Reliability of Magseed® marking before neoadjuvant systemic therapy with subsequent contrast-enhanced mammography in patients with non-palpable breast cancer lesions after treatment: the MAGMA study.

PURPOSE: To assess the reliability of excising residual breast cancer lesions after neoadjuvant systemic therapy (NAST) using a previously localized paramagnetic seed (Magseed®) and the subsequent use of contrast-enhanced spectral mammography (CESM) to evaluate response. METHODS: Observational, prospective, multicenter study including adult women (> 18 years) with invasive breast carcinoma undergoing NAST between January 2022 and February 2023 with non-palpable tumor lesions at surgery. Radiologists marked tumors with Magseed® during biopsy before NAST, and surgeons excised tumors guided by the Sentimag® magnetometer. CESMs were performed before and after NAST to evaluate tumor response (Response Evaluation Criteria for Solid Tumors [RECIST]). We considered intraoperative, surgical, and CESM-related variables and histological response. RESULTS: We analyzed 109 patients (median [IQR] age of 55.0 [46.0, 65.0] years). Magseed® was retrieved from breast tumors in all surgeries (100%; 95% CI 95.47-100.0%) with no displacement and was identified by radiology in 106 patients (97.24%), a median (IQR) of 176.5 (150.0, 216.3) days after marking. Most surgeries (94.49%) were conservative; they lasted a median (IQR) of 22.5 (14.75, 40.0) min (95% CI 23.59-30.11 min). Most dissected tumor margins (93.57%) were negative, and few patients (5.51%) needed reintervention. Magseed® was identified using CESM in all patients (100%); RECIST responses correlated with histopathological evaluations of dissected tumors using the Miller-Payne response grade (p < 0.0001) and residual lesion diameter (p < 0.0001). Also 69 patients (63.3%) answered a patient's satisfaction survey and 98.8% of them felt very satisfied with the entire procedure. CONCLUSION: Long-term marking of breast cancer lesions with Magseed® is a reliable and feasible method in patients undergoing NAST and may be used with subsequent CESM.

Strategies for the Preparation of Phosphorus Janus Dendrimers and Their Properties.

Dendrimers, being highly branched monodispersed macromolecules, predominantly exhibit identical terminal functionalities within their structural framework. Nonetheless, there are instances where the presence of two distinct surface functionalities becomes advantageous for the fulfilment of specific properties. To achieve this objective, one approach involves implementing Janus dendrimers, consisting of two dendrimeric wedges terminated by dissimilar functionalities. The prevalent method for creating these structures involves the synthesis of dendrons that possess a core functionality that complements that of a second dendron, facilitating their coupling to generate the desired dendrimers. In this comprehensive review, various techniques employed in the fabrication of phosphorus-based Janus dendrimers are elucidated, displaying the different coupling methodologies employed between the two units. The advantages of phosphorus dendrimers over classic dendrimers will be shown, as the presence of at least one phosphorus atom in each generation allows for the easy monitoring of reactions and the confirmation of purity through a simple technique such as 31P NMR, as these structures typically exhibit easily interpretable patterns.

Primary and post-chemoradiotherapy MRI detection of extramural venous invasion in rectal cancer: the role of diffusion-weighted imaging.

OBJECTIVE: To assess the added value of diffusion-weighted imaging (DWI) to high-resolution T2-weighted sequences (HRT2w) in MRI detection of extramural venous infiltration (EMVI), according to the previous experience of radiologists. METHODS: A cross-sectional study of a retrospective database including 1.5 T MRI records from 100 patients with biopsy-proven rectal cancer (2011-2016; 75 male/25 female, average 63 y/o), which included primary staging (54) and post-chemoradiotherapy follow-up MRIs (46). The reference standard was histology of surgical specimens. All cases were individually blindly reviewed by ten radiologists: three specialists in abdominal radiology, three specialized in different areas and four residents. In each case, the presence of EMVI was assessed twice: first, using just HRT2w; second, with DWI added to HRT2w. The results were pooled by experience, analyzing sensitivity, specificity, accuracy (area under ROC curve), likelihood ratios, predictive values and overstaging/understaging. RESULTS: Addition of DWI improved diagnostic performance by specialists radiologists, particularly post-chemoradiotherapy (accuracy 0.74-0.84; positive likelihood ratio 3.9-9.1; overstaging 16-8%), less so at primary staging (specificity 76-87.2%; overstaging 21-11%). Non-specialist radiologists also improved, but only at primary staging (accuracy 0.59-0.63). Residents showed small changes, except for notably increased sensitivity in both primary staging (35.7-43%) and post-chemoradiotherapy (41.7-58.3%) staging, at the expense of increased overstaging. CONCLUSIONS: The addition of DWI improved the diagnostic performance of EMVI by experienced radiologists, downgrading overstaging, especially in post-chemoradiotherapy follow-up. It resulted in fewer changes for inexperienced radiologists (enhanced primary staging) and residents (increased sensitivity).

MS/MS networking guided analysis of molecule and gene cluster families.

The ability to correlate the production of specialized metabolites to the genetic capacity of the organism that produces such molecules has become an invaluable tool in aiding the discovery of biotechnologically applicable molecules. Here, we accomplish this task by matching molecular families with gene cluster families, making these correlations to 60 microbes at one time instead of connecting one molecule to one organism at a time, such as how it is traditionally done. We can correlate these families through the use of nanospray desorption electrospray ionization MS/MS, an ambient pressure MS technique, in conjunction with MS/MS networking and peptidogenomics. We matched the molecular families of peptide natural products produced by 42 bacilli and 18 pseudomonads through the generation of amino acid sequence tags from MS/MS data of specific clusters found in the MS/MS network. These sequence tags were then linked to biosynthetic gene clusters in publicly accessible genomes, providing us with the ability to link particular molecules with the genes that produced them. As an example of its use, this approach was applied to two unsequenced Pseudoalteromonas species, leading to the discovery of the gene cluster for a molecular family, the bromoalterochromides, in the previously sequenced strain P. piscicida JCM 20779(T). The approach itself is not limited to 60 related strains, because spectral networking can be readily adopted to look at molecular family-gene cluster families of hundreds or more diverse organisms in one single MS/MS network.

A water-soluble polyphosphorhydrazone Janus dendrimer built by "click" chemistry as support for Ru-complexes in catalysis.

The field of supported catalysis has experienced increased attention with respect to the development of novel architectures for immobilizing catalytic species, aiming to maintain or enhance their activity while facilitating the easy recovery and reuse of the active moiety. Dendrimers have been identified as promising candidates capable of imparting such properties to catalysts through selective functionalization. The present study details the synthesis of two polyphosphorhydrazone (PPH) dendrons, each incorporating azide or acetylene groups at the core for subsequent coupling through "click" triazole chemistry. Employing this methodology, a novel PPH Janus dendrimer was successfully synthesized, featuring ten polyethylene glycol (PEG) chains on one side of the structure and ten Ru(p-cymene) derivatives on the other. This design was intended to confer dual properties, influencing solubility modulation, and allowing the presence of active catalytic moieties. The synthesized dendrimer underwent testing in the isomerization of allyl alcohols in organic solvents and biphasic solvent mixtures. The results demonstrated a positive dendritic effect compared with model monometallic and bimetallic species, providing a proof-of-concept for the first PPH Janus dendrimer with tested applications in catalysis.

Acne Keloidalis Nuchae: A Multicenter Retrospective Study of 142 Hispanic Patients.

INTRODUCTION: Acne keloidalis nuchae (AKN) is a primary cicatricial alopecia with mixed infiltrate. It is more common in Africans or persons of African descent. OBJECTIVES: Our objective was to describe the epidemiology and clinical and trichoscopic presentations of AKN in a large series of Hispanic patients. METHODS: This was a retrospective study from 10 different dermatological centers in Argentina, Colombia, Mexico, and Peru. Patients with a clinical diagnosis of AKN treated by 12 dermatologists experienced in trichology from 2018 to 2022 were included. The Umar classification system was used to determine severity. RESULTS: We identified 142 patients with AKN: 98% were male (n=140) with a mean age of 32 years; 108 patients had a previous history of trauma to the nuchal area (76%, P < 0.001); and 48 were positive for a history of acne (33.8%, P = 0.021). Patients with >50 months of evolution were mainly classified in classes III and IV compared to patients with an evolution of <50 months (30%, n=9 vs. 14%, n=15; P = 0.019; respectively). CONCLUSION: AKN should be considered in the differential diagnosis in the Hispanic population. Advanced stages of the disease are correlated with chronic evolution.

High clustering rates of multidrug-resistant Mycobacterium tuberculosis genotypes in Panama.

BACKGROUND: Tuberculosis continues to be one of the leading causes of death worldwide and in the American region. Although multidrug-resistant tuberculosis (MDR-TB) remains a threat to TB control in Panama, few studies have focused in typing MDR-TB strains. The aim of our study was to characterize MDR Mycobacterium tuberculosis clinical isolates using PCR-based genetic markers. METHODS: From 2002 to 2004, a total of 231 Mycobacterium tuberculosis isolates from TB cases country-wide were screened for antibiotic resistance, and MDR-TB isolates were further genotyped by double repetitive element PCR (DRE-PCR), (GTG)5-PCR and spoligotyping. RESULTS: A total of 37 isolates (0.85%) were resistant to both isoniazid (INH) and rifampicin (RIF). Among these 37 isolates, only two (5.4%) were resistant to all five drugs tested. Dual genotyping using DRE-PCR and (GTG)5-PCR of MDR Mycobacterium tuberculosis isolates revealed eight clusters comprising 82.9% of the MDR-TB strain collection, and six isolates (17.1%) showed unique fingerprints. The spoligotyping of MDR-TB clinical isolates identified 68% as members of the 42 (LAM9) family genotype. CONCLUSION: Our findings suggest that MDR Mycobacterium tuberculosis is highly clustered in Panama's metropolitan area corresponding to Panama City and Colon City, and our study reveals the genotype distribution across the country.

Imaging mass spectrometry of a coral microbe interaction with fungi.

Fungal infections are increasing worldwide, including in the aquatic environment. Microbiota that coexist with marine life can provide protection against fungal infections by secretion of metabolites with antifungal properties. Our laboratory has developed mass spectrometric methodologies with the goal of improving our functional understanding of microbial metabolites and guiding the discovery process of anti-infective agents from natural sources. GA40, a Bacillus amyloliquefaciens strain isolated from an octocoral in Panama, displayed antifungal activity against various terrestrial and marine fungal strains. Using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), the molecular species produced by this microbe were visualized in a side-by-side interaction with two representative fungal strains, Aspergillus fumigatus and Aspergillus niger. The visualization was performed directly on the agar without the need for extraction. By evaluating the spatial distributions, relative intensities and m/z values of GA40 secreted metabolites in the fungal interactions and singly grown control colonies, we obtained insight into the antifungal activity of secreted metabolites. Annotation of GA40 metabolites observed in MALDI-IMS was facilitated by MS/MS networking analysis, a mass spectrometric technique that clusters metabolites with similar MS/MS fragmentation patterns. This analysis established that the predominant GA40 metabolites belong to the iturin family. In a fungal inhibition assay of A. fumigatus, the GA40 iturin metabolites were found to be responsible for the antifungal properties of this Bacillus strain.

Harmful cyanobacterial aerosolization dynamics in the airshed of a eutrophic estuary.

In addition to obvious negative effects on water quality in eutrophic aquatic ecosystems, recent work suggests that cyanobacterial harmful algal blooms (CHABs) also impact air quality via emissions carrying cyanobacterial cells and cyanotoxins. However, the environmental controls on CHAB-derived aerosol and its potential public health impacts remain largely unknown. Accordingly, the aims of this study were to 1) investigate the occurrence of microcystins (MC) and putatively toxic cyanobacterial communities in particulate matter ≤ 2.5 µm in diameter (PM2.5), 2) elucidate environmental conditions promoting their aerosolization, and 3) identify associations between CHABs and PM2.5 concentrations in the airshed of the Chowan River-Albemarle Sound, an oligohaline, eutrophic estuary in eastern North Carolina, USA. In summer 2020, during peak CHAB season, continuous PM2.5 samples and interval water samples were collected at two distinctive sites for targeted analyses of cyanobacterial community composition and MC concentration. Supporting air and water quality measurements were made in parallel to contextualize findings and permit statistical analyses of environmental factors driving changes in CHAB-derived aerosol. MC concentrations were low throughout the study, but a CHAB dominated by Dolichospermum occurred from late June to early August. Several aquatic CHAB genera recovered from Chowan River surface water were identified in PM2.5 during multiple time points, including Anabaena, Aphanizomenon, Dolichospermum, Microcystis, and Pseudanabaena. Cyanobacterial enrichment in PM2.5 was indistinctive between subspecies, but at one site during the early bloom, we observed the simultaneous enrichment of several cyanobacterial genera in PM2.5. In association with the CHAB, the median PM2.5 mass concentration increased to 8.97 µg m-3 (IQR = 5.15), significantly above the non-bloom background of 5.35 µg m-3 (IQR = 3.70) (W = 1835, p < 0.001). Results underscore the need for highly resolved temporal measurements to conclusively investigate the role that CHABs play in regional air quality and respiratory health risk.

Treatment of osteochondritis dissecans of the patella in adolescents with nanofractured autologous matrix-induced chondrogenesis (NAMIC): A report of five cases.

PURPOSE: Osteochondritis dissecans (OCD) of the patella is a very rare affliction. The aim of this case series is to evaluate the effectiveness of the Nanofractured Autologous Matrix-Induced Chondrogenesis (NAMIC) technique for the treatment of OCD in young adults. METHODS: Five consecutive patients with patellar osteochondral lesions treated with NAMIC were prospectively studied. There were 4 males and 1 female with a mean age of 15.2 years, ranging from 12 to 18 years. Clinically, they presented pain when going up and down stairs or squatting, effusion, swelling and functional limitation. The International Cartilage Repair Society (ICRS) grade was III in 4 patients and IV in 1 patient. Patients were functionally evaluated with the Lysholm knee score, the Tegner Activity Score (TAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) and radiologically using the Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) score. RESULTS: All the scores significantly improved two years after surgery with respect to pre-operative values (Lysholm score from 63.8 ± 3.9 before surgery to 91 ± 3.2 at 2 years; Tegner activity score from 3.6 ± 0.5 to 8.2 ± 0.8 and the KOOS score from 45.2 ± 2.6 to 91.2 ± 2.4). Both the X-rays and the Magnetic Resonance Imaging (MRI) showed good joint regularity with an average MOCART of 80 ± 7.1/100. CONCLUSIONS: Treatment of juvenile patellar osteochondritis dissecans with the NAMIC technique seems to be a reliable technique in the short term to restore the patella joint surface and obtain good functional results.

Synthesis and Catalytic Properties of a Very Latent Selenium-Chelated Ruthenium Benzylidene Olefin Metathesis Catalyst.

Herein, we describe a study of the synthesis, characterization, and catalytic properties of a cis-dichlorido seleno-chelated Hoveyda-Grubbs type complex (Ru8). Such a complex has been obtained through a straightforward and high-yielding synthetic protocol in three steps from the commercially available 2-bromobenzaldehyde in good overall yield (54%). The catalytic profile, especially the latency of this complex, has been probed through selected olefin metathesis reactions such as ring-closing metathesis (RCM), self-cross-metathesis (self-CM) and ring-opening metathesis polymerization (ROMP). In addition to its high latency, the selenium Hoveyda-type complex Ru8 exhibits a switchable behavior upon thermal activation. Of interest, while the corresponding sulfur-chelated Hoveyda type catalyst is reported to be only activated by heat, the selenium analogue was found to be active upon both heat and light irradiation.

PCSK-9 Inhibitors in a Real-World Setting and a Comparison Between Alirocumab and Evolocumab in Heterozygous FH Patients.

A real-world setting study of familial hypercholesterolemia (FH) patients who received Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in a specialized referral center in Mexico City. Ten patients between the ages of 18 and 70 years, with a diagnosis of FH according to Dutch Lipid Clinic Network (DLCN) criteria, with failure to achieve their Low-density lipoprotein Cholesterol (LDL-C) goals, and with standard therapy between 2016 and 2017 enrolled in a simple randomization in which a group of 5 participants received alirocumab (75 mg every 2 weeks) and the remaining 5 patients received evolocumab (140 mg every 2 weeks). Comparative analysis was made, analyzing the means of LDL at baseline at 4, 6, and 12 weeks. The evolocumab group had an average initial LDL-C of 277 mg/dL, which, after 12 weeks of treatment, was significantly reduced to 116 mg/dL; P = 0.04 (95% confidence interval [CI]: 11.5-310.9). The alirocumab group with a mean initial LDL-C of 229 mg/dL showed a reduction of LDL-C levels at 12 weeks of treatment to 80 mg/dL; P = 0.008 (95% CI: 63.8-233.7). In conclusion, PCSK9 inhibitors are an excellent treatment option in patients with FH who do not reach their LDL-C goals with standard therapy or due to intolerance to the standard therapy. There is no difference in the lipid-lowering effect between both PSCK9 inhibitors.

Picophytoplankton dynamics in a large temperate estuary and impacts of extreme storm events.

Picophytoplankton (PicoP) are increasingly recognized as significant contributors to primary productivity and phytoplankton biomass in coastal and estuarine systems. Remarkably though, PicoP composition is unknown or not well-resolved in several large estuaries including the semi-lagoonal Neuse River Estuary (NRE), a tributary of the second largest estuary-system in the lower USA, the Pamlico-Albemarle Sound. The NRE is impacted by extreme weather events, including recent increases in precipitation and flooding associated with tropical cyclones. Here we examined the impacts of moderate to extreme (Hurricane Florence, September 2018) precipitation events on NRE PicoP abundances and composition using flow cytometry, over a 1.5 year period. Phycocyanin-rich Synechococcus-like cells were the most dominant PicoP, reaching ~ 106 cells mL-1, which highlights their importance as key primary producers in this relatively long residence-time estuary. Ephemeral "blooms" of picoeukaryotic phytoplankton (PEUK) during spring and after spikes in river flow were also detected, making PEUK periodically major contributors to PicoP biomass (up to ~ 80%). About half of the variation in PicoP abundance was explained by measured environmental variables. Temperature explained the most variation (24.5%). Change in total dissolved nitrogen concentration, an indication of increased river discharge, explained the second-most variation in PicoP abundance (15.9%). The short-term impacts of extreme river discharge from Hurricane Florence were particularly evident as PicoP biomass was reduced by ~ 100-fold for more than 2 weeks. We conclude that precipitation is a highly influential factor on estuarine PicoP biomass and composition, and show how 'wetter' future climate conditions will have ecosystem impacts down to the smallest of phytoplankton.

All-Arthroscopic Nanofractured Autologous Matrix-Induced Chondrogenesis (A-NAMIC) Technique for the Treatment of Focal Chondral Lesions of the Knee.

Nanofractured autologous matrix-induced chondrogenesis (NAMIC©) is a 1-step technique that combines nanofracture needling to induce bone marrow stimulation (BMS) and the use of cell-free collagen matrix to optimize cartilage regeneration. In this Technical Note, we describe a modification of the NAMIC procedure using mosaicplasty trephines to prepare the lesion surface and to shape collagen implants in an all-arthroscopic approach (A-NAMIC). This technique is indicated for the treatment of International Cartilage Repair Society grade III to IV knee chondral lesions of ≤4 cm2. After damaged cartilage is debrided, trephines are used to create a flat, circular lesion surfaces. Subsequently, BMS is performed with nanofracture, eliciting reproducible and stop-controlled subchondral bone perforations of 9-mm depth and 1-mm width. The collagen membrane is then cut to size with the trephine, placed over the prepared defect, and secured with fibrin glue, preventing loss of regenerating cells and growth factors to the joint space. Using trephines allows the rapid and precise creation of smooth defect surfaces with known dimensions, ensuring optimal lesion coverage. Additionally, nanofracture reduces trabecular compaction and allows for a deeper access to subchondral bone in comparison with conventional microfracture, improving lesion filling and production of cartilage with higher hyaline content.

Morphology control of metal-modified zirconium phosphate support structures for the oxygen evolution reaction.

The electrochemical oxygen evolution reaction (OER) is the half-cell reaction for many clean-energy production technologies, including water electrolyzers and metal-air batteries. However, its sluggish kinetics hinders the performance of those technologies, impeding them from broader implementation. Recently, we reported the use of zirconium phosphate (ZrP) as a support for transition metal catalysts for the oxygen evolution reaction (OER). These catalysts achieve promising overpotentials with high mass activities. Herein, we synthesize ZrP structures with controlled morphology: hexagonal platelets, rods, cubes, and spheres, and subsequently modify them with Co(ii) and Ni(ii) cations to assess their electrochemcial OER behavior. Through inductively coupled plasma mass-spectrometry measurements, the maximum ion exchange capacity is found to vary based on the morphology of the ZrP structure and cation selection. Trends in geometric current density and mass activity as a function of cation selection are discussed. We find that the loading and coverage of cobalt and nickel species on the ZrP supports are key factors that control OER performance.

An immersed boundary neural network for solving elliptic equations with singular forces on arbitrary domains.

In this paper, we present a deep learning framework for solving two-dimensional elliptic equations with singular forces on arbitrary domains. This work follows the ideas of the physical-inform neural networks to approximate the solutions and the immersed boundary method to deal with the singularity on an interface. Numerical simulations of elliptic equations with regular solutions are initially analyzed in order to deeply investigate the performance of such methods on rectangular and irregular domains. We study the deep neural network solutions for different number of training and collocation points as well as different neural network architectures. The accuracy is also compared with standard schemes based on finite differences. In the case of singular forces, the analytical solution is continuous but the normal derivative on the interface has a discontinuity. This discontinuity is incorporated into the equations as a source term with a delta function which is approximated using a Peskin's approach. The performance of the proposed method is analyzed for different interface shapes and domains. Results demonstrate that the immersed boundary neural network can approximate accurately the analytical solution for elliptic problems with and without singularity.

A Spin Coating Method To Deposit Iridium-Based Catalysts onto Silicon for Water Oxidation Photoanodes.

Silicon has shown promise for use as a small band gap (1.1 eV) absorber material in photoelectrochemical (PEC) water splitting. However, the limited stability of silicon in acidic electrolyte requires the use of protection strategies coupled with catalysts. Herein, spin coating is used as a versatile method to directly coat silicon photoanodes with an IrOx oxygen evolution reaction (OER) catalyst, reducing the processing complexity compared to conventional fabrication schemes. Biphasic strontium chloride/iridium oxide (SrCl2:IrOx) catalysts are also developed, and both catalysts form photoactive junctions with silicon and demonstrate high photoanode activity. The iridium oxide photoanode displays a photocurrent onset at 1.06 V vs reversible hydrogen electrode (RHE), while the SrCl2:IrOx photoanode onsets earlier at 0.96 V vs RHE. The differing potentials are consistent with the observed photovoltages of 0.43 and 0.53 V for the IrOx and SrCl2:IrOx, respectively. By measuring the oxidation of a reversible redox couple, Fe(CN)63-/4-, we compare the charge carrier extraction of the devices and show that the addition of SrCl2 to the IrOx catalyst improves the silicon-electrolyte interface compared to pure IrOx. However, the durability of the strontium-containing photoanode remains a challenge, with its photocurrent density decreasing by 90% over 4 h. The IrOx photoanode, on the other hand, maintained a stable photocurrent density over this timescale. Characterization of the as-prepared and post-tested material structure via Auger electron spectroscopy identifies catalyst film cracking and delamination as the primary failure modes. We propose that improvements to catalyst adhesion should further the viability of spin coating as a technique for photoanode preparation.

Locoregional staging using magnetic resonance imaging in rectal cancer: influence of diffusion-weighted imaging in the diagnostic accuracy.

OBJECTIVE: To assess whether the accuracy in locoregional staging using magnetic resonance imaging (MRI) in rectal cancer (primary or post-chemoradiotherapy) improves by adding diffusion-weighted imaging, according to the radiologist's degree of experience. METHOD: Retrospective study on 100 MRI records (1.5 T, 2011-2016) from patients with rectal cancer (reference standard: histology of surgical specimens). Ten radiologists (three experienced in rectal cancer, three specialized in other areas and four residents) individually reviewed each case twice: first, evaluating just high-resolution T2-weighted sequences; second, evaluation of diffusion-weighted plus high-resolution ones. The analysis focused on the differentiation between early (0-I) and advanced (II-IV) stages. Accuracy, sensitivity/specificity and predictive values were calculated. RESULTS: Experienced radiologists showed some worsening by adding diffusion-weighted imaging, mainly at primary staging (accuracy: 0.769 to 0.701). Inexperienced radiologists presented a post-chemoradiotherapy improvement (accuracy: 0.574 to 0.642; specificity of 19.1 to 29.8%), although with no other remarkable changes. Residents demonstrated a worsening at primary staging by adding diffusion (accuracy: 0.670 to 0.633; specificity: 45.8 to 39.6%), but post-chemoradiotherapy improvement (sensitivity: 80.6 to 87%). The differences between both reviews were not statistically significant. CONCLUSIONS: No significant differences were found in the distinction between early and advanced rectal tumors secondary to adding diffusion-weighted imaging to high-resolution T2-weighted sequences.

OBJETIVO: Evaluar si la eficacia en la estadificación locorregional por resonancia magnética (RM) del cáncer de recto (primaria o posneoadyuvancia) mejora al añadir imágenes potenciadas en difusión, según la experiencia previa del radiólogo. MÉTODO: Estudio retrospectivo sobre 100 RM de 1.5 T (2011-2016) de pacientes con cáncer rectal (estándar de referencia: estadiaje histológico de pieza quirúrgica). Diez radiólogos (tres con experiencia en cáncer rectal, tres inexpertos y cuatro residentes) evaluaron individualmente cada caso dos veces: primero, solo secuencias T2 de alta resolución; segundo, valoración conjunta con difusión. Se analizó la diferenciación entre estadios precoces (0-I) y avanzados (II-IV), y se calcularon la precisión, la sensibilidad y la especificidad, y los valores predictivos. RESULTADOS: Al agregar la difusión, los radiólogos experimentados presentaron peores resultados, sobre todo en estadiaje primario (precisión: 0.769 a 0.701). Los inexpertos mostraron mejoría posneoadyuvancia (precisión: 0.574 a 0.642; especificidad: 19.1 a 29.8%), sin otros cambios destacables. Los residentes manifestaron peores resultados en estadiaje primario (precisión: 0.670 a 0.633; especificidad: 45.8-39.6%), pero mejoría posneoadyuvancia (sensibilidad: 80.6 a 87%). Las diferencias entre ambas revisiones no fueron estadísticamente significativas. CONCLUSIONES: No se encontraron diferencias significativas en la distinción entre tumores rectales precoces y avanzados al añadir secuencias de difusión al uso de secuencias T2 de alta resolución.

Tocilizumab in glucocorticoid-resistant graves orbitopathy. A case series report of a mexican population.

PURPOSE: To describe pre- to post-treatment changes in clinical activity score (CAS) and exophthalmometry in patients with Graves orbitopathy treated with tocilizumab (TCZ). MATERIAL AND METHODS: Eight Mexican patients presenting with active Graves orbitopathy (CAS>3/7) previously treated with glucocorticoids received 1 monthly dose of TCZ for 6 months. CAS, EUGOGO severity assessment and exophthalmometry were used to evaluate clinical status, with serum measurement of thyroid-stimulating hormone receptor antibodies (TR-Ab) for biochemical evaluation before and after application of TCZ. RESULTS: Eight patients were analyzed: 6 male (75%), 2 female (25%): mean age, 45.9±11.2 years; mean weight, 85±18.3 kg. Mean TR-Ab level at treatment outset was 291.9±96.4%, mean CAS 4.1±0.3 and mean exophthalmometry 21.2±3.2 mm. After TCZ treatment, mean TR-Ab level fell to 172.7±54% (P=0.001), mean CAS to 1.1±0.6 (P=0.001) and mean exophthalmometry to 19.3±2 mm (P=0.02). CONCLUSIONS: TCZ is a therapeutic option for glucocorticoid-resistant orbitopathy, and should be considered in second line due to the cost of treatment or in first line in patients with contraindications to intravenous GC pulse therapy.

Use of PCSK9 Inhibitor in a Mexican Boy with Compound Heterozygous Familial Hypercholesterolemia: A Case Report.

We report on the case of an 8-year-old Mexican male, with a 3-year-old clinical diagnosis of familial hypercholesterolemia, and the difficulties encountered in his treatment while in our care. His treatment started with a regimen consisting of ezetimibe/simvastatin, cholestyramine, and a dietary plan of 1600 calories, with a limited intake of 200 mg of cholesterol per day. Problems arose when the patient's low-density lipoprotein cholesterol (LDL) levels did not meet ideal targets, which prompted the use of LDL cholesterol apheresis (not available in Mexico) for 6 months. As a last resort, PCSK9 inhibitors were administered but the LDL levels remained in the 600 mg/dL range. AmbryGenetics conducted a genetic test employing the Sanger method. The results suggested that there were 2 different mutations for each allele of the same LDL receptor gene (c.249delTinsGG and p.(Cys109Arg)), located in exons 3 and 4, respectively. We identified compound heterozygous mutations in our index case, with him having both the p.C109R mutation (from the maternal lineage), as well as a c.249delTinsGG mutation (from the paternal lineage). The p.C109R mutation has been previously reported, not only in Mexico, but in European regions (Germany, Czech Republic, Ireland, Italy) as well. Functional studies indicated a residual enzymatic activity of 15% to 30% for heterozygotes. To date, the variant c.249delTinsGG has not been reported. This case study illustrates the fact that in Mexico there are limited options available for treatment in such a scenario. As medical professionals, we are limited by the tools at our disposal.