Antibiotic Management for Early-Onset Sepsis in Neonates With Gestational Ages of ≥ 34 Weeks: The Kaiser Sepsis Calculator Versus the 2010 CDC Guidelines.

INTRODUCTION: The traditional approach to neonatal early-onset sepsis (NEOS) management, involving maternal risk factors and nonspecific neonatal symptoms, usually leads to unnecessary antibiotic use. This study addresses these concerns by evaluating the Kaiser sepsis calculator (KSC) in guiding antibiotic therapy for NEOS, especially in high-incidence facilities (over 4/1,000 live births), by comparing it against the 2010 Centers for Disease Control and Prevention (CDC) guidelines for neonates ≥34 weeks with suspected sepsis, thereby emphasizing its implications for personalized patient care. METHODS: This is a prospective observational study. All neonates of 34 gestational weeks or more, presenting with either maternal risk factors or sepsis symptoms within 12 hours of birth, were included in the study. The analysis focused on antibiotic recommendations by the 2010 CDC guidelines versus those by the KSC at presumed (0.5/1,000) and actual (16/1,000) sepsis incidence rates. RESULTS: NEOS was identified in 14 cases (14.1%). Compared to the KSC, at an incidence rate of 16 per 1,000, the KSC resulted in a significant 32.3% reduction in antibiotic treatment (74 cases (74.7%) vs. 42 cases (42.4%), respectively; p < 0.001). The calculator advised immediate antibiotic utilization for 13 out of 14 (92.9%) diagnosed cases, suggesting further evaluation for the remaining cases. When a presumed incidence of 0.5/1,000 was applied, the KSC indicated antibiotics less frequently than when using the actual rate of 16/1,000 (p<0.001) with two missed NEOS cases. CONCLUSIONS: Using the KSC led to a decrease of 32 cases (32.3%) in unnecessary antibiotic prescriptions compared to adherence to 2010 CDC guidelines. However, setting a presumed incidence below the actual rate risked missing NEOS. The calculator was effective when actual local incidence rates were used, ensuring no missed cases needing antibiotics.

Effectiveness of pulmonary valve-sparing strategy for transatrial-transpulmonary repair of tetralogy of Fallot: a single institution experience.

OBJECTIVE: We report the midterm results of our strategy utilizing transatrial-transpulmonary repair for tetralogy of Fallot at a single institution in a low-middle income country. METHODS: Medical records were retrospectively reviewed for 532 consecutive patients who underwent definitive repair of tetralogy of Fallot at our institution from 2010 to 2020. RESULTS: The median age and weight of patients in the study patients were 11.6 months (interquartile range, 8.6-17.2 months) and 7.5 kg (interquartile range, 6.8-8.8 kg). The pulmonary valve annulus was preserved (no transannular patch) in 398 patients (75%) and a mini-transannular patch was utilized for 134 patients (25%). The overall survival was 98% at 1 year, and 97% at 10-years follow-up, respectively. Longer postoperative ventilation time was the only risk factor correlated to early death (p = 0.004; Odds Risk, 1.04; 95% confidence intervals, 1.01-1.07). Fourteen patients required pulmonary valve replacement (2.6%, 14/532), four required surgical resection to relieve right ventricular outflow tract obstruction (0.8%, 4/532), and freedom from reoperation of the right ventricular outflow tract was 87% at 10 years. The only risk factor for right ventricular outflow tract reoperation was a postoperative systolic pressure gradient through the right ventricular outflow tract of greater than 50 mmHg (p < 0.001; HR, 47; 95% confidence intervals, 9.1-244). In total, 94.6% (471/489) of the patients were asymptomatic at the latest follow-up without significant arrhythmia. CONCLUSION: At our institution in an low-middle income country, the transatrial-transpulmonary repair for tetralogy of Fallot has excellent midterm results with few reoperations required. Close long-term follow-up is essential for patients who undergo repair with a mini-transannular patch and may eventually require pulmonary valve replacement.

Genetic diversity of G9, G3, G8 and G1 rotavirus group A strains circulating among children with acute gastroenteritis in Vietnam from 2016 to 2021.

Rotavirus group A (RVA) is the most common cause of severe childhood diarrhea worldwide. The introduction of rotavirus vaccination programs has contributed to a reduction in hospitalizations and mortality caused by RVA. From 2016 to 2021, we conducted surveillance to monitor RVA prevalence and genotype distribution in Nam Dinh and Thua Thien Hue (TT Hue) provinces where a pilot Rotavin-M1 vaccine (Vietnam) implementation took place from 2017 to 2020. Out of 6626 stool samples, RVA was detected in 2164 (32.6%) by ELISA. RT-PCR using type-specific primers were used to determine the G and P genotypes of RVA-positive specimens. Whole genome sequences of a subset of 52 specimens randomly selected from 2016 to 2021 were mapped using next-generation sequencing. From 2016 to 2021, the G9, G3 and G8 strains dominated, with detected frequencies of 39%, 23%, and 19%, respectively; of which, the most common genotypes identified were G9P[8], G3P[8] and G8P[8]. G1 strains re-emerged in Nam Dinh and TT Hue (29.5% and 11.9%, respectively) from 2020 to 2021. G3 prevalence decreased from 74% to 20% in TT Hue and from 21% to 13% in Nam Dinh province between 2017 and 2021. The G3 strains consisted of 52% human typical G3 (hG3) and 47% equine-like G3 (eG3). Full genome analysis showed substantial diversity among the circulating G3 strains with different backgrounds relating to equine and feline viruses. G9 prevalence decreased sharply from 2016 to 2021 in both provinces. G8 strains peaked during 2019-2020 in Nam Dinh and TT Hue provinces (68% and 46%, respectively). Most G8 and G9 strains had no genetic differences over the surveillance period with very high nucleotide similarities of 99.2-99.9% and 99.1-99.7%, respectively. The G1 strains were not derived from the RVA vaccine. Changes in the genotype distribution and substantial diversity among circulating strains were detected throughout the surveillance period and differed between the two provinces. Determining vaccine effectiveness against circulating strains over time will be important to ensure that observed changes are due to natural secular variation and not from vaccine pressure.

GALAD score and a proposal for GALADUS model for detecting hepatocellular carcinoma in Vietnamese patients with chronic liver disease.

OBJECTIVE: The GALAD score, a serum biomarker-based model, predicts the likelihood of hepatocellular carcinoma (HCC) in patients with chronic liver disease. We evaluated the performance of the GALAD score compared to that of liver ultrasound in detecting HCC. PATIENTS AND METHODS: This study recruited a group of 136 patients with HCC and a control group of 436 patients with cirrhosis or chronic hepatitis B or hepatitis C. The performance of the GALAD score and ultrasound in detecting HCC in these patients was analyzed using the area under the receiver operating characteristic curve (AUC). The sensitivity and specificity of the optimal GALAD score were compared to those of ultrasound. RESULTS: The AUC of the GALAD score for detecting HCC was 0.940 [95% confidence interval (CI) 0.92-0.96], higher than that of ultrasound [0.939 (0.91-0.96), p < 0.001]. At a threshold of 1.24, the GALAD score had a sensitivity of 91.2% and a specificity of 81.9% for detecting HCC. The AUC of the GALAD score for early HCC detection was 0.75 (95% CI 0.71-0.80, p < 0.001; threshold 1.13, sensitivity 87.5%, specificity 67.8%, p < 0.001). The combination of GALAD and ultrasound (GALADUS score) showed further improvement, achieving an AUC of 0.97 (95% CI 0.96-0.99; cut-off point 1.37, sensitivity 95.6%, specificity 89.2%, p < 0.001). CONCLUSIONS: In our study, the GALADUS score showed improved performance compared to the GALAD score. Therefore, we suggest that the performance of the GALAD score should be reconsidered and that it should be evaluated in combination with ultrasound for HCC detection.

Trastuzumab and first-line taxane chemotherapy in metastatic breast cancer patients with a HER2-negative tumor and HER2-positive circulating tumor cells: a phase II trial.

PURPOSE: HER2 overexpressing circulating tumor cells (CTCs) are observed in up to 25% of HER2-negative metastatic breast cancer patients. Since targeted anti-HER2 therapy has drastically improved clinical outcomes of patients with HER2-positive breast cancer, we hypothesized that patients with HER2 overexpressing CTCs might benefit from the addition of trastuzumab to chemotherapy. METHODS: In this single-arm, phase II trial, patients with HER2-positive CTCs received trastuzumab as addition to first-line treatment with taxane chemotherapy. Patients with detectable CTCs but without HER2 overexpression that received taxane chemotherapy only, were used as control group. The primary outcome measure was progression-free rate at 6 months (PFR6), with a target of 80%. In November 2022, the study was terminated early due to slow patient accrual. RESULTS: 63 patients were screened, of which eight patients had HER2-positive CTCs and were treated with trastuzumab. The median number of CTCs was 15 per 7.5 ml of blood (range 1-131) in patients with HER2-positive CTCs, compared to median 5 (range 1-1047) in the control group. PFR6 was 50% in the trastuzumab group and 54% in the taxane monotherapy group, with no significant difference in median PFS (8 versus 9 months, p = 0.51). CONCLUSION: No clinical benefit of trastuzumab was observed, although this study was performed in a limited number of patients. Additionally, we observed a strong correlation between the number of evaluable CTCs and the presence of HER2-positive CTCs. We argue that randomized studies investigating agents that are proven to be solely effective in the HER2-positive patient group in patients with HER2-positive CTCs and HER2-negative tissue are currently infeasible. Several factors contribute to this impracticality, including the need for more stringent thresholds, and the rapidly evolving landscape of cancer treatments.

Adverse childhood experiences and early initiation of substance use: A survival analysis.

OBJECTIVE: Early adversity, such as adverse childhood experiences (ACEs), is a risk factor for the development of substance use disorder (SUD). ACEs are associated with earlier initiation of substance use. This study examined the relationship between ACEs and age of initiation of substance use using survival analysis. It is hypothesized that individuals with higher ACEs will have an earlier age of initiation. METHOD: Participants were recruited from the University of Kentucky's Laboratory for Human Behavioral Pharmacology. Participants were 18 years or older, English speaking, and actively engaged in substance use. Participants were not in substance abuse treatment nor were they seeking treatment. ACE scores were calculated, and age of substance use initiation was recorded. A Cox proportional hazard model was used to examine the effect of ACE score on age of substance use initiation. RESULTS: A total of 107 participants completed the study. An average number of 2.3 ACEs (SD = 2.2) were endorsed with 24% of participants reporting 4 or more ACEs. Higher ACE scores were associated with cigarette smoking and non-medical prescription opioid use onset ( hazard ratio (HR) = 1.14, 95% CI=1.02-1.28, p = 0.02, and HR=1.19, 95% CI = 1.04-1.37, p = 0.01, respectively. CONCLUSIONS: A significant association was found between higher ACE scores and earlier initiation of cigarette and non-medical prescription opioid use, consistent with prior research. Primary prevention of ACEs, screening for ACEs during childhood, and interventions for ACEs if detected, may help to reduce the risk of substance use/SUD in adulthood.

Comparative safety of tenecteplase vs alteplase for acute ischemic stroke.

INTRODUCTION: Tenecteplase has been compared to alteplase in acute stroke randomized trials, with similar outcomes and safety measures, but higher doses of tenecteplase have been associated with higher hemorrhage rates in some studies. Limited data are available on the safety of tenecteplase outside of clinical trials. METHODS: We examined the safety measures of intracranial hemorrhage, angioedema, and serious extracranial adverse events in a 21-hospital integrated healthcare system that switched from alteplase (0.9 mg/kg, maximum dose 90 mg) to tenecteplase (0.25 mg/kg, maximum dose 25 mg) for acute ischemic stroke. RESULTS: Among 3,689 subjects, no significant differences were seen between tenecteplase and alteplase in the rate of intracranial hemorrhage (ICH), parenchymal hemorrhage, or volume of parenchymal hemorrhage. Symptomatic hemorrhage (sICH) was not different between the two agents: sICH by NINDS criteria was 2.0 % for alteplase vs 2.3 % for tenecteplase (P = 0.57), and sICH by SITS criteria was 0.8 % vs 1.1 % (P = 0.39). Adjusted logistic regression models also showed no differences between tenecteplase and alteplase: the odds ratio for tenecteplase (vs alteplase) modeling sICH by NINDS criteria was 0.9 (95 % CI 0.33 - 2.46, P = 0.83) and the odds ratio for tenecteplase modeling sICH by SITS criteria was 1.12 (95 % CI 0.25 - 5.07, P = 0.89). Rates of angioedema and serious extracranial adverse events were low and did not differ between tenecteplase and alteplase. Elapsed door-to-needle times showed a small improvement after the switch to tenecteplase (51.8 % treated in under 30 min with tenecteplase vs 43.5 % with alteplase, P < 0.001). CONCLUSION: In use outside of clinical trials, complication rates are similar between tenecteplase and alteplase. In the context of a stroke telemedicine program, the rates of hemorrhage observed with either agent were lower than expected based on prior trials and registry data. The more easily prepared tenecteplase was associated with a lower door-to-needle time.

Stroke characteristics and outcomes in urban Tanzania: Data from the Prospective Lake Zone Stroke Registry.

BACKGROUND: Stroke is a second leading cause of death globally, with an estimated one in four adults suffering a stroke in their lifetime. We aimed to describe the clinical characteristics, quality of care, and outcomes in adults with stroke in urban Northwestern Tanzania. METHODS: We analyzed de-identified data from a prospective stroke registry from Bugando Medical Centre in Mwanza, the second largest city in Tanzania, between March 2020 and October 2022. This registry included all adults ⩾18 years admitted to our hospital who met the World Health Organization clinical definition of stroke. Information collected included demographics, risk factors, stroke severity using the National Institutes of Health Stroke Scale, brain imaging, indicators for quality of care, discharge modified Rankin Scale, and in-hospital mortality. We examined independent factors associated with mortality using logistic regression. RESULTS: The cohort included 566 adults, of which 52% (294) were female with a mean age of 65 ± 15 years. The majority had a first-ever stroke 88% (498). Premorbid hypertension was present in 86% (488) but only 41% (200) were taking antihypertensive medications before hospital admission; 6% (32) had HIV infection. Ischemic strokes accounted for 66% (371) but only 6% (22) arriving within 4.5 h of symptom onset. In-hospital mortality was 29% (127). Independent factors associated with mortality were severe stroke (adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI) = 1.47-2.24, p < 0.001), moderate to severe stroke (aOR = 1.49, 95% CI = 1.22-1.84, p < 0.001), moderate stroke (aOR = 1.80, 95% CI = 1.52-2.14, p < 0.001), leukocytosis (aOR = 1.19, 95% CI = 1.03-1.38, p = 0.022), lack of health insurance coverage (aOR = 1.15, 95% CI = 1.02-1.29, p = 0.025), and not receiving any form of venous thromboembolism prophylaxis (aOR = 1.18, 95% CI = 1.02-1.37, p = 0.027). CONCLUSION: We report a stroke cohort with poor in-hospital outcomes in urban Northwestern Tanzania. Early diagnosis and treatment of hypertension could prevent stroke in this region. More work is needed to raise awareness about stroke symptoms and to ensure that people with stroke receive guidelines-directed therapy.

Leptin and interleukin-1ß levels associated with osteoarthritis in Vietnamese patients: a cross-sectional analysis.

Leptin and interleukin-1 beta (IL-1ß) are two extensively studied biomarkers associated with metabolic syndrome (MetS) and osteoarthritis (OA). Previous studies have mostly focused on either MetS or OA alone, with no available data on Vietnamese patients. This study aimed to investigate the levels of leptin and IL-1ß in this patient population and explore their association with clinical parameters of MetS and OA. The study included 164 patients with primary knee OA, who were classified into two categories based on the presence of MetS, and 78 healthy controls. The plasma leptin and IL-1ß levels were quantified by ELISA and correlated with clinical parameters. Leptin levels were higher in patients with OA (11.50±10.04 ng/mL) than in healthy controls (0.54±0.37 ng/mL) and increased in patients with MetS compared to those without MetS. IL-1ß levels were also significantly higher in OA patients (14.63±15.87 pg/mL) than in controls (7.79±5.11 pg/mL), but were not significantly different between the MetS and non-MetS groups. Leptin levels were positively correlated with body mass index, waist-to-hip ratio, visual analogue scale scores, HbA1c and insulin levels, and HOMA-IR index, whereas IL-1ß levels were only correlated with insulin levels and HOMA-IR index. ROC curve analysis revealed that leptin and IL-1ß levels could distinguish individuals with and without OA (AUC=0.96; 0.88, respectively), and individuals with and without MetS (AUC=0.82; 0.71, respectively). Our findings suggested that both leptin and IL-1ß levels were associated with both MetS and OA and may play a critical role in the pathogenesis of MetS-related OA.

Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival.

This prospective cohort study reports aneuploidy score by mFast-SeqS as a strong prognostic marker in MBC patients. mFAST-SeqS is an affordable and easily implementable method for the assessment of total ctDNA levels and, as such, provides an alternative prognostic tool. One mixed cohort (cohort A, n = 45) starting any type of treatment in any line of therapy and one larger cohort (cohort B, n = 129) consisting of patients starting aromatase inhibitors (AI) as first-line therapy were used. mFAST-SeqS was performed using plasma of blood in which CTCs (CellSearch) were enumerated. The resulting aneuploidy score was correlated with categorized CTC count and associated with outcome. The aneuploidy score was significantly correlated with CTC count, but discordance was observed in 31.6% when applying cut-offs of 5. In both cohorts, aneuploidy score was a significant prognostic marker for both PFS and OS. In the Cox regression models, the HR for aneuploidy score for PFS was 2.52 (95% CI: 1.56-4.07), and the HR for OS was 2.37 (95% CI: 1.36-4.14). Results presented here warrant further investigations into the clinical utility of this marker in MBC patients.