IL-1ß and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer's disease.

BACKGROUND: Systemic activation of the immune system can exert detrimental effects on the central nervous system. Periodontitis, a chronic disease of the oral cavity, is a common source of systemic inflammation. Neuroinflammation might be a result of this to accelerate progressive deterioration of neuronal functions during aging or exacerbate pre-existing neurodegenerative diseases, such as Alzheimer's disease. With advancing age, the progressive increase in the body's pro-inflammatory status favors the state of vulnerability to both periodontitis and Alzheimer's disease. In the present study, we sought to delineate the roles of cytokines in the pathogenesis of both diseases. METHODS: To examine the impacts of periodontitis on the onset and progression of Alzheimer's disease, 6-month-old female 3 × Tg-AD mice and their age-matched non-transgenic mice were employed. Periodontitis was induced using two different experimental models: heat-killed bacterial-induced periodontitis and ligature-induced periodontitis. To delineate the roles of pro-inflammatory cytokines in the pathogenesis of periodontitis and Alzheimer's disease, interleukin 1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were also injected into the buccal mandibular vestibule of mice. RESULTS: Here, we show that IL-1ß and TNF-α were two of the most important and earliest cytokines upregulated upon periodontal infection. The systemic upregulation of these two cytokines promoted a pro-inflammatory environment in the brain contributing to the development of Alzheimer's disease-like pathology and cognitive dysfunctions. Periodontitis-induced systemic inflammation also enhanced brain inflammatory responses and subsequently exacerbated Alzheimer's disease pathology and cognitive impairment in 3 × Tg-AD mice. The role of inflammation in connecting periodontitis to Alzheimer's disease was further affirmed in the conventional magnetization transfer experiment in which increased glial responses resulting from periodontitis led to decreased magnetization transfer ratios in the brain of 3 × Tg-AD mice. CONCLUSIONS: Systemic inflammation resulting from periodontitis contributed to the development of Alzheimer's disease tau pathology and subsequently led to cognitive decline in non-transgenic mice. It also potentiated Alzheimer's disease pathological features and exacerbated impairment of cognitive function in 3 × Tg-AD mice. Taken together, this study provides convincing evidence that systemic inflammation serves as a connecting link between periodontitis and Alzheimer's disease.

Foveal avascular zone size and mfERG metrics in diabetes and prediabetes: a pilot study of the relationship between structure and function.

PURPOSE: Previous studies have demonstrated functional and structural retinal changes in type 2 diabetes (T2DM). However, less is understood in prediabetes, which is an important precursor to T2DM. Here, we evaluate the microvasculature structure of the foveal avascular zone (FAZ) and how it is correlated with retinal function as measured by the multifocal electroretinogram (mfERG) across levels of glucose dysfunction to uncover how T2DM and prediabetes alter this structure-function relationship. METHODS: 33 subjects were included: 9 controls, 12 prediabetes, 12 T2DM with no retinopathy or edema. Subjects were aged 30-70 years, had BCVA of 20/25 or better, and had no confounding ocular conditions. Blood was collected via fingerstick to determine Hemoglobin A1c (HbA1c), which was used along with previous diagnosis, to determine study grouping. Optical coherence tomography angiography (OCTA) was used to analyze the FAZ area and was corrected for refractive error. FAZ area was measured by hand using the Heidelberg Spectralis software. mfERG (VERIS 6.3) metrics implicit time (IT) and amplitude were evaluated in the foveal region, macular region, and averaged over the posterior pole of the right eye. Regression analysis was performed between each study group parameter to determine relationships, and t tests with corrections were used to compare groups. RESULTS: FAZ area (superficial plexus) was negatively correlated with mfERG posterior pole amplitude (p < 0.01, R2 = 0.30), foveal amp (p = 0.02 R2 = 0.17) and macular amplitude (p = 0.02 R2 = 0.18) across all 33 study subjects. FAZ and mfERG metrics were not significantly different between study groups in this cohort except for IT, which was more delayed in the diabetes group compared to other groups. CONCLUSION: FAZ area is correlated with mfERG amplitudes but not IT. This suggests a link between the structural metrics and retinal function. Longitudinal follow-up work would be helpful to determine the timing of these changes in prediabetes.

Barriers to Surgical Innovation Research: A Canadian Study on Public Funding Trends.

BACKGROUND: A decline in research funding has been cited as a potential cause for limited surgical innovation in the United States. We aim to understand if this is a North American phenomenon and explore whether a lack of public funding is a barrier to surgical innovation in Canada. METHODS: Publicly available funding data from Canadian Institutes of Health Research (CIHR) were reviewed from 2008 to 2019 to determine the yearly funding distributed to surgical departments. Surgical innovation studies were identified and total yearly funding was calculated. All amounts were adjusted for inflation to reflect 2019 Canadian dollar value. RESULTS: From 2008 to 2019, surgical departments were granted 1.82-4.70% of total CIHR funding. In total, 902 grants were allocated to surgical departments and 126 (14.0%) met criteria for surgical innovation. Surgical innovation research was allocated a total annual amount ranging from 1.52 to 9.01 million CAD. There appears to be an upward trend in public funding for surgical innovation over this time period. DISCUSSION: Contrary to the landscape in the United States, there is no evidence of decreasing trends in public funding for surgical innovation in Canada. Considerations should be given to other potential barriers precluding surgeons from participating in innovation. CONCLUSION: Only a small percentage of research dollars to departments in Canada are spent on innovation research, despite an overall increasing trend in total public research funding over the past 10 years. We need to foster an environment in which surgical innovation is encouraged through medical curriculum changes, multidisciplinary collaboration opportunities, and dedicated faculty resources.

Fundus motion during mfERG testing.

PURPOSE: The purpose of this study was to assess eye movements during a multifocal ERG (mfERG) recording. This study evaluated the relationship between bivariate contour ellipse areas (BCEAs), mfERG amplitudes (Amps) and mfERG implicit times (ITs) with repeat testing and experienced subjects. METHODS: Thirty subjects were selected (15 experienced to ocular procedures and 15 novices). All were confirmed to have healthy retinas and at least 20/25 vision. MfERGs with a stimulus near 100% contrast and 4-min m-sequence were recorded on two different days using our common clinical technique, which did not constrain the head. VERIS with fundus monitoring system was used for recording with a Burian-Allen electrode. An external camera captured the fundus during each mfERG recording. The optic nerve head position was tracked in each video using a custom algorithm in order to determine BCEAs. Each subject performed one mfERG on two different days. MfERGs were analyzed for Amps and ITs for the fovea and whole eye. RESULTS: There was no correlation between the mfERG metrics and BCEAs with repeat testing. There were also no differences between the experienced and novice subjects for mfERG Amps, ITs or BCEAs. Eye movements between visits were highly correlated (multiple r = 0.67). BCEAs were larger during mfERGs (1.04 ± 0.8 deg2) than those observed in previous literature using brief viewing tasks (< 0.3 deg2). The proportion of time spent fixating within 1.0 and 2.0 degrees of the central hexagon was 68 and 93%, respectively. CONCLUSIONS: This study is the first to evaluate the stability of the retina while recording a mfERG in healthy subjects and indicates that the center of fixation during a mfERG stays within the central hexagon. Eye stability during an initial recording is the best indicator of stability on the second recording. The amount of movement during these recordings did not seem to affect the mfERG Amps or ITs. These data suggest clinical confidence with mfERGs when recording novice patients.

A Multidisciplinary Patient-Specific Opioid Prescribing and Tapering Protocol Is Associated with a Decrease in Total Opioid Dose Prescribed for Six Weeks After Total Hip Arthroplasty.

OBJECTIVE: This retrospective cohort study tested the hypothesis that implementing a multidisciplinary patient-specific discharge protocol for prescribing and tapering opioids after total hip arthroplasty (THA) will decrease the morphine milligram equivalent (MME) dose of opioids prescribed. METHODS: With institutional review board approval, we analyzed a Perioperative Surgical Home database and prescription data for all primary THA patients three months before (PRE) and three months after (POST) implementation of this new discharge opioid protocol based on patients' prior 24-hour inpatient opioid consumption. The primary outcome was total opioid dosage in MME prescribed and opioid refills for six weeks after surgery. Secondary outcomes included the number of tablets and MME prescribed at discharge, in-hospital opioid consumption, length of stay, and postoperative complications. RESULTS: Forty-nine cases (25 PRE and 24 POST) were included. Total median (10th-90th percentiles) MME for six weeks postoperatively was 900 (57-2082) MME PRE vs 295 (69-741) MME POST (mean difference = 721, 95% confidence interval [CI] = 127-1316, P = 0.007, Mann-Whitney U test). Refill rates did not differ. The median (10th-90th percentiles) initial discharge prescription in MME was 675 (57-1035) PRE vs 180 (18-534) POST (mean difference = 387, 95% CI = 156-618, P = 0.003, Mann-Whitney U test) MME. There were no differences in other outcomes. CONCLUSIONS: Implementation of a patient-specific prescribing and tapering protocol decreases the mean six-week dosage of opioid prescribed by 63% after THA without increasing the refill rate.

Systemic inflammation linking chronic periodontitis to cognitive decline.

Persistent inflammation in the systemic immune system can impose detrimental effects on the central nervous system (CNS). Neuroinflammation might be a result of this to accelerate the progressive deterioration of neuronal functions during aging. In this regard, controlling inflammation through delaying and/or preventing chronic inflammatory diseases may be a potential strategy to prevent or modify the progression of Alzheimer's Disease (AD). Periodontitis is a chronic inflammatory disease of the oral cavity that is common among the elderly, especially for those who have decline in cognitive functions. While epidemiological findings support the association of chronic periodontitis and cognitive decline, whether they have causal relationship remains unclear. Nonetheless, the possibility that periodontopathogens, systemic immune cells and inflammatory cytokines could reach the CNS should not be overlooked. The impacts of periodontitis on CNS homeostasis and inflammation as a pathophysiological factor concerning the association between periodontitis and AD will be discussed in this review. Future work should elucidate the pathological pathways involved in periodontitis-induced cerebral infections and inflammation, and define the role of the latter in AD progression.

Evaluation of a Novel Bony Landmark-Based Method for Teaching Percutaneous Insertion of Subclavian Venous Catheters in Pediatric Patients.

BACKGROUND: Surgical trainees performing subclavian vein (SCV) cannulation often incorrectly perceive needle trajectory and anatomical relations. As surface landmark-based methods derived from adult surgical practice may be less effective in younger patients, we developed and evaluated a novel bony landmark-based method for teaching SCV cannulation for central venous access device (CVAD) placement in children. METHODS: Over 2 sequential 3-year periods, pediatric surgical trainees were taught infraclavicular SCV cannulation via surface- and bony-landmark approaches, respectively. We prospectively recorded patient, surgeon and operative details on all Hickman line and port-a-cath insertions placed by trainees as the first surgeon via percutaneous infraclavicular SCV puncture and compared procedural outcomes and complications across both periods. RESULTS: Of 271 cases included in the study, trainees performed 52 (50.5%) and 92 (54.8%) procedures in the first and second periods, respectively. Patients in both periods did not differ by gender, disease, CVAD device, or prior CVAD, chemotherapy or infection status. In the second (bony landmark) period, although patients were younger (6.0 vs. 8.7 years, P = 0.003) mean procedural duration was shorter (42.5 vs. 58.3 min, P < 0.001). Also, cannulation attempts and complication rates did not differ significantly between study periods (P = 0.257 and 1.0, respectively). CONCLUSIONS: With the bony landmark approach, trainees could perform the procedures faster despite operating on younger patients, without impacting complication rates and cannulation attempts. Bony landmarks may better approximate SCV position across a range of ages, thus improving the consistency of SCV cannulation in CVAD placements in children.

Observational Study Using Ultrasound to Assess Midline Labor Epidural Analgesia Placement and Analgesic Efficacy.

OBJECTIVES: Labor epidural analgesia failure may relate to nonmidline placement of epidural catheters. We hypothesized that greater deviations of the epidural catheter insertion point from the ultrasound (US)-determined midline would be associated with less effective labor analgesia. METHODS: A prospective ethically approved cohort study was conducted. Fifty-two healthy average-sized women receiving labor epidural analgesia, inserted by the landmark technique, were approached after delivery. Immediately after removing the epidural catheter, we determined the epidural space midline using US and compared it to the epidural catheter insertion point and to the patient-identified midline (assessed by a pinprick in 1-mm increments). Correlations between the US midline-to-catheter insertion point distance and additional epidural local anesthetic requirements (primary outcome), pain verbal numeric rating scale scores (0-10) 1 hour after epidural insertion, and maternal satisfaction with analgesia were determined. The differences in distances were assessed by a Bland-Altman analysis. RESULTS: There were no significant correlations between the US midline-to-epidural catheter insertion point distance and additional epidural local anesthetic requirements (R2 = 0.138; P = .33), pain verbal numeric rating scale scores 1 hour after the epidural (R2 = 0.121; P = .40) or maternal satisfaction (R2 = 0.085; P = .57). The Bland-Altman analysis revealed that the mean ± SD US midline-to-epidural catheter insertion point distance and patient-identified midline distances were 0.38 ± 0.31 and 0.35 ± 0.46 cm, respectively. CONCLUSIONS: In our laboring population, the hypothesis that nonmidline epidural insertion is associated with less-effective labor analgesia was not confirmed in this study cohort. We found minimal differences in distances between the US midline to epidural catheter insertion point and US midline to patient-identified midline.

Extensive variation in sperm morphology in a frog with no sperm competition.

BACKGROUND: Recent comparative studies of several taxa have found that within-species variation in sperm size decreases with increasing levels of sperm competition, suggesting that male-male gamete competition selects for an optimal sperm phenotype. Previous studies of intraspecific sperm length variation have all involved internal fertilizers where some other factors-e.g., sperm storage and sperm movement along the walls of the female's reproductive tract-probably also influence and reduce sperm size variation. Thus external fertilizers, where those factors are absent, might be expected to exhibit even more variation when there is little or no sperm competition. To test that idea, we studied the sperm morphology of a North American chorus frog, the spring peeper (Pseudacris crucifer), a species in which males encounter little or no sperm competition. RESULTS: As expected, sperm size was highly variable in the spring peeper, largely due to variation in flagellum length within and among individual males, among populations and between mitochondrial lineages in southwestern Ontario. In addition, a large proportion of spermatozoa in all males was abnormal in such a way that the ability of abnormal spermatozoa to fertilize was probably compromised. There were no differences in the frequencies of abnormalities among populations or mitochondrial lineages. CONCLUSIONS: In the absence of sperm competition, we suggest that genetic drift has probably played a role in the generation of diversity in sperm morphology in this species, potentially resulting in the observed differences among populations. Such interpopulation difference in sperm morphology might be expected to increase the degree of reproductive isolation between populations even before other isolating mechanisms evolve.

Elevated transaminases in congenital central hypoventilation syndrome.

Patients with CCHS who also have Hirschsprung disease, elevated or low BMI, or pulmonary hypertension may be predisposed to elevated transaminases and may need periodic follow-up of their hepatic function https://bit.ly/3uW7AUG.

Sleep-related breathing disorders in infants with spina bifida repaired prenatally and postnatally.

STUDY OBJECTIVES: Advances in prenatal repair of myelomeningocele (MMC) have improved outcomes involving different organ systems. There is limited data on respiratory outcomes following prenatal surgical repair. We hypothesize there is no difference in respiratory outcomes between spina bifida (SB) patients who have undergone prenatal versus postnatal repair. METHODS: We performed a retrospective study of 46 infants <1 year with SB seen at Children's Hospital Los Angeles from 2004-2022. Demographic data, timing of closure, neonatal course, Chiari II malformation (CIIM), ventriculoperitoneal shunt (VPS), polysomnography (PSG) results, and need for supplemental oxygen were collected. Unpaired t-test and Chi-square Test were used to analyze results. RESULTS: 31/46 had prenatal repair of MMC; average age at repair was 27 weeks post-conception (PCA). Average age at postnatal repair was 37 PCA. There was no difference in age at PSG. There was no difference in CIIM presence (p=0.61). 60% of patients with postnatal repair and 23% in the prenatal group underwent VPS placement (p=0.01).There was no difference in PSG findings between the two groups: CAI (p=0.11), OAHI (p=0.64), average SpO2 baseline (p=0.91), average SpO2 nadir (p=0.17), average PETCO2 baseline (p=0.87), and average PETCO2 maximum (p=0.54). There were no significant differences in the proportion of patients on supplemental O2 (p=0.25), CSA or OSA between groups. CONCLUSIONS: Patients with SB who've undergone closure of neural tube defect have persistent central apneas, obstructive apneas, and significant hypoxemia. There were no differences in the frequency or severity of sleep-disordered breathing in those with prenatal repair versus postnatal repair.

Synovial Metastasis From Urothelial Carcinoma of the Renal Pelvis Causing Recurrent Hemarthrosis: A Rare Presentation.

Synovial metastases are rare for any malignancy. This case report discusses a case of synovial metastasis from urothelial carcinoma of the renal pelvis presenting with recurrent hemarthrosis. The diagnosis of malignant synovitis can be obtained by synovial fluid aspiration, which is a quick and minimally invasive method, especially when imaging is unyielding or unspecific. Unfortunately, the diagnosis is associated with a poor prognosis of about five months, and treatment is often palliative. While no clinical guidelines exist, a multimodal and multidisciplinary management approach can help address the physical and psychosocial losses suffered.

Disparities in primary pancreatic adenocarcinoma survival by Medicaid-status: A national population-based risk analysis.

BACKGROUND: Pancreatic adenocarcinoma (PAC) has one of the highest mortality rates among all malignancies. While previous research has analyzed socioeconomic factors' effect on PAC survival, outcomes of Medicaid patients are understudied. METHODS: Using the SEER-Medicaid database, we studied non-elderly, adult patients with primary PAC diagnosed between 2006 and 2013. Five-year disease-specific survival analysis was performed using the Kaplan-Meier method and adjusted analysis using Cox proportional-hazards regression. RESULTS: Among 15,549 patients (1799 Medicaid, 13,750 non-Medicaid), Medicaid patients were less likely to receive surgery (p < .001) and more likely to be non-White (p < .001). The 5-year survival of non-Medicaid patients (8.13%, 274 days [270-280]) was significantly higher than that of Medicaid patients (4.97%, 152 days, [151-182], p < .001). Among Medicaid patients, those in high poverty areas had significantly lower survival rates (152 days [122-154]) than those in medium poverty areas (182 days [157-213], p = .008). However, non-White (152 days [150-182]) and White Medicaid patients (152 days [150-182]) had similar survival (p = .812). On adjusted analysis, Medicaid patients were still associated with a significantly higher risk of mortality (aHR 1.33 [1.26-1.41], p < .0001) compared to non-Medicaid patients. Unmarried status and rurality were associated with a higher risk of mortality (p < .001). DISCUSSION: Medicaid enrollment prior to PAC diagnosis was generally associated with a higher risk of disease-specific mortality. While there was no difference in the survival between White and non-White Medicaid patients, Medicaid patients living in high poverty areas were shown to be associated with poor survival.

Disparities in hepatocellular carcinoma survival by Medicaid-status: A national population-based risk analysis.

BACKGROUND: Previous studies have demonstrated disparities in survival surrounding hepatocellular carcinoma (HCC) across a variety of socio-demographic factors; however, the relationship between Medicaid-status and HCC survival is poorly understood. METHODS: We constructed 5-year, disease-specific survival curves using the Kaplan-Meier method and performed an adjusted survival analysis using multivariate Cox-proportional hazard regression. RESULTS: We analyzed 17,059 non-elderly patients (12,194 non-Medicaid, 4875 Medicaid) diagnosed between 2006 and 2013 and found that Medicaid status was not associated with higher risk of diseases-specific death compared to other insurance types (p = .232, aHR 1.02, 95% CI: 0.983-1.07) after for controlling for a variety of co-variates (ie. marital status, urbanicity, etc.). We found no difference in the risk of death between patients enrolled in Medicaid for more than three years versus those enrolled for less than three years. In all models, rurality and unmarried status were also associated with an increased risk of death (aHR 1.11, 95% CI: 1.03-1.18, p = .002 and aHR 1.18, 95% CI: 1.13-1.23, p < .001, respectively). DISCUSSION: Those enrolled in Medicaid prior to HCC diagnosis may not be associated with a higher risk of disease-specific death compared to non-Medicaid enrolled patients.

Analysis of Uveal Melanoma 5-Year Survival Rates by Medicaid Status: A Nationwide Analysis.

PURPOSE: The survival outcomes of patients with primary uveal melanomas based on Medicaid status have not been previously discussed in the literature. METHODS: The Surveillance, Epidemiology, and End Results Medicaid database were utilized to identify patients with primary uveal melanomas diagnosed between 2006 and 2013. The Kaplan-Meier method was utilized to construct 5-year survival curves in adult, non-elderly patients. Log-rank testing was used to determine differences in survival rates, and multivariate Cox proportional hazards modeling was utilized to perform adjusted survival analysis. RESULTS: A total of 1,765 patients were included (Medicaid: 81, non-Medicaid: 1684). A total of 1683 (95.4%) were White. The average age was 51.75 years (SD = 9.5 years). Medicaid patients were more likely to be unmarried, live in a high poverty neighborhood, and live in a rural area (all p < .001). We observed no significant difference in 5-year survival rates between those enrolled in Medicaid (86.6%, 95% CI: 79.1%1-94.7%) and those not enrolled in Medicaid (85.5, 95% CI: 83.8%-87.2%) (p = .80). After controlling for socioeconomic and clinical factors, Medicaid enrollment was not associated with an increased risk of mortality compared to non-Medicaid enrollment. Age (aHR: 1.04, 95% CI: 1.02-1.06, p < .001) and tumor size >10 mm (aHR: 3.04, 95% CI: 1.49-6.21, p = .002) were associated with an increased risk of mortality. CONCLUSION: Medicaid enrollment was not associated with worse cancer-specific 5-year survival. Further research needs to be elicited to better understand the role of Medicaid enrollment in patients with primary uveal melanoma.

More Than a Perioperative Surgical Home: An Opportunity for Anesthesiologists to Advance Public Health.

Public health and the medical specialty of anesthesiology have been closely intertwined throughout history, dating back to the 1800s when Dr. John Snow used contact tracing methods to identify the Broad Street Pump as the source of a cholera outbreak in London. During the COVID-19 pandemic, leaders in anesthesiology and anesthesia patient safety came forward to develop swift recommendations in the face of rapidly changing evidence to help protect patients and healthcare workers. While these high-profile examples may seem like uncommon events, there are many common modern-day public health issues that regularly intersect with anesthesiology and surgery. These include, but are not limited to, smoking; chronic opioid use and opioid use disorder; and obstructive sleep apnea. As an evolving medical specialty that encompasses pre- and postoperative care and acute and chronic pain management, anesthesiologists are uniquely positioned to improve patient care and outcomes and promote long-lasting behavioral changes to improve overall health. In this article, we make the case for advancing the role of the anesthesiologist beyond the original perioperative surgical home model into promoting public health initiatives within the perioperative period.

Human kallikrein 6 inhibitors with a para-amidobenzylanmine P1 group identified through virtual screening.

A series of hK6 inhibitors with a para-amidobenzylamine P1 group and a 2-hydroxybenzamide scaffold linker was discovered through virtual screening. The X-ray structure of hK6 complexed with compound 9b was determined to a resolution of 1.68Å. The tertiary folding of the hK6 complexed with the inhibitor is conserved relative to the structure of the apo-protein, whereas the interaction between hK6 and the inhibitor is consistent with both the SAR and the in silico model used in the virtual screening.

X-ray crystallographic structure-based design of selective thienopyrazole inhibitors for interleukin-2-inducible tyrosine kinase.

Beginning with a screening hit, unique thienopyrazole-indole inhibitors of Itk (interleukin-2-inducible tyrosine kinase) were designed, synthesized, and crystallized in the target kinase. Although initial compounds were highly active in Itk, they were not selective. Increasing the steric bulk around a tertiary alcohol at the 5-indole position dramatically improved selectivity toward Lyk and Syk, but not Txk. Substitutions at the 3- and 4-indole positions gave less active compounds that remained poorly selective. A difluoromethyl substitution at the 5-position of the thienopyrazole led to a highly potent and selective compound. Phenyl at this position reduced activity and selectivity while pushing the side-chains of Lys-391 and Asp-500 away from the binding pocket. Novel and selective thienopyrazole inhibitors of Itk were designed as a result of combining structure-based design and medicinal chemistry.

Physical activity before and during pregnancy and maternal mental health: A systematic review and meta-analysis of observational studies.

OBJECTIVE: To examine the influence of physical activity before and during pregnancy on maternal mental health outcomes. METHODS: Ten electronic databases were searched up to May 11, 2021. Studies of all observational designs (except case studies and reviews) were included, which contained information on the relevant population (women before and or during pregnancy), exposures (objective or subjective measures of physical activity), comparator (low or no physical activity), and outcomes (diagnosis and symptom severity of depression or anxiety, quality of life scores, stress and emotions). RESULTS: Forty-four observational studies (N = 132,399) were included. 'Low' to 'very low' certainty evidence revealed that compared with low levels of PA during pregnancy, high levels of PA were associated with a reduced odds of developing prenatal depression (odds ratio (OR): 0.68, 95% confidence interval (CI): 0.58 to 0.80) and anxiety (OR: 0.67, 95% CI: 0.54 to 0.83). We also found a reduction in the severity of prenatal depressive symptoms (standardized mean difference (SMD): -0.37, 95% CI -0.57 to -0.17), prenatal anxiety symptoms (SMD: -0.45, 95% CI -0.64 to -0.27), and prenatal stress (SMD: -0.33, 95% CI -0.55 to -0.11), concurrent with improved quality of life (SMD: 0.38, 95% CI 0.23 to 0.54). PA before pregnancy did not impact the outcomes of interest. CONCLUSION: Physical activity during pregnancy is associated with a reduction in the odds and severity of prenatal depression and anxiety, as well as reduced stress and improved quality of life. PROSPERO registration number: CRD42020208469.

Postoperative Rather Than Preoperative Neutropenia Is Associated With Early Catheter-related Bloodstream Infections in Newly Diagnosed Pediatric Cancer Patients.

BACKGROUND: The relationship of early catheter-related bloodstream infections (CRBSIs) with perioperative neutropenia and antibiotic prophylaxis is not well established. We sought to evaluate perioperative factors associated with early CRBSIs in newly diagnosed pediatric cancer patients, particularly hematologic indices and antibiotic use. METHODS: We retrospectively reviewed national registry records of newly diagnosed pediatric cancer patients with port-a-caths inserted using standardized perioperative protocols where only antibiotic use was not regulated. Thirty-day postoperative CRBSI incidence was correlated with preoperative factors using logistic regression and with postoperative blood counts using linear trend analysis. RESULTS: Among 243 patients, 17 CRBSIs (7.0%) occurred at median 14 (range, 8-28) postoperative days. Early CRBSIs were significantly associated with cancer type [acute myeloid leukemia and other leukemias (AML/OLs) vs. solid tumors and lymphomas (STLs): odds ratio (OR), 5.09; P = 0.0036; acute lymphoblastic leukemia vs. STL: OR 0.83; P = 0.0446] but not preoperative antibiotics, absolute neutrophil counts and white blood cell counts. Thirty-day postoperative absolute neutrophil counts and white blood cell trends differed significantly between patients with acute lymphoblastic leukemia and STLs (OR 0.83, P < 0.05) and between AML/OLs and STLs (OR 5.09, P < 0.005), with AML/OL patients having the most protracted neutropenia during this period. CONCLUSIONS: Contrary to common belief, low preoperative absolute neutrophil counts and lack of preoperative antibiotics were not associated with higher early CRBSI rates. Instead, AML/OL patients, particularly those with prolonged neutropenia during the first 30 postoperative days, were at increased risk. Our findings do not support the use of empirical preoperative antibiotics and instead identify prolonged postoperative neutropenia as a major contributing factor for early CRBSI.