Azienda Ospedaliera Universitaria Senese

Discordant results have been generated regarding the prognostic role of Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma (FL). The use of prospective data and the adoption of the newly defined standardized SUV4 method for calculating TMTV may generate stronger evidence. We conducted a pre‐planned post hoc analysis of the prospective multicenter randomized phase III FOLL12 trial for newly diagnosed high tumor burden FL (grade 1–3a), which mandated baseline staging with PET. Baseline PET/CT scans were reviewed centrally, and TMTV was calculated using the fixed threshold of SUV4. Kaplan–Meier and Cox regression were used for survival analysis. The primary study endpoint was Progression free Survival (PFS). A total of 689 FL patients were available for TMTV definition. Median TMTV was 161 mL (IQR 50 to 388 mL) and the best cutoff value was set at 180 mL. Patients with high TMTV had a significantly lower 5‐year PFS compared to those with low TMTV: 59% (95% CI, 53–65%) vs. 74% (95% CI, 69–78%) HR 1.61 (95% CI, 1.24–2.09). Prognostic role of TMTV was independent of study arm, chemotherapy regimen, and FLIPI2. Combined with FLIPI‐2, we identified three groups with different 5‐yr PFS rates, with the lowest rates (51%) for patients with high TMTV and high FLIPI2. Combined TMTV and FLIPI model was also prognostic to predict the risk of early progression and of death. Applying the SUV4 standard method pre‐treatment TMTV is confirmed as a strong and independent predictor of PFS in FL patients. Integrating TMTV with FLIPI‐2 improves risk assessment.

Dermatological diseases such as acne, hidradenitis suppurativa (HS), and psoriasis are driven by chronic inflammation and oxidative stress. Emerging evidence highlights the role of nutrition in modulating these conditions, particularly through dietary patterns rich in antioxidants, polyphenols, and unsaturated fatty acids. Recent Findings The Mediterranean diet (MedDiet) has demonstrated potential benefits due to its anti-inflammatory and immunomodulatory effects, while very low-energy ketogenic therapy (VLEKT) has shown promise in rapidly improving disease severity. Specific nutrients, including omega-3 fatty acids, probiotics, and micronutrients, may further contribute to disease management. However, the current literature is limited by small-scale studies and the lack of standardized dietary guidelines. Purpose of Review This Consensus Statement, developed collaboratively by the Italian Association of Dietetics and Clinical Nutrition (ADI), the Italian Society of Dermatology and Sexually Transmitted Diseases (SIDeMaST), the Italian Society of Nutraceuticals (SINut), Club Ketodiets and Nutraceuticals “KetoNut-SINut” and the Italian Society of Endocrinology (SIE), Club Nutrition, Hormones and Metabolism, aimed to establish an evidence-based framework for medical nutrition therapy (MNT) of the most common inflammatory skin diseases, including acne, HS and psoriasis.

Target visceral vessels (TVVs) management during complex aortic treatments remains a critical aspect in endoluminal procedures. Bridge stent-graft (BSG) stability is essential for ensuring the effectiveness and safety of these interventions. Aim of this study was to assess the performance of the Viabahn balloon expandable (VBX) when used as BSG in association with Artivion’s inner-branched endografts. All patients consecutively treated for complex aortic pathology with Artivion inner-branched devices were prospectively enrolled, and those receiving at least one VBX as BSG were included. Primary outcome included VBX-related technical success, reinterventions and freedom from target vessel instability. Cox-regression analysis was used to identify variables independently associated with TVVs instability. Fifty-four patients were included in the study cohort. The total number of target visceral arteries bridged with a VBX through an inner branch was 159. VBX-related technical success was 99.4% (158/159). Each stent-graft was successfully delivered and deployed as planned without any intraprocedural endoleak. The VBX-related patency rate was 98% at 30 days (156/159). Three TVVs occlusions were recorded at follow-up, all asymptomatic and not requiring revascularization. A further TVV-related instability event was documented at a four-month follow-up. The mean follow-up was 11.4 ± 9.3 months. Estimates of freedom from TVVs occlusions and instability at 30 months were 96.6 and 96.0%, respectively. Cox-regression found no variables significantly associated with TVVs instability. The VBX stent-graft appears to be a safe and effective bridging option for inner-branched thoracoabdominal aortic repair. Although preliminary results are promising, larger studies with longer follow-up are needed to validate these findings.

The R‐miniCHOP regimen is the standard first‐line treatment for diffuse large B‐cell lymphoma (DLBCL) in older unfit or frail patients. Recent research suggests that replacing doxorubicin with non‐PEGylated liposomal doxorubicin (NPLD) is safe and effective for DLBCL. However, the outcomes of DLBCL patients receiving NPLD as part of a reduced‐intensity regimen approach have yet to be investigated. This study aimed to assess non‐fit DLBCL patients enrolled in the Elderly Project (EP) conducted by the Fondazione Italiana Linfomi (FIL) who were treated with R‐miniCHOP or R‐miniCOMP. The primary and secondary endpoints were overall survival (OS) and progression‐free survival (PFS), respectively. Of the 1163 cases within the EP cohort, we identified 176 patients (18%) who resulted unfit or frail at simplified geriatric assessment (sGA) and received either R‐miniCHOP (89 cases; 51%) or R‐miniCOMP (87 cases; 49%). Both cohorts exhibited similar clinical characteristics, a similar distribution of unfit and frail cases using the sGA and similar Elderly Prognostic Index (EPI) scores. After a median follow‐up of 28 months, the 3‐year OS and PFS rates were 61% and 54% respectively, with no significant difference between R‐miniCHOP and R‐miniCOMP. Notably, the therapeutic regimen had no significant impact on OS (HR 1.07, 95% CI: 0.63–1.82, p = 0.798) or PFS (HR 1.00, 95% CI: 0.62–1.6, p = 0.999) even after adjusting for propensity score (PS) and inverse probability weighting (IPW). A comprehensive survival analysis within vulnerable geriatric categories (unfit and frail patients) confirmed non‐significant variations in predictive efficacy between R‐miniCHOP and R‐miniCOMP. Of note the independent prognostic role of EPI is confirmed for both OS and PFS. This study suggests that R‐miniCHOP is still the preferred treatment for unfit and frail older DLBCL. The role of R‐miniCOMP for specific subgroups of older DLBCLs warrants confirmation in larger studies.

Background Elevated baseline systolic blood pressure (SBP) was associated with poor outcomes following dual antiplatelet therapy (DAPT) in patients with non-cardioembolic minor ischemic stroke (MIS) or high-risk transient ischemic attack (TIA) in clinical trials. Objectives We aimed to assess the impact of admission SBP on the short-term outcomes after DAPT in patients with non-cardioembolic MIS or high-risk TIA. Methods We performed an inverse probability weighted (IPW) analysis from a prospective multicentric real-world study (READAPT) including patients with non-cardioembolic MIS (National Institute of Health Stroke Scale of 0–5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, 24-h early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleedings, symptomatic intracranial hemorrhage, and 24-h hemorrhagic transformation. We used Cox proportional hazards regression with restricted cubic splines to model the continuous relationship between SBP and the hazard ratio (HR) of new vascular events. We selected SBP = 124 mm Hg as cut-off point for the IPW weighting. Outcomes were compared using Cox and generalized logistic regression analyses, adjusted for residual confounders. Results From 2278 patients in the READAPT cohort, we included 1291 MIS or high-risk TIAs (mean age 70.6 ± 11.4 years; 65.8% males). After IPW, patients with admission SBP ⩾124 mm Hg versus <124 mm Hg had a significantly higher risk of 90-day ischemic stroke or other vascular events (adjusted HR: 2.14 (95% CI 1.07%–4.98%); p = 0.033) and of 24-h early neurological deterioration (adjusted risk difference: 1.91% (95% CI 0.60%–3.41%); p = 0.006). The overall risk of safety outcomes was low, although patients with SBP ⩾124 mm Hg on admission showed higher rates of 90-day moderate-to-severe and any bleeding events (adjusted risk difference: 1.24% (95% CI 0.38%–2.14%); p = 0.004 and 6.18% (95% CI 4.19%–8.16%); p < 0.001; respectively), as well as of 24-h hemorrhagic transformation (adjusted risk difference: 1.57% (95% CI 0.60%–2.55%); p = 0.001). Subgroup analysis showed a significant interaction between admission SBP, sex, and time to DAPT start in predicting 90-day new vascular events (p for interaction <0.001 and 0.007, respectively). Conclusion In patients with non-cardioembolic MIS or high-risk TIA, higher levels of admission SBP may be associated with an increased risk of new vascular events, early neurological deterioration, and bleeding after DAPT use. Future studies should further investigate if optimizing blood pressure management may further improve prognosis.

Background and Aim According to randomized controlled trials (RCTs), dual antiplatelet therapy (DAPT) is more effective for secondary prevention of ischemic events attributable to large artery atherosclerosis (LAA) than other mechanisms. We investigated whether real‐world application may impact DAPT effectiveness and safety in the REAl‐life study on short‐term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack (READAPT, NCT05476081). Methods READAPT was an observational multicenter study including patients with minor ischemic stroke or TIA treated with short‐term DAPT. At 90 days, we assessed primary effectiveness (ischemic recurrence, severe bleeding, or vascular death) and safety (severe to moderate bleeding) outcomes. We explored associations between LAA and outcomes using Cox regression. Within patients with and without LAA, outcomes were compared between subgroups based on age, NIHSS score (for ischemic stroke patients), ABCD² score (for TIA patients), presence and number of MRI acute lesions, and DAPT regimen characteristics. Results Among 1920 analyzed patients (of 2278 enrolled), 452 had LAA. Unlike RCTs, 21.2% of patients with LAA had NIHSS > 5, and 48.2% received DAPT > 30 days. Patients with LAA had higher bleeding rates (3.5% vs. 2.1%, p = 0.004), primarily hemorrhagic infarctions and moderate bleeding, than those without LAA. However, primary effectiveness outcomes were similar (4.9% vs. 3.5%, p = 0.201) between the groups. In patients with LAA, prolonged DAPT (> 21 days), multiple MRI lesions, age ≥ 65, and loading doses increased bleeding risk. Conclusions The real‐world DAPT use in patients with LAA exceeds RCTs boundaries with possible drawbacks on treatment safety.

Introduction Patients with ischemic stroke or transient ischemic attack (TIA) and cancer face unique risks of recurrent ischemic events and bleeding. It is unclear whether this increased risk is present even in patients with minor ischemic stroke or transient ischemic attack (TIA) receiving dual antiplatelet therapy (DAPT). This study aimed to evaluate the impact of cancer on the short-term outcomes after DAPT in patients with non-cardioembolic minor ischemic stroke or high-risk TIA. Patients and methods This was a secondary analysis of the prospective multicentric READAPT study (NCT05476081), including patients with non-cardioembolic minor ischemic stroke (NIHSS ⩽ 5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events (TIA, myocardial infarction, death due to vascular causes). Secondary outcomes included 90-day mRS score distribution and all-cause mortality. The primary safety outcome was the 90-day risk of any bleeding, with secondary safety outcomes including 24-h hemorrhagic transformation. We used Inverse Probability Weighting to compare outcomes between patients with and without cancer. Results From 2278 patients in the READAPT study cohort, we included 1561 patients (mean age 70.3 ± 11.7 years; 65.4% males), of whom 206 (13.2%) had cancer, categorized as either active (27.7%) or in remission (72.3%). After weighting, overall cancer patients had a higher risk of 90-day new ischemic stroke or other vascular events (weighted HR 1.78, 95% CI 1.20–2.63, p = 0.004) and worse 90-day mRS score distribution (OR 1.24, 95% CI 1.10–1.41, p < 0.001) compared to patients without cancer. The 90-day risk of bleeding did not differ between cancer and no-cancer groups overall. When analyzing cancer subgroups, patients with active cancer had significantly higher risk of 90-day ischemic stroke or other vascular (weighted HR 2.75, 95% CI 1.70–4.45, p < 0.001) and any bleeding (weighted HR 2.51, 95% CI 1.27–4.97, p = 0.008) events compared to no-cancer patients. In contrast, patients with cancer in remission had comparable risks to those without cancer. Furthermore, hematological malignancies were associated with a substantially higher risk of 90-day new ischemic stroke or other vascular events compared to solid tumors (weighted HR 8.15, 95% CI 5.06–13.14, p < 0.001). Conclusions Patients with minor ischemic stroke or high-risk TIA and active cancer have increased risk of ischemic and bleeding events after DAPT. Conversely, patients with cancer in remission have similar outcomes compared to those with no cancer.

Background and Objectives: Reverse shoulder arthroplasty (RSA) is an effective surgical procedure for treating end-stage rotator cuff arthropathy, but it is burdened by a relatively high complication rate, mainly due to glenoid component failure. Preoperative planning and intraoperative navigation based on three-dimensional computed tomography (3D CT) scans have proven to be efficient tools for improving the accuracy and stability of the glenoid component. However, this technology is still developing, and there is currently little available research on the subject, especially where clinical outcomes are concerned. The purpose of this retrospective observational study is to report the radiographic and clinical outcomes of a consecutive series of patients that underwent RSA with the use of these new technologies, compared to a standard procedure. Materials and Methods: A consecutive series of 80 patients underwent RSA for shoulder osteoarthritis by a single surgeon at a single institution with a mean follow-up of 41.9 ± 23.6 months (range 24–108) and were divided into two groups according to the surgical technique employed (conventional or navigated surgery), and they were clinically and radiographically assessed at 1, 3, 6, and 12 months after surgery, and then annually. Results: No statistically significant differences were highlighted among the two groups according to complication rate, radiographical glenoid notching, and clinical outcomes. However, a statistically significant difference was observed in screw number and length and surgical time. In the navigated group, fewer screws with longer lengths had been implanted, with a longer surgical time. Conclusions: The use of 3D CT-based preoperative planning and intraoperative navigation is a safe procedure and produces comparable results with respect to standard instrumentation, without an increased risk of complications. It allowed to achieve higher stability of the implant, saving bone stock due to the use of fewer and longer screws than in a conventional procedure. This could also eventually result in a higher longevity of the implant itself.

Background: We previously showed that peptides encompassing the unique b3a2 or b2a2 breakpoint amino-acid sequence of oncogenic p210 induced peptide-specific T-cell responses in chronic myeloid leukemia (CML) patients. Methods: From 2007 to 2011, two multicenter peptide vaccine phase II studies, GIMEMA CML0206 and SI0207, enrolling overall 109 CML patients (68 b3a2 and 41 b2a2) with persistence of molecular disease during imatinib treatment, were carried out. Peptide vaccination schedule included the following: “immunization phase” (six vaccinations every 2 weeks); “reinforcement” phase (three monthly boosts) and “maintenance” phase (two boosts at 3-month intervals). GM-CSF (granulocyte-macrophage-colony-stimulating factor, sarmograstim) served as the immunological adjuvant. Results: The short-term results (at completion of vaccine protocol—12 months) and long-term follow-up are reported. All patients completed the vaccination schedule with no toxicity. After vaccinations, the BCR::ABL1 peptide-specific CD4+ T-cell response was documented in 80% of patients. In the short term, 30% of patients achieved a reduction in BCR::ABL1, while the majority showed stable molecular disease with fluctuations. The median follow-up since diagnosis and last vaccination are 18 and 10 years, respectively, with an overall survival (OS) rate at 18 years of 89%. In addition, 97/109 (89%) patients are alive, while 12/109 (11%) died of CML-unrelated reasons. Overall, 18/109 (16.5%) patients are in treatment-free remission (TFR) for a median time of 48 months. Conclusions: The long-term results of p210 peptide vaccinations in CML patients with persisting disease during imatinib treatment showed its feasibility, safety, absence of off-targets events, high OS and not negligible rate of successful TFR. Active immunotherapeutic approaches in CML patients with low disease burden, eventually employing newer vaccine strategies such as mRNA vaccines, may be reconsidered.

In developed countries, the gradual ageing of the population became one of the most significant socioeconomic factors of the twentieth century, as older patients are often malnourished and immunocompromised. Improved living conditions and advances in medical science have increased life expectancy extended by several decades. As people age, they experience various physiological and functional changes, often leading to atrophy and decreased efficiency in several organs and systems, including the respiratory system. The development of the airways and lung parenchyma begins during morphogenesis in utero and continues up to the age of 30 years, after which, a number of processes begin to determine the progressive ageing of the lungs and, in particular, a reduction in mucociliary clearance, a decrease in alveolar surface area, with degradation of elastin and collagen, which is associated with dilatation of the air spaces. The elderly population (>65 years of age) is at greater risk of developing tracheobronchial and lower respiratory tract diseases, due both to long-term exposure to ever-worsening air pollution, smoking, and occupational toxins, and to their fragility and comorbidity; they also have reduced exercise capacity, lower lung oxygenation, and a greater susceptibility to recurrent lung infections and chronic obstructive pulmonary disease (COPD) (Rojas et al. 2015; Brandsma et al. 2017; Bowdish 2019). Airway disease in the elderly can be divided into upper and lower airway disease. A predominant feature of lower airway disease is the involvement of the bronchioles; sometimes this may be associated with the involvement of the more proximal airways or even spread distally to the lung parenchyma (Table 1). The most common lower airway diseases in elderly patients are COPD, asthma, and bronchiectasis. Upper airway diseases, on the other hand, are a heterogeneous group of disorders and are often undiagnosed, usually because they are asymptomatic or paucisymptomatic, and therefore generally untreated. The most common upper airway disorders in older patients are tracheobronchomegaly, tracheobronchial diverticula, tracheobronchomalacia, tracheobronchopathia osteochondroplasia, Wegener’s granulomatosis, and amyloidosis (Table 2). In this chapter, we will look at the main causes of airway pathology in the elderly (Maggi et al. 2006).

Lung transplantation is a life-saving procedure for end-stage lung diseases. Size matching is critical in the donor-recipient selection process. This retrospective study analyzed 146 patients who underwent lung transplantation between 2013 and 2023. Patients who required graft resizing were assigned to the sizing group (S), non-resizing cases to the non-sizing group (NS). The primary goal was to identify predictive factors for graft resizing. Secondary endpoints included ischemia time, ventilation time, primary graft dysfunction (PGD) and hospital stay. The S group was further stratified on baseline parameters to assess differences in outcomes. Recipient height and single transplants were higher in the NS group. Donor-recipient height ratio was the only predictor for resizing (p = 0.02). Postoperative outcomes and overall survival were similar between the groups. In Group S, male patients showed higher rates of acute kidney injury (AKI) and chronic rejection, the former being associated also with anatomical resections; patients older than 50 experienced higher rates of PGD. Graft resizing is a feasible strategy for addressing size mismatch, but it is associated with increased risks of PGD and AKI, particularly in older male recipients and those undergoing anatomical resections. These findings highlight the importance of careful preoperative donor-recipient size matching.

Background and purpose Degenerative and/or herniated discs are a global cause of chronic lower back and neck pain. While multiple treatments exist, the research for long-term effective interventions with minimal side effects continues. The radioplaque gelified ethanol (RGE) (DiscoGel®, Hérouville-Saint-Clair, France), is an addition to the armamentarium of potential treatments. This study aimed to evaluate the long-term efficacy of this device in treating lumbar disc herniation through a 10-year follow-up period. Methods In this bi-centric observational study, patients treated with RGE in the lumbar spine between 2009 and 2011 were evaluated based on specific inclusion and exclusion criteria. Collected data encompassed preoperative imaging, VAS pain scores, ODI functional scores, were recorded through 10-year follow-up. Results Fifty-two participants (26 males and 26 females) with an average age of 51.7 years were enrolled in the study. Ten years after treatment, there was a statistically significant improvement in VAS pain scores and ODI percentages (p < 0.01). Additionally, significant changes in anterior, medial, and posterior disc dimensions were observed, suggesting structural adaptations due to RGE treatment. A statistically significant difference in the anterior dimension of the treated disc was found 10 years postoperatively compared to preoperative measurements (p = 0.0011). Conclusion RGE is a promising therapeutic choice for lumbar symptomatic herniation resistant to conservative treatments, offering both immediate relief and enduring benefits. Although our findings are promising, additional randomized controlled trials are essential to compare DiscoGel® with established treatments and substantiate its efficacy.

Follicle-associated epithelium (FAE) covering the lymphoid follicles of Peyer’s patches (PPs) plays a central role in mucosal immunity. Here, we investigated FAE-derived intrafollicular epithelial bodies (IFEBs) that apparently detach from the FAE and sink deep into the lymphoid tissue of the PPs. Analysis of rabbit PP FAE was carried out by a variety of microscopy and immunohistochemistry techniques using a panel of specific antibodies to determine the nature of the IFEBs. IFEBs displayed the typical features of the FAE, with cytokeratin (CK)+ epithelial cells and CK+/vimentin+ M-cell-like cells. Serial sections of PP tissues showed that the IFEBs are formations frequently separated by the overlying FAE that maintains its integrity. Further, IFEBs showed the presence of junction-associated molecules like zonulin-1 and desmoplakins. Also, IFEBs apparently disaggregate within the lymphoid tissue, as demonstrated by basement membrane disappearance and the finding of isolated epithelial cells that acquire the features of non-polarized epithelial cells. Segments of the FAE in rabbit PPs can detach, forming IFEBs that migrate inside the lymphoid tissue. Although the biological relevance of the newly described IFEBs remains to be determined, we interpreted these data as showing the highly dynamic nature of the PP-associated FAE.

Objectives Endoscopic papillectomy (EP) is the gold standard treatment for ampullary adenomas. However, EP is still burdened by a nonnegligible rate of incomplete resections (IR). Different predictors have been linked to higher rates of IR, but the interaction between these factors is still unclear. The aim of the study was to develop a scoring system (hereby called PANETH score) able to quantify the risk of IR after EP. Methods Patients who underwent EP in 19 Italian centers in 2016–2021 were included. IR was defined as the presence of residual tumor in lateral or endoampullary margins after EP. Predictors for IR were analyzed by logistic regression and were used to obtain an easy‐to‐use numeric score. The performance of the model was evaluated with a receiver operating characteristic curve analysis and tested by means of 10‐fold cross‐validation. Results A total of 430 patients were included. On multivariate analysis, laterally spreading tumor (odds ratio [OR] 5.81, 3.21–7.65; P = 0.02), intraductal extension (OR 6.92, 3.33–9.87; P < 0.0001), and bile duct dilation (OR 2.61, 1.22–4.32; P = 0.004) were significant predictors of IR. The score was calculated by the sum of regression coefficients of each predictor. A ≥3 score indicated a 4‐fold risk of IR ( P < 0.0001). The internal validation resulted in an area under the curve of 0.83 and an overall error rate of 0.11. Conclusions The proposed PANETH score may represent a reliable and easily applicable tool to predict the risk of IR after EP to optimize patient selection and risk stratification.

Solid-organ transplant patients require prolonged immunosuppression, increasing their risk of hematologic disorders. For these conditions, allogeneic hematopoietic stem cell transplantation (HSCT) is a potential treatment, but it carries significant risk of treatment-related mortality due to the high possibility of developing rare infectious complications. We report a case of a 55-years-old male with a history of bilateral lung transplantation for extrinsic allergic alveolitis in 2015, who developed acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) with TP53 mutation seven years later. During induction therapy, he experienced systemic fungal infection caused by Fusarium solani and he underwent HSCT conditioning with active intravitreal fungal infection. It is noteworthy that cases of patients undergoing HSCT after a prior lung transplant are exceedingly rare. The medical literature primarily documents cases where HSCT is performed first, followed by lung complications. Cases with the opposite timeline are extremely uncommon, and there is limited data on their outcomes; thus, the patient depicted here may help management and decision making of physicians facing this rare sequence of diseases and treatments.