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A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, p = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, p = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival ( p = 0.009) and overall survival ( p = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.

Abstract Background The ligamentum teres (LT) has received attention in patients undergoing hip arthroscopy (HA) for femoroacetabular impingement (FAI). Indeed, a better understanding of the function of the LT and its implications for clinical outcomes in the presence of a torn LT is required. This systematic review analyses the patient-reported outcome measures (PROMs) and the complication rate when an intact or torn LT is encountered during HA for FAI. Methods Studies that compared patients with an intact to those with a torn LT managed with debridement during hip arthroscopy for FAI were identified from the Web of Science, PubMed, and Embase. The minimum follow-up for inclusion was 24 months. The Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool was used to assess the risk of bias. Patient characteristics and PROMs were assessed at the baseline and last follow-up. Results The systematic review identified two studies comprising 611 patients. No statistically significant difference was found in pain, Harris Hip Score, and the activities of daily living and sports subscales of the Hip Outcome Score between patients with an intact LT and those with a torn LT treated with debridement, both of whom underwent HA for FAI. Conclusions In patients undergoing arthroscopic management for FAI, an intact or torn ligamentum teres managed with debridement does not influence postoperative PROMs. Given the importance of the LT as a structure of the hip joint and the increasing interest in HA for FAI, further standardised studies will be a valuable source for surgeons encountering this pathology.

Abstract Background Unicompartmental knee arthroplasty (UKA) is a surgical procedure for managing osteoarthritis of one joint compartment, most commonly the medial side. This systematic review investigates the causes of UKA revision. The outcomes of interest were establishing the revision rate, time to revision, and the most common causes of revision in the long- and midterm follow-up. Methods This study was conducted according to the 2020 PRISMA statement. In October 2024, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. All the clinical studies investigating the rate and causes of revision in UKA were accessed. Only studies with a minimum of 10 years of follow-up were considered. Results Data from 56 studies (13,540 patients) were collected. Of them, 65.6% were women. The mean length of the follow-up was 13.1 ± 3.0 years. The mean age of the patients was 65.6 ± 5.6 years, and the mean BMI was 28.5 ± 2.2 kg/m2. Revisions were performed in 8.8% (2641 of 30,140) of implanted UKAs. The mean time to revision was 6.5 ± 2.6 (range, 2.5 to 13.0) years. Conclusion 8.8% (2641 of 30,140) of UKAs were revised at a mean time of 6.5 ± 2.6 years. Level of evidence Level IV, systematic review.

Through the case of the amateur painter and engraver Gerolamo Imperiale, a Genoese patrician who, in the Parma of Ranuccio I Farnese, alternated university lectures at the Studium with attendance at the painters' workshops, the article intends to reflect on how amateurs were trained and their relationship with painters and the art market. Ubiquitous in seventeenth-century art literature, young members of the nobility who dabbled in painting, training alongside house painters or in the schools set up in the artists' studios, had the opportunity to engage in close contact with the work of their masters, but without being burdened by the professional constraints affecting collaborators and pupils, or by the impositions of patronage. With this in mind, we intend to examine the particular combinatorial freedom that Gerolamo Imperiale demonstrates in the invention engravings of his Parma years.

The study of motility control by smart agents offers a promising platform for systematically exploring the fundamental physical constraints underlying the functioning of bio-inspired micro-machines operating far from equilibrium. Here, we address the question of the energy expenditure required for a self-steering active agent to localise itself within a specific region of space or follow a pre-defined trajectory under the influence of fluctuations and external flows. Building on a stochastic thermodynamic formulation of the problem, we derive a generic relationship between dissipation and localisation accuracy, which reveals a fundamental dissipation-accuracy tradeoff constraining the agent’s performance. In addition, we illustrate how our framework enables the derivation of optimal steering policies that achieve localisation at minimum energy expenditure.

Soil salinity is considered one of the most limiting factors in large agricultural areas, and tomato (Solanum lycopersicum L.) is highly sensitive to this abiotic stress, which exacerbates under drought. The use of halotolerant PGPR is a promising strategy to enhance tomato tolerance and productivity in saline soils. The present study tested the capability of the recently discovered bacterial strain PVr_9 to increase tolerance to salinity in tomato plants in vitro, greenhouse and open field conditions. When inoculated with PVr_9, in vitro seedlings showed a significant increase in primary root length, number of secondary roots and fresh weight both in absence of stress and when exposed to 150 mM NaCl. In plants exposed to salt treatment, PVr_9 upregulated the salt tolerance genes SOS1 and NHX1, and the enzyme prolyl aminopeptidase involved in proline metabolism. Proteins associated with resistance against pathogens were also upregulated by PVr_9 in absence of salt stress. In greenhouse, PVr_9-inoculated tomato plants treated for 1-week with 150 mM NaCl showed a significant increase in shoot fresh biomass, chlorophyll, proline content, and APX activity. Tomato fruits from PVr_9 inoculated plants, exposed in the field to salt stress during the flowering stage, showed higher levels of carotenoids, lycopene, and l-ascorbic acid, as well as an increased antioxidant capacity compared to fruits of uninoculated plants. These results indicate PVr_9 as a potential biostimulant in tomato for better tackling soil salinization in a context of climate change and expansion of coastal salinity, while there is large scope for the improvement of the nutritional characteristics of tomato fruits.

ObjectiveThe urgent transfer of an intensive care unit (ICU) is particularly challenging because it carries a high clinical and infectious risk and is a critical node in a hospital’s patient flow. In early 2017, exceptional rainfall damaged the roof of the tertiary hospital in Udine, necessitating the relocation of one of the three ICUs for six months. We decided to assess the impact of this transfer on quality of care and patient safety using a set of indicators, primarily considering the incidence of healthcare-associated infections (HAIs) and mortality rates.MethodsWe performed a retrospective, observational analysis of structural, process, and outcome indicators comparing the pre- and posttransfer phases. Specifically, we analyzed data between July 2016 and June 2017 for the transferred ICU and examined mortality and the incidence of HAI.ResultsDespite significant changes in structural and organizational aspects of the unit, no differences in mortality rates or cumulative incidence of HAIs were observed before/after transfer. We collected data for all 393 patients (133 women, 260 men) admitted to the ICU before (49.4%) and after transfer (50.6%). The mortality rate for 100 days in the ICU was 1.90 (34/1791) before and 2.88 (37/1258) after transfer (p = 0.063). The evaluation of the occurrence of at least one HAI included 304 patients (102 women and 202 men), as 89 of them were excluded due to a length of stay in the ICU of less than 48 h; again, there was no statistical difference between the two cumulative incidences (13.1% vs. 6.9%, p = 0.075).ConclusionIn the case studied, no adverse effects on patient outcomes were observed after urgent transfer of the injured ICU. The indicators used in this study may be an initial suggestion for further discussion.

The Ornstein–Uhlenbeck (OU) process describes the dynamics of Brownian particles in a confining harmonic potential, thereby constituting the paradigmatic model of overdamped, mean-reverting Langevin dynamics. Despite its widespread applicability, this model falls short when describing physical systems where the confining potential is itself subjected to stochastic fluctuations. However, such stochastic fluctuations generically emerge in numerous situations, including in the context of colloidal manipulation by optical tweezers, leading to inherently out-of-equilibrium trapped dynamics. To explore the consequences of stochasticity at this level, we introduce a natural extension of the OU process, in which the stiffness of the harmonic potential is itself subjected to OU-like fluctuations. We call this model the OU ^2 process. We examine its statistical, dynamic, and thermodynamic properties through a combination of analytical and numerical methods. Importantly, we show that the probability density for the particle position presents power-law tails, in contrast to the Gaussian decay of the standard OU process. In turn, this causes the trapping behavior, extreme value statistics, first passage statistics, and entropy production of the OU ^2 process to differ qualitatively from their standard OU counterpart. Due to the wide applicability of the standard OU process and of the proposed OU ^2 generalisation, our study sheds light on the peculiar properties of stochastic dynamics in random potentials and lays the foundation for the refined analysis of the dynamics and thermodynamics of numerous experimental systems.

Static nonreciprocal forces between particles generically drive persistent motion reminiscent of self-propulsion. Here, we demonstrate that reciprocity-breaking fluctuations about a reciprocal mean coupling strength are sufficient to generate this behavior in a minimal two-particle model, with the velocity of the ensuing active bound state being modulated in time according to the nature of these fluctuations. To characterize the ensuing nonequilibrium dynamics, we derive exact results for the time-dependent center of mass mean-square displacement and average rate of entropy production for two simple examples of discrete- and continuous-state fluctuations in one dimension. We find that the resulting dimer can exhibit unbiased persistent motion akin to that of an active particle, leading to a significantly enhanced effective diffusivity.

Background: The ligamentum teres (LT) has received attention in patients undergoing hip arthroscopy (HA) for femoroacetabular impingement (FAI). Indeed, a better understanding of the function of the LT and its implications for clinical outcomes in the presence of a torn LT is required. This systematic review analyses the patient-reported outcome measures (PROMs) and the complication rate when an intact or torn LT is encountered during HA for FAI. Methods: Studies that compared patients with an intact to those with a torn LT managed with debridement during hip arthroscopy for FAI were identified from the Web of Science, PubMed, and Embase. The minimum follow-up for inclusion was 24 months. The Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool was used to assess the risk of bias. Patient characteristics and PROMs were assessed at the baseline and last follow-up. Results: The systematic review identified two studies comprising 611 patients. No statistically significant difference was found in pain, Harris Hip Score, and the activities of daily living and sports subscales of the Hip Outcome Score between patients with an intact LT and those with a torn LT treated with debridement, both of whom underwent HA for FAI. Conclusions: In patients undergoing arthroscopic management for FAI, an intact or torn ligamentum teres managed with debridement does not influence postoperative PROMs. Given the importance of the LT as a structure of the hip joint and the increasing interest in HA for FAI, further standardised studies will be a valuable source for surgeons encountering this pathology. [ABSTRACT FROM AUTHOR]

Introduction Historically, anterior cruciate ligament (ACL) ruptures in the paediatric age group were managed conservatively with bracing, casting, activity modification, and physical therapy. However, most of these patients had to reduce their sports activities, and secondary damages to the affected knee were prevalent. Source of data Published scientific literature in Embase, Web of Science, PubMed, and Google Scholar databases. Areas of agreement ACL reconstruction in children with open physes patients is debated. Any damage to the physes around the knee could lead to growth abnormalities and axial deviation of the knee. Areas of controversy Different grafts are available and suitable for ACL reconstruction in skeletally immature patients; however, which graft performs better remains unclear. Growing points This systematic review compared bone-patellar tendon-bone (BPTB), hamstring tendon (HT), and quadriceps tendon (QT) autografts for ACL reconstruction in skeletally immature patients. The joint laxity, Patient-reported outcome measures (PROMs), return to sport, and complications were compared. Areas timely for developing research In skeletally immature patients, HT, BPTB, and QT autografts for ACL reconstruction yielded good outcomes. Comparative studies are strongly required to establish the most suitable autograft. [ABSTRACT FROM AUTHOR]

Background: Unicompartmental knee arthroplasty (UKA) is a surgical procedure for managing osteoarthritis of one joint compartment, most commonly the medial side. This systematic review investigates the causes of UKA revision. The outcomes of interest were establishing the revision rate, time to revision, and the most common causes of revision in the long- and midterm follow-up. Methods: This study was conducted according to the 2020 PRISMA statement. In October 2024, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. All the clinical studies investigating the rate and causes of revision in UKA were accessed. Only studies with a minimum of 10 years of follow-up were considered. Results: Data from 56 studies (13,540 patients) were collected. Of them, 65.6% were women. The mean length of the follow-up was 13.1 ± 3.0 years. The mean age of the patients was 65.6 ± 5.6 years, and the mean BMI was 28.5 ± 2.2 kg/m2. Revisions were performed in 8.8% (2641 of 30,140) of implanted UKAs. The mean time to revision was 6.5 ± 2.6 (range, 2.5 to 13.0) years. Conclusion: 8.8% (2641 of 30,140) of UKAs were revised at a mean time of 6.5 ± 2.6 years. Level of evidence: Level IV, systematic review. [ABSTRACT FROM AUTHOR]

Introduction: Spinal and non-spinal pathologies can cause low back pain. Non-spinal sources of low back pain include the sacroiliac joint (SIJ) and the hip. SIJ pain can be treated either conservatively or surgically. Current strategies for managing sacroiliac joint pain are debated, and limited evidence exists. Areas covered: The present expert opinion updates current evidence on conservative and surgical modalities for SIJ pain Expert opinion: Surgical management for SIJ pain is effective. However, it exposes patients to surgery and, therefore, related complications. Conservative management may be implemented in patients with moderate SIJ pain, with less than six months of symptoms, or not eligible for surgery. Several noninvasive modalities are available, mostly centered on intra-articular injections. Corticosteroids, platelet-rich plasma, and stem cells have only midterm lasting effects, at most for nine months. Radiofrequency ablation is another methodology for pain relief. Both continuous and pulsatile radiofrequency ablation are associated with good outcomes. SIJ fusion can be performed using different techniques; however, a clear recommendation on the most appropriate modality for the management of SIJ pain is still debated. [ABSTRACT FROM AUTHOR]

The current pandemic caused by COVID-19 has underlined the importance of a joint effort and approach to ensure patient and health care worker safety in medical care throughout Europe. In addition, the recent flood disasters in Germany and other countries called for immediate joint action, in this case with regard to the prevention of water-borne infections. Environmental disasters will increase with consequences for hospitals and nursing homes. Cooperative efforts are needed for preventing and controlling associated infection outbreaks, new pathogens will appear and a geographic shift of infectious diseases previously not detected in certain areas has already been observed.This approach to infection prevention and control must entail structural as well as regulatory aspects. The principle of equal protection against infections in all European countries must be implemented. Prevention and control of infections, including nosocomial infections, infections caused by antibiotic-resistant bacteria as well as pandemics, need to be based on equal standards in all of Europe.Protection against infections and other public health risks in all European countries is the best guarantor for building trust and identification of citizens in our common Europe.Experts in the fields of hygiene, microbiology, infectiology and epidemiology have to pool the expertise on the prevention and control of infections from different European countries and define key targets for achieving a high standard of hygiene measures throughout Europe. The participants of the Rudolf Schülke Foundation International Symposium call for immediate action and priority to be given to the realization of the proposed 16-point plan.