Histological assessment of endometrial polyps resected by hysteroscopy.

OBJECTIVE: This study aimed to analyze the clinical data and pathologic aspects of endometrial polyps (EMPs) excised completely during surgical hysteroscopy and assess the connection between premalignant and malignant EMPs. PATIENTS AND METHODS: This retrospective study includes 489 participants who underwent hysteroscopy due to endometrial polyps, and the clinical features and histological findings of the resected polyps analyzed. RESULTS: Participants with EMPs were divided into six groups according to histologic findings. The histologic finding of most cases was simple benign endometrial polyp [397 patients (81.2%)]. Malignant polyp was detected in 3 patients (0.6%). The histologic findings according to age, menopausal status, and menstrual bleeding patterns at the time of presentation to the outpatient clinic were compared; however, no significant difference was observed. 237 patients were observed to have menometrorrhagia, which was the most prevalent symptom reported. The distribution of polyp sizes observed at hysteroscopy according to histologic findings was compared, but no significant difference was observed. CONCLUSIONS: EMPs are often benign but can include premalignant or malignant tissue changes. Hysteroscopy is used for direct observation of the uterine cervix and resection of existing polyps, considering the increasing frequency of its use as a diagnostic and treatment tool.

Don't chase the adenoma: A probabilistic approach to imaging before parathyroidectomy.

BACKGROUND: Preoperative imaging before parathyroidectomy can localize adenomas and reduce unnecessary bilateral neck explorations. We hypothesized that (1) the utility of preoperative imaging varies substantially depending on the preoperative probability of having adenoma(s) and (2) that a selective imaging approach based on this probability could avoid unnecessary patient costs and radiation. METHODS: We analyzed 3,577 patients who underwent parathyroidectomy for primary hyperparathyroidism from 2001 to 2022. The predicted probability of patients having single or double adenoma versus hyperplasia was estimated using logistic regression. We then estimated the relationship between the predicted probability of single/double adenoma and the likelihood that sestamibi or 4-dimensional computed tomography was helpful for operative planning. Current Medicare costs and published data on radiation dosing were used to calculate costs and radiation exposure from non-helpful imaging. RESULTS: The mean age was 62 ± 13 years; 78% were women. Adenomas were associated with higher mean calcium (11.2 ± 0.74 mg/dL) and parathyroid hormone levels (140.6 ± 94 pg/mL) than hyperplasia (9.8 ± 0.52 mg/dL and 81.4 ± 66 pg/mL). The probability that imaging helped with operative planning increased from 12% to 65%, as the predicted probability of adenoma increased from 30% to 90%. For every 10,000 patients, a selective approach to imaging that considered the preoperative probability of having adenomas could save patients up to $3.4 million and >239,000 millisieverts of radiation. CONCLUSION: Rather than imaging all patients with primary hyperparathyroidism, a selective strategy that considers the probability of having adenomas could reduce costs and avoid excess radiation exposure.

Perceptions, Utilization, and Cost Assessment of Sebaceous Hyperplasia Treatment Modalities: A Pilot Survey.

BACKGROUND: Sebaceous hyperplasia (SH) is a common, benign but cosmetically bothersome skin condition preferentially affecting older adults. Despite multiple treatment options, there is no universally accepted first-line treatment for SH nor standard pricing for said approaches.  Methods: A survey aimed at evaluating treatment approaches and their respective costs was disseminated on the Orlando Dermatology Aesthetic and Clinical Conference email listserv.  Results: Out of 224 dermatologists who participated in the survey (response rate 9.2%), most treated patients with SH (95.98%). In-office procedures were used more than pharmacologic treatments (P=<0.05). Treatments most used by respondents included electrodesiccation (ED; 83.9%), cryosurgery (35.3%), oral isotretinoin (32.6%), and carbon dioxide (CO2) laser (19.2%). Cryosurgery and ED priced between <$200 to $400. Most reported 1 to 2 sessions to achieve lesion clearance for ED, CO2 laser, and cryosurgery. Twenty-one percent reported 3-4 sessions with cryosurgery. Chemical peels, diode lasers, and photodynamic therapy required between 2-4 sessions. Respondents indicated lesions were most unlikely to recur with ED and CO2 laser. Most dermatologists (86.39%) agreed or strongly agreed that they were exposed to new treatments methods for SH through this survey and 86.49% of dermatologists were interested in learning about treatments employed by others. CONCLUSION: SH is a common issue that presents in the dermatologist's office. These data highlight the perception that ED is the most common approach employed, associated with lower costs, and requiring fewer sessions to achieve resolution. More data is needed and wanted to better determine best practices for the management of SH.J Drugs Dermatol. 2024;23(2):29-37.  doi:10.36849/JDD.7734.

Assessment of bony changes in temporomandibular joint in patients using cone beam computed tomography - a cross sectional study.

BACKGROUND AND AIM: The aim of this study is to evaluate the changes in the temporomandibular joint (TMJ) in patients with temporomandibular disorder (TMD) and the relationship between age, sex, and types of TMJ change using Cone Beam Computed Tomography (CBCT). METHODS AND MATERIAL: CBCT records of 200 patients (123 women and 67 men) were retrieved and assessed. Right and left TMJs were evaluated separately, resulting in a total of 400 TMJs. The images were analyzed using On demand 3D Application The radiographic findings were classified as erosion, proliferative changes mainly, including flattening and osteophytes of the condyle, sclerosis, Ely cyst, hypoplasia and hyperplasia of the condyles, ankylosis, and joint cavity. Data analysis was performed using descriptive statistics, paired T-tests, and repeated measure ANOVA (Analysis of Variance) in SPSS Software. RESULTS: The most prevalent types of condylar bony changes observed was osteophyte (63.5%) followed by flattening of the articular surface (42%), erosion (40%), ankylosis (10%) and sclerosis (10%). 7.5% of joints showed hyperplastic condyles but only 2% showed hypoplasia. The least prevalent change observed was Ely Cyst (1%). Osteophyte was the most prevalent change observed in all age groups and both sexes except for men aged 31 ~ 50, where flattening was more frequent. A statistically significant difference was found between sex and prevalence of erosion in the age group of 10 ~ 30 (P = 0.001); as well as between sex and condylar hyperplasia in the same age group. CONCLUSION: Based on the findings of this research, the prevalence of bony changes of TMJ from highest to lowest is as follows: osteophyte, flattening of the articular surface, erosion, ankylosis, sclerosis, hyperplastic condyles, hypoplastic condyles and Ely Cyst. CBCT is an accurate 3 dimensional imaging modality for assessment of TMJ bony structures.

Assessment of brush biopsy findings and salivary LDH levels in oral mucosal lesions of tobacco users.

Introduction: The oral brush cytology is an alternative method developed to improve the efficacy of conventional cytology in oral potentially malignant disorder (OPMD), and salivary lactate dehydrogenase (LDH) which is a cytoplasmic enzyme has been widely used as a marker for diagnosing various diseases. The purpose of the study is to evaluate the brush biopsy findings and salivary LDH levels for the early diagnosis of premalignant and malignant lesions of the oral cavity. Materials and Methods: Patients with deleterious habits including tobacco-related lesions such as leukoplakia, tobacco pouch keratosis, and oral cancer were included in the study. For each patient, saliva sample was collected, brush biopsy was done and smears were prepared. Collected saliva samples were analysed for salivary LDH levels and prepared smears were analysed for dysplastic changes and statistical analysis was performed. Results: Out of 80 samples, 30 were leukoplakia, 45 were tobacco pouch keratosis and 5 were oral cancer, and 13 samples showed positive dysplastic changes, 26 samples showed atypical dysplastic changes and 41 samples showed no signs of dysplastic changes and concluded as negative. On comparing the results of brush biopsy findings and salivary LDH levels, the mean salivary LDH value for positive dysplasia was elevated and the P value was statistically significant (P value: 0.00). Conclusion: Brush biopsy showed good potential in detecting premalignant lesions and salivary LDH levels showed a marked increase which can be used as a diagnostic biomarker and serve as a potent diagnostic aid for early detection of malignancy.

Qualitative Assessment of Collagen and Elastic Fibers in Oral Submucous Fibrosis (OSMF), OSMF with Dysplasia and Oral Squamous Cell Carcinoma Arising from OSMF: A Histochemical Study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a habit related potentially malignant disorder seen mainly in South Asian people. The malignancy arising from OSMF has been regarded as low grade with better outcome. The present study was orchestrated to histochemically analyze collagen and elastic fibres in OSMF without dysplasia, OSMF with dysplasia and OSMF turning malignant. MATERIALS AND METHODS: 100 cases (80 cases and 20 healthy controls) were included after obtaining clearance from ethical committee. All cases were subjected to Van Gieson staining for collagen and a novel simple method for elastic fibres (Orcein staining). Data were analyzed using SPSS software. RESULTS: Controls showed haphazard arrangement of collagen and elastic fibres. The collagen bundles were parallelly arranged in OSMF without dysplasia and OSMF with dysplasia; the collagen was however haphazard in cases of OSMF turning malignant. As with collagen, elastic fibres were also haphazardly arranged in the control group; in contrast, the elastic fibres were predominantly arranged in a criss-cross pattern in the other study groups. The difference in orientation and density among the groups was statistically significant. CONCLUSION: With advancement of stage there is increased collagenization of OSMF, as the condition acquires dysplastic changes and turns malignant, microenvironment alters resulting in increased activity of collagenases. However, the arrangement of more resistant elastic fibres depicts the better outcome, once OSMF shows malignant transformation, limiting locoregional and distant spread.

Inflammatory and Metabolic Biomarker Assessment in a Randomized Presurgical Trial of Curcumin and Anthocyanin Supplements in Patients with Colorectal Adenomas.

Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of precancerous lesions is key to preventing carcinogenesis progression. Natural compounds like curcumin and anthocyanins show promise in impeding adenomatous polyp progression in preclinical models. We conducted a randomized, double-blind, placebo-controlled, phase II presurgical trial in 35 patients with adenomatous polyps to explore the biological effects of curcumin and anthocyanins on circulating biomarkers of inflammation and metabolism. No significant difference in biomarker changes by treatment arm was observed. However, the network analysis before treatment revealed inverse correlations between adiponectin and BMI and glycemia, as well as direct links between inflammatory biomarkers and leptin and BMI. In addition, a considerable inverse relationship between adiponectin and grade of dysplasia was detected after treatment (corr = -0.45). Finally, a significant increase in IL-6 at the end of treatment in subjects with high-grade dysplasia was also observed (p = 0.02). The combined treatment of anthocyanins and curcumin did not result in the direct modulation of circulating biomarkers of inflammation and metabolism, but revealed a complex modulation of inflammatory and metabolic biomarkers of colon carcinogenesis.

Dermoscopic features of benign sebaceous proliferations in dogs: Description, assessment and inter-observer agreement.

BACKGROUND: Dermoscopy is a useful, noninvasive technique also used to assess sebaceous lesions in humans. Sebaceous hyperplasia, sebaceous adenoma and sebaceous epithelioma are common cutaneous lesions in dogs; however, their dermoscopic features have not been investigated. HYPOTHESIS/OBJECTIVES: The objectives of this study are to describe the dermoscopic features of canine sebaceous lesions and to assess the interobserver agreement on dermoscopic parameters. ANIMALS: Thirty-four lesions excised from 17 client-owned dogs, histologically confirmed as sebaceous proliferations, were included in this study. MATERIALS AND METHODS: Sebaceous lesions were evaluated in vivo at ×10 magnification with a handheld dermoscope. Each dermoscopic image was assessed independently by two ECVD board-certified veterinary referral clinicians and an ECVD resident. RESULTS: Thirty sebaceous hyperplasias, two sebaceous adenomas and two sebaceous epitheliomas were included. Dermoscopically, most lesions (91%) had single or multiple, well-defined, white-yellowish structures composed of grouped ovoid areas (clods). Irregular linear and, less commonly, arborising vessels were detected at the periphery of the yellow lobular-like structures in 93% of sebaceous hyperplasias and in 50% of neoplastic lesions. Erosions were seen in 6% of sebaceous hyperplasias and 50% of neoplastic lesions. Good interobserver agreement was found for white/yellowish clods (k = 0.75), yellow scales (k = 0.83), brown/grey dots (k = 0.80), erosions (k = 0.82) and red/brownish scales/crusts (k = 0.75). There was moderate agreement for fissures (k = 0.48) and vascular pattern (k = 0.51-0.53). CONCLUSIONS AND CLINICAL RELEVANCE: Dermoscopy represents a useful technique to assess sebaceous gland proliferations in dogs, as it is in humans.

Validation of a Pathological Score for the Assessment of Bronchial Biopsies in Severe Uncontrolled Asthma: Beyond Blood Eosinophils.

BACKGROUND: Blood eosinophil count (BEC) is currently used as a surrogate marker of T2 inflammation in severe asthma but its relationship with tissue T2-related changes is elusive. Bronchial biopsy could add reliable information but lacks standardization. OBJECTIVES: To validate a systematic assessment of the bronchial biopsy for the evaluation of severe uncontrolled asthma (SUA) by standardizing a pathological score. METHODS: A systematic assessment of submucosal inflammation, tissue eosinophilic count/field (TEC), goblet cells hyperplasia, epithelial changes, basement membrane thickening, prominent airway smooth muscle and submucosal mucous glands was initially agreed and validated in representative bronchial biopsies of 12 patients with SUA by 8 independent pathologists. In a second phase, 62 patients with SUA who were divided according to BEC≥300cells/mm3 or less underwent bronchoscopy with bronchial biopsies and the correlations between the pathological findings and the clinical characteristics were investigated. RESULTS: The score yielded good agreement among pathologists regarding submucosal eosinophilia, TEC, goblet cells hyperplasia and mucosal glands (ICC=0.85, 0.81, 0.85 and 0.87 respectively). There was a statistically significant correlation between BEC and TEC (r=0.393, p=0.005) that disappeared after correction by oral corticosteroids (OCS) use (r=0.170, p=0.307). However, there was statistically significant correlation between FeNO and TEC (r=0.481, p=0.006) that was maintained after correction to OCS use (r=0.419, p=0.021). 82.4% of low-BEC had submucosal eosinophilia, 50% of them moderate to severe. CONCLUSION: A standardized assessment of endobronchial biopsy is feasible and could be useful for a better phenotyping of SUA especially in those receiving OCS.

MORPHOLOGICAL ASSESSMENT OF THE LUNGS IN POST-COVID-19 SYNDROME: ANALYSIS OF AUTOPSY MATERIAL.

OBJECTIVE: The aim was to reveal the morphological features of the lungs in post-COVID-19 syndrome. PATIENTS AND METHODS: Materials and methods: The material of the study was autopsy material - fragments of the lung tissue from 96 deceased (59 men and 37 women). During the lifetime, all patients had in anamnesis COVID-19 of varying severity, and after the treatment of this infection, they had various manifestations of respiratory failure until death. The average duration of the post-COVID-19 period was 148.6±9.5 days. Based on the severity of COVID-19 in anamnesis, all cases were divided into three groups. Group 1 included 39 cases with mild COVID-19 in anamnesis. Group 2 included 24 cases with moderate severity of COVID-19 in an-amnesis. Group 3 included 33 cases with severe COVID-19 in anamnesis. Histological, histochemical, morphometric and statistical research methods were used. RESULTS: Results: Morphological features of the lungs in post-COVID-19 syndrome were the presence of pneumosclerosis; focal-diffuse immune cells infiltration; emphysematous and atelectatic changes; degenerative-desquamatic changes in the alveolar epithelium; metaplastic changes of connective tissue; dystrophic calcification; dystrophic, metaplastic and dysplastic changes in the epithelial layer of bronchial tree; hemodynamic disorders. Pneumosclerosis, focal-diffuse immune cells infiltration, alterative changes in the alveolar epithelium, emphysematous and atelectatic changes, hemodynamic disorders increased with an increase the severity of COVID-19. Metaplastic changes of connective tissue, dystrophic calcification, dystrophic, metaplastic and dysplastic changes in epithelial layer of bronchial tree did not depend on the severity of the infection. CONCLUSION: Conclusions: The changes identified by the authors help to explain pulmonary manifestations of post-COVID-19 syndrome. They should be the basis for the oncological alertness formation among doctors, the development of rehabilitation and treatment measures for such category of patients.

Assessment of Prostate Volume and Prostate-specific Antigen Density With the Segmentation Method on Magnetic Resonance Imaging.

BACKGROUND/AIM: This study aimed to compare the prostate volume (PV) and prostate-specific antigen density (PSAD) obtained using the ellipsoid volume formula or segmentation methods on magnetic resonance imaging (MRI) and further predict prostate cancer (PCa). PATIENTS AND METHODS: Retrospectively, the enrolled patients underwent prostate MRI and had PSA levels between 4 and 10 ng/ml. The PV was measured with both the ellipsoid volume formula (PVe) and the segmentation method (PVs). The transitional zone volume (TZV) was measured with the segmentation method. The PSADe, PSADs, and PSAD_TZV were calculated. Bland-Altman plots were used to compare the agreements. ROC curve analysis was used to compare the diagnostic accuracies to predict PCa. The results were also compared between the PCa and the no-PCa groups, and among tumors with different locations and different Gleason scores (GS). RESULTS: Seventy-six of the 117 enrolled patients were classified into the PCa group. There were high agreements between PVs and PVe as well as between PSADs and PSADe, while several outliers were mainly due to post-transurethral resection of the prostate changes and irregular hyperplastic nodules. The diagnostic accuracy of PSADe (AUC: 0.732) was slightly higher than that of PSADs (AUC: 0.729) and PSAD_TZV (AUC: 0.715). The PSADe and PSADs were not different among different tumor locations but were higher in GS ≥7 lesions (both p=0.006). CONCLUSION: The segmentation method can be an alternative method to measure PV and calculate PSAD before prostate biopsy, particularly in post-transurethral resection of the prostate patients or those with irregular hyperplastic nodules.

Biological Assessment of Stevioside and Sucralose as Sucrose Substitutes for Diabetics on STZ-Induced Diabetes in Rats.

Numerous food organizations have identified excessive calorie consumption and accompanying ailments as significant health risks associated with high sugar consumption. Administering stevioside (ST), sucralose (SU), and the two synergically (SU+ST) affected normal rats' weight gain. In the current study, SU showed the highest undesired effect. Indeed, administering the three treatments to diabetic rats (DR) did not improve the rats' weight gain. Although, insulin injection synergically with the treatments improved the weight gain, as recorded after three weeks. The best-improving rate was observed in the ST group. After the administration of ST and ST+SU to the DR, the blood glucose level (GL) was positively affected, with SU having no effects on reducing the GL. A considerable reduction in serum insulin (SIL) was noted in the DR+SU group. On the contrary, ST did not negatively affect the SIL, rather an improvement was recorded. In addition, giving SU did not significantly affect the ALT level in the DR or normal rats (NR). A significant improvement in total bilirubin (TBILI) was observed when insulin was injected with ST or SU in DR groups. Further, triglycerides (TG) after administering ST, SU, or ST+SU to NR had no significant difference compared to the control group (NR). Although, the three treatments markedly but not significantly lowered TG in the DR. For total cholesterol (CHO), both DR and NR had no significant effect after the three treatments. No histopathological alterations were recorded in the NR group. Diffuse and severe atrophy of the islands of Langerhans due to depletion of their cells and mild papillary hyperplasia of the pancreatic ducts were represented by a slightly folded ductal basement membrane and newly formed ductules in STZ-DR. Simultaneous atrophy and absence of the cells of islands of Langerhans besides ductal hyperplasia were evident in DR+SU. Hyperplastic ductal epithelium and atrophic Langerhans cells were seen in DR+SU+In. Degeneration and mild atrophy were observed in the islands of Langerhans structures. There was essentially no noticeable change after utilizing ST. A slight shrinkage of the Langerhans' islets was detected in DR+ST. In DR+ST+In, no histopathological alterations in the islands of Langerhans were recorded. Congestion in the stromal blood vessels associated with degenerative and necrotic changes in the cells of the islands of Langerhans in DR+SU+ST was observed. In NR+SU, congestion of the blood vessels associated with mild atrophy in the islands of Langerhans and dilatation in stromal blood vessels was noticed. In conclusion, ST is safe, and SU should be taken cautiously, such as mixing with ST and/or taken at a very low concentration to avoid its drastic effect on the human body.

T1 Mapping of the Prostate Using Single-Shot T1FLASH: A Clinical Feasibility Study to Optimize Prostate Cancer Assessment.

PURPOSE: The aim of this study was to assess the clinical feasibility of magnetic resonance imaging (MRI) T1 mapping using T1FLASH for assessment of prostate lesions. METHODS: Participants with clinical suspicion for prostate cancer (PCa) were prospectively enrolled between October 2021 and April 2022 with multiparametric prostate MRI (mpMRI) acquired on a 3 T scanner. In addition, T1 mapping was accomplished using a single-shot T1FLASH technique with inversion recovery, radial undersampling, and iterative reconstruction. Regions of interest (ROIs) were manually placed on radiologically identified prostate lesions and representative reference regions of the transitional zone (TZ), benign prostate hyperplasia nodules, and peripheral zone (PZ). Mean T1 relaxation times and apparent diffusion coefficient (ADC) values (b = 50/b = 1400 s/mm 2 ) were measured for each ROI. Participants were included in the study if they underwent ultrasound/MRI fusion-guided prostate biopsy for radiologically or clinically suspected PCa. Histological evaluation of biopsy cores served as reference standard, with grading of PCa according to the International Society of Urological Pathology (ISUP). ISUP grades 2 and above were considered clinically significant PCa for the scope of this study. Histological results of prostate biopsy cores were anatomically mapped to corresponding mpMRI ROIs using biopsy plans. T1 relaxation times and ADC values were compared across prostate regions and ISUP groups. Across different strata, T1 relaxation time, ADC values, and diagnostic accuracy (area under the curve [AUC]) were compared using statistical methods accounting for clustered data. RESULTS: Of 67 eligible participants, a total of 40 participants undergoing ultrasound/MRI fusion-guided prostate biopsy were included. Multislice T1 mapping was successfully performed in all participants at a median acquisition time of 2:10 minutes without evident image artifacts. A total of 71 prostate lesions was radiologically identified (TZ 49; PZ 22). Among those, 22 were histologically diagnosed with PCa (ISUP groups 1/2/3/4 in n = 3/15/3/1 cases, respectively). In the TZ, T1 relaxation time was statistically significantly lower for PCa compared with reference regions ( P = 0.029) and benign prostate hyperplasia nodules ( P < 0.001). Similarly, in the PZ, PCa demonstrated shorter T1 relaxation times versus reference regions ( P < 0.001). PCa also showed a trend toward shorter T1 relaxation times (median, 1.40 seconds) compared with radiologically suspicious lesions with benign histology (median, 1.47 seconds), although statistical significance was not reached ( P = 0.066). For discrimination of PCa from reference regions and benign prostate lesions, T1 relaxation times and ADC values demonstrated AUC = 0.80 and AUC = 0.83, respectively ( P = 0.519). Discriminating PCa from radiologically suspicious lesions with benign histology, T1 relaxation times and ADC values showed AUC = 0.69 and AUC = 0.62, respectively ( P = 0.446). CONCLUSIONS: T1FLASH-based T1 mapping yields robust results for quantification of prostate T1 relaxation time at a short examination time of 2:10 minutes without evident image artifacts. Associated T1 relaxation times could aid in discrimination of significant and nonsignificant PCa. Further studies are warranted to confirm these results in a larger patient cohort, to assess the additional benefit of T1FLASH maps in conjunction with mpMRI sequences in the setting of deep learning, and to evaluate the robustness of T1FLASH maps compared with potentially artifact-prone diffusion-weighted imaging sequences.

Quality assessment of Clinical Practice Guidelines (CPG) for the diagnosis and treatment of inflammatory bowel disease using the AGREE II instrument: a systematic review.

BACKGROUND: The incidence and diagnosis of inflammatory bowel disease (IBD) has increased considerably in recent years. Many clinical practice guidelines (CPG) have been developed for the management of this disease across different clinical contexts, however, little evidence exists on their methodological quality. Therefore, we aimed to systematically evaluate the quality of CPGs for the diagnosis and treatment of IBD using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. METHODS: We identified CPGs by searching databases (MEDLINE - PubMed, EMBASE, CINAHL, LILACS) and other sources of gray literature on January 2022. We included guidelines with specific recommendations for the diagnosis and treatment of IBD and evaluated them with the AGREE II instrument to assess their methodological quality. Six independent reviewers assessed the quality of the guidelines and resolved conflicts by consensus. We assessed the degree of agreement using the intraclass correlation coefficient (ICC) and change in quality over time was appraised in two periods: from 2012 to 2017 and from 2018 to 2022. RESULTS: We analyzed and evaluated 26 CPGs that met the inclusion criteria. The overall agreement among reviewers was moderate (ICC: 0.74; 95% CI 0.36 - 0.89). The mean scores of the AGREE II domains were: "Scope and purpose" 84.51%, "Stakeholder involvement" 60.90%, "Rigor of development" 69.95%, "Clarity of presentation" 85.58%, "Applicability" 26.60%, and "Editorial independence" 62.02%. No changes in quality were found over time. CONCLUSIONS: The quality of the CPGs evaluated was generally good, with a large majority of the assessed guidelines being "recommended" and "recommended with modifications"; despite this, there is still room for improvement, especially in terms of stakeholder involvement and applicability. Efforts to develop high quality CPGs for IBD need to be further optimized.

Assessment of the possibility of using biomarkers (CCL11 and TGF-beta 1) in the diagnosis of prostate gland hyperplasia in dogs.

Prostatic hyperplasia (PH) is the most common reproductive disorder in dogs and can lead to discomforting problems such as haematuria, urinary incontinence, constipation, difficulty in defecating and stiffness of the hind limbs. The diagnosis of PH is nowadays based on digital rectal examination (DRE), ultrasonography (US) and radiography (X-ray). However, markers associated with PH are barely used for diagnostic purposes. Recently, there have been reports on the use of certain biomarkers for diagnosing PH in dogs such as canine PSA (Prostate Specific Antigen), microRNA and vascular endothelial growth factor (VEGF). Nevertheless, it has been generally accepted that these biomarkers play only an auxiliary role. Accordingly, the aim of our study was to evaluate the usefulness of the CCL11 (eotaxin-1) and TGF-beta 1 markers, which are used in the diagnosis of prostate diseases in humans, in case of dogs with PH. The study was carried out on 40 dogs of different breeds divided into three groups. Group I (n = 9) comprised dogs up to 5 years of age without changes indicative of PH. Group II (n = 17) included dogs aged 5-10 that were examined and diagnosed with (PH) and Group III (n = 14) which consisted of dogs over 10 years of age who were also diagnosed with PH. The study demonstrated that CCL11 levels did not differ significantly between the study groups and the median levels were 7.27 pg/mL, 7.57 pg/mL, 6.81 pg/mL, and IQR ranges 1.55 pg/mL, 1.74 pg/mL, 2.32 pg/mL, respectively. In contrast, TGF-beta 1 levels were detectable only in 6 dogs of group III and averaged the median of 28.86 pg/mL, IQR ranges 10.07 pg/mL. The study proved that CCL11 and TGF-beta 1 markers are of a limited use when diagnosing PH in dogs as no significant correlation related to age, body weight or prostate size was found.

Nodal Assessment in Endometrial Atypical Hyperplasia.

OBJECTIVE: Atypical endometrial hyperplasia (AH) is the neoplastic precursor more often associated with endometrial cancer (EC). Nowadays, 25-50% of patients subjected to hysterectomy for preoperative AH are diagnosed with EC at the final pathological analysis. Furthermore, there is no consensus on which preoperative AH patients would benefit from sentinel lymph node mapping. This study aimed to evaluate nodal assessment and preoperative cancer risk factors in preoperative AH patients undergoing nodal surgical staging. METHODS: Patients undergoing surgical treatment for AH were retrospectively included in the analysis. Patients were divided into two groups (AH and EC groups) based on the final surgical pathology. The ESGO/ESTRO/ESP risk classification was used for EC cases. DESIGN: This was a retrospective study. RESULTS: Of the 207 AH patients treated, 152 cases met the inclusion criteria. Among preoperative AH patients with final EC diagnosis, 39 patients were in the low-risk group (25.7%), 8 in the intermediate-risk group (5.3%), 4 in high-intermediate (2.6%), and 3 patients were allocated in the high-risk group (2.0%). Fifty-four total patients underwent nodal surgical staging. Only one nodal micrometastasis (0.7%) was found at ultrastaging. Multivariate analysis showed abnormal uterine bleeding (AUB) (p = 0.01), hypertension (p < 0.01), and endometrial thickness ≥20 mm (p = 0.02) statistically more represented in patients with EC at final surgical analysis. EC risk was 2.9 (95% CI: 1.29-6.48) in AUB, 2.7 (95% CI: 1.06-6.92) in hypertension, and 3.1 (95% CI: 1.19-7.97) in endometrial thickness ≥20 mm cases. LIMITATIONS: The present study has limitations inherent in its retrospective nature. CONCLUSION: The overall risk of nodal metastases in preoperative AH patients was low. Conversely, 9.9% of the preoperative AH patients belonged to the intermediate or high-risk group for EC at the final histological examination. Preoperative cancer risk factors would identify AH patients for whom nodal staging could be suggested.

Estimation of Utility Weights for Prostate-related Health States in Korea.

OBJECTIVES: Very limited previous research has investigated the utility weights of prostate-related diseases in the general population in Korea. The purpose of this study was to calculate the utility of prostate-related health states in the Korean general public using the standard gamble (SG) method. METHODS: Seven health states for hypothetical prostate cancers, 1 for benign prostate hyperplasia, and 1 for erectile dysfunction were developed based on patient education material and previous publications. In total, 460 responses from the Korean general population were used to analyze the utility of prostate-related health states. Computer-assisted personal interviews were conducted, and utility values were measured using a visual analogue scale (VAS) and SG. Mean utility values were calculated for each prostate-related health state. RESULTS: The mean utility values of prostate cancer derived from SG ranged from 0.281 (metastatic castration-refractory prostate cancer) to 0.779 (localized prostate cancer requiring prostatectomy). The utility value of benign prostate hyperplasia was 0.871, and that of erectile dysfunction was 0.812. The utility values obtained using the SG method in all conditions were higher than the values obtained by VAS. There were no significant demographic variables affecting utility values in multivariate analysis. CONCLUSIONS: Our findings might be useful for economic evaluation and utility calculation of screening and interventions for prostate-related conditions in the general population.

Fexapotide triflutate vs oral pharmacotherapy as initial therapy for moderate-to-severe benign prostate hyperplasia patients: a cost-effectiveness analysis.

BACKGROUND: To assess the price range in which fexapotide triflutate (FT), a novel injectable, is cost-effective relative to current oral pharmacotherapy (5 α-reductase inhibitor, α-blocker, 5 α-reductase inhibitor and α-blocker combination therapy) as initial therapy followed by surgery for moderate-to-severe benign prostate hyperplasia patients with lower urinary tract symptoms (BPH-LUTS). METHODS: We developed a microsimulation decision-analytic model to track the progression of BPH-LUTS and associated costs and quality-adjusted life years in the target population. The cost-effectiveness analysis was performed from Medicare's perspective with a time horizon of 4 years using 2019 US dollars for all costs. The microsimulation model considered treatment patterns associated with nonadherence to oral medication and progression to surgery. Model parameters were estimated from large randomized controlled trials, literature and expert opinion. For each initial treatment option, simulations were performed with 1000 iterations, with 1000 patients per iteration. RESULTS: Three upfront oral pharmacotherapy options are close in cost-effectiveness, with combination therapy being the most cost-effective option. Relative to upfront oral pharmacotherapy options, FT slightly increases quality-adjusted life years (QALY) per patient (1.870 (95% CI, 1.868 to 1.872) vs. 1.957 (95% CI, 1.955 to 1.959) QALYs). Under the willingness-to-pay (WTP) threshold of $150,000 per QALY, at price per injection of $14,000, FT is about as cost-effective as upfront oral pharmacotherapy options with net monetary benefit (NMB) $279,168.54. Under the WTP threshold of $50,000 per QALY, at price per injection of $5,000, FT is about as cost-effective as upfront oral pharmacotherapy options with NMB $92,135.18. In an alternative 10-year time horizon scenario, FT price per injection at $11,000 and $4,500 makes FT as cost-effective as oral pharmacotherapies. One-way sensitivity analysis showed this result is most sensitive to upfront therapy prices, FT efficacy and initial IPSS. At price per injections of $5,000, $10,000 and $15,000, the probability that FT is either cost-effective or dominant compared to upfront oral pharmacotherapy options using a WTP threshold of $150,000 per QALY is 100%, 93% and 40%, respectively. CONCLUSIONS: Compared to upfront oral pharmacotherapy options, FT would be cost-effective at a price per injection below $14,000, assuming a WTP threshold of $150,000 per QALY.

Assessment of sex- and age-dependency of risk factors for intimal hyperplasia in heart transplant patients using the high resolution of optical coherence tomography.

BACKGROUND: Intimal hyperplasia in cardiac allograft vasculopathy (CAVIH) is limiting survival in pediatric and adult patients after heart transplantation (HTx). Analysis of risk factors for CAVIH using the high resolution of intracoronary optical coherence tomography (OCT) is scarce, particularly in children, and recommendations for CAV prevention are largely based on data obtained in adults. Whether the predictive value of risk factors is age- or sex-dependent is unknown. METHODS AND RESULTS: We used OCT to test the age- and sex-dependency of established risk factors regarding pathological CAVIH in a cohort of 102 pediatric and adult HTx patients (35% <18 years, 69% male). Modifiable parameters such as lipid values, and the diagnoses of dyslipidemia and diabetes showed age- and sex-dependent differences. Regarding CAVIH, receiver-operating characteristic analysis showed that LDL-c was relevant only in female patients (area under the curve [AUC] 0.79, p = 0.007), and total cholesterol in female (AUC 0.81; p = 0.004) and pediatric patients (AUC 0.73, p < 0.05). The association of dyslipidemia with CAVIH was stronger in adult (odds ratio [OR] 6.33) than in pediatric patients (OR 5.00) and in women (OR 6.00) than in men (OR 4.57). Diabetes was associated with CAVIH only in women (OR 11.25). CONCLUSION: In our cohort, modifiable risk factors, particularly total cholesterol and dyslipidemia, had a different impact depending on age and sex. Targeting risk factors in selected patients might improve individual CAVIH prevention.

Assessment of parathyroid gland cellularity by digital slide analysis.

BACKGROUND: Computer-aided examination of digital tissue images has attracted attention in recent years. Application in the field of parathyroid pathology has not been studied previously. It holds a potential to assist in the examination of parathyroid gland adenoma or hyperplasia. OBJECTIVES: To explore parathyroid cell detection of slide images by digital tissue analysis and compare the results to standard human processing. METHODS: 47 incisional biopsies of healthy appearing parathyroid glands were evaluated for their cellularity level. First, by the standard examination using microscopy by three independent pathologists. We compared the mean cellularity grading of the pathologists to the output of a computerized cell detection software. RESULTS: A disagreement was found between the standard human cellularity grading and the digital analysis output. However, the digital analysis reaches a 94% specificity and 48% sensitivity to predict high cellularity (>60% parenchymal cells). CONCLUSIONS: Digital analysis of parathyroid tissue can be used as a tool for hypercellularity elimination, therefore assisting in the diagnosis of parathyroid cell hyperplasia. Additional studies using more advanced algorithms are necessary for further precision enhancement.