FO014TUBULAR CELL HYPERTROPHY VIA ENDOCYCLE AND PROLIFERATION OF TUBULAR PROGENITORS ARE CENTRAL MECHANISMS OF RESPONSE AFTER AKI

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Endobronchial metastasis: an epidemiologic and clinicopathologic study of 174 consecutive cases

PURPOSE: Endobronchial metastases from extrapulmonary solid tumors are a rare event and currently available epidemiological and clinico-pathological data mainly derive from anecdotal case reports. METHODS: A series of 174 consecutive cases of endobronchial metastases from extrathoracic solid tumors were collected over a period of 18 years. Immunohistochemistry was performed in 115 cases. Complete imaging features were available in 81 patients, and analysis of the latency period between primitive tumor diagnosis and occurrence of endobronchial metastasis was obtained. RESULTS: Among all bronchoscopic examinations performed in the same period for malignancy, a mean of 5.6 cases per year consisted of endobronchial metastases (range 2-17 cases), with a statistically significant increase when comparing the periods 1992-2000 (65 cases, 37%) and 2001-2009 (109 cases, 63%) (p = 0.05). Overall, 4% of endobronchial biopsies for suspected malignancy disclosed an endobronchial metastasis from extrapulmonary tumor. Breast (52 cases, 30%), colorectal (42 cases, 24%), renal (14%), gastric (6%) and prostate (4.5%) cancers and melanoma (4.5%) were the most common metastatic neoplasms presenting as endobronchial mass. One-hundred fifty-four cases were identified after the primitive tumor diagnosis (metachronous cases, 89%), 11 cases were simultaneously evidenced in extrapulmonary and endobronchial sites (synchronous cases, 6%), while 9 occult metastatic cases (5%) first presented as endobronchial mass (anachronous cases). Overall, mean latency from extrapulmonary tumor diagnosis and endobronchial metastasis was 136 months (range, 1-300 months). The most frequent symptoms were dyspnea (23%), cough (15%) and haemoptysis (12%), while 26% of patients were totally asymptomatic. At radiology, 53% presented as multiple pulmonary nodules, while other cases presented as hilar and mediastinal mass, single peripheral nodule, atelectasis or pleural effusion. CONCLUSIONS: Endobronchial metastases from extrapulmonary tumors account for about 4% of all bronchoscopic biopsies performed for suspected malignancy and in 5% of the cases the metastasis is the first manifestation of the neoplasm

SP181PAX2+ PROGENITOR CELLS PLAY A KEY ROLE IN TUBULAR REGENERATION AFTER ACUTE KIDNEY INJURY

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Un raro caso di flogosi granulomatosa non necrotizzante in paziente sieropositivo

Si presenta il caso di un paziente di 54 anni HIV-positivo in terapia antiretrovirale dal 1996, giunto alla nostra osservazione nel 2011 per la comparsa di maculo-papule eritematose degli arti superiori. Il paziente ha contratto negli ultimi 20 anni diverse infezioni opportunistiche, epatite A, B, D e C ed ha sviluppato un’invalidante polineuropatia sensitivo-motoria di tipo assonale. L’esame istologico delle lesioni cutanee ha evidenziato una flogosi granulomatosa non necrotizzante di tipo interstiziale. Dopo un inefficace trattamento con steroidi topici si è osservata una trasformazione del quadro clinico con marcata estensione delle lesioni maculo-papulari a tutto l’ambito cutaneo con risparmio del volto e con comparsa di noduli deturpanti dei gomiti. Nel sospetto di una grave patologia sistemica con interessamento cutaneo, sono stati eseguiti accertamenti strumentali, valutazioni multidisciplinari ed una biopsia di una delle lesioni nodulari che ha portato a diagnosticare un raro quadro di flogosi granulomatosa non necrotizzante del derma superficiale e profondo con aspetti peculiari. È stato quindi iniziato trattamento con idrossiclorochina e successivamente con metotrexato, quest’ultimo sospeso dopo 1 mese per la comparsa di importanti effetti collaterali, da cui il paziente non ha tratto alcun beneficio. Attualmente è in corso di valutazione terapia con farmaco biologico anti-TNF alfa

Podocyte Regeneration Driven by Renal Progenitors Determines Glomerular Disease Remission and Can Be Pharmacologically Enhanced

Podocyte loss is a general mechanism of glomerular dysfunction that initiates and drives the progression of chronic kidney disease, which affects 10% of the world population. Here, we evaluate whether the regenerative response to podocyte injury influences chronic kidney disease outcome. In models of focal segmental glomerulosclerosis performed in inducible transgenic mice where podocytes are tagged, remission or progression of disease was determined by the amount of regenerated podocytes. When the same model was established in inducible transgenic mice where renal progenitors are tagged, the disease remitted if renal progenitors successfully differentiated into podocytes, while it persisted if differentiation was ineffective, resulting in glomerulosclerosis. Treatment with BIO, a GSK3s inhibitor, significantly increased disease remission by enhancing renal progenitor sensitivity to the differentiation effect of endogenous retinoic acid. These results establish renal progenitors as critical determinants of glomerular disease outcome and a pharmacological enhancement of their differentiation as a possible therapeutic strategy

Drug survival of IL-12/23, IL-17 and IL-23 inhibitors for moderate-to-severe plaque psoriasis: a retrospective multicenter real-world experience on 5932 treatment courses – IL PSO (Italian landscape psoriasis)

The development of several effective biological drugs for moderate-to-severe plaque psoriasis has dramatically changed the lives of patients. Despite the wide use of interleukin (IL) inhibitors, limited data are available to date regarding long-term treatment persistence

Long‐Term Effectiveness and Safety of Ixekizumab for the Treatment of moderate‐to‐Severe Plaque Psoriasis: A Five‐Year Multicenter Retrospective Study—IL PSO (Italian Landscape Psoriasis)

Introduction: The introduction of biological therapies has revolutionized the treatment of moderate-to-severe plaque psoriasis. In particular, ixekizumab, an inhibitor of interleukin17A, has shown great results in terms of effcacy and safety in both clinical trials and real-world experiences. However, there is a lack of longterm real-world data available for ixekizumab. Methods: We conducted a multicenter real-life study to evaluate the effectiveness and safety of ixekizumab in patients with moderate-to-severe plaque psoriasis. Psoriasis Area and Severity Index score (PASI) was collected at baseline and after 1, 2, 3, 4, and 5 years. The occurrence of any adverse events was recorded at each time point

Effectiveness, Tolerability, and Drug Survival of Risankizumab in a Real-World Setting: A Three-Year Retrospective Multicenter Study—IL PSO (ITALIAN LANDSCAPE PSORIASIS)

Background: Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin-23. It has been approved for moderate-to-severe plaque psoriasis and has shown efficacy and safety in clinical trials and real-world experiences. This study aimed to evaluate the long-term effectiveness, safety, and drug survival of risankizumab in a real-life setting. Materials and Methods: We included patients treated with risankizumab from January 2019 to February 2023. A Psoriasis Area and Severity Index score (PASI) was collected at weeks 0, 16, 28, 52, 104, and 156, when available. The occurrence of any adverse events was recorded at each visit. Results: We enrolled 1047 patients. At week 52, a ≥90% improvement in PASI was observed in 81.44% of patients, with a continuous improvement throughout the study (88.99% and 99.07% at weeks 104 and 156, respectively). After three years of treatment, all patients involving the scalp, palms/soles, and genitalia and 95% of patients with nail psoriasis achieved a complete or almost complete skin clearance. No significant safety findings were observed, and 90.73% of the patients were still on treatment after 36 months. Conclusions: This study supports the long-term effectiveness and safety of risankizumab in a real- world setting, even in patients involving difficult-to-treat areas