Anti-Syndecan 2 Antibody Treatment Reduces Edema Formation and Inflammation of Murine Laser-Induced CNV.

Purpose: Alteration of visual acuity in wet age-related macular degeneration (AMD) is mostly driven by vascular endothelial growth factor A (VEGF-A)-induced edema from leaky newly forming blood vessels below the retina layers. To date, all therapies aimed at alleviation of this process have relied on inhibition of VEGF-A activity. Although effective in preventing vascular leak and edema, this approach also leads to the loss of normal vasculature and multiple related side effects.

[The evolution of a luminal breast cancer to a triple-negative and its impact on disease control with sacituzumab govitecan.].

Triple negative breast cancer (TNBC) represents 15% of invasive breast cancer cases and is an aggressive subtype. Patients with metastatic TNBC have a poor prognosis. Efforts have been made to develop new therapeutic options and identify molecular biomarkers to improve overall survival and quality of life for TNBC patients.

Rare tumors II: Adrenocortical tumors, neuroendocrine tumors of the appendix, pheochromocytoma and paraganglioma, pancreatoblastoma and solid pseudopapillary tumors of the pancreas.

Very rare tumors are usually divided into two groups: One includes tumors that are rare among both children and adults; the other one encompasses tumors that frequently occur in adults but are rarely observed in children. In this review, we focus on adrenocortical tumors, neuroendocrine tumors of the appendix, pheochromocytoma and paraganglioma, pancreatoblastoma and solid pseudopapillary tumors of the pancreas, with special attention to the role of surgery as main curative intervention or as part of the multimodal treatment.

Management of liver disease and portal hypertension in cystic fibrosis: a review.

Introduction: Cystic fibrosis (CF)-associated liver disease can significantly affect the quality of life and survival of people with CF. The hepatobiliary manifestations in CF are various, with focal/multilobular biliary cirrhosis more common in children and porto-sinusoidal vascular disease (PSVD) in young adults. Portal hypertensive complications, particularly bleeding from esophagogastric varices and hypersplenism are common, while liver failure is rarer and mainly linked to biliary disease.

Emerging Treatment Options for Neuroendocrine Neoplasms of Unknown Primary Origin: Current Evidence and Future Perspectives.

Among neuroendocrine neoplasms (NENs), a non-negligible proportion (9-22%) is represented by sufferers of NENs of unknown primary origin (UPO), a poor prognostic group with largely unmet clinical needs. In the absence of standard therapeutic algorithms, current guidelines suggest that the treatment of UPO-NENs should be based on tumor clinical-pathological characteristics, disease burden, and patient conditions. Chemotherapy represents the backbone for the treatment of high-grade poorly differentiated UPO-NENs, usually providing deep but short-lasting responses.

Pediatric kidney transplantation: is it safe to perform during night-time or day-off?

Purpose: To investigate the impact of after-hours surgery on the outcomes of pediatric kidney transplantation (KT).

Methods: Medical records of pediatric KTs performed at a single institution between 2013 and 2021 were retrospectively reviewed. The population was split into three groups according to the incision time and calendar: ordinary day (8.

Mediastinal Germ-cell Tumors Relapse in a Male With Klinefelter Syndrome. Is Longer Surveillance Needed?

Germ cell tumors (GCTs) are a heterogeneous group of pediatric cancers. In up to one-third of male patients, a primary mediastinal location is associated with the presence of Klinefelter syndrome (KS). We describe a case of mediastinal GCT in a patient, with unacknowledged KS, that presented a relapse 7 years from diagnosis, that is, 2 years after the end of the follow-up program usually recommended for patients with GCT.

The contribution of the private healthcare sector during the COVID-19 pandemic: the experience of the Lombardy Region in Northern Italy.

Introduction: In Lombardy, the first European region hit by the COVID-19 pandemic, for decades the regional public healthcare service has followed a mixed delivery model with extensive involvement of private accredited providers. The study aimed at examining the role of the private sector in delivering healthcare services (diagnosis, hospitalization, and vaccination) during the pandemic.

Study Design: Healthcare system study.

Safety and antitumor activity of metformin plus lanreotide in patients with advanced gastro-intestinal or lung neuroendocrine tumors: the phase Ib trial MetNET2.

In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract.

Initial adaptation among university student: The case of the social sciences.

Students' academic and social adaptation is linked to factors such as their initial study motivations, the atmosphere of the academic environment and their perception of academic wellbeing. This paper analyses the initial adaptation of first-degree students in their first semester through a quantitative ex post facto study with a descriptive-exploratory approach, using a questionnaire as the information-gathering instrument. Findings shed light on the concept of initial adaptation itself (through the creation of an index) and validate the study of the construct through three factors: initial motivation, the academic environment and perception of academic wellbeing.

Small bowel lesions in patients with iron deficiency anaemia without overt bleeding: a multicentre study.

The diagnostic work-up in iron deficiency anaemia (IDA) patients can be challenging when bleedings or malabsorption are not clinically manifest. Lesions on the small bowel mucosa may cause IDA. We evaluated the prevalence of lesions on the small bowel mucosa detected at Videocapsule Endoscopy (VCE) in IDA patients following negative upper and lower endoscopies.

Assessing the safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic and thoracic neuroendocrine tumors: rationale and protocol of the phase II LOLA trial.

Background: Well-differentiated (WD) neuroendocrine tumors (NETs) are a group of rare neoplasms with limited therapeutic options. Cabozantinib is an inhibitor of multiple tyrosine kinases with a pivotal role in NET pathogenesis, including c-MET and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). LOLA is the first prospective phase II trial aiming to assess the safety and activity of cabozantinib combined with lanreotide in WD NETs of gastroenteropancreatic (GEP), thoracic and of unknown origin.

Comparative analysis of wild-type and chloroplast MCU-deficient plants reveals multiple consequences of chloroplast calcium handling under drought stress.

Introduction: Chloroplast calcium homeostasis plays an important role in modulating the response of plants to abiotic and biotic stresses. One of the greatest challenges is to understand how chloroplast calcium-permeable pathways and sensors are regulated in a concerted manner to translate specific information into a calcium signature and to elucidate the downstream effects of specific chloroplast calcium dynamics. One of the six homologs of the mitochondrial calcium uniporter (MCU) was found to be located in chloroplasts in the leaves and to crucially contribute to drought- and oxidative stress-triggered uptake of calcium into this organelle.

Multidisciplinary Approach to the Diagnosis of Occult Primary Neuroendocrine Neoplasm: A Clinical Challenge.

Approximately 11% to 14% of subjects with neuroendocrine neoplasms (NENs) have metastatic lesions with unknown primary origin (UPO), with the majority of UPO-NENs found in the small bowel. Herein, we assessed the available literature on UPO-NENs, focusing on clinical presentation and diagnostic techniques to identify the primary site. The identification of the primary tumor is important as it affects the prognosis; however, the clinical presentation can be non-specific in non-functioning forms.

Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors.

Purpose: Microsatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10% to 40% of patients with MSI mCRC will experience a primary resistance to ICI.

Experimental Design: In two cohorts of patients with MSI mCRC treated with ICI (exploratory, N = 103; validation, N = 35), 3' RNA sequencing was performed from primary tumors.

Tumour mutational burden as a biomarker in patients with mismatch repair deficient/microsatellite instability-high metastatic colorectal cancer treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are the standard treatment in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Tumour mutational burden (TMB) is a promising biomarker for the prediction of treatment outcomes.

Patients And Methods: We screened 203 patients with dMMR/MSI-H mCRC treated with an anti-PD-(L)1 (anti-Programmed-Death-(Ligand)1) plus or minus an anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA-4) agent at three Italian Academic Centers.

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols.

Background: To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy.

Methods: This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy.

Results: Out of 65 patients with a median age at diagnosis of 8.

BRAF V600E/RAS Mutations and Lynch Syndrome in Patients With MSI-H/dMMR Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors.

Background: We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS/BRAFV600E mutations and Lynch syndrome (LS).

Patients And Methods: Patients were defined as LS-linked if germline mutation was detected and as sporadic if loss of MLH1/PMS2 expression with BRAFV600E mutation and/or MLH1 promoter hypermethylation, or biallelic somatic MMR genes mutations were found. Progression-free survival (PFS) and overall survival (OS) were adjusted on prognostic modifiers selected on unadjusted analysis (P < .

Association of immune-related adverse events with the outcomes of immune checkpoint inhibitors in patients with dMMR/MSI-H metastatic colorectal cancer.

Background: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs.

Propranolol and infantile hemangiomas: Outcome from a tricentric study.

Introduction: The introduction of propranolol as systemic therapy for infantile hemangiomas (IH) has changed the natural history of these tumors. Cases presenting with ulceration, functional limitation, and visceral or life-threatening localization are excellent indications to medical therapy. The aim was to report the medium term follow-up after the introduction of propranolol in 3 referral centers with particular attention to outcome and surgical treatments.

Effects of prolonged proton pump inhibitor treatment on nutritional status and respiratory infection risk in cystic fibrosis: A matched cohort study.

Background: Evidence on the effectiveness of proton pump inhibitors (PPI) as adjuvant therapy to improve maldigestion in people with cystic fibrosis (pwCF) is limited and there is increasing concern on possible side effects.

Methods: We conducted a matched cohort study based on paediatric and adult pwCF who received PPI for ≥3 months. Treated patients were matched to a group of patients who never received PPI using a nearest neighbour propensity score matching based on sex, year of birth, CFTR genotype and pancreatic insufficiency.

Syndecan-2 selectively regulates VEGF-induced vascular permeability.

Vascular endothelial growth factor (VEGF)- driven increase in vascular permeability is a key feature of many disease states associated with inflammation and ischemic injury, contributing significantly to morbidity and mortality in these settings. Despite its importance, no specific regulators that preferentially control VEGF-dependent increase in permeability versus its other biological activities, have been identified. Here we report that a proteoglycan Syndecan-2 (Sdc2) regulates the interaction between a transmembrane phosphatase DEP1 and VEGFR2 by controlling cell surface levels of DEP1.

A successful treatment of a lobar atelectasis in a patient with cystic fibrosis.

Lobar atelectasis may be a complication of pulmonary exacerbations in cystic fibrosis (CF). There are no established guidelines on the management of this condition in patients with CF. Therapeutic bronchoscopy with recombinant human deoxyribonuclease (rhDNase) instillation has been described to be successful in patients not responding to conservative measures.