Screening for celiac disease,by endomysial antibodies,in patients with unexplained articular manifestations

Celiac disease (CD) is an autoimmune systemic disease characterized by not only gastrointestinal but also extraintestinal manifestations. The aim of our study was to do a serological screening for CD, by IgA endomysial antibodies (EmA), in patients with unexplained articular manifestations. Two hundred and eleven patients suffering from arthritis or arthralgia without evident cause were studied. EmA were determined by indirect immunofluorescence on human umbilical cord. Two thousand and five hundred blood donors served as control group. Out of 211 patients, 5 had EmA (2.37 %). The frequency of EmA in our patients was significantly higher than in the control group (2.37 vs. 0.28 %, p < 0.01). All patients with positive EmA were female. EmA were significantly more frequent in female patients than in female healthy subjects (3 vs. 0.4 %, p < 0.01). Medical records revealed: diarrhea (one patient), short size (one patient), anemia (three patients), weight loss (two patients) spontaneous abortion (three patients), secondary amenorrhea (one patient), early menopause (one patient) and early baby death (one patient). Biochemical analysis showed decreased level of calcium (one patient), vitamin D (one patient) and cholesterol (one patient). Unexplained liver cytolysis was observed in two patients. Radiological examination showed demineralization of two hands in one patient. Bone osteodensitometry done in one patient out of five revealed lumbar osteopenia. The articular manifestations of the five patients did not respond to corticosteroid treatment. CD must be considered among the differential diagnosis in a patient with arthritis or arthralgia.     

Effect of Olive and Sunflower Seed Oil on the Adult Skin Barrier: Implications for Neonatal Skin Care

Natural oils are advocated and used throughout the world as part of neonatal skin care, but there is an absence of evidence to support this practice. The goal of the current study was to ascertain the effect of olive oil and sunflower seed oil on the biophysical properties of the skin. Nineteen adult volunteers with and without a history of atopic dermatitis were recruited into two randomized forearm‐controlled mechanistic studies. The first cohort applied six drops of olive oil to one forearm twice daily for 5 weeks. The second cohort applied six drops of olive oil to one forearm and six drops of sunflower seed oil to the other twice daily for 4 weeks. The effect of the treatments was evaluated by determining stratum corneum integrity and cohesion, intercorneocyte cohesion, moisturization, skin‐surface pH, and erythema. Topical application of olive oil for 4 weeks caused a significant reduction in stratum corneum integrity and induced mild erythema in volunteers with and without a history of atopic dermatitis. Sunflower seed oil preserved stratum corneum integrity, did not cause erythema, and improved hydration in the same volunteers. In contrast to sunflower seed oil, topical treatment with olive oil significantly damages the skin barrier, and therefore has the potential to promote the development of, and exacerbate existing, atopic dermatitis. The use of olive oil for the treatment of dry skin and infant massage should therefore be discouraged. These findings challenge the unfounded belief that all natural oils are beneficial for the skin and highlight the need for further research.     

Incremental value of live/real time three‐dimensional transesophageal echocardiography in the assessment of ventricular septal rupture following acute myocardial infarction

Ventricular septal rupture is a serious complication following acute myocardial infarctions and is associated with a significant mortality rate. Classically, two‐dimensional transthoracic echocardiography has been used to diagnose this complication and visualize its location. Two‐dimensional transesophageal echocardiography has supplemented the transthoracic approach by providing more accurate assessment of the defect size and in guiding closure both percutaneously and intraoperatively. This modality, however, is limited to two‐dimensional views only, and a greater breadth of information is instead available through the use of three‐dimensional transesophageal echocardiography. We present a series of 11 patients in which live/real time three‐dimensional transesophageal echocardiography offered incremental benefits over two‐dimensional imaging alone.     

An ultra-high-affinity small organic ligand of fibroblast activation protein for tumor-targeting applications

We describe the development of OncoFAP, an ultra-high-affinity ligand of fibroblast activation protein (FAP) for targeting applications with pan-tumoral potential. OncoFAP binds to human FAP with affinity in the subnanomolar concentration range and cross-reacts with the murine isoform of the protein. We generated various fluorescent and radiolabeled derivatives of OncoFAP in order to study biodistribution properties and tumor-targeting performance in preclinical models. Fluorescent derivatives selectively localized in FAP-positive tumors implanted in nude mice with a rapid and homogeneous penetration within the neoplastic tissue. Quantitative in vivo biodistribution studies with a lutetium-177–labeled derivative of OncoFAP revealed a preferential localization in tumors at doses of up to 1,000 nmol/kg. More than 30% of the injected dose had already accumulated in 1 g of tumor 10 min after intravenous injection and persisted for at least 3 h with excellent tumor-to-organ ratios. OncoFAP also served as a modular component for the generation of nonradioactive therapeutic products. A fluorescein conjugate mediated a potent and FAP-dependent tumor cell killing activity in combination with chimeric antigen receptor (CAR) T cells specific to fluorescein. Similarly, a conjugate of OncoFAP with the monomethyl auristatin E-based Vedotin payload was well tolerated and cured tumor-bearing mice in combination with a clinical-stage antibody-interleukin-2 fusion. Collectively, these data support the development of OncoFAP-based products for tumor-targeting applications in patients with cancer.

Small organic ligands which selectively bind with high affinity to tumor-associated antigens are increasingly applied as targeting delivery vehicles of small payloads such as radionuclides (1, 2), drugs (3–5), and fluorophores (6, 7) to tumor sites. In principle, the use of small ligands for targeting applications offers several advantages compared to intact immunoglobulins, including superior penetration of solid neoplastic lesions (8), lower immunogenicity (9), and a reduced cost of goods (10). Low molecular weight compounds may reach their target in vivo in a matter of seconds, thanks to rapid extravasation after intravenous administration (8). A strikingly selective accumulation of small ligands in neoplastic masses has been demonstrated for a small number of targets including somatostatin receptor type 2 (SSTR-2) (11), prostate-specific membrane antigen (PSMA) (12), and carbonic anhydrase IX (CAIX) (13), for which high-affinity small organic ligands are available. Those ligands are typically specific for defined tumor entities, such as neuroendocrine tumors (11), prostate cancer (3), and clear cell renal cell carcinoma (2).¹⁷⁷Lu-DOTATATE (Lutathera), a small-molecule product targeting SSTR-2, has been approved based on phase III data in which a clinically meaningful 82% reduction in the risk of disease progression or death was demonstrated in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (14). Similar data are expected from the currently ongoing phase III VISION trial for ¹⁷⁷Lu-PSMA-617 (clinical trial no. {"type":"clinical-trial","attrs":{"text":"NCT03511664","term_id":"NCT03511664"}}NCT03511664), a radiolabeled small molecule that binds with high affinity to PSMA and that enables targeted beta particle therapy in metastatic castration-resistant prostate cancer patients (15). PHC-102, a ^99mTc-labeled small-molecule derivative targeting CAIX, exhibited favorable uptake in primary and metastatic lesions in patients with renal cell carcinoma (RCC) (2). In light of the promising performance of small organic ligands, it would be desirable to discover and develop small molecules with a broader tumor-targeting potential, therefore covering multiple cancer types.Fibroblast activation protein (FAP) is a type II integral membrane serine protease which is abundantly expressed in the stroma of more than 90% of the epithelial cancers, including malignant breast, colorectal, skin, prostate, and pancreatic cancers (16, 17), while exhibiting a restricted expression in normal adult tissues (18, 19). Haberkorn and coworkers (1, 20, 21) have recently described a series of FAP ligands capable of selective accumulation in FAP-positive tumors in mice and in patients. One of these products (named FAPI-04) showed impressive tumor to background ratios at early time points (i.e., few hours after administration) in a broad range of different cancer types in patients. More than 28 tumor types including breast, lung, pancreatic, head and neck, esophagus, and colorectal cancer presented a remarkably high uptake of a FAP-targeted small molecule labeled with gallium-68 (1, 20, 21). For this reason, FAP has recently been dubbed as “the next billion-dollar target for theranostic products” (22).Here, we describe how the chemical modification of a quinoline moiety in position 8 led to the discovery of OncoFAP, a small organic FAP ligand with a dissociation constant in the subnanomolar concentration range. OncoFAP exhibited a strikingly selective and efficient tumor-targeting performance when equipped with various types of payloads, including radionuclides, fluorophores, and cytotoxic drugs. The targeting delivery of radionuclides to solid tumors is rapidly gaining in popularity, as it may open theranostic opportunities, associated with the use of gallium-68 for positron emission tomography (PET) imaging and of lutetium-177 for therapeutic applications (23). The delivery of fluorescein to tumors enables the conditional activation of chimeric antigen receptor (CAR) T cells, which display a potent biocidal activity only in the presence of fluorescein-labeled adaptor molecules specific to a tumor antigen (24, 25). Finally, small-molecule–drug conjugates (SMDCs) promise to represent a valid alternative to antibody–drug conjugates for cancer therapy, with better tumor penetration and a lower cost of goods (8, 26, 27).     

Solid-state dye-sensitized solar cells based on Zn1−xSnxO nanocomposite photoanodes

Solid-state dye-sensitized solar cells (ss-DSSCs) comprising Sn²⁺-substituted ZnO nanopowder were purposefully tailored via a co-precipitation method. The solar cells assembled in this work were sensitized with N719 ruthenium dye and insinuated with spiro-OMeTAD as a solid hole transport layer (HTL). Evidently, significant enhancement in cell efficiency was accomplished with Sn²⁺ ions-substituted ZnO photoelectrodes by maintaining the weight ratio of SnO at 5%. The overall power conversion efficiency was improved from 3.0% for the cell with pure ZnO to 4.3% for the cell with 5% SnO substitution. The improvement in the cell efficiency with Sn²⁺-substituted ZnO photoelectrodes is attributed to the considerably large surface area of the nanopowders for dye adsorption, efficient charge separation and the suppression of charge recombination provided by SnO. Furthermore, the energy distinction between the conduction band edges of SnO and ZnO implied a type II band alignment. Moreover, the durability as well as the stability of 15 assembled cells were studied to show the outstanding long-term stability of the devices made of Sn²⁺ ion substituted ZnO, and the PCE of each cell remained stable and ∼96% of its primary value was retained for up to 100 h. Subsequently, the efficacy was drastically reduced to ∼35% after 250 h of storage.

Solid-state dye-sensitized solar cells (ss-DSSCs) comprising Sn²⁺-substituted ZnO nanopowder were purposefully tailored via a co-precipitation method.     

Comparison of Tc-99m MAA Planar Versus SPECT/CT Imaging for Lung Shunt Fraction Evaluation Prior to Y-90 Radioembolization: Are We Overestimating Lung Shunt Fraction?

CardioVascular and Interventional Radiology - To compare lung shunt fraction (LSF) prior to Y-90 radioembolization calculated using planar imaging versus SPECT/CT in patients with hepatocellular...     

Stabilization of anterior mandibular fracture using different osteosynthesis devices: perioperative clinical notes

Oral and Maxillofacial Surgery - There is still no definitive consensus about the ideal technique in the treatment of anterior mandibular fractures. Therefore, this study aimed to determine...     

First experience of the use of a generic of plerixafor in peripheral blood stem cell mobilization in multiple myeloma and lymphoma patients

Mobilization failure in patients is a major therapeutic concern which makes subsequent ASCT impossible. A new growth factor called Plerixafor (Mozobil®) developed by the pharmaceutical industry (Sanofi-aventis, France), is a chemoreceptor antagonist, CXCR4 type, which disrupts the interaction of SDFI and CXCR4, thereby enhancing the effect of G-CSF mobilization and is especially indicated for mobilization failure. Currently, there is a generic of plerixafor developed by the pharmaceutical industry (Hetero Drugs Ltd, India). The brand name of this medicine is Mozifor®. The objective of this study was to evaluate if generic plerixafor has the same efficacy and safety as originator plerixafor when used with G-CSF in the mobilization of PBSCs for autologous ASCT in multiple myeloma (MM) and lymphoma failure patients. The 32 patients received plerixafor were divided in two groups. The first group concerns the 11 consecutive patients prospectively received generic plerixafor (Mozifor®) in the period between January to July 2020. These were compared with a retrospective control cohort (second group n = 21) who had been treated between 2009 and 2019 with originator plerixafor (Mozobil®). For the Mozifor® group, the mean CD34+ was 4.54x10⁶/kg(1.56-6.79), the median time to achieve an absolute neutrophil count >0.5 G/L was 13 days (range: 8–21). The median time to self-sustained platelet count >20 G/L was 15 days (range: 8–24). For the Mozobil® group, the mean CD34+ was 3.1x10⁶/kg (0.56-8.91) (p=0.86), the median time to achieve an absolute neutrophil count >0.5 G/L was 10 days (range 7–23). The median time to self-sustained platelet count >20 G/L was 13 days (range: 7–29). Our study showed that the generic of plerixafor was practically identical to that of the originator (Mozobil®) with no significant difference (p = 0.52). This study demonstrates the safety and feasibility of mobilization PBSC with generic plerixafor in ASCT in MM and lymphoma. Although these outcomes are encouraging, prospective comparison with other traditional auto-HCT regimens used for patients with MM and lymphoma is warranted.