Performance of Tumor Surveillance for Children With Cancer Predisposition.

Importance: Pediatric oncology patients are increasingly recognized as having an underlying cancer predisposition syndrome (CPS). Surveillance is often recommended to detect new tumors at their earliest and most curable stages. Data on the effectiveness and outcomes of surveillance for children with CPS are limited. Objective: To evaluate the performance of surveillance across a wide spectrum of CPSs. Design, Setting, and Participants: This cohort study reviewed surveillance outcomes for children and young adults from birth to age 23 years with a clinical and/or molecular CPS diagnosis from January 1, 2009, through September 31, 2021. Patients were monitored using standard surveillance regimens for their corresponding CPS at a specialty pediatric oncology center. Patients with hereditary retinoblastoma and bone marrow failure syndromes were excluded. Data were analyzed between August 1, 2021, and December 6, 2023. Exposure: Cancer predisposition syndrome. Main Outcomes and Measures: Outcomes of surveillance were reviewed to evaluate the incidence, spectrum, and clinical course of newly detected tumors. Surveillance modalities were classified for accuracy and assessed for common strengths and weaknesses. Results: A total of 274 children and young adults (mean age, 8 years [range, birth to 23 years]; 144 female [52.6%]) with 35 different CPSs were included, with a median follow-up of 3 years (range, 1 month to 12 years). During the study period, 35 asymptomatic tumors were detected in 27 patients through surveillance (9.9% of the cohort), while 5 symptomatic tumors were detected in 5 patients (1.8% of the cohort) outside of surveillance, 2 of whom also had tumors detected through surveillance. Ten of the 35 tumors (28.6%) were identified on first surveillance imaging. Malignant solid and brain tumors identified through surveillance were more often localized (20 of 24 [83.3%]) than similar tumors detected before CPS diagnosis (71 of 125 [56.8%]; P < .001). Of the 24 tumors identified through surveillance and surgically resected, 17 (70.8%) had completely negative margins. When analyzed across all imaging modalities, the sensitivity (96.4%), specificity (99.6%), positive predictive value (94.3%), and negative predictive value (99.6%) of surveillance were high, with few false-positive (6 [0.4%]) or false-negative (5 [0.3%]) findings. Conclusions and Relevance: These findings suggest that standardized surveillance enables early detection of new tumors across a wide spectrum of CPSs, allowing for complete surgical resection and successful treatment in the majority of patients.

Interobserver and intraobserver variations in radial head fracture classification-assessment of two classification systems.

OBJECTIVE: The aim of this study was to evaluate the intra- and interobserver variation of two classification systems for radial head fractures (Mason and Charalambous classifications) using plain radiographs. MATERIAL AND METHODS: Five observers classified 30 radial head fractures as per the two classifications using anteroposterior and lateral elbow radiographs. Assessments were done on two occasions, at least 6 weeks apart. RESULTS: The interobserver and intraobserver variation of the Mason classification showed fair (mean kappa = 0.33) and moderate agreement (mean kappa = 0.43) respectively. The interobserver and intraobserver variation of the Charalambous classification showed moderate agreement for both (mean kappa = 0.42 and 0.49 respectively). A greater proportion of radial head fractures could be classified using the Charalambous classification compared with the Mason classification (P < 0.001). With the Charalambous classification, the inter-observer variation was better when assessing fracture morphology (4 morphology groups) versus fracture displacement (2 displaced/un-displaced groups) (p = 0.010). CONCLUSIONS: The Mason and Charalambous classifications for radial head fractures confer similar reliability when using plain radiographs, but the latter allows a greater proportion of fractures to be classified. Raters may agree more on fracture morphology as compared to fracture displacement. Our findings also demonstrate the limitations of using plain radiographs in classifying radial head fractures for clinical or research purposes, and suggest that evaluation with more sensitive modalities such as Computed Tomography may be preferable.

Comparing outcomes of biopsy-proven anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis patients treated with cyclophosphamide in the 20th and 21st centuries: a 23-year study.

BACKGROUND: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disorder associated with significant morbidity and mortality. Approximately 80-90% of patients have circulating ANCAs. Long-term outcomes appear to be improving. This retrospective study analyses the incidence and patient outcomes over a period of 23 years at a single tertiary centre. METHODS: Outcomes of patients diagnosed with AAV between 1 January 1988 and 31 December 2010 were collected retrospectively. Data including patient demographics, age of diagnosis, dates of starting renal replacement therapy, death and biochemistry results were collected. Patients were divided into two cohorts (1988-99 and 2000-10) and analysed using Stata software (StataCorp, College Station, TX, USA). RESULTS: A complete dataset was obtained for 273 patients. Of these patients, 101 were diagnosed between 1988 and 1999 while 172 were diagnosed between 2000 and 2010. The number of patients diagnosed with AAV increased from 2.2/million in 1988 to 10.3/million in 2010. A higher proportion of patients (56.4%) in the earlier cohort presented with creatinine >500 µmol/L compared with the later cohort (30.2%; P < 0.001). Overall patient survival improved significantly between the two cohorts. Cohort 1 had a median survival of 59 months compared with 125 months for Cohort 2 (P = 0.003). CONCLUSIONS: This study shows that AAV is being diagnosed at an earlier stage, resulting in improved outcomes. This may be because of improvements in the management of AAV and chronic kidney disease.

Effect of Long-Term, Low-Dose Aspirin Therapy on Renal Graft Function.

OBJECTIVES: Despite improvements in immunosuppressive protocols for renal transplant, long-term success of renal transplant is still limited by the occurrence of interstitial fibrosis and tubular atrophy. Some studies have shown that aspirin decreases the severity of kidney ischemia-reperfusion injury and the development of tubular atrophy in animal models. This study aimed to assess the effects of aspirin therapy started at the time of transplant on long-term graft function. MATERIALS AND METHODS: We compared renal graft function of 82 patients on low-dose aspirin 75 mg once daily who underwent renal transplant between 1 January 2000 and 31 December 2010 from a single center with 65 patients not taking aspirin. For each patient, the following measurements were collected: age, sex, creatinine level, type of donor, cold ischemia time, occurrence of acute allograft rejections, number of HLA mismatches, first transplant, intake of statins, number of antihypertensive medications, and number of days posttransplant. Patients were excluded from the study who were on aspirin before transplant or who had coronary artery disease. RESULTS: Multilevel modelling was used to compare renal allograft function, as measured by serum creatinine levels, between patients taking and not taking aspirin after kidney transplant. Aspirin was not significantly associated with creatinine levels (P = .59) after adjusting for other relevant variables. CONCLUSIONS: Low-dose aspirin started at the time of transplant has a negligible effect on renal allograft function over the 15-year study period posttransplant.

Urgent referral for suspected CNS cancer: which clinical features are associated with a positive predictive value of 3 % or more?

BACKGROUND: Urgent referral for suspected central nervous system (CNS) cancer is recommended, but little analysis of the referral criteria diagnostic performance has been conducted. New 2015 NICE guidance recommends direct brain imaging for patients with symptoms with positive predictive values (PPV) of 3 %, but further guidance is needed. METHODS: A 12-month retrospective evaluation of 393 patients referred under previous 2005 NICE 2-week rule criteria was conducted. Analysis was based on the three groups of symptoms forming the referral criteria, (1) CNS symptoms, (2) recent onset headaches, (3) rapidly progressive subacute focal deficit/cognitive/behavioural/personality change. Comparison was made with neuroimaging findings. RESULTS: Twelve (3.1 %) of 383 patients who attended clinic had CNS cancer suggesting the combination of clinical judgement and application of 2005 criteria matched the 2015 guideline's PPV threshold. PPVs for the three groups of symptoms were (1) 4.1 % (95 % CIs 2.0 to 7.4 %), (2) 1.2 % (0.1 to 4.3 %) and (3) 3.7 % (0.1 to 19.0 %). Sensitivities were (1) 83.3 % (95 % CIs 51.6 to 97.9 %), (2) 16.7 % (2.1 to 48.4 %), and (3) 8.3 % (0.2 to 38.5 %); specificities were (1) 37.2 % (32.3 to 42.3 %), (2) 55.5 % (50.3 to 60.7 %) and (3) 93.0 % (89.9 to 95.4 %). Of 288 patients who underwent neuroimaging, 59 (20.5 %) had incidental findings, most commonly cerebrovascular disease. CONCLUSIONS: The 2015 guidance is less prescriptive than previous criteria making clinical judgement more important. CNS symptoms had greatest sensitivity, while PPVs for CNS symptoms and rapidly progressive subacute deficit/cognitive/behavioural/personality change were closest to 3 %. Recent onset headaches had the lowest sensitivity and PPV.

Unprotected intercourse in the 2 weeks prior to requesting emergency intrauterine contraception.

BACKGROUND: Previous emergency contraception studies have excluded women who report >1 episode of unprotected or underprotected intercourse. Thus, clinical recommendations are based on exposure to a single episode of underprotected intercourse. OBJECTIVE: We sought to assess the prevalence and timing of underprotected intercourse episodes among women requesting emergency contraception and to examine the probability of pregnancy following an emergency contraception regimen including placement of either a copper intrauterine device or a levonorgestrel intrauterine device with simultaneous administration of an oral levonorgestrel pill in women reporting multiple underprotected intercourse episodes, including episodes beyond the Food and Drug Administration-approved emergency contraception time frame (6-14 days). STUDY DESIGN: Women seeking emergency contraception who had a negative pregnancy test and desired either a copper intrauterine device or levonorgestrel emergency contraception regimen enrolled in this prospective observational study. At enrollment, participants reported the number and timing of underprotected intercourse episodes in the previous 14 days. Two weeks later, participants reported the results of a self-administered home pregnancy test. RESULTS: Of the 176 women who presented for emergency contraception and received a same-day intrauterine device, 43% (n = 76) reported multiple underprotected intercourse episodes in the 14 days prior to presenting for emergency contraception. Women with multiple underprotected intercourse episodes reported a median of 3 events (range 2-20). Two-week pregnancy data were available for 172 (98%) participants. Only 1 participant had a positive pregnancy test. Pregnancy occurred in 0 of 97 (0%; 95% confidence interval, 0-3.7%) women with a single underprotected intercourse episode and 1 of 75 (1.3%; 95% confidence interval, 0-7.2%) women reporting multiple underprotected intercourse episodes; this includes 1 of 40 (2.5%; 95% confidence interval, 0-13.2%) women reporting underprotected intercourse 6-14 days prior to intrauterine device insertion. CONCLUSION: Women seeking emergency contraception from clinics commonly reported multiple recent underprotected intercourse episodes, including episodes occurring beyond the Food and Drug Administration-approved emergency contraception time frame. However, the probability of pregnancy was low following same-day intrauterine device placement.

Is C-reactive protein the single most useful predictor of difficult laparoscopic cholecystectomy or its conversion? A pilot study.

INTRODUCTION: Both converted and difficult laparoscopic cholecystectomies (LC) have impact on operating time and training of juniors. The aim of this study is to evaluate parameters that predict difficult LC or conversion (C), and find predictive values for different cut-off points of C-reactive protein (CRP) for conversion. MATERIALS AND METHODS: A retrospective cohort study of cholecystectomies performed from January 2011 to December 2012 at NHS trust was undertaken. Association of intra-operative difficulties or conversion with the following factors was studied: Age, gender, CRP, white blood cell count (WBC), history of pancreatitis, and endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Two hundred and ninety one patients were analysed (222 laparoscopic, 45 difficult LC and 24 C). Only 141 patients had a recorded CRP. Median CRP was highest for patients who were converted (286.20) compared to those who had difficult LC (67.40) or LC (7.05). Those patients who did not have preoperative CRP (8/150, 5.3%) had less chance of conversion than those who had CRP (16/141, 11.34%) (P = 0.063). Patients with CRP of ≤220 (3/91, 3.2%) had significantly less chance of conversion than those with CRP >220 (13/21, 61.9%) (P < 0.001). High preoperative CRP, WBC count and ERCP, were predictors of conversion. These factors were only marginally better than CRP alone in predicting conversion. CONCLUSION: CRP can be a strong predictor of conversion of LC. Further validation of the results is needed.

A directed miniscreen for genes involved in the Drosophila anti-parasitoid immune response.

Drosophila larvae react against eggs from the endoparasitoid wasp Leptopilina boulardi by surrounding them in a multilayered cellular capsule. Once a wasp egg is recognized as foreign, circulating macrophage-like cells, known as plasmatocytes, adhere to the invader. After spreading around the wasp egg, plasmatocytes form cellular junctions between the cells, effectively separating the egg from the hemocoel. Next, a second sub-type of circulating immunosurveillance cell (hemocyte), known as lamellocytes, adhere to either the wasp egg or more likely the plasmatocytes surrounding the egg. From these events, it is obvious that adhesion and cell shape change are an essential part of Drosophila's cellular immune response against parasitoid wasp eggs. To date, very few genes have been described as being necessary for a proper anti-parasitization response in Drosophila. With this in mind, we performed a directed genetic miniscreen to discover new genes required for this response. Many of the genes with an encapsulation defect have mammalian homologues involved in cellular adhesion, wound healing, and thrombosis, including extracellular matrix proteins, cellular adhesion molecules, and small GTPases.

Use of herbal remedies by Hispanic patients: do they inform their physician?

PURPOSE: This study measured the knowledge and use of herbs among Hispanics and assessed their experiences when discussing herb use with their physician. METHODS: Self-administered questionnaires were collected from 620 Hispanic patients seeking treatment in urban health centers. RESULTS: Most (80.3%) reported using herbs. Herb users were more comfortable speaking Spanish (91.9% vs 80.2%) and had been in the United States less than 5 years (47.0% vs 29.4%). More users considered herbs as drugs (60.5% vs 39.6%). Users were more aware that herbs could harm a baby if taken during pregnancy (56.4% vs 36.0%). The majority did not know the English name for 23 of the 25 herbs. A majority indicated their physician was unaware of their herb use. Few (17.4%) responded that their physicians asked about herb use. Only 41.6% thought their physician would understand their herb use, and 1.8% believed their physician would encourage continued use. There were no significant differences between herb users and nonusers in their perception of patient-physician communication levels. CONCLUSION: Primary care physicians need to be aware that most Hispanic patients are likely to use herbs. It is important to initiate and encourage discussion of their patient's interest in and use of these therapies.