 0.08±0.94% and for the left palm and left wrist 0.22±0.87%. Similarly, the bias and precision for SpO(2) at the right sole and right ankle was -0.03±0.93% and for the left sole and left ankle was -0.01±0.93%.
Our results show that the wrist and ankle can be used as alternative sites to measure SpO(2) in newborn infants in place of the routinely used palm or sole.
Mesenchymal stem/stromal cells (MSC) are promising candidates for use in cell-based therapies. In most cases, therapeutic response appears to be cell-dose dependent. Human term placenta is rich in ...MSC and is a physically large tissue that is generally discarded following birth. Placenta is an ideal starting material for the large-scale manufacture of multiple cell doses of allogeneic MSC. The placenta is a fetomaternal organ from which either fetal or maternal tissue can be isolated. This article describes the placental anatomy and procedure to dissect apart the decidua (maternal), chorionic villi (fetal), and chorionic plate (fetal) tissue. The protocol then outlines how to isolate MSC from each dissected tissue region, and provides representative analysis of expanded MSC derived from the respective tissue types. These methods are intended for pre-clinical MSC isolation, but have also been adapted for clinical manufacture of placental MSC for human therapeutic use.
Patients with metastatic triple-negative breast cancer were treated with standard chemotherapy or the anti–Trop-2 antibody–drug conjugate sacituzumab govitecan. Patients receiving the drug conjugate ...had significantly longer progression-free and overall survival as well as more frequent myelotoxic effects and diarrhea.
Background: Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. ...We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed.
Methods: To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (
n = 70), meconium aspiration syndrome (
n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) (“other”:
n = 43), and congenital diaphragmatic hernia (
n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen Pa
o
2 <60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained Pa
o
2 of 60 mm Hg or greater.
Results: Baseline oxygenation index and Pa
o
2 were 48 ± 2 and 41 ± 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO 28% and 23 with HFOV 23%;
p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (
p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (
p <0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%).
Conclusions: We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN. (J Pediatr 1997;131:55-62)
Tenosynovial giant cell tumor (TGCT) is a rare benign tumor that involves the synovium, bursa, and tendon sheath, resulting in reduced mobility of the affected joint or limb. The current standard of ...care for TGCT is surgical resection. However, some patients have tumor recurrence, present with unresectable tumors, or have tumors that are in locations where resection could result in amputations or significant debility. Therefore, the development of systemic agents with activity against TGCT to expand treatment options is a highly unmet medical need. Pathologically, TGCT is characterized by the overexpression of colony-stimulating factor 1 (CSF-1), which leads to the recruitment of colony-stimulating factor-1 receptor (CSF-1R) expressing macrophages that make up the primary cell type within these giant cell tumors. The binding of CSF-1 and CSF-1R controls cell survival and proliferation of monocytes and the switch from a monocytic to macrophage phenotype contributing to the growth and inflammation within these tumors. Therefore, molecules that target CSF-1/CSF-1R have emerged as potential systemic agents for the treatment of TGCT. Given the role of macrophages in regulating tumorigenesis, CSF1/CSF1R-targeting agents have emerged as attractive therapeutic targets for solid tumors. Pexidartinib is an orally bioavailable and potent inhibitor of CSF-1R which is one of the most clinically used agents. In this review, we discuss the biology of TGCT and review the pre-clinical and clinical development of pexidartinib which ultimately led to the FDA approval of this agent for the treatment of TGCT as well as ongoing clinical studies utilizing pexidartinib in the setting of cancer.
To determine the changes in pulmonary mechanics before and during early dexamethasone therapy, and to evaluate the effect of dexamethasone on the duration of mechanical ventilation in very low birth ...weight (VLBW) ventilator-dependent infants at risk for chronic lung disease (CLD).
A prospective randomized trial was conducted. Forty-three patients (birth weight 600 to 1500 g, gestational age 24 to 32 weeks) who failed to be weaned from the respirator at 7 to 14 days of age were enrolled; 23 infants received a 7-day course of dexamethasone (0.5 mg/kg/day intravenously for 3 days, 0.25 mg/kg/day for 3 days, and 0.1 mg/kg/day for 1 day), and 20 patients were in the control group. At similar mean airway pressure (MAP) and fractional inspired oxygen concentration (FiO2), respiratory system mechanics were measured before and on days 2, 5, and 7 of the study. Airway pressure, flow and tidal volume (VT) were recorded and only mechanical breaths were analyzed. Respiratory compliance (Crs) and respiratory resistance (Rrs) were calculated by two factor least mean square analysis.
Eighty-three percent of infants in the dexamethasone group and 90% in the control group received surfactant in the first 24 hours of life. There was a significant increase in Crs and VT in the dexamethasone group as compared with the control group (P < .001). No major changes in Rrs were observed. Dexamethasone therapy significantly decreased FiO2 and MAP P < .001) and facilitated successful weaning from mechanical ventilation. In addition to a shorter duration of mechanical ventilation (P < .01), the occurrence of CLD (FiO2 > 0.21 at 36 weeks of corrected gestational age, chest radiograph changes) was significantly decreased in the dexamethasone group (P < .01). Except for a transient increase in blood pressure and serum glucose, there were no significant differences in infection rates, intraventricular hemorrhage, or retinopathy of prematurity. Thirteen patients in the control group received dexamethasone at a later age.
Our findings indicate that: 1) early dexamethasone therapy in VLBW infants markedly improves respiratory compliance and tidal volume, reduces FiO2 and MAP requirements, and facilitates extubation in these infants; 2) early dexamethasone therapy reduces the duration of mechanical ventilation and decreases CLD (at 28 days and 36 weeks) in a population of VLBW infants largely treated with surfactant.
Background and Aims: Adductor canal block (ACB) is now an established component of multimodal analgesia for knee replacement surgery and is slowly replacing femoral nerve block (FNB). It is also ...gaining popularity for providing pain relief in knee arthroscopies including anterior cruciate ligament reconstruction surgery (ACLR). Data is lacking from the Indian subcontinent on comparing ACB to the traditional FNB for ACLR. Hence, we conducted the present study to compare ACB and FNB in ACLR under general anesthesia.
Material and Methods: Sixty patients were randomized to receive either ACB or FNB under ultrasound guidance. Postoperatively, quadriceps muscle strength (straight leg raise and time up and go; TUG test) and quality of analgesia (numeric rating scale; NRS and patient satisfaction score) were assessed every 6 hour, and thereafter, up to 48 hours. The time of rescue analgesia and total analgesic consumption (tramadol) were also recorded. Data was statistically analyzed and P < 0.05 was considered to be significant.
Results: Patients receiving ACB had significantly less quadriceps weakness (P < 0.001) compared to FNB on postoperative day (POD) 1. In addition, patient satisfaction score was statistically higher (P < 0.05) in FNB on POD1. Both the above parameters were comparable on POD2. No statistically significant difference was recorded in NRS, time for rescue analgesia, and total analgesic consumption among the two groups.
Conclusion: ACB preserves quadriceps motor strength while providing analgesia comparable to FNB in patients undergoing ACLR. However, patient satisfaction score is better with FNB than ACB.
•Chemotherapy induces microbiome disruption, inflammation, and cognitive decline.•The resulting microbiome disruption relates to cognitive decline and inflammation.•Those cognitively impaired have ...unique chemotherapy-induced microbiome alterations.
Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.
Analysis of archival samples from cohorts of pregnant women may be key to discovering prognosticators of stillbirth and pregnancy/perinatal complications. Growth hormone (GH) and its receptor (GHR) ...are pivotal in feto-placental development and pregnancy maintenance. We report a rapid, optimized method for genotyping the GHR full-length versus exon 3-deleted isoform (GHR
d3
). TaqMan single nucleotide polymorphism (SNP) genotyping proved superior to standard multiplex polymerase chain reaction (PCR) in allele detection and GHR genotyping from archived samples, including those with poor genomic deoxyribonucleic acid quality/quantity such as formalin fixed, paraffin embedded, blood, and serum. Furthermore, this assay is suitable for high through put 96 or 384-well plate quantitative PCR machines with automated genotype calling software. The TaqMan genotyping assay can increase the data obtained from precious archival human samples.
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