Search

We report on a school-based randomized control trial study comparing two morphological interventions with untaught controls: one focusing on direct instruction targeting print morphological decoding (direct decoding condition) and the other on inquiry-focused pedagogy using oral morphological analysis (inquiry-analysis condition). We identified 63 Grade 3 children with below-average morphological awareness following screening (from N = 163). This sub-sample showed average pseudoword decoding but poor language and word reading abilities. Following a 13-week supplemental intervention randomized within the 63 children, results showed a statistically significant main effect of intervention on standardized reading vocabulary measures at immediate post-test in the direct decoding condition. Pre-test morphological awareness moderated reading vocabulary effects for the untaught control group. Statistically significant moderation of growth in sentence comprehension at post- by pre-test morphological awareness was also evident in the inquiry-analysis condition. Universal screening for below-average morphological awareness followed by inquiry-based or direct instruction interventions focusing on the meaning dimensions of morphemes may be modestly efficacious for supporting reading vocabulary and sentence comprehension in such at risk learners, potentially aiding school-wide literacy improvement.

Background Intratumoral heterogeneity (ITH) and subclonal antigen expression blunt antitumor immunity and are associated with poor responses to immune-checkpoint blockade immunotherapy (ICB) in patients with cancer. The underlying mechanisms however thus far remained elusive, preventing the design of novel treatment approaches for patients with high ITH tumors.Methods We developed a mouse model of lung adenocarcinoma with defined expression of different neoantigens (NeoAg), enabling us to analyze how these impact antitumor T-cell immunity and to study underlying mechanisms. Data from a large cancer patient cohort was used to study whether NeoAg architecture characteristics found to define tumor immunogenicity in our mouse models are linked to ICB responses in patients with cancer.Results We demonstrate that concurrent expression and clonality define NeoAg architectures which determine the immunogenicity of individual NeoAg and drive immune evasion of tumors with heterogenous NeoAg expression. Mechanistically, we identified concerted interplays between concurrent T-cell responses induced by cross-presenting dendritic cells (cDC1) mirroring the tumor NeoAg architecture during T-cell priming in the lymph node. Depending on the characteristics and clonality of respective NeoAg, this interplay mutually benefited concurrent T-cell responses or led to competition between T-cell responses to different NeoAg. In tumors with heterogenous NeoAg expression, NeoAg architecture-induced suppression of T-cell responses against branches of the tumor drove immune evasion and caused resistance to ICB. Therapeutic RNA-based vaccination targeting immune-suppressed T-cell responses synergized with ICB to enable control of tumors with subclonal NeoAg expression. A pan-cancer clinical data analysis indicated that competition and synergy between T-cell responses define responsiveness to ICB in patients with cancer.Conclusions NeoAg architectures modulate the immunogenicity of NeoAg and tumors by dictating the interplay between concurrent T-cell responses mediated by cDC1. Impaired induction of T-cell responses supports immune evasion in tumors with heterogenous NeoAg expression but is amenable to NeoAg architecture-informed vaccination, which in combination with ICB portrays a promising treatment approach for patients with tumors exhibiting high ITH.

ABSTRACT Purpose: To compare the perioperative outcomes of robot-assisted radical prostatectomy (RARP) with pelvic lymph-nodes dissection (PLND) when the same surgeon performs RARP and PLND versus one surgeon performs RARP and another surgeon performs PLND. Materials and Methods: From January 2022 to March 2023, data of consecutive patients who underwent RARP with PLND were prospectively collected. The surgeries were performed by two "young" surgeons with detailed profile. Specifically for the study purpose, one surgeon performed RARP, and the other surgeon performed PLND. A set of surgeries performed according to the standard setup (i.e., the same surgeon performing both RARP and PLND) was retrieved from the institutional database and used as comparator arm. To test the study hypothesis, patients were divided into two groups: "dual-surgeon" versus "single-surgeon". Results: Fifty patients underwent RARP and PLND performed according to dual-surgeon setup and were compared to the last 50 procedures performed according to the standard single-surgeon setup. Patients in the groups had comparable baseline characteristics. Dual-surgeon interventions had significantly shorter median total operative (194 [IQR 178–215] versus 174 [IQR 146–195] minutes, p

Abstract Background Pancreatic cancer (PC) first‐line therapy often consists of polychemotherapy regimens, but choosing a second‐line therapy after disease progression, especially following first‐line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab‐paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. Methods The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. Results AG was well‐tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second‐line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first‐line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first‐line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second‐line OS and PFS. Conclusions This study represents the largest real‐world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first‐line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first‐line therapy.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.

Vertical neglect represents a visuospatial deficit occurring as a possible consequence of acquired brain injury (ABI). Differently from unilateral spatial neglect on horizontal space, vertical neglect is poorly studied in the literature and rarely assessed in clinical practice. In the available studies, the terms “radial,” “vertical,” and “altitudinal” neglect are often used interchangeably, although they do not describe the same spatial dimension. “Altitudinal” and “vertical” refer to the sagittal plane, whereas “radial” refers to the transverse plane. The term “vertical” is sometimes used interchangeably with respect to both axes. The aim of this systematic review was to identify the main characteristics of vertical neglect after ABI, the diagnostic tools used, and the treatment options. We also proposed a clarification of the manifestations and characteristics of vertical and radial neglect. The 23 articles reviewed, showed that the vertical neglect occurred more frequently on the lower space than on the upper space, that its presence was associated with horizontal neglect, and that it could also occur with compromise of the radial space, with the near radial being more common. The most frequent etiology associated with vertical neglect is vascular, particularly ischaemic. The lesions side are very heterogeneous and include both cortical and subcortical areas and all lobes, although the temporal lobe is most affected. With regard to the assessment tools, paper and pencil tasks are the most commonly used diagnostic tools to identify vertical neglect, although in recent years the use of computer-based tasks increased. Taken together, our results suggest that vertical neglect may be underestimated in patients with right hemisphere lesions and should always be assessed, especially in cases where the patient shows signs of horizontal neglect. The clinical assessment of vertical neglect is very important since it can lead to important functional limitations in everyday life, such as poor wheelchair handling, stumbling over unnoticed obstacles located below (or above), walking down stairs, taking off shoes.

Neuroblastoma (NB) is a pediatric tumor composed of adrenergic (ADRN) and mesenchymal-like (MES) cells which derive from the dysregulation of normal cell differentiation imposed by NB Core Regulatory Circuitries (CRCs) [...]

Genome-wide association studies (GWASs) have contributed to the study of neuroblastoma (NB) genetics by identifying common risk variants that activate cancer-related processes associated with NB susceptibility [...]

Introduction: Crystalluria is an important indicator of renal stone recurrence. Mechanisms underlying urinary stone formation are still not fully understood and raising interests has been giving to intestinal commensal bacteria for their contribute in maintaining urinary solutes equilibrium. The aim of our phase II study was to examine the administration of potassium citrate, magnesium and probiotics in order to reduce crystalluria. Materials and Methods: Since May 2021, we enrolled 23 patients candidates for ureterorenolithotripsy for calcium oxalate kidney stones with crystalluria and a normal metabolic profile. The analysis was validated by the Institution's Ethical Committee (no. approval STS CE Lazio 1/N-823). At discharge, patients were provided with daily food supplementation for 20 days of 1 billion Lactobacillus paracasei LPC09, 1 billion Lactobacillus plantarum LP01, 1 billion Bifidobacterium breve BR03, potassium (520 mg), citrate (1400 mg), and magnesium (80 mg). Crystalluria was re-assessed at 1, 3, 6, and 12-months follow-up by polarized light microscopy. Results: After one month from the oral supplementation, no patient reported crystalluria; at 3 months, among the 20 participants available for re-evaluation, still no patient reported crystalluria. Instead, crystalluria was reported in three patients (15%) at 6 months, and in five patients (25%) at 12 months follow-up. Conclusions: The oral supplementation with Lactobacillus spp. and Bifidobacterium spp. was found able to reduce the prevalence of crystalluria in a cohort of patients with diagnosis of calcium oxalate kidney stones with crystalluria candidate to ureterorenolithotripsy. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by well-established environmental exposures (most notably, cigarette smoking) and incompletely defined genetic factors. The chromosome 4q region harbors multiple genetic risk loci for COPD, including signals near HHIP, FAM13A, GSTCD, TET2, and BTC. Leveraging RNA-Seq data from lung tissue in COPD cases and controls, we estimated the co-expression network for genes in the 4q region bounded by HHIP and BTC (~70MB), through partial correlations informed by protein-protein interactions. We identified several co-expressed gene pairs based on partial correlations, including NPNT-HHIP, BTC-NPNT and FAM13A-TET2, which were replicated in independent lung tissue cohorts. Upon clustering the co-expression network, we observed that four genes previously associated to COPD: BTC, HHIP, NPNT and PPM1K appeared in the same network community. Finally, we discovered a sub-network of genes differentially co-expressed between COPD vs controls (including FAM13A, PPA2, PPM1K and TET2). Many of these genes were previously implicated in cell-based knock-out experiments, including the knocking out of SPP1 which belongs to the same genomic region and could be a potential local key regulatory gene. These analyses identify chromosome 4q as a region enriched for COPD genetic susceptibility and differential co-expression. Author summary: Complex diseases, such as chronic obstructive pulmonary disease (COPD), are characterized by multifactorial causes, including multiple genetic variants and a variety of molecular functions. A 70 megabase genomic region on chromosome 4 harbors some of the strongest genetic associations to COPD based on genome-wide association studies (GWAS). In this work we study the co-expression patterns of genes located in this genomic region. We developed a new approach to compute partial correlations between pairs of expressed genes, using prior information regarding the mediating genes from protein-protein interaction networks. We identified potential biological connections between several of the COPD-related GWAS genes in this region, including BTC, NPNT, PPM1K and HHIP, suggesting possible functional co-regulation. Furthermore, by comparing COPD cases and control subjects, we found multiple network edges whose co-expression changed between health and disease, particularly the edge between CXCL10 and CXCL11. Some of these genes were previously implicated in cell-based knock-out experiments, suggesting a common regulator, namely SPP1. These analyses provide insight into regional gene regulation of GWAS genes that may be related to COPD pathogenesis. [ABSTRACT FROM AUTHOR]

This study examines the determinants of the overeducation phenomenon among migrants in Lombardy, Italy, and how it has evolved over the last 14 years. The target population consists of legal and undocumented individuals with original citizenship from countries defined as 'high migratory pressure countries', who declared themselves as 'employed'. Italy has one of the highest rates of overeducation among non‐EU citizens in the European Union, and there is also a significant gap between the overeducation rates of Italian nationals and non‐EU citizens in the country. The study explores various factors contributing to overeducation and how the individual and migratory characteristics affecting it evolved. The chosen period encompasses years affected by the consequences of the economic crisis and the pandemic emergency. A significant time effect, different according to gender, is detected: more specifically, a decrease in the probability of being overeducated in the post‐crisis years in comparison with the preceding ones for men. More years since migration and having attended primary or secondary education in Italy appear to significantly lessen the likelihood of overeducation. Predicted probabilities demonstrate that being a woman and originating from certain countries, such as some eastern European non‐EU countries (Ukraine and Moldova) and the Philippines, disadvantage foreign workers in terms of overeducation. [ABSTRACT FROM AUTHOR]

In pursuing sustainable refrigeration solutions, integrating phase change materials (PCMs) within sun-powered refrigerators emerges as a promising avenue to mitigate challenges associated with sun radiation intermittency and reliance on large battery systems. This paper comprehensively examines incorporating PCMs into sun-powered refrigerators to address critical issues hindering the widespread adoption of solar refrigeration technologies, particularly in medicine and perishable goods. The primary objective of this study is to assess the efficacy of PCM integration in achieving grid disconnection and enabling autonomous operation of sun-powered refrigerators. Through experimentation and data analysis, our findings elucidate the transformative impact of PCM utilization on the performance and sustainability of solar refrigeration systems. Key outcomes from the experimental trials demonstrate that incorporating PCMs facilitates prolonged operation of sun-powered refrigerators, even without direct sunlight. By harnessing the thermal storage capabilities of PCMs, the refrigeration unit achieves grid independence, thereby mitigating reliance on conventional power sources and large battery configurations. In conclusion, integrating phase change materials is pivotal to achieving energy autonomy and sustainability in sun-powered refrigeration systems. Through collaborative efforts and continued innovation, PCM-enabled refrigeration technologies hold immense promise in revolutionizing cold chain logistics and enhancing global access to vital medical resources and foodstuffs. [ABSTRACT FROM AUTHOR]

Aims: The revolution in the therapeutic approach to type 2 diabetes (T2D) requires a rethinking of the positioning of basal insulin (BI) therapy. Given the considerable number of open questions, a group of experts was convened with the aim of providing, through a Delphi consensus method, practical guidance for doctors. Methods: A group of 6 experts developed a series of 29 statements on: the role of metabolic control in light of the most recent guidelines; BI intensification strategies: (1) add-on versus switch; (2) inertia in starting and titrating; (3) free versus fixed ratio combination; basal-bolus intensification and de-intensification strategies; second generation analogues of BI (2BI). A panel of 31 diabetologists, by accessing a dedicated website, assigned each statement a relevance score on a 9-point scale. The RAND/UCLA Appropriateness Method was adopted to assess the existence of disagreement among participants. Results: Panelists showed agreement for all 29 statements, of which 26 were considered relevant, one was considered not relevant and two were of uncertain relevance. Panelists agreed that the availability of new classes of drugs often allows the postponement of BI and the simplification of therapy. It remains essential to promptly initiate and titrate BI when required. BI should always, unless contraindicated, be started in addition to, and not as a replacement, for ongoing treatments with cardiorenal benefits. 2BIs should be preferred for their pharmacological profile, greater ease of self-titration and flexibility of administration. Conclusion: In a continuously evolving scenario, BI therapy still represents an important option in the management of T2D patients. [ABSTRACT FROM AUTHOR]

Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased TFH responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization. Computational modeling of TFH priming and the GC response suggested that enhanced activation/antigen loading on dendritic cells and increased capture of antigen delivered in the second dose by follicular dendritic cells contribute to these effects, predictions we verified experimentally. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines. Editor's summary: A key feature of effective vaccines is that the delivery strategy optimizes immune responses. Bhagchandani et al. sought to optimize immune responses using prolonged exposure to a protein subunit vaccine called escalating-dose immunization (EDI). They immunized mice with an adjuvanted HIV envelope protein subunit and tested different numbers of doses, dose ratios, and time intervals between doses. A two-dose regimen for which 20% of the vaccine was administered in the first dose and 80% was given in the second dose 7 days later induced effective follicular helper T cell and antigen-specific germinal center B cell responses that were also reflected in higher antibody titers. This response was linked to enhanced antigen capture and presentation by dendritic cells. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Background: We assessed the prevalence of complications from percutaneous ethanol injection (PEI) for benign and cystic thyroid nodules (CTNs) and their management. Methods: We conducted a systematic review with meta-analysis of data from published observational studies on PEI of CTNs. We also included unpublished retrospectively collected data on complications after PEI from all consecutive patients with cytologically benign CTNs who underwent PEI at the Unit of Endocrinology and Metabolic Diseases, AOU University of Campania Luigi Vanvitelli (Naples, Italy) between June 1, 2021, and March 31, 2024. A random effects meta-analysis was performed on the prevalence rate data. Pooled prevalence data were presented with confidence intervals (CIs). The I2 statistic index was used to quantify the heterogeneity. The details of the complications and the management were qualitatively described. Results: The literature search yielded 1189 studies, of which 48 studies were included in the systematic review and meta-analysis, in addition to our institutional experience (3670 CTNs in total). The overall quality of each included study was judged as fair. The prevalence of "Overall" complications of PEI was 32% ([CI 25–40%], I2 92.7%, 967 of 3195 thyroid nodules [TNs]). The prevalence of "Minor" complications of PEI was 32% ([CI 25–40%], I2 92.7%, 952 of 3195 TNs). The prevalence of "Major" complications of PEI was 2% ([CI 1–2%], I2 0%, 22 of 3670 TNs). Sensitivity analyses did not modify the results. The pooled prevalence rate of local pain was 21% (CI [16–27] I2 90.3). Local pain was typically transient and mild, sometimes moderate, and requiring analgesics for few days. The pooled prevalence rate of dysphonia was 1% (CI [1–2], I2 0). Dysphonia was transient and could last from several hours to 12 months after PEI. Conclusions: Complications of PEI for benign and CTNs are relatively common, but most are minor and usually transient, not requiring treatment. Dysphonia was a major complication, but it was uncommon and transient. PEI for CTNs could be considered a generally safe technique. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the second most diagnosed cancer in men. Focal laser ablation has been proposed as an alternative to radical treatments in carefully selected patients in order to achieve long-term cancer control and reduce the morbidity associated with surgery and radiation therapy. This study aimed to evaluate the oncological and functional outcomes of transperineal laser ablation (TPLA) as the focal therapy for localized prostate cancer. We assessed that TPLA is a safe, painless, and effective technique with good oncological results and the preservation of continence and sexual outcomes. Introduction and objectives: To evaluate the oncological and functional outcomes of transperineal laser ablation (TPLA) as the focal therapy for localized prostate cancer (PCa) after a 12-month follow-up. Materials and methods: Patients with low- and intermediate-risk localized PCa were prospectively treated with focal TPLA between July 2021 and December 2022. The inclusion criteria were the following: clinical stage < T2b; PSA < 20 ng/mL; International Society of Urological Pathology (ISUP) grade ≤ 2; MRI-fusion biopsy-confirmed lesion classified as PI-RADS v2.1 ≥ 3. Intra-, peri-, and post-operative data were collected. Variables including age, PSA, prostate volume (PVol), Charlson's Comorbidity Index (CCI), International Prostate Symptom Score (IPSS) with QoL score, International Index of Erectile Function (IIEF-5), International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF), and Male Sexual Health Questionnaire—Ejaculatory Dysfunction Short Form (MSHQ-EjD) were collected at baseline and at 3, 6 and 12 months after TPLA. Post-operative mpMRI was performed at 3 and 12 months. Finally, all patients underwent prostatic re-biopsy under fusion guidance at 12 months. The success of this technique was defined as no recurrence in the target treated lesion at the 12-month follow up. Results: Twenty-four patients underwent focal TPLA. Baseline features were age [median 67 years (IQR 12)], PSA [5.7 ng/mL (3.9)], PVol [49 mL (27)], CCI [0 (0)], IPSS [11 (9)], IPSS-QoL [2 (2)], IIEF-5 [21 (6)], ICIQ-SF [0 (7)], MSHQ-EjD ejaculation domain [14 (4)] and bother score [0 (2)]. Median operative time was 34 min (IQR 12). Median visual analogue scale (VAS) 6 h after TPLA was 0 (IQR 1). The post-operative course was regular for all patients, who were discharged on the second post-operative day and underwent catheter removal on the seventh post-operative day. No patient had incontinence at catheter removal. A significant reduction in PSA (p = 0.01) and an improvement in IPSS (p = 0.009), IPSS-QoL (p = 0.02) and ICIQ-SF scores (p = 0.04) compared to baseline were observed at the 3-month follow-up. Erectile and ejaculatory functions did not show any significant variation during the follow-up. No intra- and peri-operative complications were recorded. Three Clavien–Dindo post-operative complications were recorded (12%): grade 1 (two cases of urinary retention) and grade 2 (one case of urinary tract infection). At the 12-month follow-up, eight patients showed mpMRI images referable to suspicious recurrent disease (PIRADS v2.1 ≥ 3). After re-biopsy, 7/24 patients' (29%) results were histologically confirmed as PCa, 3 of which were recurrences in the treated lesion (12.5%). The success rate was 87.5%. Conclusions: The focal TPLA oncological and functional results seemed to be encouraging. TPLA is a safe, painless, and effective technique with a good preservation of continence and sexual outcomes. Recurrence rate at 12 months was about 12.5%. [ABSTRACT FROM AUTHOR]

Context The impairment of bone microarchitecture is a key determinant of skeletal fragility in patients with chronic kidney disease (CKD). The trabecular bone score (TBS) has been developed as a reliable noninvasive index of bone quality. However, its utility in this setting is still debated. Objective The aim of this systematic review and meta-analysis was to summarize the available evidence about TBS as a marker of skeletal fragility across the spectrum of CKD. Methods PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until July 2023 for studies reporting data about TBS in patients with CKD. Effect sizes were pooled through a random-effect model. Results Compared to controls, lower TBS values were observed in CKD patients not on dialysis (−0.057, 95%CI:[−0.090, −0.024], P <.01), in dialysis patients (−0.106, 95%CI:[−0.141, −0.070], P <.01), and in kidney transplant recipients (KTRs) (−0.058, 95%CI:[−0.103, −0.012], P =.01). With respect to fracture risk, TBS was able to predict incident fractures in nondialysis patients at unadjusted analyses (hazard ratio [HR] per SD decrease: 1.45, 95%CI:[1.05, 2.00], P =.02), though only a nonsignificant trend was maintained when fully adjusting the model for FRAX® (HR = 1.26, 95%CI:[0.88, 1.80], P =.21). Dialysis patients with prevalent fractures had lower TBS values compared to unfractured ones (−0.070, 95% CI:[−0.111, −0.028], P <.01). Some studies supported a correlation between TBS and fracture risk in KTRs, but results could not be pooled due to the lack of sufficient data. Conclusion CKD patients are characterized by an impairment of bone microarchitecture, as demonstrated by lower TBS values, across the whole spectrum of kidney disease. TBS can also be helpful in the discrimination of fracture risk, with lower values being correlated with a higher risk of prevalent and incident fractures. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) first‐line therapy often consists of polychemotherapy regimens, but choosing a second‐line therapy after disease progression, especially following first‐line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab‐paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. Methods: The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. Results: AG was well‐tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second‐line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first‐line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first‐line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second‐line OS and PFS. Conclusions: This study represents the largest real‐world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first‐line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first‐line therapy. [ABSTRACT FROM AUTHOR]

Introduction Several ‘ultra-minimally-invasive’ surgical treatments (uMISTs) have been developed, aiming to relieve benign prostatic obstruction (BPO) and spare ejaculatory function; however, such techniques do not always ensure substantial improvements in uroflowmetry parameters. The aim of the present study was to evaluate the 2-year functional outcomes of thulium laser transurethral incision of the prostate (ThuIP) as an alternative to uMISTs. Material and methods Data of consecutive patients affected by BPO with indication to surgical intervention and a strong will to spare ejaculatory function were collected on a dedicated prospectively maintained database. A specific “trifecta” was identified as the contemporary presence of: (1) post-operative Qmax ≥15 ml/s; (2) absence of early (within 90 days) complications; and (3) preserved antegrade ejaculation. Results 120 patients underwent ThuIP and were analysed. Median catheterisation time was 2 days (IQR 2-2). Significant improvements in IPSS and IPSS-QoL scores and uroflowmetry parameters were observed at all follow-up times. At the last follow-up visit (24 months) the median ΔIPSS was -12 (-17; -9), median ΔIPSS-QoL was -3 (-4; -2), median ΔQmax was +7.7 ml/s (+5.2; +11.0), and median ΔPVR was -50 ml (-100; 0) (all p-values <0.001). Fourteen patients reported postoperative absence of antegrade ejaculation (11.7%). Overall, trifecta was achieved in 86 patients (71.7%) at 6 months, in 79 patients (65.8%) at 12 months, and in 75 patients (62.5%) at 24 months. Conclusions ThuIP allows for a significant improvement in uroflowmetry parameters and patient-reported outcomes at 2-year follow-up. Moreover, antegrade ejaculation is preserved in approximately 90% of cases. [ABSTRACT FROM AUTHOR]