Citations

Abstract Patching whole slide images (WSIs) is an important task in computational pathology. While most of the are designed to classify or detect the presence of pathological lesions in a WSI, the confounding role and redundant nature of normal histology are generally overlooked. In this paper, we propose and validate the concept of an “atlas of normal tissue” solely using samples of WSIs obtained from normal biopsies. Such atlases can be employed to eliminate normal fragments of tissue samples and hence increase the representativeness the remaining patches. We tested our proposed method by establishing a normal atlas using 107 normal skin WSIs and demonstrated how established search engines like Yottixel can be improved. We used 553 WSIs of cutaneous squamous cell carcinoma to demonstrate the advantage. We also validated our method applied to an external dataset of 451 breast WSIs. The number of selected WSI patches was reduced by 30% to 50% after utilizing the proposed normal atlas while maintaining the same indexing and search performance in leave-one-patient-out validation for both datasets. We show that the proposed concept of establishing and using a normal atlas shows promise for unsupervised selection of the most representative patches of the abnormal WSI patches.

PURPOSE Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019. METHODS We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials. RESULTS Patients with DS exhibited more frequent minimal residual disease (MRD) ≥0.01% at end induction (30.8% v 21.5%; P < .001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P < .0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P < .0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P < .0001), and within NCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 × 103/μL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P = .0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P < .0001), and induction death (3.4% v 0.8%; P < .0001). Mucositis, infections, and hyperglycemia were significantly more frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P = .005). CONCLUSION Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.

AbstractBackgroundDiarrhea and rectal urgency are risk factors for fecal incontinence (FI). The effectiveness of bowel modifiers for improving FI is unclear.MethodsIn this double‐blind, parallel‐group, randomized trial, women with urge FI were randomly assigned in a 1:1 ratio to a combination of oral clonidine (0.1 mg twice daily) with colesevelam (1875 mg twice daily) or two inert tablets for 4 weeks. The primary outcome was a ≥50% decrease in number of weekly FI episodes.Key ResultsFifty‐six participants were randomly assigned to clonidine–colesevelam (n = 24) or placebo (n = 32); 51 (91%) completed 4 weeks of treatment. At baseline, participants had a mean (SD) of 7.5 (8.2) FI episodes weekly. The primary outcome was met for 13 of 24 participants (54%) treated with clonidine–colesevelam versus 17 of 32 (53%) treated with placebo (p = 0.85). The Bristol stool form score decreased significantly, reflecting more formed stools with clonidine–colesevelam treatment (mean [SD], 4.5 [1.5] to 3.2 [1.5]; p = 0.02) but not with placebo (4.2 [1.9] to 4.1 [1.9]; p = 0.47). The proportion of FI episodes for semiformed stools decreased significantly from a mean (SD) of 76% (8%) to 61% (10%) in the clonidine–colesevelam group (p = 0.007) but not the placebo group (61% [8%] to 67% [8%]; p = 0.76). However, these treatment effects did not differ significantly between groups. Overall, clonidine–colesevelam was well tolerated.Conclusions and InferencesCompared with placebo, clonidine–colesevelam did not significantly improve FI despite being associated with more formed stools and fewer FI episodes for semiformed stools.

Case: We present a case report of a 64-year-old man who developed a rare Bipolaris species fungal periprosthetic joint infection (PJI) after revision arthroplasty for complications associated with a metal-on-metal total hip arthroplasty. The patient underwent a 2-stage debridement with antibiotic bead placement and implant retention, along with chronic antifungal suppression. At the 2-year follow-up, the patient remained asymptomatic. Conclusion: Fungal PJI with filamentous fungi such as Bipolaris species is a rare clinical entity. This case report highlights the clinical presentation and management of this rare condition.

Objective Limited evidence to date has examined public perceptions of cochlear implants among adult hearing aid users with moderate to profound hearing loss. The current work was conceived with the chief objective of characterizing the perceptions surrounding cochlear implants among the prospective candidate pool. Study design National cross-sectional survey study. Setting United States. Patients Adults between 50 and 80 years of age with self-reported moderate to moderately severe (n = 200) or moderately severe to profound (n = 200) hearing loss currently using hearing aids. Results The overall survey response rate was 12%. Median age at time of survey for the 400 respondents was 66 years (interquartile range, 60–71 yr) and included 215 (54%) men. In total, 26% did not think of hearing loss as a medical condition, and another 23% were unsure. Overall, 63% of respondents had heard of cochlear implants, but only 2% indicated they were very familiar with them. Despite 52% of respondents reporting “very positive” or “somewhat positive” feelings about cochlear implants, only 9% indicated they were “very likely” to get a cochlear implant in the future, including 7% of those with estimated moderately severe to profound hearing loss at time of survey. Conclusions Even among people with presumed qualifying levels of hearing loss, there exists a widespread lack of familiarity with cochlear implantation as a viable treatment option. This limited awareness seems influenced by a generally poor appreciation for hearing loss as a chronic disease state that warrants treatment. However, among those familiar with cochlear implants, they are generally viewed favorably.

Guillain-Barré syndrome (GBS) describes a neurological syndrome characterised by acute, areflexic paralysis, often preceded by an immune stimulating event such as infection or surgery. Spinal surgery as an inciting event is very uncommon with few reported cases. When paraparesis develops in close proximity of surgery, surgical complications should be considered, but if an asymptomatic clinical interval precedes a progressive ascending weakness this association weakens and may support an immunological mechanism. GBS after lumbar surgery is wholly unexpected and thus there are significant challenges in recognising and making the diagnosis. We report a case of fulminant GBS that progressed to loss of all motor function following elective lumbar spine surgery.

AbstractAimThis study aims to assess the association of obesity and CRP concentrations in adult patients with rheumatoid arthritis (RA), and its influence on measures of disease activity.MethodsA comprehensive search was performed using Scopus, Web of Science, MEDLINE, and EMBASE, from the time of their inception to November 2021. Observational studies that evaluated the association between CRP concentrations and obesity or overweight in patients with RA were considered eligible. Correlation coefficients were pooled using the inverse variance method, while effect sizes were pre‐calculated for adjusted standardized regression coefficients (β).ResultsA total of 10 studies, which comprised 4024 patients, were included in this systematic review. Individually, most studies report a significant association between CRP concentrations and a higher body mass index or other adiposity measures, but the statistical significance was not sustained when pooling their data together. Through the estimates provided in the present review, it is noted that CRP tends to be more elevated in female patients with RA that have a higher BMI. However, this association is not present in men.ConclusionCRP tends to be elevated in female patients with RA that have a higher BMI. Further research is required to assess this possible sex‐related difference and to aid shared decision‐making in order to avoid over‐treatment and increased burden in patients with obesity and RA.PROSPERO registration number: CRD42022314580.

We investigated the impact of sarcopenia on adjuvant chemotherapy dosing in advanced epithelial ovarian cancer (EOC). The chemotherapy dosing and toxicity of 173 eligible patients who underwent cytoreductive surgery and adjuvant chemotherapy at a single institution were analyzed. Patients with a skeletal muscle index less than 39 cm2/m2 measured on a CT scan were considered sarcopenic. Sarcopenic and non-sarcopenic patients were compared with regard to relative dose intensity (RDI), completion of scheduled chemotherapy, toxicity, and survival. A total of 62 (35.8%) women were sarcopenic. Sarcopenic women were less likely to complete at least six cycles of chemotherapy (83.9% vs. 95.5%, p = 0.02). The mean RDI for both carboplatin (80.4% vs. 89.4%, p = 0.03) and paclitaxel (91.9% vs. 104.1%, p = 0.03) was lower in sarcopenic patients compared to non-sarcopenic patients. Despite these differences in chemotherapy, there was no difference in neutropenia or median overall survival (3.99 vs. 4.57 years, p = 0.62) between the sarcopenic and non-sarcopenic women, respectively. This study highlights the importance of considering lean body mass instead of body weight or surface area in chemotherapy dosing formulas for sarcopenic women with advanced EOC. Further research is needed to optimize chemotherapy strategies based on individual body composition, potentially leading to improved dosing strategies in this population.