Urinary Tract Infection Predictors in Patients Undergoing Retrograde IntraRenal Surgery for Renal Stones: Does the Instrument Make the Difference?

Background: Retrograde intrarenal surgery (RIRS) using flexible ureterorenoscopes is a cornerstone approach for renal stone removal, yet it carries a significant risk of postoperative urinary tract infection (UTI). With the emergence of single-use ureterorenoscopes, there is growing interest in their potential to mitigate this risk. This study aimed to compare the postoperative infection rates between single-use and multi-use ureterorenoscopes in RIRS procedures and to identify predictors of postoperative UTI. Methods: Data were collected from 112 consecutive patients who underwent RIRS for renal stones between March 2022 and September 2023. Peri-operative variables including age, gender, body mass index (BMI), stone size, stone location, type of ureterorenoscope, Hounsfield Units (HU), pre-operative hydronephrosis, laboratory analysis, and operative time were evaluated. Univariate and multivariate logistic regression analyses were performed to assess the predictors of postoperative UTI. Results: Of the cohort, 77 surgeries (68.7%) utilized multi-use ureterorenoscopes, while 35 (31.3%) utilized single-use devices. Stone diameter, number of stones, type of ureterorenoscope, and operative time were significant predictors of postoperative UTI in the univariate analysis. Multivariable logistic regression showed that operative time (OR, 1.3; 95% CI, 0.55-0.99; p = 0.03) and type of ureterorenoscope (multi-use vs. single-use) (OR, 1.14; 95% CI, 1.08-1.2; p < 0.001) were independent predictors of postoperative UTI. Conclusions: In conclusion, this study highlights that multi-use ureterorenoscopes and prolonged operative time are associated with an increased risk of postoperative UTI in RIRS procedures. Careful pre-operative evaluation and meticulous patient selection are essential to minimize the occurrence of postoperative UTIs and optimize patient outcomes in RIRS for renal stones.

Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources.

Background: Chronic discogenic low back pain (LBP) poses a significant global burden, yet effective therapeutic interventions directly targeting the underlying degenerative process remain elusive. After demonstrating promising results in preclinical studies, intradiscal injection of cell-based treatments has been increasingly investigated in the clinical setting. However, most clinical trials failed to reach publication, with the few available reports showing only minor improvements. The aim of this study was to analyze the prospective clinical trials registered on ClinicalTrials.gov investigating cell therapies for LBP, with a specific emphasis on identifying critical obstacles hindering study completion, including trial design and funding sources. Methods: A systematic search of prospective clinical trials investigating cell-based treatments for chronic LBP due to intervertebral disc degeneration was performed on ClinicalTrials.gov. Extracted data encompassed study design, recruitment, experimental treatment modalities, investigated outcomes, current status, completion date, publication status, and funding sources. Fisher's exact test assessed associations between categorical variables, while a multiple logistic regression model aimed to identify factors potentially linked to the publication status of the studies. Results: Our search identified 26 clinical trials. Among these, only 7 (26.9%) were published, and none of the other studies marked as completed reported any results on ClinicalTrials.gov. Fifty percent of included trials were funded by universities, whereas the rest was sponsored by industry (38.5%) or private institutions (11.5%). Experimental treatments primarily involved cell-based or cell-derived products of varying sources and concentrations. Products containing carriers, such as hyaluronic acid or fibrin, were more frequently funded by industry and private organizations (p = 0.0112). No significant differences emerged when comparing published and nonpublished studies based on funding, as well as between publication status and other variables. Conclusion: Most clinical trials exploring cell-based disc regenerative therapies for chronic LBP have never reached completion, with only a small fraction reporting preliminary data in publications.

Bilateral simultaneous hip and knee replacement: an epidemiological nationwide study from 2001 to 2016.

BACKGROUND: Several studies have compared the pros and cons of simultaneous bilateral versus staged bilateral hip and knee replacement but the outcomes of these two surgical options remains a matter of controversy. This study aimed to evaluate demographic features, incidence and hospitalization rates of bilateral one stage total hip and knee arthroplasty in Italy. METHODS: The Italian Ministry of Health's National Hospital Discharge Reports (SDO) were used to gather data. This study referred to the adult population (+ 20 years of age) from 2001 to 2015 for hip arthroplasty and from 2001 to 2016 for knee arthroplasty. RESULTS: Overall, 1,544 bilateral simultaneous hip replacement were carried out. The incidence rate was 0.21 cases per 100,000 adult Italian residents. Male/female ratio was 1.1. The average days of hospital stay was 11.7 ± 11.8 days. The main primary codified diagnosis was: osteoarthrosis, localized, primary, pelvic region and thigh (ICD code: 715.15). 2,851 bilateral simultaneous knee replacement were carried out. The incidence rate was 0.37 cases per 100,000 adult Italian residents. Male/female ratio was 0.6. The average days of hospital stay was 7.7 ± 5.8 days. The main primary codified diagnosis was: osteoarthrosis, localized, primary, lower leg (ICD code: 715.16). CONCLUSIONS: The burden of hip and knee osteoarthrosis as a leading cause of bilateral joint replacement is significant in Italy. The national registers' longitudinal analysis may provide data for establishing international guidelines regarding the appropriate indications for one stage bilateral simultaneous hip or knee replacement versus two stage.

Video-Assisted Informed Consent in Endoscopic Urology: A Randomized Trial on Ureteroscopy.

Purpose: The aim of this study is to evaluate the possible benefits of using video consent in the preoperative ureteroscopy (URS) consent process. Material and Methods: Prospective randomized trials took place at two Italian tertiary-care centers from March 2022 to September 2022. Patients were randomly assigned to two groups: Group A (standard verbal/written informed consent) and Group B (informed consent supported by video). We investigated the impact of both types of informed consent on patient anxiety levels using the Spielberger State-Trait Anxiety Inventory (STAI) questionnaire both pre- and post-consent. In addition, using the Visual Analogue Scale, analysis of the effect of informed consent on postoperative pain and the number of calls for assistance during hospitalization as secondary outcomes was done. To assess the satisfaction level related to the whole process, patients were asked to rate their experience on a scale of 1-10, with 1 indicating "not satisfied" and 10 indicating "completely satisfied." Results: Overall, 166 patients were randomized 1:1 in each group. The multivariable regression model demonstrated that video-assisted informed consent significantly increased the difference between post- and pre-consent STAI with a reduced level of anxiety. The video-assisted informed consent significantly predicted the number of assistance calls during hospitalization. Conclusions: Video consent for ureteroscopies is a valid tool to improve procedure awareness and satisfaction. Video consent is able to reduce procedure-related patient anxiety and postoperative assistance calls, thus proving to be useful in obtaining better-informed consent for endourological procedures.

Trifecta Outcomes of Robot-Assisted Partial Nephrectomy Using the New Hugo™ RAS System Versus Laparoscopic Partial Nephrectomy.

(1) Background: Laparoscopic partial nephrectomy (LPN) is still performed in many referred urological institutions, representing a valid alternative to robot-assisted partial nephrectomy (RAPN). We aimed to compare trifecta outcomes of LPN and RAPN with the Hugo™ RAS System. (2) Methods: Between October 2022 and September 2023, eighty-nine patients underwent minimally invasive partial nephrectomy (group A, RAPN = 27; group B, Laparoscopic PN = 62) for localized renal tumors at our Institution. Continuous variables were presented as median and IQR and compared by means of the Mann-Whitney U test, while categorical variables were presented as frequencies (%) and compared by means of the χ2 test. (3) Results: Group A showed a higher rate of male patients (81.5% vs. 59.7%, p = 0.04) and a higher trend towards larger clinical tumor size (34 vs. 29 mm, p = 0.14). All the other baseline variables were comparable between the two groups (all p > 0.05). Regarding post-operative data, group A displayed a lower operative time (92 vs. 149.5 min, p = 0.005) and a shorter hospital stay (3 vs. 5, p = 0.002). A higher rate of malignant pathology was evidenced in group A (77.8% vs. 58.1%, p = 0.07) as well as a lower trend towards positive surgical margins (3.7% vs. 4.8%, p = 0.82), even if not statistically significant. (4) Conclusions: The rate of trifecta achievement was 92.6% and 82.3% for group A and B (p = 0.10), respectively. In terms of trifecta outcomes, RAPN using the Hugo™ RAS System showed comparable results to LPN performed by the same experienced surgeon.

Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength.

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156-0.366]) vs non-diabetic subjects 0.352% [0.269-0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46-30.10] vs non-diabetic subjects 76.24 MPa [26.81-132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p<0.0001), and GSK3B (p=0.0456) were higher, while collagen (COL1A1) was lower in T2D (p=0.0482). AGEs content was associated with SOST and WNT5A (r=0.9231, p<0.0001; r=0.6751, p=0.0322), but inversely correlated with LEF-1 and COL1A1 (r=-0.7500, p=0.0255; r=-0.9762, p=0.0004). SOST was associated with glycemic control and disease duration (r=0.4846, p=0.0043; r=0.7107, p=0.00174), whereas WNT5A and GSK3B were only correlated with glycemic control (r=0.5589, p=0.0037; r=0.4901, p=0.0051). Finally, Young's modulus was negatively correlated with SOST (r=-0.5675, p=0.0011), AXIN2 (r=-0.5523, p=0.0042), and SFRP5 (r=-0.4442, p=0.0437), while positively correlated with LEF-1 (r=0.4116, p=0.0295) and WNT10B (r=0.6697, p=0.0001). These findings suggest that Wnt signaling and AGEs could be the main determinants of bone fragility in T2D.

Type 2 diabetes is a long-term metabolic disease characterised by chronic high blood sugar levels. This in turn has a negative impact on the health of other tissues and organs, including bones. Type 2 diabetes patients have an increased risk of fracturing bones compared to non-diabetics. This is particularly true for fragility fractures, which are fractures caused by falls from a short height (i.e., standing height or less), often affecting hips or wrists. Usually, a lower bone density is associated with higher risk of fractures. However, patients with type 2 diabetes have increased bone fragility despite normal or higher bone density. One reason for this could be the chronically high levels of blood sugar in type 2 diabetes, which alter the properties of proteins in the body. It has been shown that the excess sugar molecules effectively 'react' with many different proteins, producing harmful compounds in the process, called Advanced Glycation End-products, or AGEs. AGEs are ­ in turn ­thought to affect the structure of collagen proteins, which help hold our tissues together and decrease bone strength. However, the signalling pathways underlying this process are still unclear. To find out more, Leanza et al. studied a signalling molecule, called sclerostin, which inhibits a signalling pathway that regulates bone formation, known as Wnt signaling. The researchers compared bone samples from both diabetic and non-diabetic patients, who had undergone hip replacement surgery. Analyses of the samples, using a technique called real-time-PCR, revealed that gene expression of sclerostin was increased in samples of type 2 diabetes patients, which led to a downregulation of Wnt signaling related genes. Moreover, the downregulation of Wnt genes was correlated with lower bone strength (which was measured by compressing the bone tissue). Further biochemical analysis of the samples revealed that higher sclerostin activity was also associated with higher levels of AGEs. These results provide a clearer understanding of the biological mechanisms behind compromised bone strength in diabetes. In the future, Leanza et al. hope that this knowledge will help us develop treatments to reduce the risk of bone complications for type 2 diabetes patients.

Accuracy of two-dimensional digital planning in uncemented primary hip arthroplasty: monocentric analysis of eight hundred implants.

PURPOSE: In the last decades, there has been a refinement in total hip arthroplasty, which allowed surgeons to achieve the highest performance and better patient outcomes. Preoperative planning in primary hip arthroplasty is an essential step that guides the surgeon in restoring the anatomy and biomechanics of the joint. This study aims to evaluate the accuracy of the 2D digital planning, considering cup sizing, stem sizing, and limb length discrepancy. Additionally, we conducted a multivariable analysis of demographic data and comorbidities to find factors influencing preoperative planning. METHODS: This retrospective study analyzed the planning accuracy in 800 consecutive uncemented primary total hip arthroplasty. We compared the preoperatively planned total hip arthroplasty with postoperative results regarding the planned component size, the implanted size, and the lower limb length restoration. Therefore, we investigated factors influencing planning accuracy: overweight and obesity, sex, age, past medical history, comorbidities, and implant design. All the surgeries were performed in the posterolateral approach by one expert surgeon who did the preoperative planning. The preoperative planning was determined to be (a) exact if the planned and the implanted components were the same size and (b) accurate if exact ± one size. The restoration of postoperative limb length discrepancy was classified into three groups: ± 3 mm, ± 5 mm, and ± 10 mm. This assessment was performed through a digital method 2D based on a standard hip X-ray. RESULTS: This court of 800 implants showed that planning was exact in 60% of the cups and 44% of the stems and was accurate in 94% of the cups and 80% of the stems. The postoperative limb length discrepancy was ± 3 mm in 91% and ± 5 mm in 97%. CONCLUSIONS: This study showed preoperative 2D digital planning great precision and reliability, and we demonstrated that it was accurate in 94% of the cups and 80% of the stems. Therefore, the preoperative limb length discrepancy analysis was essential to guarantee the recovery of the operated limb's correct length.

Intraoperative Cone-Beam Computed Tomography Navigation Versus 2-Dimensional Fluoroscopy in Single-Level Lumbar Spinal Fusion: A Comparative Analysis.

OBJECTIVE: Several studies have advocated for the higher accuracy of transpedicular screw placement under cone-beam computed tomography (CBCT) compared to conventional 2-dimensional (2D) fluoroscopy. The superiority of navigation systems in perioperative and postoperative outcomes remains a topic of debate. This study aimed to compare operative time, screw placement time and accuracy, total radiation dose, perioperative and postoperative outcomes in patients who underwent transpedicular screw fixation for degenerative lumbar spondylolisthesis (DLS) using intraoperative CBCT navigation versus 2D fluoroscopy. METHODS: A retrospective analysis was conducted on patients affected by single-level DLS who underwent posterior lumbar instrumentation with transpedicular screw fixation using surgical CBCT navigation (NV group) or 2D fluoroscopy-assisted freehand technique (FH group). Demographics, screw placement time and accuracy, operative time, total radiation dose, intraoperative blood loss, screw revision rate, complications, and length of stay (LOS) were assessed. RESULTS: The study included a total of 30 patients (NV group: n = 15; FH group: n = 15). The mean screw placement time, operative time, and LOS were significantly reduced in the NV group compared to the FH group (p < 0.05). The total radiation dose was significantly higher in the NV group (p < 0.0001). No significant difference was found in terms of blood loss and postoperative complications. CONCLUSION: This study suggests that intraoperative CBCT-navigated single-level lumbar transpedicular screw fixation is superior in terms of mean screw placement time, operative time, and LOS compared to 2D fluoroscopy, despite a higher intraoperative radiation exposure.

Skill Transfer from Laparoscopic Partial Nephrectomy to the Hugo™ RAS System: A Novel Proficiency Score to Assess Surgical Quality during the Learning Curve.

Background/Objectives: The absence of validated tools to assess the skill transfer from laparoscopy to robotic surgery remains an unsolved issue in the context of robot-assisted partial nephrectomy (RAPN). We aimed to describe and validate a novel proficiency score to critically evaluate the surgical quality of RAPN with the Hugo™ RAS System (Medtronic, Minneapolis, MN, USA). Methods: Between October 2022 and September 2023, 27 consecutive patients underwent off-clamp RAPN for localized renal tumors at our institution. To analyze the learning curve (LC), the cohort was chronologically divided into two phases of 6 months each. Proficiency was defined as the achievement of trifecta while maintaining a comparable intraoperative time in the interquartile range of laparoscopic partial nephrectomy performed by the same surgeon. A logistic binary regression model was built to identify predictors of proficiency achievement. Results: A proficiency score was achieved in 14 patients (74.1%). At univariable analysis, number of consecutive procedures > 12 (OR 13.7; 95%CI 2.05-21.1, p = 0.007), pathological tumor size (OR 0.92; 95%CI 0.89-0.99, p = 0.04) and essential blood hypertension (OR 0.16; 95%CI 0.03-0.82, p = 0.02) were found to be predictors of proficiency score. At multivariable analysis, after adjusting for potential confounding factors, number of consecutive procedures > 12 (OR 8.1; 95%CI 1.44-14.6, p = 0.03) was the only independent predictor of proficiency score achievement. Conclusions: Our results showed that the skills of an experienced laparoscopic surgeon are transferrable to the novel Hugo™ RAS System in the context of nephron-sparing surgery. Improved surgical quality may be expected after completing the first 12 consecutive procedures.

No differences in terms of complications, readmissions, reoperations, and patient-reported outcomes in simultaneous bilateral versus staged bilateral total knee arthroplasty in selected patients.

BACKGROUND: The safety and the clinical success of simultaneous bilateral total knee arthroplasty (BTKA) is controversial. The aim of this study was to compare complications and patient-reported outcomes following simultaneous BTKA (simBTKA) versus staged BKTA (staBTKA) in patients affected by bilateral symptomatic end-stage knee osteoarthritis (OA). METHODS: Data from patients who underwent simBTKA or staBTKA at a single institution from January 2017 to December 2020, with a minimum 1-year follow up period were retrospectively collected. Differences in terms of complications and clinical success were compared among the simBTKA and staBTKA patient groups. Alpha was set at 0.05. RESULTS: A total of 173 patients were included in this study. The results revealed no statistically significant differences between the two groups in terms of mortality, revision rate, readmission rate, local and systemic complications and patient-reported outcomes. SimBTKA group had a shorter operating room time (96 (73-119) vs. 195 (159-227); P < 0.0001), and length of hospital stay (4 (3-5) vs. 7 (6-9); P < 0.0001) compared with the staBTKA group. CONCLUSIONS: SimBTKA performed in a selected patient population at a high-volume center can be considered comparable to staBTKA in terms of safety, postoperative complications, 30-day readmissions and patient satisfaction. Consequently, reduced operating room time and hospital stay renders simBTKA a cost-effective and advantageous option, not only for patients, but also for healthcare institutes. Furthermore, the current study also highlights the importance of correct patient selection based on clinical preoperative characteristics.

Interventional treatments for low back pain due to sacroiliac joint dysfunction: a systematic review of the literature.

PURPOSE: This systematic review aimed to report the current evidence in the literature about the efficacy of interventional treatments in the management of low back pain (LBP) due to sacroiliac joint dysfunction. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Medline, EMBASE, Scopus, CINAHL, Cochrane Library, and CENTRAL bibliographic databases were searched. The search was performed from October to December 2021, and articles from the inception of the database to December 2021 were searched. RESULTS: Fourteen studies were included for qualitative synthesis. Five studies used the traditional radiofrequency approach (tRF), five studies used cooled radiofrequency approach (cRF), one study used botulinum toxin (BT), two studies used steroid injection, triamcinolone (TA) and local anesthetics injections, and one study used pulsed radiofrequency (PRF) denervation. Two studies used sham as a comparator. CONCLUSIONS: Cooled radiofrequency seems to be the most effective treatment in improving pain and functionality, while intra-articular injections are helpful only as diagnostic tools. However, due to the lack of high-quality studies, it was not possible to draw significant conclusions.

Arthroscopic microfracture and associated techniques in the treatment of osteochondral lesions of the talus: A systematic review and metanalysis.

BACKGROUND: Osteochondral lesions of the talus are common in patients suffering even minor trauma; timely diagnosis and treatment can prevent the development of early osteoarthritis. The objectives of this systematic review and meta-analysis were to evaluate the effects of additional procedures on arthroscopic ankle microperforations for osteochondral lesions. METHODS: A systematic literature search was conducted using PubMed-Medline, Cochrane Central, and Google Scholar to select clinical studies analyzing the efficacy of platelet-rich plasma (PRP), hyaluronic acid (HA), and bone marrow concentrate (BMC) procedures. Ten articles following PRISMA guidelines with a total of 464 patients were included in this review. Quality assessment using MINORS was performed, and all studies demonstrated high quality. RESULTS: The results of the systematic review showed benefits in all patients undergoing infiltrative therapy with PRP, hyaluronic acid, and BMC. The best results in terms of AOFAS score and VAS scale were found in patients undergoing PRP injection. The meta-analysis showed improvements in pain relief and return to daily activities in patients undergoing arthroscopic microperforations and PRP, although not reporting statistically significant results (p = 0.42). CONCLUSION: All treatment strategies reported better scores compared to the control groups. Among the various treatments analyzed, the addition of PRP appears to be the most valuable probably for the larger population receiving this treatment, showing excellent outcomes in pain reduction, clinical outcomes, and return to daily activities. LEVEL OF EVIDENCE: II.

Anterior Cruciate Ligament Repair Augmented With Dynamic Intraligamentary Stabilization Is Equivalent to Hamstring Autograft Reconstruction at Short- and Mid-Term Follow-Up: A Systematic Review.

PURPOSE: To compare clinical outcomes, knee stability and complications, failure, and revision rates after anterior cruciate ligament repair (ACLr) with dynamic intraligamentary stabilization (DIS) versus anterior cruciate ligament reconstruction (ACLR) with hamstring autograft for primary ACL ruptures at short and mid-term follow-up. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of PubMed/MEDLINE and Scopus was performed. Studies that evaluated patients undergoing ACLr with DIS or ACLR with hamstring autograft were considered for inclusion. Studies were excluded if patients were affected by concomitant meniscal, ligamentous, or chondral injuries needing surgical treatment, because of their potential confounding effect on postoperative outcomes. The Risk of Bias-2 tool was used to assess the risk of bias in the included studies. The quality of available evidence was rated according to Grading of Recommendations Assessment, Development, and Evaluation recommendations. The study protocol was registered in the PROSPERO database (ID: CRD42023394558). RESULTS: Five randomized controlled trials comparing the outcomes of ACLr with DIS versus ACLR with hamstring autograft met the inclusion criteria. No major differences in terms of patient-reported outcomes (International Knee Documentation Committee subjective form, Lysholm score, Tegner activity scale, Knee injury and Osteoarthritis Outcome Score, visual analog scale satisfaction) or rates of complications, revisions, and failures were found in included studies at all time points. Repair showed greater International Knee Documentation Committee subjective form scores at 5 years in one study, whereas ACLR displayed significantly increased knee stability at 6 months and 5 years in 2 different studies, although the clinical relevance of these differences is doubtful. CONCLUSIONS: The results of this study suggest that ACLr with DIS is not inferior to ACLR with hamstring autograft in terms of rates of clinical outcomes, knee stability, risk of failure, complications, and revision surgery. Therefore, ACLr with DIS may be a viable alternative to ACLR with hamstring autograft in selected patients. LEVEL OF EVIDENCE: Level I, systematic review of Level I studies.

ISSLS PRIZE in Basic Science 2024: superiority of nucleus pulposus cell- versus mesenchymal stromal cell-derived extracellular vesicles in attenuating disc degeneration and alleviating pain.

PURPOSE: To investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model. METHODS: EVs were isolated from healthy human NPCs cultured under standard (NPCSTD-EVs) and Tie2-enhancing (NPCTie2+-EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1ß. Thereafter, 16 Sprague-Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPCSTD-EVs, NPCTie2+-EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs. RESULTS: NPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes. CONCLUSION: Our results underscore the regenerative potential of young NPC-derived EVs, particularly NPCTie2+-EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics.

Adrenalectomy for Metastasis: The Impact of Primary Histology on Survival Outcome.

Adrenalectomy is commonly considered a curative treatment in case of adrenal gland as site of metastasis. In the present study, we evaluated the impact of primary tumor histology on survival outcomes after a minimally invasive adrenal mastectomy for a solitary metachronous metastasis. From May 2004 to August 2020, we prospectively collected data on minimally invasive adrenalectomies whose pathological examination showed a metastasis. All patients only received metastasectomies that were performed with curative intent, or to achieve non-evidence of disease status. Adjuvant systemic therapy was not administered in any case. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were applied to identify independent predictors of CSS. Out of 235 laparoscopic and robotic adrenalectomies, the pathologic report showed metastases in 60 cases. The primary histologies included 36 (60%) renal cell carcinoma (RCC), 9 (15%) lung cancer, 6 (10%) colon cancer, 4 (6.7%) sarcoma, 3 (5%) melanoma and 2 (3.3%) bladder cancer. RCC displayed significantly longer survival rates with a 5-year CSS of 55.9%, versus 22.8% for other histologies (log-rank p = 0.01). At univariable analysis, disease-free interval (defined as the time from adrenalectomy to evidence of disease progression) < 12 months and histology were predictors of CSS (p = 0.003 and p < 0.001, respectively). At multivariable Cox analysis, the only independent predictor of CSS was primary tumor histology (p = 0.005); patients with adrenal metastasis from colon cancer and bladder cancer showed a 5.3- and 75.5-fold increased risk of cancer death, respectively, compared to patients who had RCC as primary tumor histology. Oncological outcomes of adrenal metastasectomies are strongly influenced by primary tumor histology. A proper discussion of the role of surgery in a multidisciplinary context could provide optimal treatment strategies.

Machine learning can predict anterior elevation after reverse total shoulder arthroplasty: A new tool for daily outpatient clinic?

The aim of the present study was to individuate and compare specific machine learning algorithms that could predict postoperative anterior elevation score after reverse shoulder arthroplasty surgery at different time points. Data from 105 patients who underwent reverse shoulder arthroplasty at the same institute have been collected with the purpose of generating algorithms which could predict the target. Twenty-eight features were extracted and applied to two different machine learning techniques: Linear regression and support vector regression (SVR). These two techniques were also compared in order to define to most faithfully predictive. Using the extracted features, the SVR algorithm resulted in a mean absolute error (MAE) of 11.6° and a classification accuracy (PCC) of 0.88 on the test-set. Linear regression, instead, resulted in a MAE of 13.0° and a PCC of 0.85 on the test-set. Our machine learning study demonstrates that machine learning could provide high predictive algorithms for anterior elevation after reverse shoulder arthroplasty. The differential analysis between the utilized techniques showed higher accuracy in prediction for the support vector regression. Level of Evidence III: Retrospective cohort comparison; Computer Modeling.

Wharton's Jelly mesenchymal stromal cell-derived extracellular vesicles promote nucleus pulposus cell anabolism in an in vitro 3D alginate-bead culture model.

Background: Intradiscal transplantation of mesenchymal stromal cells (MSCs) has emerged as a promising therapy for intervertebral disc degeneration (IDD). However, the hostile microenvironment of the intervertebral disc (IVD) may compromise the survival of implanted cells. Interestingly, studies reported that paracrine factors, such as extracellular vesicles (EVs) released by MSCs, may regenerate the IVD. The aim of this study was to investigate the therapeutic effects of Wharton's Jelly MSC (WJ-MSC)-derived EVs on human nucleus pulposus cells (hNPCs) using an in vitro 3D alginate-bead culture model. Methods: After EV isolation and characterization, hNPCs isolated from surgical specimens were encapsulated in alginate beads and treated with 10, 50, and 100 µg/mL WJ-MSC-EVs. Cell proliferation and viability were assessed by flow cytometry and live/dead staining. Nitrite and glycosaminoglycan (GAG) content was evaluated through Griess and 1,9-dimethylmethylene blue assays. hNPCs in alginate beads were paraffin-embedded and stained for histological analysis (hematoxylin-eosin and Alcian blue) to assess extracellular matrix (ECM) composition. Gene expression levels of catabolic (MMP1, MMP13, ADAMTS5, IL6, NOS2), anabolic (ACAN), and hNPC marker (SOX9, KRT19) genes were analyzed through qPCR. Collagen type I and type II content was assessed with Western blot analysis. Results: Treatment with WJ-MSC-EVs resulted in an increase in cell content and a decrease in cell death in degenerated hNPCs. Nitrite production was drastically reduced by EV treatment compared to the control. Furthermore, proteoglycan content was enhanced and confirmed by Alcian blue histological staining. EV stimulation attenuated ECM degradation and inflammation by suppressing catabolic and inflammatory gene expression levels. Additionally, NPC phenotypic marker genes were also maintained by the EV treatment. Conclusions: WJ-MSC-derived EVs ameliorated hNPC growth and viability, and attenuated ECM degradation and oxidative stress, offering new opportunities for IVD regeneration as an attractive alternative strategy to cell therapy, which may be jeopardized by the harsh microenvironment of the IVD.