Positive Biopsy Results Research Articles

Abstract 4141448: Evaluation of cardiac amyloidosis with cardiac MRI and association with endomyocardial biopsy findings

Introduction: Late gadolinium enhancement (LGE) observed on cardiac magnetic resonance imaging (CMR) has emerged as a potential indicator of myocardial involvement in cardiac amyloidosis (CA). However, discerning which LGE patterns in amyloidosis distinguish it from other cardiomyopathies remains unclear. This study aims to compare LGE characteristics in a predominantly African American cohort who underwent endomyocardial biopsies. Despite advancements in cardiac imaging techniques, the endomyocardial biopsy remains the gold standard for amyloidosis diagnosis. Insights garnered from this analysis could enhance diagnostic precision and facilitate earlier detection. Methods: In this retrospective study at MedStar Union Memorial Hospital in Baltimore, MD, patients who underwent both endomyocardial biopsy and CMR were included. The study compared individuals with biopsy-proven amyloidosis (both AL and ATTR) to those with negative biopsy results. LGE patterns were selected based on their frequent use in CMR interpretation. Statistical analysis employed Pearson chi-square and t-tests. Results: The cohort comprised 42 patients who underwent biopsy, with 13 patients (31%) with positive biopsy results. Among them, 24 were men (57%), and 81% identified as African American. Demographic, anthropomorphic, and objective clinical findings are detailed in Table 1. The average age of the cohort was 68 years, with those with biopsy-proven amyloidosis significantly older (75 vs. 61 years, p = 0.002). Although the biopsy-positive group exhibited a lower absolute NT-pro-BNP, the difference was not statistically significant. The most prevalent LGE patterns among the biopsy-positive group were diffuse (62%) and basal (31%). Notably, 69% of biopsy-positive patients exhibited an LGE pattern described as infiltrative. However, 38% of the biopsy-negative group also manifested infiltrative patterns on LGE, a difference not statistically significant compared to the biopsy-positive group. The positive predictive value of an infiltrative LGE pattern was low (45%). Conclusion: This study compares CMR LGE patterns in biopsy proven CA. Despite findings of an infiltrative LGE pattern on CMR, when using endomyocardial biopsy as the gold standard, the positive predictive value of LGE in differentiating CA patients was low. Further research and larger studies are warranted to explore additional imaging modalities or biomarkers that may complement or refine the diagnostic algorithm for CA.

Machine Learning to Differentiate Malignant and Non-malignant Pleural Effusion Findings

Introduction: This study developed a method using machine learning techniques to differentiate between malignant and non-malignant pleural effusions, analyzing texture parameters in computed tomography scans Method: The study involved forty-one patients, with their computed tomography examinations classified into three groups: True Positive - patients with both cytopathological analysis and pleural biopsy indicating malignancy; True Negative - patients with negative results in both tests; and False Negative - patients with negative cytopathological analysis but positive pleural biopsy results. Four machine learning methods were applied across three analyses: True Positive versus True Negative, True Positive versus False Negative, and True Negative versus False Negative. The logistic regression model demonstrated notable effectiveness, achieving an Area Under the Curve of 0.84 ± 0.02 in the True Positive versus True Negative analysis and 0.81 ± 0.05 in the True Positive versus False Negative comparison. In the True Negative versus False Negative analysis, the Naive Bayes model achieved an Area Under the Curve of 0.72 ± 0.02. Results: Statistically significant differences were observed in the liquid Lactate Dehydrogenase and protein content between the True Positive and True Negative groups (p-values of 0.0390 and 0.0249, respectively), and in the liquid pH level between the True Positive and False Negative groups (p-value of 0.0254). The use of textural features in combination with machine learning techniques provided a reliable classification for investigating suspected pleural effusion findings. This method represents a potential tool for assisting in clinical diagnosis and decision-making, enhancing the accuracy of pleural effusion assessments Conclusion: In conclusion, our approach not only improves diagnostic accuracy but also offers a faster and non-invasive alternative, significantly benefiting clinical decision-making and patient care.

Retrospective Analysis of Specimen Quality in Temporal Artery Biopsies for Giant Cell Arteritis and Disease Association in North Midlands, England.

Background Temporal artery biopsy (TAB) is the recommended index diagnostic method for giant cell arteritis (GCA). Per the British Society for Rheumatology (BSR) guidelines, we assessed our procedural performance. Additionally, we evaluated the occurrence of GCA diagnosis in immunosuppressed patients and other comorbidities. Methods Following the audit registration, a retrospective analysis of prospectively collected data was conducted from 2017 to 2022 at a large university hospital in North Midlands, England. Data on demographics and comorbidities were gathered. The study's primary outcome was adherence to BSR guidelines and our service provisions. Secondary outcomes included examining the relationship between biopsy-confirmed GCA and other comorbidities. Statistical analysis was carried out using SPSS version 29 (IBM Corporation, Armonk, New York, United States of America). Two-sample t-test and Chi-square/Fisher exact test were used for continuous and categorical variables, respectively. Holm-Bonferroni method was incorporated to adjust for multiple comparisons. Results A total of 156 patients who underwent temporal artery biopsy (TAB) were included in the study, with a male-to-female ratio of 0.44:1. The median age was 73. Among the patients, 19% were smokers. The procedures were performed by either a vascular surgeon (119, 76%) or by an ophthalmologist (37, 24%). Two-thirds of the patients underwent TAB within seven days of referral. In 73, 47% of cases, the post-fixation biopsy sample size exceeded 10 mm. Positive biopsy results were found in 45 patients (29%). GCA was confirmed in 39% of patients with polymyalgia rheumatica (PMR), 24% with diabetics, 20% with hypothyroidism, 29% with hypertension, 32% with hyperlipidaemia,and 26% with other inflammatory diseases. However, the p-value was below the statistically significant threshold. The biopsy outcome was also not dependent on the speciality, time from referral to biopsy, nor on the length of the post-fixation specimen. Conclusions Temporal artery biopsy remains a valuable and crucial diagnostic tool in challenging equivocal cases of giant cell arteritis (GCA), although it is limited by its sensitivity, but there is also room for improvement. There is still uncertainty regarding the relationship between biopsy positivity, post-fixation sample size, and the interval between referral and procedure. Additionally, the speciality of the clinician performing the biopsy does not appear to significantly influence the likelihood of a positive result. We still do not fully understand why this is, but the association of the GCA with other comorbidities was unpredictably insignificant.

Lesion size may affect diagnostic capabilities of MRI-guided ultrasound fusion biopsy and cognitive targeted biopsy for clinically significant prostate cancer

MRI-guided targeted biopsy (MRGB) was recommended as part of biopsy paradigm of prostate cancers by current guidelines. This study aimed to analyze the diagnostic efficacy of MRGB and systemic biopsy (SB), and to compare diagnostic capabilities within subgroups of MRGB: MRI-cognitive biopsy (MRCB) and MRI-fusion biopsy (MRFB). We retrospectively enrolled patients who underwent MRGB for suspicious malignant lesion(s) identified on MRI in a single tertiary center, sample size was 74 patients. An mpMRI was performed prior to biopsy and reviewed by an experienced radiologist specialized in prostate cancer. Per-person results of MRGB and each concomitant SB were analyzed as independent biopsies for its positive biopsy rate and positive core percentage. Per-lesion results of MRFB and MRCB were compared for the detection rate. Variables of interest were analyzed with t-test, chi-squared test, and logistic regression analysis. Statistical analyses were performed with IBM Statistical Product and Service Solutions (SPSS), Version 23 (IBM, Armonk, New York). Total of 74 patients fulfilled the inclusion criteria and were enrolled. MRFB had higher PCa detection rate comparing to both MRCB and SB (56.1%, 30.3%, and 33.9% respectively, p value = 0.036); clinically significant prostate cancer (csPCa) detection rate was also significantly higher in MRFB group (43.9%, 24.2%, and 16.9% in each group respectively, p value = 0.011). In per-lesion analysis, MRCB and MRFB had no significant difference in PCa and csPCa detection rate (41.0% vs. 26.2% and 29.5% vs. 16.7% respectively, p value = 0.090 and 0.103). In the lesion ≦ 1.3 cm group, MRFB could achieve higher PCa detection rate, comparing to MRCB (36.4% vs. 14.3%, p value = 0.047); there were also higher positive rates for PCa and csPCa per biopsied cores (22.1% vs. 6.8% and 15.6% vs. 2.7%, p value = 0.029 and 0.028, respectively). Further logistic regression of multi-variate analysis in subgroup of lesion ≦ 1.3 cm revealed that PIRADS score and biopsy method were significant predictors of positive biopsy result for PCa (p value = 0.045 and 0.026, respectively) and for csPCa (p value = 0.043 and 0.025, respectively). In patients receiving trans-perineal prostate biopsy, MRFB had higher cancer detection rate than MRCB and SB. In per lesion comparison, MRFB and MRCB had similar diagnostic accuracy. However, in lesions with diameter less than 1.3 cm, MRFB can provided better diagnose value for PCa and csPCa than MRCB.

Surgical advantage of modified labial salivary gland biopsy using chalazion forceps: a prospective randomized controlled study

Labial salivary gland biopsy (LSGB) is one of the specific diagnostic criteria for primary Sjögren's syndrome (pSS). In traditional LSGB, there is no lower lip fixation device, the field of view is unclear due to intraoperative bleeding, and the incision is large, which is unfavourable for healing. The use of auxiliary devices to improve the shortcomings of traditional LSGB technique would be meaningful. Therefore, this case–control study aimed to assess the value of modified LSGB using chalazion forceps as compared with traditional LSGB. After obtaining written informed consent from all participating parents and patients, we randomly assigned 217 eligible participants to undergo LSGB using chalazion forceps (n = 125) or traditional LSGB (n = 92). The outcome variables were surgical time, incision length, intraoperative bleeding, pain score at 24 h after surgery, incision healing status at 7 days after surgery, gland collection, and pathological results. The final diagnostic results of the two surgical methods were compared, and the match rates between the pathological results and the final clinical diagnoses were compared between the two groups. The data were analysed using parametric and nonparametric tests. Compared with the traditional group, the modified group had a smaller incision, shorter operative time, less blood loss, lower 24 h pain score, and better Grade A incision healing at 7 days after surgery (p < 0.01). There was no statistically significant difference between the patients in the two surgical-method groups in terms of the positive biopsy results and the final diagnosis based on expert opinions (p > 0.05). By multivariable regression analysis, only a focus score (FS) of ≥ 1 (p < 0.01), dry eye disease (p < 0.05) and anti-nuclear antibodies (ANA) titre ≥ 1:320 (p < 0.05) were correlated with the diagnosis of pSS. The positive biopsy results of patients in the different surgical-method groups had a biopsy accuracy of > 80.0% for the diagnosis of pSS. The positive biopsy results in the different surgical-method groups were consistent with the expert opinions and the 2016 ACR-EULAR primary SS classification criteria. The modified LSGB using an auxiliary chalazion forceps offers a good safety with a small incision, shorter operative time, less bleeding, reduced pain and a low incidence of postoperative complications.The match rate of LSGB pathological results of the proposed surgical procedure with the final diagnosis of pSS is high.

Impact of quantitative CT texture analysis on the outcome of CT-guided bone biopsy

Texture analysis can provide new imaging-based biomarkers. Texture analysis derived from computed tomography (CT) might be able to better characterize patients undergoing CT-guided percutaneous bone biopsy. The present study evaluated this and correlated texture features with bioptic outcome in patients undergoing CT-guided bone biopsy. Overall, 123 patients (89 female patients, 72.4 %) were included into the present study. All patients underwent CT-guided percutaneous bone biopsy with an 11 Gauge coaxial needle. Clinical parameters and quantitative imaging features were investigated. Random forest classifier was used to predict a positive biopsy result. Overall, 69 patients had osteolytic metastasis (56.1 %) and 54 had osteoblastic metastasis (43.9 %). The overall positive biopsy rate was 72 %. The developed radiomics model demonstrated a prediction accuracy of a positive biopsy result with an AUC of 0.75 [95 %CI 0.65 – 0.85]. In a subgroup of breast cancer patients, the model achieved an AUC of 0.85 [95 %CI 0.73 – 0.96]. In the subgroup of non-breast cancer patients, the signature achieved an AUC of 0.80 [95 %CI 0.60 – 0.99]. Quantitative CT imaging findings comprised of conventional and texture features can aid to predict the bioptic result of CT-guided bone biopsies. The developed radiomics signature aids in clinical decision-making, and could identify patients at risk for a negative biopsy.

Associations of systemic immune‐inflammation index with high risk for prostate cancer in middle‐aged and older US males: A population‐based study

AbstractBackgroundSystemic immune‐inflammation index (SII) provides convincing evaluation of systemic immune and inflammatory condition in human body. Its correlation with prostate cancer (PCa) risk remains uncharted. The principal objective of this investigation was to elucidate the association between SII and the risk for PCa in middle‐aged and elderly males.Materials and MethodsAnalysis entailed multivariate linear and logistic regression, generalized additive model, and smoothing curve fitting using resource from 2007 to 2010 National Health and Nutrition Examination Survey (NHANES). To ascertain robustness and consistency of this association across different demographic strata, we conducted rigorous subgroup analyses and interaction tests.ResultsAmong 3359 participants, those with elevated SII displayed higher total prostate‐specific antigen (tPSA) levels, higher risk for PCa, and lower free/total PSA (f/t PSA) ratio. Specifically, each unit increase of log2 (SII) was associated with a 0.22 ng/mL increase in tPSA (β: 0.22, 95% confidence intervals [CI] 0.05–0.38), a 2.22% decline in f/t PSA ratio (β: −2.22, 95% CI −3.20 to −1.23), and a 52% increased odds of being at high risk for PCa (odds ratio [OR]: 1.52, 95% CI 1.13–2.04). People in the top quartile of log2 (SII) exhibited 0.55 ng/mL increased tPSA (β: 0.55, 95% CI 0.19–0.90), 4.39% reduced f/t PSA ratio (β: −4.39, 95% CI −6.50 to −2.27), and 168% increased odds of being at high risk for PCa (OR: 2.68, 95% CI 1.32–5.46) compared to those in the bottom quartile.ConclusionSystemic immune and inflammatory condition, as represented by SII, is independently and positively associated with tPSA levels and the risk for PCa, as well as independently and negatively associated with f/t PSA ratio among middle‐aged and older US males. These findings may enhance the effectiveness of PCa screening in predicting positive biopsy results.

Correlation of nasopharyngeal carcinoma symptoms based on Digby’s score with biopsy results of nasopharyngeal masses of new patients in ENT-HNS clinic at prof. Dr. I.G.N.G Ngoerah State Hospital

Introduction: Nasopharyngeal carcinoma is a disease that may cause mortality and shows with many clinical symptoms in the nose, ear, eyes, and nervous system. This study aimed to help clinical workers decide which patient with these symptoms must be referred or not. Methods: Primary data from the ENT Clinic of Prof. Dr. dr. I.G.N.G Ngoerah was used from January 2022 to March 2022. Descriptive analysis and logistic regression were employed to describe the relationship between patients’ demographic, clinical symptoms with the diagnosis of NPC from histopathology examination. Results: There are 40 patients in this study, with 22 patients have positive results of NPC, and 18 patients with negative results of NPC. Nasal mass, nasal symptoms and fulfillment of Digby’s score are the most related to NPC’s positive biopsy results (OR: 10, p=0.04; OR: 37. p=0,02; OR: 4.5, p=0,038 respectively). Conclusion: NPC has wide variety of symptoms, and it must be kept in mind that these symptoms can be NPC and must consider to refer to ENT-HNS Specialist.

Risk factors for sentinel lymph node metastasis in Korean acral and non-acral melanoma patients.

Breslow thickness, ulceration, and mitotic rate are well-known prognostic factors for sentinel lymph node (SLN) metastasis in cutaneous melanoma. We investigated risk factors, including especially the degree of pigmentation, for SLN metastasis in Korean melanoma patients. We enrolled 158, composed of Korean 107 acral and 51 non-acral melanoma patients who underwent SLN biopsy. Clinicopathologic features such as Breslow thickness, ulceration, mitotic rate, and the degree of pigmentation were evaluated. The recurrence-free survival (RFS) rate and date of recurrence were determined. Fifty-four patients (34.2%) had a positive SLN biopsy result. In a multivariate analysis, Breslow thickness (odds ratio [OR] 1.93; 95% confidence interval [CI], 1.12-3.47; p = .022) and heavy pigmentation (OR 13.14; 95% CI, 2.96-95.20, p = .002) were associated with SLN metastasis. Positive SLN patients had a higher rate of loco-regional and/or distant recurrence (hazard ratio 6.32; 95% CI, 3.39-11.79; p < .001). Heavy pigmentation was associated with poor RFS. Heavy pigmentation is an independent predictor of SLN metastasis in both acral and non-acral melanoma. Our results suggest the need for in-depth SLN evaluation of cutaneous melanoma patients with heavy pigmentation and provide clinicians with important information for determining patient prognosis.

Comparison of optical coherence tomography and in vivo reflectance confocal microscopy with dermoscopy for the diagnosis and management of nonmelanoma skin cancer: A randomized controlled trial

AbstractBackgroundOptical coherence tomography (OCT) and reflectance confocal microscopy (RCM) can yield improved diagnostic accuracy of nonmelanoma skin cancer (NMSC) in comparison with dermoscopy alone.ObjectivesThe aim of this study was to compare the diagnostic performance of OCT and RCM together and individually with that of dermoscopy.MethodsPatients with lesions suspicious for NMSC were randomized into two groups in a prospective, single‐centre study. In the intervention group (IG), every lesion was examined with dermoscopy, OCT and RCM, while in the control group (CG), every lesion was examined with dermoscopy alone.ResultsA total of 365 lesions of 250 patients (105 female, 145 male) were included in the study. A total of 208 basal cell carcinomas (BCCs), 65 squamous cell carcinomas (SCCs) and 31 SCCs in situ were examined histologically. The IG involved significantly fewer biopsies than the CG (14 vs. 27, p = 0.029) and required fewer additional inpatient stays due to positive biopsy results (2 vs. 12, p = 0.001). For the diagnosis of BCC, diagnostic accuracy was 81% with dermoscopy, 84% with OCT, 83% with RCM and 85% with the combination of OCT and RCM (OCT/RCM). The diagnostic accuracy of OCT for BCC subtypes was as follows: superficial, 89%; nodular, 79%; sclerodermiform, 82%; and nodular‐cystic BCC, 75%. For the diagnosis of SCC, diagnostic accuracy was 85% with dermoscopy, 87% with OCT, 89% with RCM and 87% with OCT/RCM. For the diagnosis of in situ SCC, diagnostic accuracy was 87% with dermoscopy, 89% with OCT, 89% with RCM and 91% with OCT/RCM.ConclusionsDiagnostic accuracy increased with OCT and RCM and was even higher when both methods were used together. OCT and RCM could facilitate optimization of lesion management by reducing the number of punch biopsies and reducing additional inpatient stays due to positive biopsy results.

Follow-Up of Men Who Have Undergone Focal Therapy for Prostate Cancer with HIFU-A Real-World Experience.

To determine oncological and functional outcomes and side effects after focal therapy of prostate cancer (PCa) with high-intensity focused ultrasound (HIFU). This retrospective single-center study included 57 consecutive patients with localised PCa. Aged 18-80 with ≤2 suspicious lesions on mpMRI (PIRADS ≥ 3), PSA of ≤15 ng/mL, and an ISUP GG of ≤2. HIFU was performed between November 2014 and September 2018. All men had an MRI/US fusion-guided targeted biopsy (TB) combined with a TRUS-guided 10-core systematic biopsy (SB) prior to focal therapy. HIFU treatment was performed as focal, partial, or hemiablative, depending on the prior histopathology. Follow-up included Questionnaires (IIEF-5, ICIQ, and IPSS), prostate-specific antigen (PSA) measurement, follow-up mpMRI, and follow-up biopsies. The median age of the cohort was 72 years (IQR 64-76), and the median PSA value before HIFU was 7.3 ng/mL (IQR 5.75-10.39 ng/mL). The median follow-up was 27.5 (IQR 23-41) months. At the time of the follow-up, the median PSA value was 2.5 ng/mL (IQR 0.94-4.96 ng/mL), which shows a significant decrease (p < 0.001). In 17 (29.8%) men, mpMRI revealed a suspicious lesion, and 19 (33.3%) men had a positive biopsy result. Only IIEF values significantly decreased from 16 (IQR 10.75-20.25) to 11.5 (IQR 4.5-17) (p < 0.001). The rate of post-HIFU complications was low, at 19.3% (11 patients). The limitation of this study is the lack of long-term follow-up. HIFU as a therapy option for nonmetastatic, significant prostate cancer is effective in the short term for carefully selected patients and shows a low risk of adverse events and side effects.

Predicting Positive Repeat Prostate Biopsy Outcomes: Comparison of Machine Learning Approaches to Identify Key Parameters and Optimal Algorithms.

Innovative strategies are necessary to enhance prostate cancer diagnosis whilst reducing unnecessary and invasive repeat biopsies. This study aimed to determine the significant parameters affecting repeat prostate biopsy outcomes and develop an optimal machine learning algorithm for predicting positive repeat prostate biopsy results. We analysed data from 174 men who underwent repeated prostate biopsies between January 2008 and December 2022. Systematic multiple-core, ultrasound-targeted prostate biopsies were performed, each two samples from prostatic transitional zone and peripheral zone were obtained bilaterally. Clinical characteristics were collected, including patients' age, initial prostate volume, prostate-specific antigen (PSA) level, free PSA (fPSA)/PSA ratio, biopsy core numbers, pathological result; The time interval between first and latest prostate biopsy; Latest PSA level, fPSA/PSA ratio, biopsy core numbers; And final pathological diagnosis. Six feature selection methods, namely, variable ranking, correlation matrix, random forest regression, recursive feature elimination, cross-validation and forward selection, were employed to identify key influencing factors for repeat biopsy outcomes. Subsequently, the performance of seven machine learning algorithms, namely, multivariable logistic regression (LR), K-nearest neighbour search (KNN), support vector classification (SVC), decision tree (DT), random forest classifier (RF), naïve Bayes classifier (NBC) and gradient booster tree (GB), was assessed based on accuracy, misclassification, recall, specificity, precision and receiver operating characteristic (ROC) area under the curve (AUC). About 70% of patients were used as the training dataset, meanwhile remaining 30% as validation dataset. 52 were ultimately diagnosed with prostate cancer following the final pathological examination. The remaining 122 patients were negative. Amongst six feature selection methods, the variable ranking emerged as the most effective method for identifying the essential factors influencing repeat biopsy results. Amongst the machine learning algorithms, SVC demonstrated superior accuracy (0.7365), low recall rate (0.2500) and low misclassification rate (0.2093) for both patients with cancer and healthy individuals. Meanwhile, the ROC curve of SVC showed a relatively high AUC (0.6871). We developed an SVC-based machine learning algorithm for predicting positive repeat prostate biopsy results. Our analysis revealed that initial and latest prostate volumes, initial and latest PSA levels, latest fPSA/PSA ratio and age are significant factors for this model.

Prevalence, persistence, clearance and risk factors for HPV infection in rural Uyghur women in China

BackgroundThe incidence of cervical cancer in Uyghur women ranks first among those in Han and other ethnic minority groups. We aimed to understand the natural history of HPV in Uyghur women.MethodsA longitudinal cohort study on the natural history of HPV infection in rural Uyghur women in China was conducted between May 2013 and May 2014. A total of 11000 women from South Xinjiang underwent HPV screening by careHPV and liquid-based cytology. Ultimately, a total of 298 women with positive HPV and normal biopsy results or CIN1 were enrolled to participate in a study including follow-up HPV testing for two years.ResultsThe HPV infection rate in Uyghur women was 9.15%. Among the participants, the careHPV test showed that 298 women were HPV-positive, and histology showed CIN1 or normal results for these women at baseline. Among these patients, after 24 months of initial recruitment, 92 (30.87%) patients had persistent HPV infections, and 206 (69.13%) had cleared HPV infection. Univariate analysis showed that persistent HPV infection was associated with age and shower frequency (P < 0.001 and P = 0.047, respectively).ConclusionsOur results suggest that women over the age of 50 years who have been infected with HR-HPV for more than 1 year should be regularly screened and monitored for HPV. In addition, education should be strengthened to improve poor health habits in these women.

Diagnostic Accuracy of Urinary PCA3 for Prostate Cancer in Thai Patients With PSA Levels of 3 to 10 ng/ml Undergoing an Initial Prostate Biopsy

Purpose: To examine the diagnostic accuracy of the urinary prostate cancer gene 3 score for prostate cancer in Thai patients with prostate-specific antigen levels of 3 to 10 ng/ml undergoing an initial prostate biopsy. Materials and methods: In this prospective, single-center study, urine samples were collected after prostate massage. Urinary prostate cancer gene 3 mRNA levels were measured by real-time quantitative polymerase chain reaction. Data, including age, biopsy results, preoperative prostate-specific antigen levels, prostate-specific antigen density, prostate-specific antigen velocity, prostate volume, and prostate imaging findings, were collected between June 1, 2020, and May 15, 2021. Results: The median prostate-specific antigen level of the 70 included patients was 6.31 ng/ml. Sixteen patients had positive biopsy results (22.9%). The prostate cancer gene 3 score (695.09 vs 268.79, P &lt; .01), prostate-specific antigen density (0.19 vs 0.13, P &lt; .01), and prostate-specific antigen velocity (2.68 vs 0.44, P &lt; .01) significantly differed between the positive and negative biopsy groups. The predictive power of the prostate cancer gene 3 score was evaluated using receiver operating characteristic curves. At a prostate cancer gene 3 score threshold of 366.02, the sensitivity and specificity were 78.57% and 79.25%, respectively. Meanwhile, the areas under the curve of the prostate cancer gene 3 score, prostate-specific antigen velocity, and prostate-specific antigen density were better than that of prostate-specific antigen for predicting a positive biopsy. Conclusion: Our study confirmed the diagnostic accuracy of prostate cancer gene 3 for predicting a positive biopsy in Thai men with prostate-specific antigen levels of 3 to 10 ng/mL. Combining the prostate cancer gene 3 score and prostate-specific antigen derivatives might be helpful for identifying patients who can avoid unnecessary biopsies and subsequent complications.

Clinical Approach to Ocular Cicatricial Pemphigoid.

To evaluate the demographic data, ocular and systemic findings, clinical management, and outcomes of patients with ocular cicatricial pemphigoid (OCP). The medical records of 11 patients diagnosed as having OCP in the ophthalmology department of Ege University between 2008 and 2021 were evaluated retrospectively. The patients' mean follow-up time was 14±5.76 months. All eyes (100%) had conjunctival involvement and 18 (81.81%) had corneal involvement. According to the Tauber staging system, 7 (31.81%), 8 (36.36%), and 7 (31.81%) of the eyes were stage 2, 3, and 4, respectively. The diagnosis was confirmed in 6 (66.66%) of 9 patients who underwent biopsy. Amniotic membrane transplantation was performed in 7 eyes, entropion surgery in 2 eyes, and electrocauterization for trichiasis in 5 eyes. Systemic involvement was observed in 45.45% (5/11) of patients, most commonly oral mucosal involvement (18.18%). Review of medical records showed that alkylating agents, steroids, and dapsone were used in patients treated before 2020. Mycophenolate mofetil was preferred to be used in combination with corticosteroids. Although treatment responses before mycophenolate mofetil usage could not be evaluated well because of loss to follow-up, 4 (66.66%) of 6 patients who received steroid treatment combined with mycophenolate mofetil showed partial or complete clinical remission. No serious side effects and drug withdrawal were observed. OCP is a sight-threatening autoimmune disease that affects older adults. Although positive biopsy results are valuable for diagnosis, negative results do not exclude the diagnosis. The main treatment is systemic immunosuppressives. Disease activity can be suppressed, especially with early initiation of drug therapy. These patients require a multidisciplinary approach. Especially in the presence of isolated ocular findings, ophthalmologists should be able to make the decision to start immunosuppressive treatment, and systemic treatment should not be delayed.

Children with Hirschsprung disease in a developing country: A cohort study of the predictors of a positive rectal biopsy result.

Chronic constipation, which may be habitually or pathologically caused, is one of the most common complaints in children. One of the important pathological causes is Hirschsprung's disease (HD), which is diagnosed via multiple modalities, mainly rectal biopsy. Our aim was to compare the presentation and different predictive factors for positive rectal biopsy results in a developing country in the Middle East, such as Jordan. This cohort study was conducted at the Jordan University Hospital (JUH). All consecutive children aged <14 years who presented with refractory constipation and underwent rectal biopsies between January 2014 and December 2019 were retrospectively enrolled in the study. In the entire cohort study, 79 patients were enrolled: 45 (57%) were males and 34 (43%) were females. Regarding the biopsy results, 51 (64.6%) cases of refractory constipation without HD and 28 (35.4%) patients with refractory constipation with HD were diagnosed with open rectal biopsies. The male-to-female ratio of HD patients was 3:1. Moreover, 3 (10.7%) children who passed the meconium within the first 24 to 48 hours showed features of HD, while 17 (60.7%) children with delayed passage of the meconium showed features of HD. Abdominal distension was found to be a positive predictor of positive biopsy results (odds ratio [OR] = 4.09, P = .011), and soiling was found to be a negative predictor of positive biopsy results (OR = 0.07, P = .024). In developing countries, children presenting with HD seem to have similar symptoms and signs to those observed with traditional sampling and staining techniques.

Analysis of Liquid Biopsy Performance for the Detection of Lymphoma in Dogs with a Focus on Recurrent Copy Number Variants in Matched Plasma and Lymph Node Aspirates: Implications for a Comparative Oncology Model

Introduction Liquid biopsy has shown great promise for the detection and monitoring of lymphoma in humans. Recently, similar technology has been developed and made commercially available for dogs. Because the canine and human cancer genomes share such high homology (>90%), and certain lymphoma subtypes are highly similar in terms of their biologic and molecular features between the two species, the study of lymphoma in dogs affords unique opportunities for the genomic characterization of the disease, comparative oncology studies, and the development and assessment of novel therapies. The current study describes the performance of a next-generation sequencing-based liquid biopsy assay for the detection of canine lymphoma, and in a subset of patients, analyzes concordance for prognostic copy number variants between matched plasma samples and lymph node aspirate specimens. Methods As part of a larger clinical research collection program for the CANcer Detection in Dogs (CANDiD) study (Flory, 2022), blood samples were collected following diagnosis but prior to undergoing therapy from a cohort of 116 client-owned dogs with lymphoma (63 intermediate to large B-cell, 21 intermediate to large T-cell, 6 T-zone, and 26 unphenotyped). Lymphomas with inconclusive immunophenotype or other types of indolent lymphomas were excluded. A subset of dogs analyzed for the current study also had matched cytology specimens available from lymph node fine needle aspirates (FNA). Blood samples and FNA specimens were subjected to DNA extraction, library preparation, and next-generation sequencing. Sequencing data were analyzed using an internally developed bioinformatics pipeline to detect genomic alterations associated with the presence of cancer. Specific analysis focused on FNA-plasma concordance for recurrent copy number variants that have been previously identified in canine lymphoma patients and have prognostic potential (i.e., gains in chromosomes 13 and 31 and losses in chromosome 14) (Richards, 2015; Thomas, 2003). Results The overall detection rate for lymphoma by liquid biopsy was 92.2% (107/116); with detection rates of 57% for localized/regional disease (Stages I and II) and 95% for disseminated disease (Stages III, IV, and V). By immunophenotype, the detection rate for B-cell lymphoma was 97%, T-cell 91%, T-zone 50%, and unphenotyped 92%. In the subset of lymphoma-diagnosed dogs with matched plasma and FNA samples, the majority of cases had at least one of the prognostic copy number alterations previously reported in canine lymphoma patients (13G, 14L, 31G), demonstrating the potential of liquid biopsy to noninvasively detect clinically important biomarkers. A variety of genomic alterations were identified in patients with positive liquid biopsy results, including single nucleotide variants in common oncogenes and tumor suppressor genes (e.g., TP53 mutations), and copy number variants across the genome. Some of these variants are also important biomarkers in human lymphoma, in particular TP53 mutations (Chakravarty, 2017), highlighting the potential for canine liquid biopsy testing to support comparative oncology studies for the benefit of both species. Conclusion A novel next-generation sequencing-based liquid biopsy tool has demonstrated the ability to identify genomic alterations in blood samples of dogs with lymphoma, including recurrent CNVs previously described in canine lymphoma patients, and variants in genes previously described in human and canine lymphoma tissue. These findings, along with the high degree of homology between human and canine lymphomas, support the utility of liquid biopsy for the study of lymphoma in dogs as a comparative oncology model for accelerated biomarker discovery and therapeutic development in both species.

A retrospective study of cases of canine demodicosis submitted to a commercial diagnostic laboratory servicing the United Kingdom and Ireland (2017–2018): Part 1 – Signalment, lesion distribution, treatments, and concurrent diseases

Canine demodicosis, due to an overpopulation of Demodex spp. mites, remains one of the most common dermatological diseases encountered in small animal practice. The aims of this study were to interrogate submitted histories and diagnostic report results from a large cohort of dogs (n = 508) diagnosed with demodicosis either through histological analysis or the finding of Demodex spp. mites on skin scrapings by a UKAS accredited commercial laboratory servicing the United Kingdom (UK) and Ireland in the years 2017 and 2018. The main findings revealed that short-coated breeds were more likely to develop juvenile-onset (JO) demodicosis, whereas medium- and long-coated breeds were more likely to develop adult-onset (AO) disease. Pododemodicosis was reported more commonly in adult, long-coated breeds. Skin scrapings were positive in only 83.3% of samples that had a corresponding positive biopsy result; this finding highlights the necessity to perform further diagnostic tests if demodicosis remains clinically suspected despite a negative skin scraping result. Concurrent underlying diseases, potentially associated with immunosuppression, were reported in 42/221 (19%) of dogs with AO demodicosis. Serum allergy and Sarcoptes ELISA assays were positive in individual animals in both the JO and AO groups; the clinical significance of these latter findings requires careful interpretation in dogs with confirmed demodicosis.

Autoantibodies Against Trisulfated Heparin Disaccharide and Fibroblast Growth Factor Receptor-3 May Play a Role in the Pathogenesis of Neuropathic Corneal Pain.

The aim of this study was to describe cases of patients with presumable dysimmune small-fiber neuropathy (SFN)-related neuropathic corneal pain (NCP), presenting with autoantibodies against trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor-3 (FGFR-3). This study was a case series of 3 patients with NCP with positive anti-TS-HDS and/or anti-FGFR-3 autoantibodies and systemic SFN as confirmed by positive skin biopsy results. All 3 patients were women with a mean age of 34.3± 6.1 years. They suffered from moderate to severe persistent chronic ocular discomfort (10/10, 10/10, and 9/10 on a visual analogue scale, respectively). Although 1 patient suffered from ocular pain and photophobia alone, the other 2 patients experienced additional non-ocular pain. One of the patients had pain on her face and head, and 1 patient reported neck and lower back pain. Two patients had high anti-TS-HDS IgM titers, whereas 1 patient had both high anti-TS-HDS IgM and anti-FGFR-3 IgG titers. Skin biopsy confirmed the presence of SFN in all patients by demonstrating decreased intraepidermal nerve fiber density. The presence of anti-TS-HDS and anti-FGFR-3 autoantibodies in patients with NCP with positive skin biopsy findings for SFN highlights the potential role of dysimmune SFN in the pathogenesis of this disease.

Advantages of an alternate-day glucocorticoid treatment strategy for the treatment of IgG4-related disease: A preliminary retrospective cohort study.

Alternate-day glucocorticoid (GC) therapy is a treatment option that can reduce GC-associated adverse events. We investigated the safety and efficacy of alternate-day GC therapy in patients with immunoglobulin G4-related disease (IgG4-RD).Medical records of patients with IgG4-RD who were followed for at least one year at St. Luke’s International Hospital, Tokyo, Japan, from 2004 to 2020 were reviewed. Patients who fulfilled comprehensive IgG4-RD diagnostic criteria were divided into alternate-day or daily GC treatment groups based on their treatment protocol. The effect of alternate-day GC therapy on glucocorticoid toxicity index (GTI) score was evaluated using multilinear analysis with adjustments for cumulative GC doses until each assessment point and propensity scores (PS) for alternate-day GC therapy. Kaplan–Meier curves and Cox proportional hazard models were used to assess the efficacy of alternate-day GC therapy for disease control.Among the 67 patients with IgG4-RD, patients with alternate-day (n = 13) and daily (n = 31) GC treatments were analyzed after excluding 23 ineligible patients. The median (interquartile range) age was 64 (60–70) years, 29 (65.9%) were male patients, 26 (59.1%) patients had positive biopsy results, and the median follow-up period was 1643 days. Significantly more patients with alternate-day GC treatment used concomitant immunosuppressants (11 [84.6%] vs 11 [35.5%]; P = .007). The alternate-day strategy significantly lowered the GTI score after adjusting for cumulative GC dose until the assessment and PS (adjusted coefficient: −29.5 [−54.3, −4.8], P = .021 at 12 months; −20.0 [−39.8, −0.1], P = .049 at 24 months). Serious infections were numerically less frequent in the alternate-day group (incidence ratio [95% confidence interval [CI]: 0.45 [0.05, 3.63], P = .45). Most patients (92.3%) in the alternate-day GC treatment group and all patients in the daily GC treatment group showed treatment responses in the remission induction therapy. The PS-adjusted hazard ratio of alternate-day GC treatment for disease flares was not significant (1.55 [0.53, 4.51]; P = .43).The alternate-day treatment strategy significantly reduced GC-related adverse events regardless of the cumulative GC dose. Alternate-day GC treatment is a feasible option for patients with IgG4-RD, without a significant increase in disease flares particularly when combined with immunosuppressants.