Aortic valve replacement versus conservative treatment in asymptomatic severe aortic stenosis: long-term follow-up of the AVATAR trial.

BACKGROUND AND AIMS: The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, clinical trials.gov). METHODS: The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure (HF), as compared to conservative treatment strategy. RESULTS: A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either early AVR group (n=78) or conservative treatment group (n=79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group (hazard ratio [HR] early surgery vs. conservative treatment 0.42; 95% confidence interval [CI] 0.24-0.73, p=0.002). The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, p=0.012 for all-cause death, and HR 0.21; 95% CI 0.06-0.73, p=0.007 for HF hospitalizations). CONCLUSIONS: The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting. TRIAL REGISTRATION NUMBER: NCT02436655 (ClinicalTrials.gov).

Cytoreductive chemotherapy in induction therapy plays a key role in the prognosis of patients with low-risk acute promyelocytic leukaemia.

In order to explore the risk factors of relapse and potential optimized therapeutic regimen of low-risk acute promyelocytic leukaemia (APL), here we retrospectively analysed 282 patients who were diagnosed between February 2014 and September 2021. The median follow-up was 59 (9-102) months. The 5-year overall survival and cumulative relapse incidence were 97.9% and 5.9%, respectively. In terms of different cytoreductive therapies, 86 patients were administered with hydroxycarbamide (30.5%), 113 with anthracyclines or cytarabine (40.1%), 31 with etoposide (11.0%) and 52 with no cytoreductive therapy (18.4%) during the induction therapy. The hydroxycarbamide treatment group did not decrease the relapse rate compared to the no cytoreduction group (11.4% vs. 5.9%, p = 0.289). Compared with the hydroxycarbamide group, the anthracyclines/cytarabine treatment group showed improved 5-year RFS (88.145% vs. 98.113%, p = 0.008). Multivariate Cox regression analysis revealed that myeloblasts in bone marrow at diagnosis, and PML-RARA transcript level of 6.5% or more after induction therapy were associated with a subsequent risk of relapse. The only factor positively reducing the relapse rate was anthracyclines/cytarabine cytoreductive treatment. In conclusion, cytoreductive chemotherapy in induction therapy plays a potential key role in the prognosis of low-risk APL.

Low-Risk Staphylococcus aureus Bacteremia Patients Do Not Require Routine Diagnostic Imaging: A Multicenter, Retrospective, Cohort Study.

BACKGROUND: Stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low or high risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes. METHODS: We performed a retrospective cohort study at 7 Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence. Primary outcome was the proportion of patients whose treatment plan changed due to detected metastatic infections, as evaluated by both actual therapy administered and by linking a adjudicated diagnosis to guideline-recommended treatment. Secondary outcomes were 90-day relapse-free survival and factors associated with the performance of diagnostic imaging. RESULTS: Of 377 patients included, 298 (79%) underwent diagnostic imaging. In 15 of these 298 patients (5.0%), imaging findings during patient admission had been interpreted as metastatic infections that should extend treatment. Using the final adjudicated diagnosis, 4 patients (1.3%) had clinically relevant metastatic infection. In a multilevel multivariable logistic regression analysis, 90-day relapse-free survival was similar between patients without imaging and those who underwent imaging (81.0% versus 83.6%; adjusted odds ratio, 0.749; 95% confidence interval, .373-1.504). CONCLUSIONS: Our study advocates risk stratification for the management of SAB patients. Prerequisites are follow-up blood cultures, bedside infectious diseases consultation, and a critical review of disease evolution. Using this approach, routine imaging could be omitted in low-risk patients.

Socioeconomic disadvantage and racial/ethnic disparities in low-risk cesarean birth in California.

Our objective was to assess the relationship of socioeconomic disadvantage and race/ethnicity with low-risk cesarean birth. We examined birth certificates (2007-18) linked with maternal hospitalization data from California; the outcome was cesarean birth among low-risk deliveries (i.e., nulliparous, term, singleton, vertex [NTSV]). We used GEE Poisson regression with an interaction term for race/ethnicity (7 groups) and a measure of socioeconomic disadvantage (census tract-level neighborhood deprivation index [NDI], education, or insurance). Among 1,815,933 NTSV births, 26.6% were cesarean. When assessing the joint effect of race/ethnicity and socioeconomic disadvantage among low-risk births, risk of cesarean birth increased with socioeconomic disadvantage for most racial/ethnic groups, and disadvantaged Black individuals had the highest risks; e.g., Black individuals with a high school education or less had a risk ratio of 1.49 (95% CI 1.45-1.53), relative to White individuals with a college degree. The disparity in risk of cesarean birth between Black and White individuals was observed across all strata of socioeconomic disadvantage. Asian American and Hispanic individuals had higher risks than White individuals at lower socioeconomic disadvantage; this disparity was not observed at higher levels of disadvantage. Black individuals have a persistent, elevated risk of cesarean birth, relative to White individuals, regardless of socioeconomic disadvantage.

Determinants of active surveillance uptake in a diverse population-based cohort of men with low-risk prostate cancer: The Treatment Options in Prostate Cancer Study (TOPCS).

BACKGROUND: Active surveillance (AS) is the preferred strategy for low-risk prostate cancer (LRPC); however, limited data on determinants of AS adoption exist, particularly among Black men. METHODS: Black and White newly diagnosed (from January 2014 through June 2017) patients with LRPC ≤75 years of age were identified through metro-Detroit and Georgia population-based cancer registries and completed a survey evaluating factors influencing AS uptake. RESULTS: Among 1688 study participants, 57% chose AS (51% of Black participants, 61% of White) over definitive treatment. In the unadjusted analysis, patient factors associated with initial AS uptake included older age, White race, and higher education. However, after adjusting for covariates, none of these factors was significant predictors of AS uptake. The strongest determinant of AS uptake was the AS recommendation by a urologist (adjusted prevalence ratio, 6.59, 95% CI, 4.84-8.97). Other factors associated with the decision to undergo AS included a shared patient-physician treatment decision, greater prostate cancer knowledge, and residence in metro-Detroit compared with Georgia. Conversely, men whose decision was strongly influenced by the desire to achieve "cure" or "live longer" with treatment and those who perceived their LRPC diagnosis as more serious were less likely to choose AS. CONCLUSIONS: In this contemporary sample, the majority of patients with newly diagnosed LRPC chose AS. Although the input from their urologists was highly influential, several patient decisional and psychological factors were independently associated with AS uptake. These data shed new light on potentially modifiable factors that can help further increase AS uptake among patients with LRPC.

Low Colorectal Cancer Risk After Resection of High-Risk Pedunculated Polyps.

BACKGROUND: Post-fecal immunochemical test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas. Due to an expected higher risk of colorectal cancer (CRC), postpolypectomy surveillance is recommended, generating a substantially increased load on endoscopy services. The aim of our study was to investigate postpolypectomy CRC risk in a screening population of FIT+ subjects after resection of low-risk adenomas (LRAs) or high-risk adenomas (HRAs). METHODS: We retrieved data from a cohort of patients undergoing postpolypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were postpolypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia, and location of the index lesion. We adopted as comparators FIT+/colonoscopy-negative and FIT- patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables. RESULTS: Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had an LRA, and 22,709 (26.0%) an HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.92-1.53) was not increased compared with the FIT+/colonoscopy-negative group, while for HRAs a significant increase in CRC incidence (HR, 1.53; 95% CI, 1.14-2.04) was found. The presence of 1 or more risk factors among proximal location, nonpedunculated morphology, and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR, 1.85; 95% CI, 1.36-2.52). Patients with only distal pedunculated polyps without high-grade dysplasia, representing 39.2% of HRA, did not have increased risk compared with the FIT- group (HR, 0.87; 95% CI, 0.59-1.28). CONCLUSIONS: CRC incidence is significantly higher in patients with HRAs diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without high-grade dysplasia, an observation that could potentially reduce the burden of surveillance in FIT programs.

Outcomes from low-risk ductal carcinoma in situ: a systematic review and meta-analysis.

PURPOSE: The current standard of treatment for ductal carcinoma in situ (DCIS) is surgery with or without adjuvant radiotherapy. With a growing debate about overdiagnosis and overtreatment of low-risk DCIS, active surveillance is being explored in several ongoing trials. We conducted a systematic review and meta-analysis to evaluate the recurrence of low-risk DCIS under various treatment approaches. METHODS: PubMed, Embase, Web of Science, and Cochrane were searched for studies reporting ipsilateral breast tumour event (IBTE), contralateral breast cancer (CBC), and breast cancer-specific survival (BCSS) rates at 5 and 10 years in low-risk DCIS. The primary outcome was invasive IBTE (iIBTE) defined as invasive progression in the ipsilateral breast. RESULTS: Thirty three eligible studies were identified, involving 47,696 women with low-risk DCIS. The pooled 5-year and 10-year iIBTE rates were 3.3% (95% confidence interval [CI]: 1.3, 8.1) and 5.9% (95% CI: 3.8, 9.0), respectively. The iIBTE rates were significantly lower in patients who underwent surgery compared to those who did not, at 5 years (3.5% vs. 9.0%, P = 0.003) and 10 years (6.4% vs. 22.7%, P = 0.008). Similarly, the 10-year BCSS rate was higher in the surgery group (96.0% vs. 99.6%, P = 0.010). In patients treated with breast-conserving surgery, additional radiotherapy significantly reduced IBTE risk, but not total-CBC risk. CONCLUSION: This review showed a lower risk of progression and better survival in women who received surgery and additional RT for low-risk DCIS. However, our findings were primarily based on observational studies, and should be confirmed with the results from the ongoing trials.

Pre-surgical cryoablation in ≤ 2 cm ER + /HER2-tumors. Prognostic factors for the presence of residual invasive carcinoma.

BACKGROUND: Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of cryoablation is demonstrated, it could provide a minimally invasive alternative to surgery. PURPOSE: To determine the success of ultrasound-guided cryoablation in achieving the absence of Residual Invasive Cancer (RIC) for patients with ER + /HER2- tumors ≤ 2cm and sonographically negative axillary nodes. MATERIALS AND METHODS: This prospective study was carried out from April 2021 to June 2023, and involved 60 preoperative cryoablation procedures on ultrasound-visible, node-negative (cN0) infiltrating ductal carcinomas (IDC). Standard diagnostic imaging included mammography and tomosynthesis, supplemented by ultrasound-guided biopsy. MRI was performed in patients with associated intraductal carcinoma (DCIS) and an invasive component on core needle biopsy (18 out of 22 cases). All tumors were tagged with ferromagnetic seeds. A triple-phase protocol (freezing-thawing-freezing) with Argon was used, with an average procedure duration of 40 min. A logistic regression model was applied to determine significant correlation between RIC and the study variables. RESULTS: Fifty-nine women (mean age 63 ± 8 years) with sixty low-risk unifocal IDC underwent cryoablation prior to surgery. Pathological examination of lumpectomy specimens post-cryoablation revealed RIC in only one of 38 patients with pure IDC and in 4 of 22 mixed IDC/DCIS cases. All treated tumors had clear surgical margins, with no significant procedural complications. CONCLUSIONS: Cryoablation was effective in eradicating 97% of pure infiltrating ER + /HER2-tumors ≤ 2cm, demonstrating its potential as a surgical alternative in selected patients.

Determination of Factors Associated with Upstage in Atypical Ductal Hyperplasia to Identify Low-Risk Patients Where Active Surveillance May be an Alternative.

BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, "regional"; OR 19.28, 95% CI 3.47-106.97, p < 0.001, "linear"). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.

Tracking dynamic evolution of low- and intermediate-risk differentiated thyroid cancer: Identification of individuals at risk of recurrence.

OBJECTIVE: The generally good prognosis of low- and intermediate-risk differentiated thyroid cancer (DTC) underscored the need to identify those few patients who relapse. DESIGN: Records of 299 low- or intermediate-risk DTC patients (mean follow-up 8.2 ± 6.2 years) were retrospectively reviewed. The sample was classified following the American Thyroid Association (ATA) dynamic risk stratification (DRS) system. PATIENTS AND MEASUREMENT: After classifying patients according to DRS at the first visit following initial therapy (FU1), structural recurrence occurred in 2/181 (1.1%), 5/81 (6.2%) and 13/26 (50.0%) with excellent, indeterminate and biochemical incomplete response to treatment, respectively. All relapses but one happened within 5 years from FU1. Univariate analysis comparing excellent, indeterminate and biochemical incomplete with structural incomplete responses at the end of the follow-up, identified tumour size (p < .001), T status (<0.001), positive lymph nodes (N) (p < .01), multifocality (p < .004), need of additional radioactive iodine (RAI) (p < .0001) and first DRS status (p < .0003) as risk factors of recurrence. In the multivariate analysis, only RAI remained statistically significant (p < .02). Comparison between excellent and indeterminate with biochemical and structural incomplete responses, identified tumour size (p < .0004), T (p < .01), N (p < .0001), bilaterality (p < .03), first DRS status (p < .0001) and RAI (p < .001) as recurrence risk factors. T (p < .01) and first DRS (p < .0006) were confirmed in the multivariate analysis. CONCLUSIONS: Patients with DTC classified as low- or intermediate-risk of recurrence with excellent response to treatment at FU1 rarely develop structural disease and this occurs almost exclusively in the first 5 years. Initial DRS status is an accurate tool for determining the risk of recurrence.

Radiotherapy in localized prostate cancer: a multicenter analysis evaluating tumor control and late toxicity after brachytherapy and external beam radiotherapy in 1293 patients.

BACKGROUND AND PURPOSE: Comparing oncological outcomes and toxicity after primary treatment of localized prostate cancer using HDR- or LDR-mono-brachytherapy (BT), or conventionally (CF) or moderately hypofractionated (HF) external beam radiotherapy. MATERIALS AND METHODS: Retrospectively, patients with low- (LR) or favorable intermediate-risk (IR) prostate cancer treated between 03/2000 and 09/2022 in two centers were included. Treatment was performed using either CF with total doses between 74 and 78 Gy, HF with 2.4-2.6 Gy per fraction in 30 fractions, or LDR- or HDR-BT. Biochemical control (BC) according to the Phoenix criteria, and late gastrointestinal (GI), and genitourinary (GU) toxicity according to RTOG/EORTC criteria were assessed. RESULTS: We identified 1293 patients, 697 with LR and 596 with IR prostate cancer. Of these, 470, 182, 480, and 161 were treated with CF, HF, LDR-BT, and HDR-BT, respectively. For BC, we did not find a significant difference between treatments in LR and IR (p = 0.31 and 0.72). The 5­year BC for LR was between 93 and 95% for all treatment types. For IR, BC was between 88% in the CF and 94% in the HF group. For CF and HF, maximum GI and GU toxicity grade ≥ 2 was between 22 and 27%. For LDR-BT, we observed 67% grade ≥ 2 GU toxicity. Maximum GI grade ≥ 2 toxicity was 9%. For HDR-BT, we observed 1% GI grade ≥ 2 toxicity and 19% GU grade ≥ 2 toxicity. CONCLUSION: All types of therapy were effective and well received. HDR-BT caused the least late toxicities, especially GI.

Thirty years of active surveillance for low-risk thyroid cancer, lessons learned and future directions.

Active Surveillance is a non-invasive strategy designed to identify a minority of patients with low-risk papillary thyroid carcinoma who might experience clinical progression and benefit from additional definitive treatments. Global experience suggests that these tumors typically show minimal changes in size during active surveillance, often demonstrating very slow growth or even size reduction. Moreover, the rate of lymph node metastases is low and can be effectively managed through rescue surgery, without impacting cancer-related mortality. However, despite 30 years of experience demonstrating the safety and feasibility of active surveillance for appropriately selected patients, this approach seems to have limited adoption in specific contexts. This limitation can be attributed to various barriers, including disparities in access to accurate information about the indolent nature of this disease and the prevalence of a maximalist mindset among certain patients and medical settings. This review aims to revisit the experience from the last three decades, provide current insights into the clinical outcomes of active surveillance trials, and propose a systematic approach for its implementation. Furthermore, it intends to emphasize the importance of precise patient selection and provides new perspectives in the field.

A nomogram for predicting adverse pathologic features in low-risk papillary thyroid microcarcinoma.

BACKGROUND: Identifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients. METHODS: A total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors. RESULTS: Most PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p < 0.05). Other factors (age, gender, family history of thyroid cancer, history of autoimmune thyroiditis, and BRAFV600E mutation) had no significant correlation with adverse pathologic features (p > 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAFV600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580-0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit. CONCLUSION: Tumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.

RAI therapy in low-risk papillary thyroid cancer: recurrence reduction and long-term outcomes in the Turkish population.

PURPOSE: Papillary thyroid cancer (PTC) is the most common thyroid malignancy, characterized by its slow progression and favorable prognosis. This study re-evaluates the efficacy of radioactive iodine (RAI) therapy versus no RAI in low-risk PTC patients following total thyroidectomy. METHODS: A retrospective analysis was conducted on 588 patients treated between 2010 and 2016 at a major tertiary center in Turkey. Patients were divided into two cohorts: those receiving total thyroidectomy (TT) with high-dose RAI (100 mCi) and those receiving TT alone. A matched cohort of 138 patients per group was analyzed to minimize bias. RESULTS: Follow-up data indicated that at 24 months, the RAI group demonstrated a higher percentage of excellent treatment responses (86%) compared to the non-RAI group (74%). Long-term follow-up showed that 99.3% of the RAI group achieved no evidence of disease (NED), versus 90.6% in the non-RAI group. Recurrence rates were significantly lower in the RAI group (1%) compared to the non-RAI group (5.8% with a > 2.0 ng/ml cut-off for biological events). CONCLUSION: In summary, the findings from this study underscore the efficacy of RAI therapy in reducing recurrence rates and enhancing long-term disease control in low-risk papillary thyroid cancer patients. While total thyroidectomy alone is effective, the addition of RAI therapy provides a marked improvement in treatment responses and reduces the risk of disease recurrence. This indicates that personalized treatment plans incorporating RAI may offer significant advantages in managing low-risk PTC.

Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis.

The association between patient and disease characteristics, and the risk of disease progression in patients with prostate cancer on active surveillance.

PURPOSE: The objective of this study was to identify and assess patient and disease characteristics associated with an increased risk of disease progression in men with prostate cancer on active surveillance. METHODS: We studied patients with low-risk (ISUP GG1) or favorable intermediate-risk (ISUP GG2) PCa. All patients had at least one repeat biopsy. Disease progression was the primary outcome of this study, based on pathological upgrading. Univariate and multivariate Cox proportional hazard analyses were used to evaluate the association between covariates and disease progression. RESULTS: In total, 240 men were included, of whom 198 (82.5%) were diagnosed with low-risk PCa and 42 (17.5%) with favorable intermediate-risk PCa. Disease progression was observed in 42.9% (103/240) of men. Index lesion > 10 mm (HR = 2.85; 95% CI 1.74-4.68; p < 0.001), MRI (m)T-stage 2b/2c (HR = 2.52; 95% CI 1.16-5.50; p = 0.02), highest PI-RADS score of 5 (HR 3.05; 95% CI 1.48-6.28; p = 0.002) and a higher PSA level (HR 1.06; 95% CI 1.01-1.11; p = 0.014) at baseline were associated with disease progression on univariate analysis. Multivariate analysis showed no significant baseline predictors of disease progression. CONCLUSION: In AS patients with low-risk or favorable intermediate-risk PCa, diameter of index lesion, MRI (m)T-stage, height of the PI-RADS score and the PSA level at baseline are significant predictors of disease progression to first repeat biopsy.

Human Papilloma Virus Infection and Gene Subtypes Analysis in Women Undergoing Physical Examinations: A 2015-2020 Study in Wenzhou, China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is closely related to cervical cancer. The epidemiologic characteristics of cervical HPV have regional differences. Therefore, it is necessary to develop the most favorable policies according to the actual situation of each region to prevent and reduce the prevalence of cervical cancer. This retrospective cross-sectional study investigated the prevalence, gene subtypes, and temporal trends of HPV in women undergoing physical examination in Wenzhou, to provide a decision-making basis for further prevention and control of HPV. METHODS: A total of 31 131 cervical exfoliated cell specimens obtained from physical examinations in Wenzhou, a coastal city of China, from 2015 to 2020 were collected. The age distribution was analyzed using the chi-squared test, and the time change trend was analyzed using the Mann-Kendall trend test. On this basis, the distribution characteristics of the HPV subtypes were analyzed. RESULTS: The total prevalence rate was 9.55%, and the prevalence rate in different age groups ranged from 7.77% to 14.16%. The prevalence rate in different years was 8.84%-11.83%. The prevalence rate was bimodal; it was highest in the group 25 years old, followed by the group >61 years old. The top five high-risk gene subtypes were HPV52, HPV58, HPV53, HPV16, and HPV39, whereas the low-risk subtypes were HPV61, HPV81, HPV44, HPV43, and HPV55. Of all the positive samples, 76.03% were infected with a high-risk subtype. CONCLUSION: Most female HPV patients in Wenzhou are infected with high-risk gene subtypes. Therefore, physical examination and screening for HPV should be further strengthened, and the corresponding vaccination policy should focus on high-risk gene subtypes.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is closely related to the occurrence of cervical cancer. The epidemic characteristics of cervical HPV have regional differences, Therefore, it is necessary to formulate the most favorable policies according to the actual situation of each region, so as to prevent and reduce the prevalence of cervical cancer. This retrospective cross-sectional study investigated the prevalence, gene subtypes and temporal trends of HPV in women undergoing physical examination in Wenzhou. To provide decision-making basis for further prevention and control of HPV. METHODS: A total of 31,131 cervical exfoliated cell specimens obtained from physical examinations in Wenzhou, a coastal city of China from 2015 to 2020, were collected. The age distribution was analyzed by the chi-squared test, and the time change trend was analyzed by the Mann­Kendall trend test. On this basis, the distribution characteristics of HPV subtypes were analyzed. RESULTS: The total prevalence rate was 9.55%, and the prevalence rate in different age groups ranged from 7.77% to 14.16%. The prevalence rate in different years was 8.84%-11.83%. The prevalence rate was bimodal; it was highest in the group less than or equal to 25 years old, followed by the group greater than 61 years old. The top five high-risk gene subtypes were HPV52, HPV58, HPV53, HPV16 and HPV39, while for low-risk were HPV61, HPV81, HPV44, HPV43 and HPV55, respectively. Of all the positive samples, 76.03% were infected with a high-risk subtype.

MRI characteristics predict risk of pathological upgrade in patients with ISUP grade group 1 prostate cancer.

OBJECTIVE: This study aims to analyse multiparametric MRI (mpMRI) characteristics of patients diagnosed with ISUP grade group (GG) 1 prostate cancer (PC) on initial target plus systematic MRI/TRUS fusion-guided biopsy and investigate histopathological progression during follow-up. METHODS: A retrospective single-centre cohort analysis was conducted on consecutive patients with mpMRI visible lesions (PI-RADS ≥ 3) and detection of ISUP-1-PC at the time of initial biopsy. The study assessed clinical, mpMRI, and histopathological parameters. Subcohorts were analysed with (1) patients who had confirmed ISUP-1-PC and (2) patients who experienced histopathological upgrading to ISUP ≥ 2 PC during follow-up either at re-biopsy or radical prostatectomy (RP). RESULTS: A total of 156 patients (median age 65 years) between March 2014 and August 2021 were included. Histopathological upgrading to ISUP ≥ 2 was detected in 55% of patients during a median follow-up of 9.5 months (IQR 2.2-16.4). When comparing subgroups with an ISUP upgrade and sustained ISUP 1 PC, they differed significantly in contact length of the index lesion to the pseudocapsule, ADC value, PI-RADS category, and the MRI grading group (mGG) (p < 0.05). In the ISUP GG ≥ 2 subgroup, 91% of men had PI-RADS category 4 or 5 and 82% exhibited the highest mGG (mGG3). In multivariate analysis, mGG was the only independent parameter for predicting ISUP ≥ 2-PC in these patients. CONCLUSIONS: MRI reveals important information about PC aggressiveness and should be incorporated into clinical decision-making when ISUP-1-PC is diagnosed. In cases of specific MRI characteristics adverse to the histopathology, early re-biopsy might be considered. CLINICAL RELEVANCE STATEMENT: In cases with clear MRI characteristics for clinically significant prostate cancer (e.g., mGG 3 and/or PI-RADS 5, cT3, or clear focal PI-RADS 4 lesions on MRI) and ISUP GG 1 PC diagnosed on initial prostate biopsy, MRI findings should be incorporated into clinical decision-making and early re-biopsy (e.g., within 6 months) might be considered. KEY POINTS: MRI reveals important information about prostate cancer (PC) aggressiveness. MRI should be incorporated into clinical decision-making when ISUP GG 1 PC is diagnosed on initial prostate biopsy. In cases of specific MRI characteristics adverse to the histopathology, early re-biopsy might be considered.

Targets for De-implementation of Unnecessary Testing Before Low-Risk Surgery: A Qualitative Study.

INTRODUCTION: Despite multispecialty recommendations to avoid routine preoperative testing before low-risk surgery, the practice remains common and de-implementation has proven difficult. The goal of this study as to elicit determinants of unnecessary testing before low-risk surgery to inform de-implementation efforts. METHODS: We conducted focused ethnography at a large academic institution, including semi-structured interviews and direct observations at two preoperative evaluation clinics and one outpatient surgery center. Themes were identified through narrative thematic analysis and mapped to a comprehensive and integrated checklist of determinants of practice, the Tailored Implementation for Chronic Diseases framework (TICD). RESULTS: Thirty individuals participated (surgeons, anesthesiologists, primary care physicians, physician assistants, nurses, and medical assistants). Three themes were identified: (1) Shared Values (TICD Social, Political, and Legal Factors), (2) Gaps in Knowledge (TICD Individual Health Professional Factors, Guideline Factors), and (3) Communication Breakdown (TICD Professional Interactions, Incentives and Resources, Capacity for Organizational Change). Shared Values describe core tenets expressed by all groups of clinicians, namely prioritizing patient safety and utilizing evidence-based medicine. Clinicians had Gaps in Knowledge related to existing data and preoperative testing recommendations. Communication Breakdowns within interdisciplinary teams resulted in unnecessary testing ordered to meet perceived expectations of other providers. CONCLUSIONS: Clinicians have knowledge gaps related to preoperative testing recommendations and may be amenable to de-implementation efforts and educational interventions. Consensus guidelines may streamline interdisciplinary communication by clarifying interdisciplinary needs and reducing testing ordered to meet perceived expectations of other clinicians.

Usefulness of a predictive model to hospitalize patients with low-risk community-acquired pneumonia.

INTRODUCTION: A high proportion of patients with low-risk community-acquired pneumonia (CAP) (classes I-III of the Pneumonia Severity Index) are hospitalized. The purpose of this study was to determine whether validated severity scales are used in clinical practice to make admission decisions, identify the variables that influence this decision, and evaluate the potential predictive value of these variables. MATERIALS AND METHODS: A prospective, observational study of patients ≥ 18 years of age with a diagnosis of low-risk CAP hospitalized or referred from the Emergency Department to outpatient consultations. A multivariate logistic regression predictive model was built to predict the decision to hospitalize a patient. RESULTS: The study population was composed of 1,208 patients (806 inpatients and 402 outpatients). The severity of CAP was estimated in 250 patients (20.7%). The factors that determined hospitalization were "abnormal findings in complementary studies" (643/806: 79.8%; due to respiratory failure in 443 patients) and "signs of clinical deterioration" [64/806 (7.9%): hypotension (16/64, 25%); hemoptoic expectoration (12/64, 18.8%); tachypnea (10/64, 15.6%)]. In total, ambulatory management was not contraindicated in 24.7% of hospitalized patients (199). The predictive model built to decide about hospitalization had a good power of discrimination (AUC 0.876; 95%CI: 0.855-0.897). CONCLUSIONS: Scales are rarely used to estimate the severity of CAP at the emergency department. The decision to hospitalize or not a patient largely depends on the clinical experience of the physician. Our predictive model showed a good power to discriminate the patients who required hospitalization. Further studies are warranted to validate these results.