Tumor nuclear grade,estrogen receptor,and progesterone receptor: Their value alone or in combination as indicators of outcome following adjuvant therapy for breast cancer

Summary Previous reports by us have shown that the outcome of breast cancer patients who have received systemic adjuvant therapy is influenced by tumor estrogen or progesterone receptor (ER or PR) content or by nuclear grade. This publication provides information regarding the relative merit of those three markers. Findings from patients receiving L-PAM plus 5-FU (PF) or PF plus tamoxifen (PFT) indicate that the disease-free survival and survival within each regimen was almost identical when related to either ER, PR, or nuclear grade. Those having tumors with either of the receptors 10 fmol or a good nuclear grade had a better outcome through five postoperative years than did those with ER or PR 0–9 fmol or poor nuclear grade. The magnitude of the difference was similar for each of the three discriminants. Since they were found to be of equal predictive value, one marker might well serve as a substitute for another. Cox regression analyses, however, clearly indicate that ER, PR, and nuclear grade have an independent influence on outcome and that a more accurate assessment of outcome is obtained when more than one marker is employed. Thus, information should be obtained on as many markers as possible. This conclusion is supported by observations presented which indicate that nuclear grade in combination with either or both of the receptors is a better predictor than either marker alone and that, as indicated by life table probability values and relative odds ratios, an increasing number of favorable tumor prognostic indicators results in a better patient outcome particularly in PFT-treated patients. A possible explanation is considered for why the separation of receptor/nuclear grade categories is more orderly and pronounced in PF-treated patients receiving tamoxifen than in those given PF alone. See Appendix I     

Is There an Association Between Negative Patient-Experience Comments and Perioperative Outcomes After Primary Total Hip Arthroplasty?

BackgroundMultiple stakeholders are interested in improving patient experience after primary total hip arthroplasty due to shifts toward patient-centered care. Patient free-text narratives are a potentially valuable but largely unexplored source of data.MethodsThe records of 383 patients who underwent primary total hip arthroplasty between August 2016 and August 2019 were combined with vendor-supplied patient satisfaction data, which included patient free-text comments and the Press Ganey satisfaction survey. A total of 1295 patient comments were analyzed for sentiment, and negative comments were categorized into nine themes. Postoperative outcomes, patient-reported outcome measures, and traditional measures of satisfaction were compared between patients who provided a negative comment vs those who did not. Multivariable regression was used to determine perioperative variables associated with providing a negative comment.ResultsOf the 1295 patient comments: 54% were positive, 24% were negative, 10% were mixed, and 12% were neutral. Top two themes of negative comments were room condition (25%) and inefficient communication (23%). There were no differences in studied outcomes (eg. peak pain intensity, length of stay, or improvements in hip injury and osteoarthritis outcome scores Jr. and pain visual analog scale scores at 6-week follow-up) between those who provided negative comments vs those who did not (P > .05). However, patients who made negative comments were less likely to recommend their hospital care to peers (P < .001). Finally, patients who had >2 allergies (P = .024) were more likely to provide negative comments.ConclusionThe present study demonstrates that patient satisfaction appears not to be a reliable sole proxy for traditional objective outcome measures of pain relief and functional improvement.     

Applying international organization for standards 9001 to create an effective surgical quality committee

BackgroundEfforts to improve surgical safety are limited by several factors and no consensus exists regarding the most effective way to improve surgical quality. The use of ISO 9001 quality standards within healthcare is recognized but has not been widely applied for improving surgical outcomes.MethodsA surgical quality committee was created using ISO 9001:2015 standards. Quality objectives were assessed to understand how any suggested changes will be impacted due to risks and opportunities inherent in the system.ResultsThe initial quality focus was on surgical site infections in 5 services. Change in surgical infection ratio from 2018 to 2019 showed significant improvement: coronary bypass 1.288 vs. 0.901; Colon 1.359 vs. 0.589; Hysterectomy 2.119 vs. 1.022; Knee 1.391 vs. 0.306; Hip 0 vs. 0.302.ConclusionsThis is one of the first studies using ISO 9001 to improve surgical quality. The results indicate both acceptance and success of applying continual improvement strategies.     

Updates on bacterial resistance and empirical antibiotics treatment of complicated acute appendicitis in children

Objective: Through historical comparison with our previous study published 10 years ago, this paper aims to provide latest analysis of local bacteriology of acute complicated appendicitis and evaluate the effects of early escalation of potent antibiotics on course of postoperative recovery.Methods: A 5-year retrospective review of all children receiving emergency laparoscopic appendicectomies for acute appendicitis from December 2014 to November 2019 was conducted.Results: 257 cases of acute appendicitis were included, 126 were complicated appendicitis (38 gangrenous, 88 ruptured). 96 had positive peritoneal swab culture, 53 (42.1%) grew resistant bacterial strains, including extended spectrum beta-lactamase producing E. coli (ESBL E. coli), Pseudomonas aeruginosa, against traditional empirical triple antibiotics. The prevalence had significantly increased over the past decade (p = 0.008). In our patients, piperacillin/tazobactam, ertapenem, gentamicin provided coverage of 69.8%, 45.3% and 45.3% respectively. For patients with early escalation of postoperative antibiotics, no statistical significance was identified in terms of postoperative complications (p = 0.883), or duration of antibiotics (p = 0.0615).Conclusion: Growing prevalence of resistant strains were observed over the decade. Piperacillin/tazobactam provided the best coverage (69.8%) against resistant bacterial strains in our patients. Early escalation of antibiotics failed to reduce postoperative complications and antibiotics duration.Type of Study: Clinical Research, Retrospective Historical Comparative StudyLevel of Evidence: Level III     

Response rates in metastatic neuroendocrine tumors receiving peptide receptor radionuclide therapy and implications for future treatment strategies

BackgroundPeptide receptor radionuclide therapy is a targeted therapy used to treat unresectable somatostatin receptor-positive neuroendocrine tumors. The objective of this study was to evaluate response rates among neuroendocrine tumors of different primaries and identify factors relevant to future treatment strategies.MethodsWe retrospectively reviewed patients who received peptide receptor radionuclide therapy for neuroendocrine tumors from 2018 to 2019 at our institution. Patients were assessed with computed tomography/magnetic resonance imaging and ⁶⁸Ga-DOTATATE-positron emission tomography before and after 2 or 4 cycles of peptide receptor radionuclide therapy. Tumor response was evaluated by RECIST 1.1. Statistics included multinomial logistic regression models and Fisher exact test.ResultsTwenty-seven patients underwent 92 cycles of peptide receptor radionuclide therapy: pancreas (n = 11), small bowel (n = 7), and other (n = 9) neuroendocrine tumors. Overall, 30% (8 of 27) had partial response, 59% (16 of 27) stable disease, and 11% (3 of 27) progressed. Pancreatic neuroendocrine tumors responded differently from small bowel neuroendocrine tumors regardless of cycle number (P = .01). The majority of pancreatic neuroendocrine tumors (6 of 11) had partial response to peptide receptor radionuclide therapy, while all small bowel neuroendocrine tumors had stable disease. Pancreatic neuroendocrine tumors stable after 2 cycles were more likely to respond to additional cycles versus other neuroendocrine tumors (probability: 60% vs 11%).ConclusionPatients with unresectable advanced or metastatic pancreatic neuroendocrine tumors may benefit from a full course of peptide receptor radionuclide therapy, whereas other neuroendocrine tumors appear less likely to respond. Large prospective studies are needed to confirm these findings.     

Structural spinal abnormalities on MRI and associations with weight status in a general pediatric population

BACKGROUND CONTEXTSeveral spinal abnormalities have been studied using magnetic resonance imaging (MRI). However, in children these studies were sparsely performed in general populations. Examining young children's spines is important since the shape of the bone is largely determined during the growth spurt. Furthermore, it is so far unknown if associations between weight status and spinal abnormalities, which are known for adolescents and adults, are already present in young children.PURPOSEWe aimed to present the prevalence of structural abnormalities in the prepubertal pediatric spine on MRI and their association with measures of the children's body weight and body composition.STUDY DESIGNCross-sectional study embedded in a prospective population-based birth cohort study.PATIENT SAMPLEFor this study, participants from the Generation R Study were selected based on the availability of MRI data of the lumbar spine and accelerometry data at the age of 9 years.OUTCOME MEASURESThe presence of structural abnormalities of intervertebral discs and vertebrae was scored on MRI. The body mass index-standard deviation [BMI-SD] score was calculated from objectively measured weight and height, and body composition measurements were obtained by a dual-energy X-ray absorptiometry scan.METHODSA semiquantitative scoring tool to assess the intervertebral discs and vertebrae of the lumbar spine on conventional MRI was designed for this purpose. Proportions of children with spinal abnormalities on at least one lumbar vertebral level were presented. Logistic regression was used to analyze associations between abnormalities and weight and body composition. We declare not to have any financial conflicts of interests.RESULTSWe included 559 children (median age of 9.88 years (interquartile range 6.74–10.02), 48.5% boys). Most frequently observed abnormalities of the intervertebral discs were abnormal signal intensity (24.9%), decreased or collapsed disc height (37.6%), disc bulging (73.3%), and abnormal nuclear shape (29.1%). Vertebral endplate irregularities and lumbosacral transitional vertebrae were seen in respectively 40% and 9.3% of the participants. Except for disc bulging, all abnormalities were predominantly present at the L5 level. Only the presence of endplate irregularities was associated with a higher body weight (BMI SD score (odds ratio [OR] 1.50 [95% confidence interval [CI] 1.21–1.86]) and BMI SD change (OR 1.48 [95% CI 1.07–2.03])) and increased body mass values in body composition measurements (% body fat (OR 1.05 [95% CI 1.02–1.09), fat mass index (OR 1.23 [95% CI 1.09–1.39]), and fat-free mass index (OR 1.30 [95% CI 1.06–1.59])) in adjusted analyses.CONCLUSIONSStructural spinal abnormalities, especially disc bulging, endplate irregularities, and an abnormal disc height, are already present in children aged 9 years from a Dutch population-based cohort. Of those abnormalities, endplate irregularities are associated with various weight and body composition measurements.     

Repeated Independent Exposures to Domoic Acid Do Not Enhance Symptomatic Toxicity in Outbred or Seizure-Sensitive Inbred Mice

Domoic acid (DA) is an environmental neurotoxin to humans. Thiswork examines whether repeated exposure to subsymptomatic orsymptomatic nonlethal doses of domoic acid leads to enhancedsymptomatic toxicity in ICR outbred and DBA inbred strains oflaboratory mice. A multiple independent exposure paradigm wasdesigned in which doses were administered intraperito neallyevery other day for 7 days to achieve four separate exposuresto domoic acid. We first examined the effect of repeated exposureon serum clearance of domoic acid. Serum domoic acid levelsdid not differ following a single or repeated exposure. We nextexamined the effect of repeated exposure on symptomatic toxicity.The mean toxicity scores did not show a significant differencebetween single and repeated exposures of either subsymptomatic(0.5 mg/ kg) or symptomatic sublethal (2.0 mg/kg) doses of domoicacid. We then examined the effects of repeated domoic acid exposureon a second strain of mouse. DBA mice were chosen based upontheir sensitivity to kainic acid-induced seizures; however,the ICR mice were more sensitive to low-dose domoic acid toxicity,particularly in terms of onset and duration of stereotypic scratchingbehavior. Our results indicate that both strains of mice havecomparable concentration-dependent toxic responses to domoicacid; however, differences exist in the magnitude of the responseand in specific symptoms. The mean toxicity scores did not showa significant difference when a single exposure (1.0 and 2.0mg/kg domoic acid) and repeated exposure of the same dose werecom pared in the DBA mice. This study provides no evidence thatshort-term repeated exposure to domoic acid in laboratory micealters domoic acid clearance from the serum, or leads to a moresensitive or a greater neurotoxic response.     

Renal immunoblastic sarcoma complicating immunosuppressive therapy for wegener granulomatosis

A renal tumor developing in a patient receiving cyclophosphamide (Cytoxan) therapy for Wegener granulomatosis is reported. The tumor was similar histologically to the "immunoblastic" sarcoma that develops in renal allograft recipients as a complication of immunosuppressive therapy. This case report strengthens the cause and effect relationship between immunosuppressive drug usage and the subsequent development of neoplasia.