Search Results (1,251)

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

With the in-depth application of digital transformation in the oil industry, data-driven methods provide a new technical path for drilling engineering safety evaluation. In this paper, a data-driven drilling safety level evaluation system is proposed. By integrating the three-dimensional visualization technology of wellbore trajectory and the prediction model of friction torque, a dynamic and intelligent drilling risk evaluation framework is constructed. The Python platform is used to integrate geomechanical parameters, real-time drilling data, and historical working condition records, and the machine learning algorithm is used to train the friction torque prediction model to improve prediction accuracy. Based on the K-means clustering evaluation method, a three-tier drilling safety classification standard is established: Grade I (low risk) for friction (0–100 kN) and torque (0–10 kN·m), Grade II (medium risk) for friction (100–200 kN) and torque (10–20 kN·m), and Grade III (high risk) for friction (>200 kN) and torque (>20 kN·m). This enables intelligent quantitative evaluation of drilling difficulty. The system not only dynamically optimizes bottom-hole assembly (BHA) and drilling parameters but also continuously refines the evaluation model’s accuracy through a data backtracking mechanism. This provides a reliable theoretical foundation and technical support for risk early warning, parameter optimization, and intelligent decision-making in drilling engineering. Full article

Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome (NS) in adults, and it can be primary (idiopathic) with an unknown cause or secondary due to a variety of conditions (lupus, infections, malignancies, medications, etc.). It progresses to chronic kidney disease (CKD) in up to 60% of patients, and 10 to 30% develop end-stage kidney disease (ESKD). This retrospective study examines the importance of specific factors, including baseline demographic and clinical data, kidney biopsy PH findings, and selected biochemical parameters, influencing MN outcomes after 10 years of follow-up. The cohort included 94 individuals in whom a diagnosis of MN was established by percutaneous biopsy of the left kidney’s lower pole at the University Clinical Center of Serbia (UCCS) between 2008 and 2013. According to the outcomes, patients were divided into three groups: the recovery (Rec) group, with complete remission, including normal serum creatinine (Scr) and proteinuria (Prt), the group with development of chronic kidney disease (CKD), and the group with development of end-stage kidney disease (ESKD). Nephropathologists graded pathohistological (PH) results from I to III based on the observed PH findings. During the follow-up period, 33 patients were in the Rec group, CKD developed in 53 patients, and ESKD developed in 8 patients. Baseline creatinine clearance levels (Ccr), Scr, and uric acid (urate) were found to be significantly associated with the outcomes (p < 0.001). The lowest values of baseline Scr and urate were observed in the Rec group. The presence of acute kidney injury (AKI) or CKD at the time of kidney biopsy was associated with the more frequent development of ESKD (p = 0.02). Lower Ccr was associated with a higher likelihood of progressing to CKD (B = −0.021, p = 0.014), whereas older age independently predicted progression to ESKD (B = 0.02, p = 0.032). Based on this study, it was concluded that the most important biochemical and clinical factors that are associated with the outcomes of this disease are the values of Scr, Ccr, and urate and the existence of CKD at the time of kidney biopsy. Unlike most previous studies, the presence of HTN had no statistical significance in the outcome of the disease. Full article

Background: Doppler-guided haemorrhoidal artery ligation with rectoanal repair (HAL-RAR) is a minimally invasive alternative to conventional haemorrhoidectomy. While associated with reduced postoperative pain and quicker recovery, data on its safety, recurrence rates, and applicability across haemorrhoid grades remain limited, particularly in Australian settings. Methods: A retrospective review was conducted on 128 consecutive patients who underwent elective HAL-RAR at a single institution between February 2022 and December 2024. Data on demographics, operative details, postoperative outcomes, and recurrence were collected. Outcomes were stratified by haemorrhoid grade. Multivariate logistic regression was used to identify predictors of recurrence, day-case completion, and conversion to excisional surgery. Results: The median age was 49 years, and 77.3% had Grade II or III haemorrhoids. HAL-RAR was completed as a day case in 76.6% of patients. Postoperative urinary retention occurred in 3.9%, return to theatre in 0.8%, and 30-day readmission in 7.0%. The symptomatic recurrence rate was 17.6%. Grade IV haemorrhoids were independently associated with increased recurrence (aOR 3.64, 95% CI 1.03–12.84), reduced likelihood of day-case management (aOR 0.14, 95% CI 0.03–0.93), and higher conversion to excisional haemorrhoidectomy (aOR 7.23, 95% CI 1.13–46.40). Conclusions: HAL-RAR is a safe, effective, and low-morbidity option for the management of Grade II and III haemorrhoids, suitable for day-case surgery. In selected Grade IV cases, it may offer benefit, although with higher recurrence and conversion risk. Careful patient selection is essential, and longer-term prospective studies are needed to assess durability. Full article

With climate change, the spatial and temporal patterns of precipitation are altered to a certain degree, which potentially affects the grey water footprint (GWF) of total nitrogen (TN) in agriculture, thereby threatening water security in the Yangtze River Basin (YRB), the largest river in China. The current study constructs an assessment framework for climate change impacts on the GWF of agricultural TN by coupling Shared Socioeconomic Pathways (SSPs) with the InVEST model. The framework consists of four components: (i) data collection and processing, (ii) simulating the two critical indicators (L_TN and W) in the GWF model based on the InVEST model, (iii) calculating the GWF and GWF index (GI) of TN, and (iv) calculating climate change impact index on GWF of agricultural TN (CI) under two SSPs. It is applied to the YRB, and the results show the following: (i) GWFs are 959.7 and 961.4 billion m³ under the SSP1-2.6 and SSP5-8.5 climate scenarios in 2030, respectively, which are both lower than that in 2020 (1067.1 billion m³). (ii) The GI values for TN in 2030 under SSP1-2.6 and SSP5-8.5 remain at “High” grade, with the values of 0.95 and 1.03, respectively. Regionally, the water pollution level of Taihu Lake is the highest, while that of Wujiang River is the lowest. (iii) The CI values of the YRB in 2030 under SSP1-2.6 and SSP5-8.5 scenarios are 0.507 and 0.527, respectively. And the CI values of the five regions in the YRB are greater than 0, indicating that the negative effects of climate change on GWFs increase. (iv) Compared with 2020, L_TN and W in YRB in 2030 under the two SSPs decrease, while the GI of TN in YRB rises from SSP1-2.6 to SSP5-8.5. The assessment framework can provide strategic recommendations for sustainable water resource management in the YRB and other regions globally under climate change. Full article

Cultivated land quality is a key factor in ensuring sustainable agricultural development. Exploring differences in cultivated land quality under distinct cropping systems is essential for developing targeted improvement strategies. This study takes place in Shenyang City—located in the typical black soil region of Northeast China—as a case area to construct a cultivated land quality evaluation system comprising 13 indicators, including organic matter, effective soil layer thickness, and texture configuration. A minimum data set (MDS) was separately extracted for paddy and upland fields using principal component analysis (PCA) to conduct a comprehensive evaluation of cultivated land quality. Additionally, an obstacle degree model was employed to identify the limiting factors and quantify their impact. The results indicated the following. (1) Both MDSs consisted of seven indicators, among which five were common: ≥10 °C accumulated temperature, available phosphorus, arable layer thickness, irrigation capacity, and organic matter. Parent material and effective soil layer thickness were unique to paddy fields, while landform type and soil texture were unique to upland fields. (2) The cultivated land quality index (CQI) values at the sampling point level showed no significant difference between paddy (0.603) and upland (0.608) fields. However, their spatial distributions diverged significantly; paddy fields were dominated by high-grade land (Grades I and II) clustered in southern areas, whereas uplands were primarily of medium quality (Grades III and IV), with broader spatial coverage. (3) Major constraint factors for paddy fields were effective soil layer thickness (21.07%) and arable layer thickness (22.29%). For upland fields, the dominant constraints were arable layer thickness (27.57%), organic matter (25.40%), and ≥10 °C accumulated temperature (23.28%). Available phosphorus and ≥10 °C accumulated temperature were identified as shared constraint factors affecting quality classification in both systems. In summary, cultivated land quality under different cropping systems is influenced by distinct limiting factors. The construction of cropping-system-specific MDSs effectively improves the efficiency and accuracy of cultivated land quality assessment, offering theoretical and methodological support for land resource management in the black soil regions of China. Full article

Background/Objectives: Mutations in the BRCA1 and BRCA2 genes are well-known risk factors for ovarian cancer. They are also associated with response to platinum-based chemotherapy; however, their definitive impact on patient prognosis remains not fully understood. This study aimed to investigate the influence of BRCA mutation status on the age of ovarian cancer onset and on treatment outcomes in patients with high-grade serous ovarian cancer. Methods: This single-center retrospective analysis included newly diagnosed FIGO stage III and IV HGSOC patients treated between June 2018 and April 2023. Patients’ age, tumor histology, CA125 levels, BRCA mutation status, type of treatment (neoadjuvant or adjuvant chemotherapy), and surgical outcomes were collected and analyzed. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Results: Pathogenic mutations were identified in 25 patients (15 in BRCA1, 10 in BRCA2). Patients with a BRCA mutation were diagnosed at a significantly younger age (median 58.78 years) compared to non-carriers (66.81 years; p < 0.001), with BRCA1 carriers being diagnosed the youngest (median 46.52 years). The study found no statistically significant difference in progression-free survival (PFS) between BRCA carriers and non-carriers. However, a significant improvement in overall survival (OS) was observed for patients with a BRCA1 mutation (p = 0.036). No significant OS difference was found for BRCA2 carriers. Conclusions: BRCA mutations, particularly in the BRCA1 gene, are associated with an earlier onset ovarian cancer. BRCA1 mutation appears to be a favorable prognostic factor for overall survival in patients with HGSOC. Our findings demonstrate the clinical implications of different BRCA mutations and support the need for further research in larger cohorts to confirm their influence on prognostic effects. Full article

Background: Renal trauma accounts for approximately 3–5% of all trauma cases, predominantly affecting young males. The most common etiology is blunt trauma, particularly due to road traffic accidents, and it frequently occurs as part of polytrauma involving multiple organ systems. Management strategies are primarily dictated by hemodynamic stability, overall clinical condition, comorbidities, and injury severity graded according to the AAST classification. This study aimed to evaluate the effectiveness of non-operative management (NOM) in high-grade renal trauma (AAST grades III–V), beyond its established role in low-grade injuries (grades I–II). Secondary endpoints included the identification of independent prognostic factors for NOM failure and in-hospital mortality. Methods: We conducted a retrospective observational study including patients diagnosed with blunt renal trauma who presented to the Emergency Department of Policlinico Umberto I in Rome between 1 January 2013 and 30 April 2024. Collected data comprised demographics, trauma mechanism, vital signs, hemodynamic status (shock index), laboratory tests, blood gas analysis, hematuria, number of transfused RBC units in the first 24 h, AAST renal injury grade, ISS, associated injuries, treatment approach, hospital length of stay, and mortality. Statistical analyses, including multivariable logistic regression, were performed using SPSS v28.0. Results: A total of 244 patients were included. Low-grade injuries (AAST I–II) accounted for 43% (n = 105), while high-grade injuries (AAST III–V) represented 57% (n = 139). All patients with low-grade injuries were managed non-operatively. Among high-grade injuries, 124 patients (89%) were treated with NOM, including observation, angiography ± angioembolization, stenting, or nephrostomy. Only 15 patients (11%) required nephrectomy, primarily due to persistent hemodynamic instability. The overall mortality rate was 13.5% (33 patients) and was more closely associated with the overall injury burden than with renal injury severity. Multivariable analysis identified shock index and active bleeding on CT as independent predictors of NOM failure, whereas ISS and age were significant predictors of in-hospital mortality. Notably, AAST grade did not independently predict either outcome. Conclusions: In line with the current international literature, our study confirms that NOM is the treatment of choice not only for low-grade renal injuries but also for carefully selected hemodynamically stable patients with high-grade trauma. Our findings highlight the critical role of physiological parameters and overall ISS in guiding management decisions and underscore the need for individualized assessment to minimize unnecessary nephrectomies and optimize patient outcomes. Full article

The deformation characteristics of the surrounding rock in tunnel groups are considered critical for the design of support structures and the assurance of the long-term safety of deep-buried diversion tunnels. The deformation behavior of surrounding rock in tunnel groups was investigated to guide structural support design. Field tests and numerical simulations were performed to analyze the distribution of ground stress and the ground reaction curve under varying conditions, including rock type, tunnel spacing, and burial depth. A solid unit–structural unit coupled simulation approach was adopted to derive the two-liner support characteristic curve and to examine the propagation behavior of concrete cracks. The influences of surrounding rock strength, reinforcement ratio, and secondary lining thickness on the bearing capacity of the secondary lining were systematically evaluated. The following findings were obtained: (1) The tunnel group effect was found to be negligible when the spacing (D) was ≥65 m and the burial depth was 1600 m. (2) Both P_0.3 and P_max of the secondary lining increased linearly with reinforcement ratio and thickness. (3) For surrounding rock of grade III (IV), 95% u_lim and 90% u_lim were found to be optimal support timings, with secondary lining forces remaining well below the cracking stress during construction. (4) For surrounding rock of grade V in tunnels with a burial depth of 200 m, 90% u_lim is recommended as the initial support timing. Support timings for tunnels with burial depths between 400 m and 800 m are 40 cm, 50 cm, and 60 cm, respectively. Design parameters should be adjusted based on grouting effects and monitoring data. Additional reinforcement is recommended for tunnels with burial depths between 1000 m and 2000 m to improve bearing capacity, with measures to enhance impermeability and reduce external water pressure. These findings contribute to the safe and reliable design of support structures for deep-buried diversion tunnels, providing technical support for design optimization and long-term operation. Full article

Cellulite, characterised by cutaneous dimpling, surface irregularities, and dermal atrophy skin texture, affects up to 90% of post-pubertal females. It is a multifactorial condition involving anatomical, hormonal, and metabolic components, primarily affecting the thighs and buttocks. Despite numerous available therapies, there remains a high demand for effective, non-invasive, and well-tolerated treatment options. This single-centre, in vivo, prospective study evaluated the efficacy of a non-pharmacological, thermogenic topical cream-gel combined with manual massage in women with symmetrical grade II or III cellulite (Nürnberger–Müller scale). A total of 56 female participants (aged 18–55 years) were enrolled and instructed to apply the product twice daily for eight weeks to the thighs and buttocks. Efficacy was assessed using instrumental skin profilometry (ANTERA^® 3D CS imaging system), dermatological clinical grading, and patient self-assessment questionnaires. Quantitative analysis showed a mean reduction of 23.5% in skin indentation volume (p < 0.01) and a mean decrease of 1.1 points on the cellulite severity scale by week 8. Patient-reported outcomes revealed 85.7% satisfaction with visible results and 91% satisfaction with product texture and ease of application. Dermatological evaluation confirmed no clinically significant adverse reactions, and only 3.5% of participants reported mild and transient skin sensitivity. These findings suggest that this topical cream-gel formulation, when used in conjunction with manual massage, represents a well-tolerated and non-invasive option for the cosmetic improvement of moderate to severe cellulite. Full article

Background/Objectives: In gastric cancer, only a subset of patients benefit clinically from neoadjuvant chemoimmunotherapy, underscoring the need for robust biomarkers that can predict treatment responses and guide personalized immunotherapy. This study aimed to characterize the immune microenvironment of gastric tumors and identify predictive markers associated with therapeutic efficacy. Methods: We prospectively enrolled 16 patients with histologically confirmed, PD-L1–positive (CPS ≥ 1) gastric adenocarcinoma (T_2–4N_0–1M₀). All patients received eight cycles of FLOT chemotherapy combined with pembrolizumab. Treatment response was assessed by Mandard tumor regression grading. Spatial transcriptomic profiling (10x Genomics Visium) and multiplex immunofluorescence were used to evaluate tumor-infiltrating immune cell subsets and PD-1 expression at baseline and after treatment. Results: Transcriptomic analysis differentiated the immune landscapes of responders from non-responders. Responders exhibited elevated expression of IL1B, CXCL5, HMGB1, and IFNGR2, indicative of an inflamed tumor microenvironment and type I/II interferon signaling. In contrast, non-responders demonstrated upregulation of immunosuppressive genes such as LGALS3, IDO1, and CD55, along with enrichment in oxidative phosphorylation and antigen presentation pathways. Multiplex immunofluorescence confirmed a higher density of FoxP3⁺ regulatory T cells in non-responders (median 5.36% vs. 2.41%; p = 0.0032). Notably, PD-1⁺ CD8⁺ T cell and PD-1⁺ FoxP3⁺ Treg frequencies were significantly elevated in non-responders, suggesting that PD-1 expression within cytotoxic and regulatory compartments may contribute to immune evasion. No substantial differences were observed in PD-L1 CPS or PD-1⁺ B cells and PD-1⁺ macrophages. Conclusions: Our findings identify PD-1⁺ CD8⁺ T cells and PD-1⁺ FoxP3⁺ Tregs as potential biomarkers of resistance to neoadjuvant chemoimmunotherapy in gastric cancer. Transcriptional programs centered on IL1B/CXCL5 and LGALS3/IDO1 define distinct immune phenotypes that may guide future combination strategies targeting both effector and suppressive arms of the tumor immune response. Full article

Background: While carotid pathologies are well-established risk factors for stroke, their specific effects on outcomes following stroke that cannot be classified as atherosclerotic remain unclear. In this study, we aimed to determine whether carotid pathologies are associated with functional dependence (FD) 3 months after small vessel occlusion (SVO) stroke. Methods: This retrospective study included patients with a first-ever SVO stroke admitted to a single cerebrovascular-specialty hospital between October 2021 and March 2024. Standardized ultrasound criteria were used to grade the carotid plaques. The modified Rankin scale (mRS) was used to assess functional outcomes at 3 months. Logistic regression analysis was performed to identify FD predictors (mRS of ≥2). Results: Of the 372 included patients, 276 achieved functional independence and 96 experienced FD at 3 months. Univariable analysis revealed an association between carotid plaque grade III and FD (odds ratio [OR], 2.46; 95% confidence interval [CI], 1.05–6.51; p = 0.049). However, this association was not significant in the multivariable model. Overall, age (adjusted OR, 1.07; 95% CI 1.03–1.10, p < 0.001), NIHSS at initial presentation (adjusted OR, 1.84; 95% CI, 1.55–2.18; p < 0.001), and diabetes (adjusted OR, 2.84; 95% CI, 1.37–5.92; p = 0.005) were independently associated with FD 3 months after SVO stroke. Conclusions: Carotid plaque severity was not independently associated with functional outcomes 3 months after SVO stroke. Age, NIHSS at initial presentation, and diabetes were identified as independent FD predictors. Future in-depth studies are warranted to confirm the complex interplay of factors influencing functional outcomes in patients with SVO stroke and carotid pathologies simultaneously. Full article

To prevent the occurrence of excavation face instability incidents during shield tunneling, this study takes the Bailuyuan tunnel of the ‘Hanjiang-to-Weihe River Water Diversion Project’ as the engineering background. A three-dimensional discrete element method simulation was employed to analyze the tunneling process, revealing the displacement response of the excavation face to various tunneling parameters. This led to the development of a risk assessment method that considers both tunneling parameters and geological conditions for deep-buried shield tunnels. The above method effectively overcomes the limitations of finite element method (FEM) studies on shield tunneling parameters and, combined with the Analytic Hierarchy Process (AHP), enables rapid tunnel analysis and assessment. The results demonstrate that the displacement of the excavation face in shield tunnel engineering is significantly influenced by factors such as the chamber earth pressure ratio, cutterhead opening rate, cutterhead rotation speed, and tunneling speed. Specifically, variations in the chamber earth pressure ratio have the greatest impact on horizontal displacement, occurring predominantly near the upper center of the tunnel. As the chamber earth pressure ratio decreases, horizontal displacement increases sharply from 12.9 mm to 267.3 mm. Conversely, an increase in the cutterhead opening rate leads to displacement that first rises gradually and then rapidly, from 32.1 mm to 121.1 mm. A weighted index assessment model based on AHP yields a risk level of Grade II, whereas methods from other scholars result in Grade III. By implementing measures such as adjusting the grouting range, cutterhead rotation speed, and tunneling speed, field applications confirm that the risk level remains within acceptable limits, thereby verifying the feasibility of the constructed assessment method. Construction site strategies are proposed, including maintaining a chamber earth pressure ratio greater than 1, tunneling speed not exceeding 30 mm/min, cutterhead rotation speed not exceeding 1.5 rpm, and a synchronous grouting range of 0.15 m. Following implementation, the tunnel construction successfully passed the high-risk section without any incidents. This research offers a decision-making framework for shield TBM operation safety in complex geological environments. Full article

BE following RT after breast-conserving surgery is a common concern, impacting patients’ quality of life. This study introduces a clinically meaningful classification system for BE and retrospectively evaluates its incidence among patients treated with normofractionated (nfRT) and hypofractionated (hfRT) regimens. Data from 1156 patients treated between 2011 and 2021 were analyzed. BE was graded according to the CTC and a so-called “WST classification” (grade 1: lymphatic drainage performed by the patient; grade 2: professional lymphatic drainage; grade 3: surgery). A total of 33%/17% developed BE according to the WST classification/CTC. Grade III BE was not reported. About 70% experienced a remission of BE during follow-up. Risk factors for the development of BE included RT of lymphatic drainage, complete axillary dissection compared to sentinel node dissection, and CTX. CTX was not confirmed in multivariate analysis. The incidence of BE did not differ significantly between the nfRT and hfRT groups, affirming the safety and comparability of hfRT regarding BE risk (HR: 0.833, p = 0.1219). This study emphasizes the importance of precise and standardized BE classification for improved treatment outcomes. Given its comparable risk profile and potential for enhanced therapy adherence, the findings support hfRT as a preferred regimen aligned with the current guidelines. Full article

Purpose: Neoadjuvant endocrine therapy (NET) represents a valuable treatment option for hormone receptor-positive (HR+)/HER2-negative breast cancer, particularly in postmenopausal women. This study aimed to evaluate the clinical and histopathological efficacy of NET and to explore early and late changes in Ki-67 and progesterone receptor (PgR) expression as indicators of endocrine response. Methods: A prospective cohort of 127 postmenopausal patients with stage cT1–4N0–3M0 HR+/HER2− breast cancer was enrolled between 2019 and 2021. Patients received NET (mostly letrozole) for a mean of 7.7 months. In 80 cases, a second core biopsy was performed after four weeks. Tumor size, histological grade, and biomarkers (Ki-67, PgR) were assessed pre- and post-treatment. Results: NET led to a significant reduction in tumor size, with median shrinkage of 47.0% (from 32.0 mm to 17.0 mm, p < 0.0001). Breast-conserving surgery (BCS) was performed in 52.2% of patients and lymph node negativity (pN0) was observed in 50.4%. Median Ki-67 decreased from 20.0% at baseline to 5.0% after four weeks (p < 0.0001) and remained low in surgical specimens (median 5.0%, p < 0.0001). In 33.3% of patients, Ki-67 dropped below 2.7%, and 67.0% showed a concordant decrease in both Ki-67 and PgR. PgR expression declined significantly during treatment (p < 0.0001). HER2 status conversion was noted in 6.4% of patients during treatment. Pathological complete response (pCR) occurred in 3.5%, while minimal or moderate residual disease (RCB I–II) was identified in 71.3% of cases. Conclusions: NET effectively reduced tumor burden and histological aggressiveness, enabling higher rates of BCS. Early reduction in Ki-67 and PgR may serve as surrogate markers of endocrine responsiveness, supporting their use for treatment stratification and monitoring during NET in HR+/HER2− breast cancer. Full article