Nevin Manimala

Clin Exp Med. 2023 Oct 7. doi: 10.1007/s10238-023-01190-2. Online ahead of print.

ABSTRACT

PD-L1 expression is known to predict the benefits of immune checkpoint inhibitor therapy for triple-negative breast cancer (TNBC). We examined whether the PD-L1 expression evaluated in biopsy specimens accurately reflects its expression in the whole tumor. Immunohistochemistry was performed on 81 biopsy and resection specimens from patients with TNBC to determine their PD-L1 status. We found PD-L1-positive tumors in 23 (28%) biopsy specimens and primarily PD-L1-negative tumors in 58 (72%). The PD-L1 status was reevaluated in matching postoperative specimens of primarily PD-L1-negative tumors. Of them, 31% (18/58) were positive, whereas 69% (40/58) were negative. Considering the pre- and postoperative analyses, 41 (51%) patients had PD-L1-positive tumors, while 40 had PD-L1-negative tumors. We found 18 (22%) more PD-L1-positive tumors while examining the resection specimens compared to biopsies, and the difference was statistically significant (p = 0.0038). Diagnostic biopsies do not fully reflect the PD-L1 expression in TNBC. Our results suggest that a significant subset of TNBC patients may be misclassified as PD-L1-negative and disqualified from anti-PD-L1 therapy.

PMID:37804360 | DOI:10.1007/s10238-023-01190-2

Knee Surg Sports Traumatol Arthrosc. 2023 Oct 7. doi: 10.1007/s00167-023-07578-7. Online ahead of print.

ABSTRACT

PURPOSE: This study reports the five-year functional outcomes from a prospective cohort study comparing robotic-arm assisted total knee arthroplasty (RO TKA) versus conventional manual total knee arthroplasty (CO TKA).

METHODS: This prospective single-surgeon study included 120 patients with symptomatic end-stage knee arthritis undergoing primary TKA. This included 60 consecutive patients undergoing CO TKA followed by 60 consecutive patients undergoing RO TKA using a semi-automated robotic device. Study patients were reviewed at one, two, and five years after surgery and the following outcomes recorded: The University of California at Los Angeles activity-level (UCLA), Knee Society Score (KSS), Oxford Knee Score (OKS) Forgotten Joint Score (FJS), and any complications.

RESULTS: There were no statistical differences between RO TKA and CO TKA in the median UCLA score (p = N.S), median KSS (p = N.S), and median OKS (p = N.S) at five-year follow-up. RO-TKA was associated with statistically significant improvements in the FJS at one (p = 0.001), two (p = 0.003), and five (p = 0.025) years of follow-up compared with CO TKA. There was no statistical difference in the incidence of knee stiffness requiring manipulation under anesthesia between the two treatment groups (p = N.S).

CONCLUSION: Patients in both treatment groups had excellent functional outcomes with comparable patient reported outcomes at five-year follow-up. RO TKA was associated with statistically significant improvements in the FJS compared with CO TKA, but these differences did not reach the minimal clinically important difference at any follow-up interval. There was no overall difference in complications between the two treatment groups at five-year follow-up.

LEVEL OF EVIDENCE: II (Prospective cohort study).

PMID:37804346 | DOI:10.1007/s00167-023-07578-7

World J Urol. 2023 Oct 7. doi: 10.1007/s00345-023-04623-5. Online ahead of print.

ABSTRACT

PURPOSE: To compare the effects of different preoperative antibiotic prophylaxis (ABP) regimens on the incidence of sepsis after percutaneous nephrolithotomy (PCNL) in patients with negative urine culture.

METHODS: A single-center, randomized controlled trial (June 2022-December 2023) included 120 patients with negative preoperative urine cultures for upper urinary tract stones who underwent PCNL (chictr.org.cn; ChiCTR2200059047). The experimental group and the control group were respectively given different levofloxacin-based preoperative ABP regimes, including 3 days before surgery and no ABP before surgery. Both groups were given a dose of antibiotics before the operation. The primary outcome was differences in the incidence of postoperative sepsis.

RESULTS: A total of 120 subjects were included, including 60 patients in the experimental group and 60 patients in the control group. The baseline characteristics of the two groups were comparable and intraoperative characteristics also did not differ. The sepsis rate was not statistically different between the experimental and control groups (13.3% vs.13.3%, P = 1.0). A multivariate logistic regression analysis revealed that body mass index (BMI) (OR = 1.3; 95% CI = 1.1-1.6; P = 0.003) and operating time (OR = 1.1; 95% CI = 1.0-1.1; P = 0.012) were independent risk factors of sepsis.

CONCLUSION: Our study showed that prophylactic antibiotic administration for 3 days before surgery did not reduce the incidence of postoperative sepsis in patients with negative urine cultures undergoing PCNL. For this subset of patients, we recommend that a single dose of antibiotics be given prior to the commencement of surgery seems adequate.

PMID:37804339 | DOI:10.1007/s00345-023-04623-5

Acta Diabetol. 2023 Oct 7. doi: 10.1007/s00592-023-02190-0. Online ahead of print.

ABSTRACT

AIMS: Observational studies have reported that autoimmune diseases are associated with gestational diabetes mellitus (GDM), but the causality is unknown. The study aimed to evaluate the potential causal effect of autoimmune diseases on GDM.

METHODS: A two-sample Mendelian randomization (MR) study was designed using the summary statistics of GDM (123,579 individuals) and three common autoimmune diseases, including inflammatory bowel disease (IBD, 59,957 individuals), rheumatoid arthritis (RA, 80,799 individuals) and systemic lupus erythematosus (SLE, 14,267 individuals), from the genome-wide association study (GWAS). The fixed-effects inverse variance weighted (IVW) was used to deduce the causal association between autoimmune diseases and GDM, and sensitivity analyses were further performed.

RESULTS: The inverse variance weighting (IVW) method showed that RA and SLE increased the risk of GDM (RA: OR = 1.076, 95%CI = 1.033-1.122, P = 4.649E-04; SLE: OR = 1.025, 95%CI = 1.001-1.049, P = 0.044). But there were no any associations of IBD with GDM (P > 0.05). No significant horizontal pleiotropy was found by MR Egger regression (IBD: P for intercept = 0.905; RA: P for intercept = 0.103; SLE = P for intercept = 0.608).

CONCLUSION: This two-sample MR study found that both SLE and RA are positively associated with the risk of GDM. Our findings provide help for the future prevention and treatment of GDM to reduce associated maternal and fetal complications. However, more research is needed to obviate the role of the GC and the HCQ to ensure this relationship is causal.

PMID:37804336 | DOI:10.1007/s00592-023-02190-0

JACC Heart Fail. 2023 Sep 20:S2213-1779(23)00520-6. doi: 10.1016/j.jchf.2023.07.028. Online ahead of print.

ABSTRACT

BACKGROUND: Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed.

OBJECTIVES: This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision.

METHODS: Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy control subjects (HCs). Significant changes in protein intensities were determined with nonpaired Student’s t-tests and were further classified by using the Boruta algorithm. The proteins’ diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation.

RESULTS: Patients with PPCM presented with a mean (± SD) left ventricular ejection fraction of 33.5 ± 9.3% vs 57.0 ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs.

CONCLUSIONS: Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers.

PMID:37804308 | DOI:10.1016/j.jchf.2023.07.028

J Adolesc Health. 2023 Oct 5:S1054-139X(23)00415-9. doi: 10.1016/j.jadohealth.2023.08.006. Online ahead of print.

ABSTRACT

PURPOSE: This paper uses data from a 3-arm Cluster Randomized Control Trial, Suubi4Her (N = 1260; 14-17-year-old school-going girls) to (1) assess the relationship between peer pressure and adolescent risk-taking behaviors; and (2) test the mediating effect of peer pressure on an intervention on adolescent risk-taking behaviors.

METHODS: Students in the southwestern region of Uganda were assigned to three study arms: control (n = 16 schools, n = 408 students) receiving usual care comprising of sexual and reproductive health curriculum; and two active treatment arms: Treatment 1 (n = 16 schools, n = 471 students) received everything the control arm received plus a savings led intervention. Treatment 2 (n = 15 schools, n = 381 students) received everything the control and treatment arms received plus a family strengthening intervention. We used multilevel models to assess the relationship between peer pressure and risk-taking behaviors. We ran structural equation models for mediation analysis.

RESULTS: Using baseline data, we found that direct peer pressure was significantly associated with substance use risk behaviors, (β = 0.044, 95% CI = 0.008, 0.079). We also found a statistically significant effect of the intervention on acquiring STIs through the mediating effect of sexual risk-taking significant (β = -0.025, 95% CI: -0.049, -0.001, p = .045) and total indirect (β = -0.042, 95% CI: -0.081, -0.002, p = .037) effects. Also, there was a significant mediation effect of the intervention on substance use through peer pressure (β = -0.030, 95% CI: -0.057, -0.002, p = .033).

DISCUSSION: Overall, the study points to the role of peer pressure on adolescent girls’ risk-taking behaviors; and a need to address peer pressure at an early stage.

PMID:37804302 | DOI:10.1016/j.jadohealth.2023.08.006

Cytotherapy. 2023 Oct 7:S1465-3249(23)01050-2. doi: 10.1016/j.jcyt.2023.09.002. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: Exosome therapy for traumatic spinal cord injury (TSCI) is a current research hotspot, but its therapeutic effect and the best source of stem cells for exosomes are unclear.

METHODS: The Web of Science, PubMed, Embase, Cochrane, and Scopus databases were searched from inception to March 28, 2023. Literature screening, data extraction and risk of bias assessment were performed independently by two investigators.

RESULTS: A total of 40 studies were included for data analysis. The findings of our traditional meta-analysis indicate that exosomes derived from stem cells significantly improve the motor function of TSCI at various time points (1 week: weighted mean difference [WMD] = 1.58, 95% confidence interval [CI] 0.87-2.30] 2 weeks: WMD = 3.12, 95% CI 2.64-3.61; 3 weeks: WMD = 4.44, 95% CI 3.27-5.60; 4 weeks: WMD = 4.54, 95% CI 3.42-5.66). Four kinds of stem cell-derived exosomes have been studied: bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, umbilical cord mesenchymal stem cells and neural stem cells. The results of the network meta-analysis showed that there was no significant statistical difference in the therapeutic effect among the exosomes derived from four kinds of stem cells at different treatment time points. Although exosomes derived from bone marrow mesenchymal stem cells are the current research focus, exosomes derived from neural stem cells have the most therapeutic potential and should become the focus of future attention.

CONCLUSIONS: The exosomes derived from stem cells can significantly improve the motor function of TSCI rats, and the exosomes derived from neural stem cells have the most therapeutic potential. However, the lower evidence quality of animal studies limits the reliability of experimental results, emphasizing the need for more high-quality, direct comparative studies to explore the therapeutic efficacy of exosomes and the best source of stem cells.

PMID:37804282 | DOI:10.1016/j.jcyt.2023.09.002

Neuromodulation. 2023 Oct 5:S1094-7159(23)00737-7. doi: 10.1016/j.neurom.2023.08.004. Online ahead of print.

ABSTRACT

OBJECTIVES: Deep brain stimulation (DBS) is a well-established surgical therapy for movement disorders that comprises implantation of stimulation electrodes and a pacemaker. These procedures can be performed separately, leaving the possibility of externalizing the electrodes for local field potential recording or testing multiple targets for therapeutic efficacy. It is still debated whether the temporary externalization of DBS electrodes leads to an increased risk of infection. We therefore aimed to assess the risk of infection during and after lead externalization in DBS surgery.

MATERIALS AND METHODS: In this retrospective study, we analyzed a consecutive series of 624 DBS surgeries, including 266 instances with temporary externalization of DBS electrodes for a mean of 6.1 days. Patients were available for follow-up of at least one year, except in 15 instances. In 14 patients with negative test stimulation, electrodes were removed. All kinds of infections related to implantation of the neurostimulation system were accounted for.

RESULTS: Overall, infections occurred in 22 of 624 surgeries (3.5%). Without externalization of electrodes, infections were noted after 7 of 358 surgeries (2.0%), whereas with externalization, 15 of 252 infections were found (6.0%). This difference was significant (p = 0.01), but it did not reach statistical significance when comparing groups within different diagnoses. The rate of infection with externalized electrodes was highest in psychiatric disorders (9.1%), followed by Parkinson’s disease (7.3%), pain (5.7%), and dystonia (5.5%). The duration of the externalization of the DBS electrodes was comparable in patients who developed an infection (6.1 ± 3.1 days) with duration in those who did not (6.0 ± 3.5 days).

CONCLUSIONS: Although infection rates were relatively low in our study, there was a slightly higher infection rate when DBS electrodes were externalized. On the basis of our results, the indication for electrode externalization should be carefully considered, and patients should be informed about the possibility of a higher infection risk when externalization of DBS electrodes is planned.

PMID:37804281 | DOI:10.1016/j.neurom.2023.08.004

J Emerg Nurs. 2023 Oct 7:S0099-1767(23)00235-0. doi: 10.1016/j.jen.2023.08.011. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to identify the symptoms used to assess angina, determine how emergency nurses make triage decisions for potential acute coronary syndrome, and determine emergency nurses’ initial actions.

METHODS: This was a cross-sectional, survey-based design. Emergency nurses were recruited through a posting on the Emergency Nurses Association website and through postcards. Measures included demographic data, assessment of angina, and the Nurses’ Cardiac Triage Instrument. Data were analyzed using descriptive statistics and ordinal logistic regression.

RESULTS: A total of 414 registered nurses with a mean age of 41.7 (SD = 12.0) years participated. They were predominantly female (80.7%), had a baccalaureate degree (60.1%), and worked as a registered nurse for a median 10.0 years. Common terms used to assess angina were chest pain (79.5%), chest pressure (77.3%), chest tightness (72.9%), and chest discomfort (72.5%). The severity of chest pressure (median 5.0, interquartile range 1.0) and nature of chest pain (median 5.0, interquartile range 1.0) had the highest overall median scores to support initial cardiac triage decisions. Associated symptoms of diaphoresis, fatigue, and shortness of breath along with health history contributed to decision making.

DISCUSSION: Emergency nurses primarily used chest symptoms and health history when deciding to evaluate for acute coronary syndrome in the emergency department. Associated symptoms of diaphoresis, fatigue, and shortness of breath, along with health history, also contributed to decision making. Initial registered nurse actions were to obtain an electrocardiogram, prepare the patient for the cardiac catheterization laboratory, and notify the emergency physician of the patient’s admission.

PMID:37804278 | DOI:10.1016/j.jen.2023.08.011

J Clin Endocrinol Metab. 2023 Oct 6:dgad581. doi: 10.1210/clinem/dgad581. Online ahead of print.

ABSTRACT

CONTEXT: Chronic hyperglycaemia in patients with diabetes mellitus (DM) causes retinal damage and leakage, resulting in vision loss. Although diabetic retinopathy (DR) and diabetic kidney disease (DKD) are usually correlated, the relationship between diabetic macular oedema (DME) and DKD remains unknown.

OBJECTIVE: To assess whether DME presence can predict renal failure in patients with DM and chronic kidney disease (CKD).

DESIGN: This retrospective cohort study used data from the TriNetX network.

SETTING: One-hundred and twenty healthcare organisations.

PATIENTS: Electronic medical records of approximately 90 million patients were reviewed. The study population was classified into DME and non-DME cohorts.

MAIN OUTCOME MEASURES: Primary and secondary outcomes were new-onset end-stage renal disease (ESRD) and all-cause mortality, respectively. Covariate factors were incorporated to reduce confounding effects.

RESULTS: Before matching, the DME cohort used more medication and had poorer renal function and blood sugar control than the non-DME cohort. Subsequently, the two groups were well-matched in demographics, socioeconomic status, lifestyle, comorbidities, and medication usage. The DME cohort had a significantly higher risk of ESRD, dialysis, and renal transplantation than the non-DME cohort. Subgroup analyses showed consistent results irrespective of follow-up duration, initial estimated glomerular filtration rate, or glycated haemoglobin levels. Additionally, the DME cohort had a lower risk of all-cause mortality than the non-DME cohort.

CONCLUSIONS: Statistically significant 5-year increased risks of ESRD, dialysis, and renal transplantation were observed in patients with concurrent DME. Therefore, close monitoring and follow-up of the renal function in DM patients with DME are necessary and strongly recommended.

PMID:37804118 | DOI:10.1210/clinem/dgad581