Surgical Morbidity of Full-Thickness Chest Wall Resection for Breast Cancer: A Retrospective Study of a National Database.

BACKGROUND: Full-thickness chest wall resection (FTCWR) is an underused modality for treating locally advanced primary or recurrent breast cancer invading the chest wall, for which little data exist regarding morbidity and mortality. We examined the postoperative complication rates in breast cancer patients undergoing FTCWR using a large multinational surgical outcomes database. METHODS: A retrospective cohort analysis was conducted using the American College of Surgeons National Surgical Quality Improvement Program database. All patients undergoing FTCWR for breast cancer between 2007 and 2016 were identified (n = 137). Primary outcome measures included 30-d postoperative morbidity, composite respiratory complications, and hospital length of stay (LOS). The secondary aim was to compare the postoperative morbidity of FTCWR to those of patients undergoing mastectomy. One-to-one coarsened exact matching was conducted between two groups, which were then compared with respect to morbidity, mortality, reoperations, readmissions, and LOS. RESULTS: The overall rate of postoperative morbidity was 11.7%. Two patients (1.5%) had respiratory complications requiring intubation. Median hospital LOS was 2 d. In the coarsened exact matching analysis, 122 patients were included in each of the two groups. Comparison of matched cohorts demonstrated an overall morbidity for the FTCWR group of 11.5% compared with 8.2% for the mastectomy group (8.2%) (P = 0.52). CONCLUSIONS: FTCWR for the local treatment of breast cancer can be performed with relatively low morbidity and respiratory complications. This is the largest study looking at postoperative complications for FTCWR in the treatment of breast cancer. Future studies are needed to determine the long-term outcomes of FTCWR in this patient population.

Evaluating the Radiosensitization Effect of Hydroxyapatite Nanoparticles on Human Breast Adenocarcinoma Cell Line and Fibroblast.

BACKGROUND: Nanohydroxyapatite (nHAP) exhibit anti-proliferative effects on various cancer cells. However, to date, there are only a few studies on the radiosensitization effect of nHAP. The present study aimed to investigate the possible enhancement of the radiosensitization effect of nHAP on human breast adenocarcinoma cancer (MCF-7) and fibroblast. METHODS: nHAP was extracted from fish scales using the thermal alkaline method and characterized at Babol University of Medical Sciences (Babol, Iran) in 2017. The anti-proliferative and the radiosensitization effects of nHAP were investigated by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT), clonogenic assay, and apoptosis assay. MCF-7 cells and fibroblasts were incubated with different concentrations of nHAP and at different periods. The MTT solution was added and the absorbance was measured at 570 nm. The MCF-7 cells were exposed to 0, 1.5, 3.5, and 5 Gy X-ray irradiation and incubated for 10-14 days. The data were compared using the one-way analysis of variance (ANOVA) followed by the post hoc tests (Tukey's method). RESULTS: The results showed that nHAP significantly inhibited the growth of MCF-7 cells compared with controls (P<0.001), but the difference was not statistically significant for fibroblasts (P=0.686 at 400 µg/mL at 72 hours). After 48 hours, the proliferation of MCF-7 cells and fibroblasts was inhibited by about 81% and 34% at 400 µg/mL concentration, respectively. The radiosensitization enhancement factor for MCF-7 cells and fibroblasts at a dose of 3.5 Gy and 100 µg/mL concentration were 1.87 and 1.3, respectively. CONCLUSION: nHAP can be considered as a breast cancer radiosensitization agent with limited damage to the surrounding healthy tissue.

Patient-reported factors influencing the treatment decision-making process of older women with non-metastatic breast cancer: a systematic review of qualitative evidence.

PURPOSE: Older women (≥ 70 years old) with breast cancer undergo different treatments than young women. Studies have examined factors that influence this disparity, but synthesized patient-reported data are lacking in the literature. This study aims to identify, appraise, and synthesize the existing qualitative evidence on patient-reported factors influencing older women's decision to accept or decline breast cancer treatment. METHODS: A systematic review was performed in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA) principles. Medline, Embase, CINAHL, and PsycINFO were searched for qualitative studies describing patient-reported factors influencing the decision-making process of older women (≥ 70 years old) with non-metastatic invasive breast cancer. Quality was assessed using the Standards for Reporting Qualitative Research (SRQR) criteria. Common ideas were coded, thematically organized, and synthesized within a theoretical framework. RESULTS: Of 5998 studies identified, 10 met eligibility criteria. The median SRQR total score was 13.04 (IQR 12.84-13.81). The studies represented a range of cancer treatments; most of the studies focused on surgery and primary endocrine therapy. Our data show that the most common patient-reported factors in the decision-making process included treatment characteristics, personal goals/beliefs, patient characteristics, physician's recommendation, and personal/family experience. These factors led the patient to either accept or decline treatment, and were not consistent across all studies included. Studies used different interview guides, which may have affected these results. CONCLUSIONS: This systematic review highlights the complexity of factors that influence an older woman's treatment decision-making process. Acknowledging and addressing these factors may improve discussions about treatment choices between older women and their health care providers, and encourage maximization of a patient-centered approach.

Concurrent risk-reduction surgery in patients with increased lifetime risk for breast and ovarian cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database.

BACKGROUND: Patients with genetic susceptibility to breast and ovarian cancer are eligible for risk-reduction surgery. Surgical morbidity of risk-reduction mastectomy (RRM) with concurrent bilateral salpingo-oophorectomy (BSO) is unknown. Outcomes in these patients were compared to patients undergoing RRM without BSO using a large multi-institutional database. METHODS: A retrospective cohort analysis was conducted using the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP) 2007-2016 datasets, comparing postoperative morbidity between patients undergoing RRM with patients undergoing RRM with concurrent BSO. Patients with genetic susceptibility to breast/ovarian cancer undergoing risk-reduction surgery were identified. The primary outcome was 30-day postoperative major morbidity. Secondary outcomes included surgical site infections, reoperations, readmissions, length of stay, and venous thromboembolic events. A multivariate analysis was performed to determine predictors of postoperative morbidity and the adjusted effect of concurrent BSO on morbidity. RESULTS: Of the 5470 patients undergoing RRM, 149 (2.7%) underwent concurrent BSO. The overall rate of major morbidity and postoperative infections was 4.5% and 4.6%, respectively. There was no significant difference in the rate of postoperative major morbidity (4.5% vs 4.7%, p = 0.91) or any of the secondary outcomes between patients undergoing RRM without BSO vs. those undergoing RRM with concurrent BSO. Multivariable analysis showed Body Mass Index (OR 1.05; p < 0.001) and smoking (OR 1.78; p = 0.003) to be the only predictors associated with major morbidity. Neither immediate breast reconstruction (OR 1.02; p = 0.93) nor concurrent BSO (OR 0.94; p = 0.89) were associated with increased postoperative major morbidity. CONCLUSION: This study demonstrated that RRM with concurrent BSO was not associated with significant additional morbidity when compared to RRM without BSO. Therefore, this joint approach may be considered for select patients at risk for both breast and ovarian cancer.

Evolving surgical treatment decisions for male breast cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database.

BACKGROUND: Male breast cancer (MBC) is a rare malignancy, and gender-specific treatment outcomes are currently lacking. The use of a large, multi-national surgical-outcomes database may provide a better understanding of treatment patterns and postoperative morbidity in men who undergo oncological breast surgery. METHODS: A retrospective cohort analysis was conducted between 2007 and 2016 using the American College of Surgeons National Surgical Quality Improvement Program database (NSQIP), examining MBC treatment patterns and postoperative complication rates. All men undergoing surgery for the treatment of invasive or in situ carcinoma of the breast were identified. Clinical characteristics, demographics, and surgical treatment options most frequently used for this population were described. In addition, the 30-day postoperative complication rates in the surgical treatment of male breast cancer were evaluated. RESULTS: A total of 1773 MBC patients with a median age of 65 years (IQR 56-74 years) were included in this analysis. Mean body mass index (BMI) was 29.1 (IQR 25.4-33.8). In this study population, 177 (10.0%) had a diagnosis of in situ breast cancer, while the remaining 1596 (90.0%) had invasive disease. While most men underwent mastectomy, 282 (15.9%) had breast-conserving surgery. There were 74 (4.2%) patients who underwent immediate breast reconstruction. In addition, 118 (6.7%) patients elected to have a contralateral prophylactic mastectomy. Overall, the rate of morbidity was 4.6%, comprising mostly of wound complications (3.2%). CONCLUSION: Analysis of this large, prospective multi-institutional cohort revealed that complication rates are low and comparable to reported rates in the female breast cancer population. What is also significant about this analysis is that the cohort demonstrated the importance of cosmetic considerations in MBC patients, as some men decide to undergo breast-conserving surgery or immediate breast reconstruction. Contralateral prophylactic mastectomy in the treatment of MBC is also performed.

Preoperative localization of colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Preoperative colorectal tumor localization is crucial for appropriate resection and treatment planning. As the localization accuracy of conventional colonoscopy is considered to be low, several localization techniques have been developed. We systematically reviewed the tumor localization error rates of several preoperative endoscopic techniques and synthesized information on risk factors for localization errors and procedure-related adverse events. METHODS: MEDLINE, EMBASE, the Cochrane Library, and the grey literature were searched. Studies were included if they reported tumor localization errors in patients with colorectal cancer undergoing resection with curative intent. Using random-effects models, pooled incidence of tumor localization errors were derived for conventional colonoscopy and colonoscopic tattooing. Due to the lack of comparative studies, a direct comparison of the pooled estimates was performed. Procedure-related adverse events, risk factors for localization errors, and the localization outcomes of other techniques such as colonoscopic clip placement, radioguided occult colonic lesion identification, and the use of magnetic endoscope imaging were also synthesized. RESULTS: A total of 38 non-randomized controlled and observational studies were included in this review (2578 patients underwent conventional colonoscopy and 643 colonoscopic tattooing). The pooled incidence of localization errors with conventional colonoscopy was 15.4 % (95 % CI 12.0-18.7), whereas that of colonoscopic tattooing was 9.5 % (95 % CI 5.7-13.3), mean difference 5.9 % (95 % CI 0.65-11.14, p = 0.03). Adverse events secondary to tattooing were infrequent, and most were cases of ink spillage. Limited information was available for other localization techniques. CONCLUSION: Conventional colonoscopy has a higher incidence of localization error compared to colonoscopic tattooing for localization of colorectal cancer. Colonoscopic tattooing is safe and leads to fewer tumor localization errors. Given the widespread adoption of laparoscopic resections for colorectal cancer, routine colonoscopic tattooing should be adopted. However, studies directly comparing different localization techniques are needed.

miR-27a and miR-214 exert opposite regulatory roles in Th17 differentiation via mediating different signaling pathways in peripheral blood CD4+ T lymphocytes of patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is one of the most prevalent autoimmune diseases, which involves the central nervous system. In this illness, Treg/Th17 cell imbalance causes the defect. Several studies revealed that T helper 17 (Th17) cells play a crucial role in pathogenesis, inflammation, and autoimmunity of several autoimmune diseases such as MS. In the present study, we assessed transcript levels of miR-27a and miR-214, in purified CD4+ T cells of MS patients, during relapsing and remitting phases in inducing differentiation of T naïve cells to Th17 cells. Forty RR-MS patient samples including those in relapsing (n=20) and remitting (n=20) phases were participated in this study. In addition, transcript levels of IL-17A, RORγt, IL-23R, Foxp3, and TGF-ß in purified CD4+ T cells of patients in relapsing and remitting phases of RRMS patients were compared to healthy controls. Expression levels of miR-27a and miR-214 were measured by RT-qPCR and compared to healthy control group (n=10). Data indicated upregulation of miR27a in relapsing phase of multiple sclerosis compared to remitting phase and healthy volunteers while miR-214 downregulated in relapsing phase of MS compared to remitting phase and healthy volunteers. In silico studies demonstrated pathways which miR-27a and miR-214 could effect on CD4+ T cell lineage fate including TGF-ß and mTOR signaling, respectively. Our data suggest that miR-27a may probably inhibit negative regulators of Th17 cell differentiation, thus promoting its differentiation while miR-214 has an adverse effect.

The effect of the glycolipoprotein extract (G-90) from earthworm Eisenia foetida on the wound healing process in alloxan-induced diabetic rats.

Diabetes is now regarded as a major public health problem. The number of patients is estimated to increase to over 439 million cases by 2030. One of the major health clinical problems in patients with diabetes patients is impaired wound healing. Diabetic foot ulcer is a major complication of diabetes mellitus in 12 to 25% of patients, which increases the risk of damage in the limbs or amputation. The earthworm Eisenia foetida glycolipoprotein (as known G-90) is a blend of macromolecules with some biological properties including mitogenicity, anticoagulation, fibrinolysis, bacteriostatic and antioxidatiaon. Given the biological properties of G-90, this study was conducted to investigate the effect of extract obtained from the homogenate of Eisenia foetida (G-90) on the wound healing process in alloxan-induced diabetic rats. The results of the present study revealed that treatment by using G-90 can speed up the wound healing process, which is exactly similar to the effect of D-panthenol treatment in rats. These findings also demonstrated that G-90 treatment decreases the risk of infection in the wound site compared with D-panthenol treatment. In addition, histological analysis indicated that a better extracellular matrix formation with increased fibroblast proliferation, neovascularization, collagen synthesis and early epithelial layer formation was observed in G-90 treated group. Therefore, the G-90 could be considered as a new wound healing agent introducing promising therapeutic approaches in both human and veterinary medicine. Copyright © 2016 John Wiley & Sons, Ltd.

The impact of blood transfusion on perioperative outcomes following gastric cancer resection: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: Red blood cell transfusions (RBCT) carry risk of transfusion-related immunodulation that may impact postoperative recovery. This study examined the association between perioperative RBCT and short-term postoperative outcomes following gastrectomy for gastric cancer. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we compared outcomes of patients (transfused v. nontransfused) undergoing elective gastrectomy for gastric cancer (2007-2012). Outcomes were 30-day major morbidity, mortality and length of stay. The association between perioperative RBCT and outcomes was estimated using modified Poisson, logistic, or negative binomial regression. RESULTS: Of the 3243 patients in the entire cohort, we included 2884 patients with nonmissing data, of whom 535 (18.6%) received RBCT. Overall 30-day major morbidity and mortality were 20% and 3.5%, respectively. After adjustment for baseline and clinical characteristics, RBCT was independently associated with increased 30-day mortality (relative risk [RR] 3.1, 95% confidence interval [CI] 1.9-5.0), major morbidity (RR 1.4, 95% CI 1.2-1.8), length of stay (RR 1.2, 95% CI 1.1-1.2), infections (RR 1.4, 95% CI 1.1-1.6), cardiac complications (RR 1.8, 95% CI 1.0-3.2) and respiratory failure (RR 2.3, 95% CI 1.6-3.3). CONCLUSION: Red blood cell transfusions are associated with worse postoperative short-term outcomes in patients with gastric cancer. Blood management strategies are needed to reduce the use of RBCT after gastrectomy for gastric cancer.

CONTEXTE: Les transfusion de globules rouges (TGR) entrainent une immunosuppression qui peut entraver la récupération post-opératoire. Cette étude évalue l'association entre les TGR péri-opératoires et l'issue post-opératoire après gastrectomie pour cancer gastrique (CG). MÉTHODES: Le registre de l'ACS-NSQIP fut utilisé pour comparer l'issue des patients subissant une gastrectomie élective pour CG de 2007 à 2012, selon la TGR. La morbidité majeure et mortalité à 30 jours, et la durée d'hospitalisation furent analysées. L'association entre la TGR et les résultats post-opératoires fut estimée par régressions de Poisson modifiée, logistique, et binomiale. RÉSULTATS: Parmi 3243 gastrectomies, 2884 patients avec des données complètes furent inclus, dont 535 (18,6 %) furent transfusés. La morbidité globale à 30 jours était 20 % et la mortalité 3,5 %. Après avoir contrôlé pour les caractéristiques démographiques et cliniques pertinentes, les TGR démontraient une association indépendante avec une morbidité majeure (risque relatif [RR] 3,1; intervalle de confiance [IC] à 95 % 1,9-5,0), une mortalité (RR 1,4; IC à 95 % 1,2-1,8), et une durée d'hospitalisation (RR 1,2; IC à 95 % 1,1-1,2) accrues. Les TGR étaient aussi associées aux complications infectieuses (RR 1,4; IC à 95 % 1,1-1,6), cardiaques (RR 1,8; IC à 95 % 1,0-3,2), et respiratoires (RR 1,4; IC à 95 % 1,6-3,3). CONCLUSION: Les TGR sont associées à une détérioration de l'issue post-opératoire après gastrectomie pour CG, dont la morbidité majeure, la mortalité, et la durée d'hospitalisation. Des stratégies multidisciplinaires de gestion du risque transfusionnel sont nécessaires afin de limiter l'utilisation des TGRs après gastrectomie pour CG.

The association of adjuvant therapy with survival at the population level following pancreatic adenocarcinoma resection.

BACKGROUND: Using a retrospective observational cohort approach, the overall survival (OS) following curative-intent resection of pancreatic adenocarcinoma (PC) was defined at the population level according to adjuvant treatment, and predictors of OS were identified. METHODS: Patients undergoing resection of PC in the province of Ontario between 2005 and 2010 were identified using the provincial cancer registry, and linked to databases that include all treatments received and outcomes experienced in the province. Pathology reports were abstracted for staging and margin status. Patients were identified as having received chemotherapy (CT), chemoradiation therapy (CRT), or no adjuvant treatment (NAT). Kaplan-Meier survival analysis of patients surviving ≥ 6 months was performed, and predictors of OS identified by log-rank test. Cox multivariable analysis was used to define independent predictors of OS. RESULTS: Among the 473 patients undergoing PC resection, the median survival was 17.8 months; for the 397 who survived ≥ 6 months following surgery, the 5-year OS for the CT, CRT, and NAT groups was 21%, 16%, and 17%, respectively (p = 0.584). Lymph node-negative patients demonstrated improved OS associated with chemotherapy on multivariable analysis (HR = 2.20, 95% CI = 1.25-3.83 for NAT vs. CT). CONCLUSIONS: Following PC resection, only patients with negative lymph nodes demonstrated improved OS associated with adjuvant chemotherapy.

A systematic review of the effects of resident duty hour restrictions in surgery: impact on resident wellness, training, and patient outcomes.

BACKGROUND: In 2003, the Accreditation Council for Graduate Medical Education (ACGME) mandated 80-hour resident duty limits. In 2011 the ACGME mandated 16-hour duty maximums for PGY1 (post graduate year) residents. The stated goals were to improve patient safety, resident well-being, and education. A systematic review and meta-analysis were performed to evaluate the impact of resident duty hours (RDH) on clinical and educational outcomes in surgery. METHODS: A systematic review (1980-2013) was executed on CINAHL, Cochrane Database, Embase, Medline, and Scopus. Quality of articles was assessed using the GRADE guidelines. Sixteen-hour shifts and night float systems were analyzed separately. Articles that examined mortality data were combined in a random-effects meta-analysis to evaluate the impact of RDH on patient mortality. RESULTS: A total of 135 articles met the inclusion criteria. Among these, 42% (N = 57) were considered moderate-high quality. There was no overall improvement in patient outcomes as a result of RDH; however, some studies suggest increased complication rates in high-acuity patients. There was no improvement in education related to RDH restrictions, and performance on certification examinations has declined in some specialties. Survey studies revealed a perception of worsened education and patient safety. There were improvements in resident wellness after the 80-hour workweek, but there was little improvement or negative effects on wellness after 16-hour duty maximums were implemented. CONCLUSIONS: Recent RDH changes are not consistently associated with improvements in resident well-being, and have negative impacts on patient outcomes and performance on certification examinations. Greater flexibility to accommodate resident training needs is required. Further erosion of training time should be considered with great caution.

The use of antibacterial activity of ZnO nanoparticles in the treatment of municipal wastewater.

Nanotechnology holds great potential in advanced water and wastewater treatment to improve treatment efficiency. Zinc oxide nanoparticles (ZnO NPs) have received considerable attention due to their unique antibacterial activities toward various microorganisms that are commonly found in the environment. In the present study, ZnO NPs were synthesized through both mechano-chemical and sol-gel methods. The synthesized ZnO NPs were characterized through X-ray diffraction and transmission electron microscopy techniques. Then, their antibacterial activities against separated wastewater bacteria were evaluated by determining the zone inhibitor, the minimum inhibitory concentration, and the minimum bactericidal concentration. The results were compared with those obtained from wastewater after chlorine disinfection and ultraviolet (UV) disinfection. These studies demonstrated that the antibacterial activity of ZnO NPs depends on the type and the strain of bacteria. They have also demonstrated that the activity increases as the concentration of ZnO NPs increases. Overall, the experimental results suggest that ZnO NPs can potentially be an antibacterial reagent to treat wastewater. They can particularly be applied as a complementary method with UV disinfection. Thus, they can be developed as antibacterial agents to improve wastewater quality.

Proteomic Analyses of the G Protein-Coupled Estrogen Receptor GPER1 Reveal Constitutive Links to Endoplasmic Reticulum, Glycosylation, Trafficking, and Calcium Signaling.

The G protein-coupled estrogen receptor 1 (GPER1) has been proposed to mediate rapid responses to the steroid hormone estrogen. However, despite a strong interest in its potential role in cancer, whether it is indeed activated by estrogen and how this works remain controversial. To provide new tools to address these questions, we set out to determine the interactome of exogenously expressed GPER1. The combination of two orthogonal methods, namely APEX2-mediated proximity labeling and immunoprecipitation followed by mass spectrometry, gave us high-confidence results for 73 novel potential GPER1 interactors. We found that this GPER1 interactome is not affected by estrogen, a result that mirrors the constitutive activity of GPER1 in a functional assay with a Rac1 sensor. We specifically validated several hits highlighted by a gene ontology analysis. We demonstrate that CLPTM1 interacts with GPER1 and that PRKCSH and GANAB, the regulatory and catalytic subunits of α-glucosidase II, respectively, associate with CLPTM1 and potentially indirectly with GPER1. An imbalance in CLPTM1 levels induces nuclear association of GPER1, as does the overexpression of PRKCSH. Moreover, we show that the Ca2+ sensor STIM1 interacts with GPER1 and that upon STIM1 overexpression and depletion of Ca2+ stores, GPER1 becomes more nuclear. Thus, these new GPER1 interactors establish interesting connections with membrane protein maturation, trafficking, and calcium signaling.

A Deep Learning Decision Support Tool to Improve Risk Stratification and Reduce Unnecessary Biopsies in BI-RADS 4 Mammograms.

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset. Materials and Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016. In this multicenter study, iBRISK was further assessed on an independent, retrospective dataset (January 2015-June 2019) from three major health care institutions in Texas, with Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions. Data were dichotomized and trichotomized to measure precision in risk stratification and probability of malignancy (POM) estimation. iBRISK score was also evaluated as a continuous predictor of malignancy, and cost savings analysis was performed. Results: The iBRISK model's accuracy was 89.5%, area under the receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.92, 0.95), sensitivity was 100%, and specificity was 81%. A total of 4209 women (median age, 56 years [IQR, 45-65 years]) were included in the multicenter dataset. Only two of 1228 patients (0.16%) in the "low" POM group had malignant lesions, while in the "high" POM group, the malignancy rate was 85.9%. iBRISK score as a continuous predictor of malignancy yielded an AUC of 0.97 (95% CI: 0.97, 0.98). Estimated potential cost savings were more than $420 million. Conclusion: iBRISK demonstrated high sensitivity in the malignancy prediction of BI-RADS 4 lesions. iBRISK may safely obviate biopsies in up to 50% of patients in low or moderate POM groups and reduce biopsy-associated costs.Keywords: Mammography, Breast, Oncology, Biopsy/Needle Aspiration, Radiomics, Precision Mammography, AI-augmented Biopsy Decision Support Tool, Breast Cancer Risk Calculator, BI-RADS 4 Mammography Risk Stratification, Overbiopsy Reduction, Probability of Malignancy (POM) Assessment, Biopsy-based Positive Predictive Value (PPV3) Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by McDonald and Conant in this issue.

Density functional theory study of nitrogen-14 nuclear quadrupole coupling parameters of L-histidine: hydrogen-bonded system.

The calculations of nitrogen-14 nuclear quadrupole parameters, nuclear quadrupole coupling constant, χ, and asymmetry parameter, η, of L-His were done in two distinct environments: one as a free fully optimized molecule, an isolated molecule with the geometrical parameters taken from X-ray, and the other in the orthorhombic and monoclinic solid states. The most probable interacting molecules with the central molecule in the crystalline phase were considered in the hexameric clusters to include hydrogen-bonding effects in the calculations. The computations were performed with PW91P86/6-31++G** and B3LYP6-31++G** methods using the Gaussian 98 program. The good agreement between the nitrogen-14 quadrupole parameters of the free His and imidazole molecules with their microwave available data demonstrates that the applied level of theory and the 6-31++G** basis set are suitable to obtain reliable electric field gradient values. In the solid state, the shifts of quadrupole coupling parameters from the monomer to the solid phase are reasonably well reproduced for the amino and imino sites of imidazole ring in a hexameric cluster. That implies the fact that the hexameric cluster worked effectively to generate the results which are compatible with the experiment. The quadrupole coupling constant values of -N(+) H(3) group are in fair agreement with the experiment. This discrepancy is due to the absences of vibrational effects and the rotation of -N(+) H(3) group around N-C(α) bond.

Simultaneous detection of Hb constant spring (α142, TAA>CAA, α2) and the α2 IVS-I donor site (-TGAGG) deletion by a simple polymerase chain reaction-based method in Iran.

Hb Constant Spring (Hb CS, codon 142, TAA>CAA, α2) (HBA2:c.427T>C) and α2 IVS-I donor site (GAGGTGAGG>GAGG - - - - -) (HBA2:c.95+2_95+6delTGAGG) are nondeletional α-thalassemia (α-thal) mutations found all over the world. Identification of α-thal genotypes in at-risk couples for severe anemia or in highly heterogeneous populations requires rapid, accurate and cost-effective genotyping methods. In this study, a pair of primers were used to specifically amplify an 883 bp fragment from the α2-globin gene in order to simultaneously identify these two mutations by a PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. We determined the genotypic frequencies of Hb CS and the α2 IVS-I donor site mutations after amplification and enzymatic digestion with Tru9I in 238 northern Iranian samples referred for α-thal testing. Hb CS and the α2 IVS-I donor site mutations accounted for 21 (8.8%) and 29 (12.2%) of the nondeletional cases. This genotyping assay has proven to be a rapid, reliable and useful diagnostic tool for simultaneous detection of these two anomalies for genetic counseling or further prenatal diagnosis.

Outcomes of Interventions for Angiosarcoma.

Objective: Angiosarcoma is a rare malignant vascular tumor, and the management and outcome of this disease are not well-described. The aim of this study was to report the incidence, patient demographics, and outcomes of angiosarcoma based on national data. Methods: Data on patients with angiosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Inverse probability treatment weights (IPTW) were used to assess the survival benefit of operation with additional chemo or radiation therapy compared to operation alone. These variables were further compared against patients who did not receive an operation despite being initially offered one. Cox regression was used to assess survival. Statistical analyses were performed on RStudio. Results: For this study, 5,135 patients (46% men; median age 69, range 0-102) with angiosarcoma were identified in the SEER database between 1975 and 2016. The age-adjusted incidence rate was 1-4%. Patients were mostly non-Hispanic Caucasian (75.4%). The average tumor size was 4.7 cm, range (.1-98.9). Tumor grades were high at presentation (Grade III 17.2, Grade IV 19, and unknown 50.6%), but half were considered localized tumors. Most patients underwent an operation (66.1%). In 5.6% of patients, the operation was recommended but not performed. The overall 5-year survival was 26.7% (95% CI 25.4-28.1%). IPTW with adjusted Cox proportional hazard model demonstrated worse survival, showing that operation compared to no operation and operation with chemo/radiation compared to operation alone had worse survival between months 0 and 25 but had improved survival after month 25. Conclusions: The incidence of angiosarcoma is low and long-term survival is poor. Multimodal therapy in the form of neoadjuvant or adjuvant chemo/radiation therapy offers significant long-term survival benefits over operation alone.

A call to bridge the divide in breast reconstruction research: A systematic review.

PURPOSE: Breast reconstruction is an important component of comprehensive breast cancer care. Although reconstructive plans require multidisciplinary clinical-decision making, research in cross-discipline collaborations is often limited. This study aims to evaluate multidisciplinary involvement in breast reconstruction outcomes research. METHODS: A systematic review of breast reconstruction literature published from 2000 to 2019 using Ovid MEDLINE, Ovid EMBASE, and PubMed databases was conducted. English language articles published in North America or Europe with n ≥ 12 nonpediatric patients were included. Articles concerning procedures not performed in the context of breast cancer care or articles that did not evaluate at least one outcome, diagnostic test, or risk factor were excluded. Authors' affiliations were used to define multidisciplinary involvement. Quality of research was evaluated using the level of evidence,  journal impact factor (IF), and altmetrics. RESULTS: Of the 1679 articles screened, 784 met the stated eligibility criteria. Only half (50.6%) of these articles involved an author outside the discipline of plastic surgery. Compared to nonmultidisciplinary studies, multidisciplinary studies were more likely to be designated with a higher level of evidence (I or II) (p<0.001), published in journals with higher IF (p<0.05), have higher usage (p = 0.03), and mentions (p = 0.02). There was no difference in citations, captures, and social media posts (p>0.05). CONCLUSION: Breast reconstruction outcomes research often fails to offer author collaborations from nonplastic surgery disciplines. Multidisciplinary involvement in breast cancer care research is strongly recommended to improve the quality and impact of clinical studies in breast reconstruction.

A comprehensive molecular characterization of beta thalassemia in a highly heterogeneous population.

In Iran, the prevalence of beta-thalassemia trait is approximately 4-8% in most areas, and in Mazandaran province 10% of the population are carriers. Twenty four beta-globin gene mutations were identified in 1635 persons with beta-thalassemia trait using reverse dot blot and restriction fragment length polymorphism analysis. The predominant mutations included IVSII-1 (G-A) (61%), codon 30 (G-C) (7.5%), codon 22 (-7bp) (6.2%), codon 8 (-AA) (5.4%) and IVSI-5 (G-C) (3.6%). These mutations were in different haplotypes, with IVSII-1 being the most heterogeneous. Other less frequent mutations included IVS-II-745 (C-G), codon 44 (-C), codon 39 (C-T), codon 5 (-CT), IVS I-110 (G-A), IVSI-130 (G-C), Fr8/9 (+G), IVSI-1 (G-A), and IVSI (-25bp). All rare mutations except IVSI-130 were encountered in a unique haplotype. The diversity of these mutations reflects the historical admixture of genes in the region. The high prevalence of IVSII-1 (G-A) compared to other parts of the country and the world suggests a founder effect. Our data provide a basis for genetic counseling and prenatal diagnosis.

Skeletal muscle metabolism in cystic fibrosis and primary ciliary dyskinesia.

Previous studies have reported differences in muscle function and metabolism between patients with cystic fibrosis (CF) and healthy controls (HC), but it is currently unknown whether these abnormalities are specific to CF or also seen in other airway diseases. In this study, we used magnetic resonance spectroscopy (MRS) during exercise to assess muscle metabolism in CF patients. Twenty patients with CF and 20 age, gender, and habitual activity-matched HCs and a respiratory disease comparison group with primary ciliary dyskinesia (PCD; n = 10) were studied. Phosphorus MRS (P-MRS) was used to characterize muscle bioenergetic metabolism at rest and after high-, moderate-, and low-intensity exercise. CF patients exhibited lower resting ATP/phosphocreatine (PCr) ratio and significantly higher end-exercise pH values compared with both HC and PCD patients. Both CF and PCD patients demonstrated significantly slower PCr recovery time constants after high-intensity exercise. Our results suggest that not only there are specific abnormalities of muscle metabolism in CF patients but also there is a nonspecific impact of respiratory disease on muscle function.