Crystal, Solution, and Computational Study of the Structure of Ortho-Lithium N,N-Diisopropyl-P,P-Diphenylphosphinothioic Amide.

The first crystal structure of an ortho-lithium phosphinothioic amide complexed with tetramethylethylenediamine 12 is reported. The complex consists of a spirane in which the spiro-lithium is N,N- and C,S-chelated by the diamine and organophosphorus ligands, respectively. The analogous ortho anion 14 obtained by Sn(IV)/Li transmetallation in THF has also been synthesized. Nuclear magnetic resonance study of both anions showed that they exist as monomers in solution and are involved in dynamic processes including the restricted rotation around the P-N bond. 14 is converted at room temperature by nucleophilic cyclization to the dearomatized anion 15, which evolves after a few hours to the benzophosphindole sulfide 16. Density functional theory calculations supported the aggregation state in solution and were used to explore the conformational space of anion 12, the mechanism of ortho-lithiation directed by P(X)-N (X=O, S) groups, and the mechanism of formation of 15.

Breast density quantification in dual-energy mammography using virtual anthropomorphic phantoms.

PURPOSE: Breast density is a significant risk factor for breast cancer and can impact the sensitivity of screening mammography. Area-based breast density measurements may not provide an accurate representation of the tissue distribution, therefore volumetric breast density (VBD) measurements are preferred. Dual-energy mammography enables volumetric measurements without additional assumptions about breast shape. In this work we evaluated the performance of a dual-energy decomposition technique for determining VBD by applying it to virtual anthropomorphic phantoms. METHODS: The dual-energy decomposition formalism was used to quantify VBD on simulated dual-energy images of anthropomorphic virtual phantoms with known tissue distributions. We simulated 150 phantoms with volumes ranging from 50 to 709 mL and VBD ranging from 15% to 60%. Using these results, we validated a correction for the presence of skin and assessed the method's intrinsic bias and variability. As a proof of concept, the method was applied to 14 sets of clinical dual-energy images, and the resulting breast densities were compared to magnetic resonance imaging (MRI) measurements. RESULTS: Virtual phantom VBD measurements exhibited a strong correlation (Pearson's r > 0.95 $r > 0.95$ ) with nominal values. The proposed skin correction eliminated the variability due to breast size and reduced the bias in VBD to a constant value of -2%. Disagreement between clinical VBD measurements using MRI and dual-energy mammography was under 10%, and the difference in the distributions was statistically non-significant. VBD measurements in both modalities had a moderate correlation (Spearman's ρ $\rho \ $ = 0.68). CONCLUSIONS: Our results in virtual phantoms indicate that the material decomposition method can produce accurate VBD measurements if the presence of a third material (skin) is considered. The results from our proof of concept showed agreement between MRI and dual-energy mammography VBD. Assessment of VBD using dual-energy images could provide complementary information in dual-energy mammography and tomosynthesis examinations.

Inter- and Intra-Operator Variability of Regularized Backscatter Quantitative Ultrasound for the Characterization of Breast Masses.

OBJECTIVES: Here we report on the intra- and inter-operator variability of the backscatter coefficient (BSC) estimated with a new low-variance quantitative ultrasound (QUS) approach applied to breast lesions in vivo. METHODS: Radiofrequency (RF) echo signals were acquired from 29 BIRADS 4 and 5 breast lesions in 2 sequential cohorts following 2 imaging protocols: cohort 1) radial and antiradial views, and cohort 2) short- and long-axis views. Protocol 2 was implemented after retraining and discussion on how to improve reproducibility. Each patient was scanned by at least 2 of 3 radiologists; each performed 3 acquisitions with transducer and patient repositioning in between acquisitions. BSC was estimated using a low-variance QUS approach based on regularization. Intra- and inter-operator variability of the intra-lesion median BSC was evaluated with a multifactorial ANOVA test (P-values) and the intraclass correlation coefficient (ICC). RESULTS: Inter-operator variability was only significant in the first protocol (P < .007); ICCinter = .77 (95% CI .71-.82), indicating good inter-operator agreement. In the second protocol, the inter-operator variability was not significant (P > .05) and agreement was excellent (ICCinter = .92 [.89-.94]). In both protocols, the intra-operator variability was not significant. CONCLUSIONS: Our findings demonstrate the need for standardizing image acquisition protocols for backscatter-based QUS to reduce inter-operator variability and ensure its successful translation to the characterization of suspicious breast masses.

Retrasos en el tratamiento del cáncer de mama: una enfermedad peligrosa.

No disponible.

Crisis de casos de cáncer de mama detectados en tamizaje durante el segundo año de la pandemia en el Incan.

No disponible.

Impacto de la pandemia de Covid-19 en el tamizaje de cáncer de mama y algunas estrategias para actuar pronto y seguro.

Desde el comienzo de la pandemia de Covid-19 los servi-cios de prevención de cáncer de mama han sido aplazados gravemente. Esta acción provocó la reducción en el número acumulado de mastografías de detección a nivel mundial e incrementó las disparidades en salud, sobre todo entre las mujeres vulnerables. Si bien la evidencia que respalda las es-trategias para rescatar el tamizaje con mastografía en la fase de resolución de la pandemia no es suficiente, hay algunas consideraciones pragmáticas que pueden guiar su recupera-ción y garantizar su continuidad. Una de estas estrategias es prever los retrasos en el tamizaje y abordarlos a través de programas seguros que se alineen con la situación epidemio-lógica actual. Las acciones planteadas en el presente ensayo están en consonancia con las iniciativas internacionales de garantizar la continuidad de los programas de tamizaje de cáncer de mama en atención a que el cuidado de las mujeres sea una acción prioritaria, continua y permanente.

Un llamado a mejorar la calidad de los servicios de tamizaje con mastografía: hablando del programa Reconocimiento INCan.

No disponible.

The apparent diffusion coefficient (ADC) on 3-T MRI differentiates myometrial invasion depth and histological grade in patients with endometrial cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) with apparent diffusion coefficient (ADC) measurement provides additional information about tumor microstructure with potential relevance for staging and predicting aggressive disease in patients with endometrial cancer (EC). PURPOSE: To determine whether ADC values in EC diverge according to the tumor's histologic grade and myometrial invasion depth. MATERIAL AND METHODS: A sample of 48 pathologically confirmed cases of EC were reviewed retrospectively. The sample was distributed as follows: G1 (n = 9); G2 (n = 18); G3 (n = 21); with myometrial invasion <50% (n = 31); and with myometrial invasion ≥50% (n = 17). DW images were performed at 3.0T with b factors of 0-1000/mm2. The region of interest (ROI) was defined within the tumor with T1-weighted and T2-weighted imaging and copied manually to an ADC map. The tumor's grade and myometrial invasion's depth were determined by postoperative histopathological tests. RESULTS: The means of ADCmin and ADCmean values were significantly lower for patients with G2 and G3 endometrial tumors than G1. The same tendency was observed in myometrial invasion, as both ADCmin and ADCmean values were lower for patients with deep than for those with superficial myometrial invasion. The cut-off values of the ADCmin and ADCmean that predicted high-grade tumors were 0.69 × 10-3 mm2/s and 0.82 × 10-3 mm2/s, respectively, while those for myometrial infiltration were 0.70 × 10-3 mm2/s (ADCmin) and 0.88 × 10-3 mm2/s (ADCmean). CONCLUSION: ADCmin and ADCmean values correlated with histologic tumor grade and myometrial invasion depth; therefore, it is suggested that ADC on MRI may be a useful indicator to predict malignancy of ECs.

Immobilized Gold Nanoparticles Prepared from Gold(III)-Containing Ionic Liquids on Silica: Application to the Sustainable Synthesis of Propargylamines.

A cycloaurated phosphinothioic amide gold(III) complex was supported on amorphous silica with the aid of an imidazolium ionic liquid (IL) physisorbed in the SiO2 pores (SiO2⁻IL) and covalently bonded to the SiO2 (SiO2@IL). Gold(0) nanoparticles (AuNPs) were formed in situ and subsequently immobilized on the SiO2⁻IL/SiO2@IL phase. The resulting catalytic systems Au⁻SiO2⁻IL and Au⁻SiO2@IL promoted the solvent-free A³ coupling reaction of alkynes, aldehydes, and amines in high yields under solvent-free conditions with very low catalyst loading and without the use of additives. The Au⁻SiO2@IL catalyst showed good recyclability and could be reused at least five times with yields of propargylamines of ≥80%. This synthetic method provides a green and low cost way to effectively prepare propargylamines. Additionally, 31P high resolution magic angle spinning (HRMAS) NMR spectroscopy is introduced as a simple technique to establish the Au loading of the catalyst.

Idiopathic granulomatous mastitis. Experience at a cancer center.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a benign breast disease that has been described as a rare granulomatous inflammation (GI). It can mimic inflammatory breast cancer. MATERIAL AND METHODS: We included women with a diagnosis of IGM referred to an oncologic hospital between January 01, 2007 and to March 31, 2011, with diagnosis of breast cancer, in whom biopsy reported GI, without other cause related. The aim of this study was to review the clinical, radiologic and pathologic characteristics of a cohort of women with IGM. RESULTS: We analyzed 58 patients; mean age was 38 ± 12 years. Mammography showed diffuse asymmetry (n = 19) and focal asymmetry (n = 13); breast ultrasound showed heterogeneous and hypoechoic areas (n = 28) and lumps (n = 21) as the most frequent lesions. All biopsies showed lobulocentric GI. Treatment included antibiotics (n = 20), steroids (n = 8), both treatments (n = 20), surgical excision (n = 3) and observation (n = 7). Forty-three patients (74%) had complete remission; mean time to remission was 9.5 ± 5.8 months. Fifteen (26%) had partial remission. Any patient had progression or relapse. CONCLUSIONS: IGM is a benign breast condition that may mimic breast inflammatory cancer. Ultrasonography and mammography findings reveal characteristic data that can be useful for establishing the diagnosis; however, biopsy is the gold standard for its diagnosis and should be taken in any patient even with a mild suspicion of cancer.

Unusual metastases to the breast from different extramammary malignancies: a multimodality imaging approach in a case series.

Extramammary metastases are uncommon and usually related to a poor prognosis, but the radiologist can suspect the diagnosis based on the patient's clinical history and specific imaging findings. Several imaging procedures may be used to evaluate breast metastases from different extramammary malignancies, including mammography, ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography-CT (PET-CT). The clinical and imaging presentation of these metastases is contingent upon how the illness spreads, however, they have the potential to resemble either benign or malignant breast tumors. Metastases that disseminate hematologically tend to appear as a single round or oval mass with circumscribed margins. Sonographically, they are usually hypoechoic, and with CT or MRI, they usually enhance. Lymphatic dissemination, for example, frequently reveals significant asymmetry with skin thickening and diffuse breast edema, which is compatible with an inflammatory breast carcinoma. Knowing the many types of cancers that have the potential to spread to the breast as well as being able to accurately diagnose them is crucial to prevent a needless mastectomy and provide guidance for subsequent treatment. The purpose of this article is to provide a better understanding of the imaging features and immunohistochemistry (IHC) of secondary tumors of the breast by presenting eight distinctive cases, which will enable radiologists to recognize this entity.

[In situ and invasive carcinoma identified through an opportunistic screening mammography in asymptomatic women in Mexico City]. / Carcinoma in situ e infiltrante identificado por tamizaje mamográfico oportunista en mujeres asintomáticas de la Ciudad de México.

OBJECTIVE: To describe the mammographic findings and carcinoma detection rate in asymptomatic women of Mexico City, that participated in an opportunistic screening program. MATERIALS AND METHODS: 39 491 participants were included, with mammograms performed and interpreted in the National Cancer Institute, from 2008 to 2011. The mammographic findings, type of lesion and true positives (TP), are described by age groups. We calculated the crude effect of age on the classification BIRADS (Breast Imaging Reporting and Data System) 0 and the type of lesion. RESULTS: The median age was 50 (45-57) years. 80.5% were classified as BIRADS 2, 11.4%(0), 4.1%(1), 3.5%(3), 0.5%(4) y 0.1%(5). Malignant lesions were detected in 1.3 and 3.3 per 1000 and the proportion of true positives (TP) was 8.2% and 20.6%, in women of 41-50 and 51-70 years, respectively. CONCLUSIONS: Although some cases are detected in women 40 to 50 years, in women over 50 years the screening by mammography is more efficient, with a higher proportion of cases detected and fewer false positives.

Relationship between Health Inequalities and Breast Cancer Survival in Mexican Women.

OBJECTIVE: We aimed to analyze the relationship between the survival of patients with breast cancer and health inequalities. METHODS: A retrospective cohort study of women with stage III breast cancer according to public healthcare was conducted. Groups were stratified according to the course of treatment and the presence of chronic disease other than cancer. Survival functions were estimated by using the Kaplan-Meier estimator, while the Cox proportional hazards model was employed for prognostic assessment. RESULTS: The study was performed on 964 breast cancer patients. One hundred and seventy-six patients (18.23%) died during the follow-up period and 788 (81.77%) were alive at the end of the follow-up period. Education, marital status, personal history of prior biopsies, and socioeconomic status (SES) were found to be linked with survival. However, only SES exceeded the baseline risk of mortality when the treatment cycle was interrupted (full treatment: unadjusted 4.683, p = 0.001; adjusted 4.888 p = 0.001, partial treatment: unadjusted 1.973, p = 0.012; adjusted 4.185, p = 0.001). The same effect was observed when stratifying by the presence of chronic disease other than cancer (with chronic disease adjusted HR = 4.948, p = 0.001; unadjusted HR = 3.303, p = 0.001; without chronic disease adjusted HR = 4.850, p = 0.001; unadjusted HR = 5.121, p = 0.001). CONCLUSION: Since lower SES was linked with a worse prognosis, strategies to promote preventive medicine, particularly breast cancer screening programs and prompt diagnosis, are needed.

Physicians' attitudes and perceived barriers to adherence to the national breast cancer clinical practice guidelines in Mexico: a survey study.

BACKGROUND: Adherence to clinical practice guidelines improves outcomes for patients with breast cancer. However, their implementation may not be feasible in low- and middle-income countries. This study aimed to evaluate physicians' adherence, attitudes, and barriers towards the Colima Consensus, which is the Mexican national breast cancer clinical practice guideline. METHODS: A cross-sectional, 31-item survey was e-mailed to Consensus attendees and members of the Mexican Society of Oncology and Mexican Mastology Association. Descriptive statistics, univariate, and multivariate analysis were used to analyze the associations between participants' characteristics, adherence, attitudes, and barriers. RESULTS: Of 439 respondents, 78% percent adhered to Consensus recommendations and 94% believed it was applicable to their clinical practice. Forty percent reported using the Consensus as their sole breast cancer guideline. This was associated with being a surgical oncologist (OR 3.3, 95% CI 2.0-5.3) and practicing at a public hospital (OR 2.1, 95% CI 1.2-3.7). The most common barriers to adherence were lack of resources and logistical problems. Regarding attitudes towards the Consensus, 90% considered it a good educational tool, 89% considered it a reliable source of information, and 90% thought it improved quality of care. CONCLUSIONS: We showed high levels of adherence and positive attitudes towards the Colima Consensus, with a significant proportion of physicians using it as their only guideline. Lack of resources and logistical issues were the main barriers to adherence. Our results highlight the relevance of local breast cancer guidelines and suggest a need for the creation of resource-stratified guidelines.

A C∧S-Cyclometallated Gold(III) Complex as a Novel Antibacterial Candidate Against Drug-Resistant Bacteria.

The worldwide emergence and spread of infections caused by multidrug-resistant bacteria endangers the efficacy of current antibiotics in the clinical setting. The lack of new antibiotics in the pipeline points to the need of developing new strategies. Recently, gold-based drugs are being repurposed for antibacterial applications. Among them, gold(III) complexes have received increasing attention as metal-based anticancer agents. However, reports on their antibacterial activity are scarce due to stability issues. The present work demonstrates the antibacterial activity of the gold(III) complex 2 stabilized as C∧S-cycloaurated containing a diphenylphosphinothioic amide moiety, showing minimum inhibitory concentration (MIC) values that ranged from 4 to 8 and from 16 to 32 mg/L among Gram-positive and Gram-negative multidrug-resistant (MDR) pathogens, respectively. Complex 2 has a biofilm inhibitory activity of only two to four times than its MIC. We also describe for the first time a potent antibacterial synergistic effect of a gold(III) complex combined with colistin, showing a bactericidal effect in less than 2 h; confirming the role of the outer membrane as a permeability barrier. Complex 2 shows a low rate of internalization in Staphylococcus aureus and Acinetobacter baumannii; it does not interact with replication enzymes or efflux pumps, causes ultrastructural damages in both membrane and cytoplasmic levels, and permeabilizes the bacterial membrane. Unlike control antibiotics, complex 2 did not generate resistant mutants in 30-day sequential cultures. We detected lower cytotoxicity in a non-tumoral THLE-2 cell line (IC50 = 25.5 µM) and no acute toxicity signs in vivo after an i.v. 1-mg/kg dose. The characterization presented here reassures the potential of complex 2 as a new chemical class of antimicrobial agents.

Whole lesion histogram analysis of apparent diffusion coefficient predicts therapy response in locally advanced rectal cancer.

BACKGROUND: Whole-tumor apparent diffusion coefficient (ADC) histogram analysis is relevant to predicting the neoadjuvant chemoradiation therapy (nCRT) response in patients with locally advanced rectal cancer (LARC). AIM: To evaluate the performance of ADC histogram-derived parameters for predicting the outcomes of patients with LARC. METHODS: This is a single-center, retrospective study, which included 48 patients with LARC. All patients underwent a pre-treatment magnetic resonance imaging (MRI) scan for primary tumor staging and a second restaging MRI for response evaluation. The sample was distributed as follows: 18 responder patients (R) and 30 non-responders (non-R). Eight parameters derived from the whole-lesion histogram analysis (ADCmean, skewness, kurtosis, and ADC10th, 25th, 50th, 75th, 90th percentiles), as well as the ADCmean from the hot spot region of interest (ROI), were calculated for each patient before and after treatment. Then all data were compared between R and non-R using the Mann-Whitney U test. Two measures of diagnostic accuracy were applied: the receiver operating characteristic curve and the diagnostic odds ratio (DOR). We also reported intra- and interobserver variability by calculating the intraclass correlation coefficient (ICC). RESULTS: Post-nCRT kurtosis, as well as post-nCRT skewness, were significantly lower in R than in non-R (both P < 0.001, respectively). We also found that, after treatment, R had a larger loss of both kurtosis and skewness than non-R (∆%kurtosis and ∆skewness, P < 0.001). Other parameters that demonstrated changes between groups were post-nCRT ADC10th, ∆%ADC10th, ∆%ADCmean, and ROI ∆%ADCmean. However, the best diagnostic performance was achieved by ∆%kurtosis at a threshold of 11.85% (Area under the receiver operating characteristic curve [AUC] = 0.991, DOR = 376), followed by post-nCRT kurtosis = 0.78 × 10-3 mm2/s (AUC = 0.985, DOR = 375.3), ∆skewness = 0.16 (AUC = 0.885, DOR = 192.2) and post-nCRT skewness = 1.59 × 10-3 mm2/s (AUC = 0.815, DOR = 168.6). Finally, intraclass correlation coefficient analysis showed excellent intraobserver and interobserver agreement, ensuring the implementation of histogram analysis into routine clinical practice. CONCLUSION: Whole-tumor ADC histogram parameters, particularly kurtosis and skewness, are relevant biomarkers for predicting the nCRT response in LARC. Both parameters appear to be more reliable than ADCmean from one-slice ROI.

[Validity and reliability of mammographic interpretation by Mexican radiologists, using the BI-RADS system]. / Validez y reproducibilidad de la interpretación de la mamografía por radiólogos mexicanos, mediante el sistema BI-RADS.

OBJECTIVE: Mammographic interpretation using the BI-RADS system determines if a patient will continue in the regular screening program or needs additional studies for breast cancer diagnosis, hence the importance of its evaluation. Sensitivity, specificity, diagnostic accuracy of mammographic interpretation and inter- and intra-observer variation, were assessed in a random sample of 29 radiologists from the Mexican Ministry of Health. MATERIAL AND METHODS: Eighty diagnostic and screening mammographic studies were selected from the National Cancer Institute in Mexico City. Under the same conditions, two interpretations using the BI-RADS system were performed by each of the participating radiologists. RESULTS: Sensitivity in the first and second measurement was 72 and 74% respectively, while the specificity was 80% for the first and 82% for second. Multivariate analysis showed a positive association between the last year number of interpreted mammograms, the number of courses taken and diagnostic accuracy (beta=0.00002, 95% CI 0.000004, 0.00003, p=0.02, beta=0.005, CI 95% -0.0004, 0.01, p=0.07, respectively). Inter-observer agreement was low in both measurements (kappa=0.24, kappa=0.25, respectively). However, after combining BI-RADS categories in 2, agreement increased to 0.46 for both measurements. The intra-observer agreement was good (kappa=0.67). CONCLUSIONS: The number of mammographic studies interpreted the previous year is a good measure of the experience of the radiologist and is reflected in the diagnostic accuracy of mammographic interpretation. Courses on mammographic interpretation also have a positive impact on performance.

Chelation-Assisted Interrupted Copper(I)-Catalyzed Azide-Alkyne-Azide Domino Reactions: Synthesis of Fully Substituted 5-Triazenyl-1,2,3-triazoles.

We describe the synthesis of 1,4-(disubstituted)-5-triazenyl-1,2,3-triazoles through a ligand-free domino copper(I)-catalyzed azide-alkyne-azide process of chelating aryl azides bearing N-P═O, P═O, and SO3H groups at the ortho position with a wide variety of acetylenes. DFT calculations reveal that Cu-chelation is a crucial factor in the interception of the CuAAC intermediate by the azide. The crystal structure of the catalytic species has been determined by X-ray diffraction.