0 3What ' s known on the subject? and What does the study add? Few studies supported the expanded indications for nephron-sparing surgery (NSS) in selected patients with 4.1 -7 cm renal tumours in the size range (T1b). However, all these comparative studies included both imperative and elective partial nephrectomy and patient selection for analysis was based on pathological stage (pT1) and not on clinical stage (cT1).Patients with clinically organ-confi ned RCC (cT1) who are candidates for elective PN have a limited risk of clinical understaging. NSS is not associated with an increased risk of recurrence and cancer-specifi c mortality both in cT1a and cT1b tumours OBJECTIVE• To compare the oncological outcomes of patients who underwent elective partial nephrectomy (PN) or radical nephrectomy (RN) for clinically organconfi ned renal masses ≤ 7 cm in size (cT1). PATIENTS AND METHODS• The records of 3480 patients with cT1N0M0 disease were extracted from a multi-institutional database and analyzed retrospectively. RESULTS• In patients who underwent PN, the risk of clinical understaging was 3.2% in cT1a cases and 10.6% in cT1b cases.• With regard to the cT1a patients, the 5-and 10-year cancer-specifi c survival (CSS) estimates were 94.7% and 90.4%, respectively, after RN and 96.1% and 94.9%, respectively, after PN (log-rank test: P = 0.01).• With regard to cT1b patients, the 5-year CSS probabilities were 92.6% after RN and 90% after PN, respectively (log-rank test: P = 0.89).• Surgical treatment failed to be an independent predictor of CSS on multivariable analysis, both for cT1a and cT1b patients.• Interestingly, PN was oncologically equivalent to RN also in patients with pT3a tumours (log-rank test: P = 0.91). CONCLUSIONS• Elective PN is not associated with an increased risk of recurrence and cancerspecifi c mortality in both cT1a and cT1b tumours.• Data from the present study strongly support the use of partial nephrectomy in patients with clinically T1 tumours, according to the current recommendations of the international guidelines. KEYWORDSclinical staging , nephron-sparing surgery , partial nephrectomy , radical nephrectomy , renal cancer Study Type -Therapy (cohort) Level of Evidence 2b

E 5 5 9What ' s known on the subject? and What does the study add? The interest in metastatic renal cell carcinoma has increased in the last few years, mainly due to the advent of targeted therapies, but metastasectomy remains the sole therapy that can lead to a complete and durable regression, even if only in a minority of patients. The literature reports quite large series of metastasectomies for the most common sites of metastasis, e.g. lung, liver, bone, adrenal and brain, whereas little is known about the management of metastasis in ' atypical ' sites.The prognosis of patients submitted to metastasectomy for a metastasis in an atypical site is equivalent to patients with lung metastasis. The characteristics of the primary tumour in these patients are not indicative, but atypical metastasis (AM) are often located in superfi cial sites and frequently associated with other metastases. So, physical examination should be included in all follow-up regimens and a complete re-staging should be performed after the diagnosis of an AM. OBJECTIVE• To review the clinical characteristics and oncological results in patients submitted to surgical removal of metastasis from renal cell carcinoma (RCC) in atypical sites (atypical metastasis [ AM ] , i.e. metastasis in sites other than the chest, liver, bone, adrenal, brain, kidney, and lymph nodes), compared with patients submitted to metastasectomy due to a lung metastasis (LM). PATIENTS AND METHODS• From an institutional database of ≈ 1800 patients surgically treated for a RCC, we retrospectively identifi ed 37 cases that had undergone metastasectomy for AM and 57 operated for LM.• Clinicopathological features of the primary RCC and metastasis, and cancerspecifi c survival (CSS) computed from the time of metastasectomy of patients with AM and LM, were compared.• A univariate and multivariable analysis applying a Cox regression model was used to evaluate CSS. RESULTS• The patients with AM and LM were followed for an average of 40.8 and 50.7 months from metastasectomy, respectively ( P = 0.372).• There were no signifi cant differences in the characteristics of the primary tumour between patients with AM and LM.• In the cases with AM and LM the diagnosis was simultaneous with that of the primary tumour in 32.4% and 24.6%, ( P = 0.40) respectively, and, when metachronous, occurred at an average delay of 53.4 and 44.3 months ( P = 0.370).• More frequently in the cases with AM other metastases had been diagnosed in the previous medical history (35.2 vs 8.8%, P = 0.001) or simultaneously (48.6 vs 8.8%, P = 0.001).• CSS from metastasectomy was affected by the synchronicity in diagnosis between metastasis and primary tumour, and by the simultaneous presence of other metastases, while the type of metastasis (AM vs LM) did not affect CSS. In fact, metastasectomy in AM was as effective as in LM. CONCLUSION• AM are an exceptional presentation of metastatic RCC, but the role of surgery is similar to that of pulmonary metastasis. In these cases, metastasectomy is accepted as possible care...

Gene therapies using adeno-associated viruses (AAVs) are among the most promising strategies to treat or even cure hereditary and acquired retinal diseases. However, the development of new efficient AAV vectors is slow and costly, largely because of the lack of suitable non-clinical models. By faithfully recreating structure and function of human tissues, human induced pluripotent stem cell (iPSC)derived retinal organoids could become an essential part of the test cascade addressing translational aspects. Organ-on-chip (OoC) technology further provides the capability to recapitulate microphysiological tissue environments as well as a precise control over structural and temporal parameters. By employing our recently developed retina on chip that merges organoid and OoC technology, we analyzed the efficacy, kinetics, and cell tropism of seven first-and second-generation AAV vectors. The presented data demonstrate the potential of iPSC-based OoC models as the next generation of screening platforms for future gene therapeutic studies.

Synovial sarcoma (SS) primarily occurs in the para-articular soft tissue of the lower extremities in young adults and it is extremely rare in the prostatic region. We report a case of a 46-year-old man who presented with urinary retention. Pelvic ultrasound (US) examination, computed tomography (CT), and magnetic resonance imaging (MRI) demonstrated an 8.5 cm mass that appeared to originate in the prostatic fascia of the right lobe. Preoperative prostatic ultrasound transrectal needle biopsy revealed mesenchymal neoplastic tissue. Patient underwent surgery. The final pathologic findings were consistent with the diagnosis of monophasic synovial sarcoma.

Aims In this work, the survival and mortality data of 54 consecutive patients admitted to the Intensive Care Unit (ICU) and suffering from severe respiratory insufficiency imputable to viral SARS - CoV - 2 infection were analyzed and shared, after a critical review of the evidence in order to optimize the most dedicated clinical and treatment strategy, for a future ‘targeted’ management in the care of the possible return flu outbreak. Methods At our Emergency Department of the Crema Hospital, from the beginning of the pandemic until the end of June 2020, 54 consecutive patients admitted to ICU suffering from severe acute respiratory infection (SARI) and severe respiratory distress (ARDS) attributable to viral SARS - CoV - 2 infection were recruited. The recruitment criterion was based on refractory hypoxia, general condition and clinical impairment, comorbidities and CT images. The incoming parameters of the blood chemistry and radiology investigations and the timing of the gold - tracheal intubation were compared. Medical therapy was based on the application of shared protocols. Results The onset of symptoms was varyng, i.e. within the range of 1–14 days. The average time from the admission to the emergency room to the admission to intensive care was approximately 120 h. The average number of days of hospitalization in the ICU was 28 days. With a majority of male patients, the most significant age group was between 60 and 69 years. There were 21 deaths and, compared to the survivors, the deceased ones were older at an average age of about 67 years (vs an average age of the survivors of about 59 years). From the available data entering the ICU, the surviving patients presented average better values of oximetry and blood gas analysis, with a lower average dosage of D-Dimer than the deceased. Ones with a presence of bilateral pneumonia in all patients, the worsening of the ARDS occurred in 31 patients. 9 out of 25 patients early intubated died, while 12 out of 23 patients died when intubation was performed after 24 h of non-invasive ventilation. The presence of multiple comorbidities was shown in 17 of 28 patients and revealed an additional adverse prognostic factor. Also, more than one complication in the same patient were detected; after respiratory worsening, renal failure was more frequently found in 16 patients. Some particular complications such as lesions induced by ventilation with barotrauma mechanism (VILI), ischemic heart disease and the appearance of central and peripheral neurological events were detected too. Considerations SARS - CoV - 2 disease is caused by a new coronavirus that has its main route of transmission through respiratory droplets and close contact, resulting in a sudden onset of the clinical syndrome with acute respiratory infection (SARI) and severe respiratory distress (ARDS). But it can also appear with other symptoms such as gastrointestinal or neurological events, as to be consi...

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Enhancing the differentiation potential of human induced pluripotent stem cells (hiPSC) into disease‐relevant cell types is instrumental for their widespread application in medicine. Here, we show that hiPSCs downregulated for the signaling modulator GLYPICAN‐4 (GPC4) acquire a new biological state characterized by increased hiPSC differentiation capabilities toward ventral midbrain dopaminergic (VMDA) neuron progenitors. This biological trait emerges both in vitro, upon exposing cells to VMDA neuronal differentiation signals, and in vivo, even when transplanting hiPSCs at the extreme conditions of floor‐plate stage in rat brains. Moreover, it is compatible with the overall neuronal maturation process toward acquisition of substantia nigra neuron identity. HiPSCs with downregulated GPC4 also retain self‐renewal and pluripotency in stemness conditions, in vitro, while losing tumorigenesis in vivo as assessed by flank xenografts. In conclusion, our results highlight GPC4 downregulation as a powerful approach to enhance generation of VMDA neurons. Outcomes may contribute to establish hiPSC lines suitable for translational applications.

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