Objectives
Current surgical policy recommends comprehensive excision of tumorous calcifications in breast cancer patients following neoadjuvant chemotherapy (NAC) regardless of MRI outcomes, despite ...MRI defining tumor response superior to mammography. The current study examines MRI prediction of response in tumors with vs without calcifications, using post-NAC surgical pathology as the standard of reference.
Methods
Retrospective analysis of 114 NAC patients between 2011 and 2018 including demographics, mammography, 3 T-MRI, and pathology compared two sub-groups: without (
n
= 62) or with (
n
= 52) mammographic calcifications. In the calcification cohort, the mammographic extent of calcifications and MRI enhancement overlapped. MRI prediction of response to NAC was correlated with pathology. Two-tailed paired
T
and Fisher’s exact tests and Cohen’s kappa coefficient were applied for analysis.
Results
There was no significant difference between the two sub-groups regarding demographics. Tumors demonstrated equivalent features regarding size, lymph node involvement, and DCIS component. ER-negative/HER2-positive tumors more commonly exhibited calcifications (33%
n
= 17 calcified vs 13%
n
= 8 non-calcified;
p
< 0.05); triple negative pathology rarely calcified (6%
n
= 3 calcified vs 33%
n
= 20 non-calcified;
p
< 0.05). NME was more common with calcifications (62%
n
= 32 calcified vs 29%
n
= 18 non-calcified;
p
< 0.05) and mass enhancement without (90%
n
= 56 non-calcified vs 81%
n
= 42 calcified;
p
< 0.05). Both groups responded similarly to NAC (pCR = 37% non-calcified vs 38% calcified); response on MRI equally correlated with pathology (69% both subgroups;
p
= 0.988).
Conclusion
We propose utilizing post-NAC MRI findings rather than mammography in planning surgery, as MRI prediction is independent of the presence or absence of calcifications. Prospective studies to evaluate this approach are warranted.
Key Points
•
No difference was found in demographic, clinical, pathology, or imaging characteristics between patients with or without tumoral calcifications on mammography prior to neoadjuvant chemotherapy
.
•
Residual mammographic calcifications are inadequate predictors of residual invasive disease. MRI accurately recognized complete response and correctly correlated with post-treatment surgical pathology in 69% of patients, regardless of the presence or absence of mammographic calcifications
.
•
We propose utilizing post-NAC MRI findings rather than mammography in planning post-NAC surgery, as MRI prediction of response is independent of the presence or absence of calcifications
.
1-
Cpyruvate, the most widely used compound in dissolution-dynamic nuclear polarization (dDNP) magnetic resonance (MR), enables the visualization of lactate dehydrogenase (LDH) activity. This ...activity had been demonstrated in a wide variety of cancer models, ranging from cultured cells, to xenograft models, to human tumors in situ. Here we quantified the LDH activity in precision cut tumor slices (PCTS) of breast cancer xenografts. The Michigan Cancer Foundation-7 (MCF7) cell-line was chosen as a model for the luminal breast cancer type which is hormone responsive and is highly prevalent. The LDH activity, which was manifested as 1-
Clactate production in the tumor slices, ranged between 3.8 and 6.1 nmole/nmole adenosine tri-phosphate (ATP) in 1 min (average 4.6 ± 1.0) on three different experimental set-ups consisting of arrested vs. continuous perfusion and non-selective and selective RF pulsation schemes and combinations thereof. This rate was converted to an expected LDH activity in a mass ranging between 3.3 and 5.2 µmole/g in 1 min, using the ATP level of these tumors. This indicated the likely utility of this approach in clinical dDNP of the human breast and may be useful as guidance for treatment response assessment in a large number of tumor types and therapies ex vivo.
Germline
pathogenic variant (PV) carriers have high lifetime risk of developing breast cancer and therefore subjected to intense lifetime screening. However, solid data on the effectiveness of ...high-risk screening of the
carrier population is limited.
Retrospectively, we analyzed 346 women diagnosed with breast tumors. Patients were divided according to the timing of
PVrecognition, before (BRCA-preDx awareness, N = 62) or after (BRCA-postDx awareness group, N = 284) cancer diagnosis.
Median follow-up times were 131.42 and 93.77 months in the BRCA-preDx awareness and BRCA-postDx awareness groups, respectively. In the BRCA-preDx awareness group, 78.7% of the patients had invasive tumors and 21.3% were diagnosed with pure ductal carcinoma
. In contrast, in the BRCA-postDx awareness group over 93% of women were diagnosed with invasive cancer and only 6.4% had
disease. The mode of tumor detection differed significantly between the groups: 71.9% in the BRCA-postDx awareness group and 26.2% in the BRCA-preDx awareness group were diagnosed after personally palpating a lump. Tumor size and nodal involvement were significantly more favorable in the BRCA-preDx awareness group. T stage was significantly lower in the BRCA-preDx awareness group: 54.84% at T1 and 20.96% at Tis. In the BRCA-postDx awareness group, only 37.54% were at T1 and 6.49% at Tis. The N stage was also significantly lower in the BRCA-preDx awareness group: 71% had no lymph node metastases, compared with 56.1% in the BRCA-postDx awareness group. Additionally, therapeutic procedures varied between the groups: BRCA-preDx awareness group patients underwent more breast conserving surgeries. Axillary lymph node dissection was done in 38% of women in the BRCA-postDx awareness group and in only 8.7% of the BRCA-preDx awareness group patients. Interestingly, improved survival was found among patients who underwent high-risk screening (hazard ratio=0.34).
High-risk screening might facilitate downstaging of detected breast tumor among
carrier population.
Abstract Objective To compare the obstetric characteristics of twin pregnancies conceived by in vitro fertilization (IVF) and ovulation induction with those conceived spontaneously. Design Case ...control study. Setting: Tertiary Medical Center. Patients: All twin deliveries that were achieved by IVF ( n = 558) and ovulation induction ( n = 478) from January 1988 through December 2002 were evaluated. Each group was compared with a control group that conceived spontaneously ( n = 3694) and was delivered during the same period. Interventions: Ovulation induction, IVF-ET. Main outcome measures: Obstetrical complications. Results Multivariate analysis showed that patients who conceived with the assistance of IVF and ovulation induction had a significantly higher risk for gestational diabetes mellitus (odds ratio OR = 2.41, 95% confidence interval CI = 1.77–3.29 and OR = 1.71, CI = 1.2–2.42, respectively), cesarean section (OR = 2.17, 95% CI = 1.74–2.70 and OR = 1.76, CI = 1.43–2.16, respectively), and a lower gestational age at birth in the IVF group (OR = 0.91, 95% CI = 0.88–0.94), compared with their controls. Conclusions After controlling for maternal age, and nulliparity we demonstrated that twin pregnancies conceived with the assistance of IVF and ovulation induction are at increased risk for gestational diabetes mellitus, and delivery by cesarean section. In addition, IVF conceived pregnancies have a lower gestational age at birth.
Sonographic evaluation of congenital skeletal dysplasias is often challenging. Ultrasound may be limited in demonstrating the skeleton and may overlook specific signs of skeletal abnormality. ...Computed tomography (CT) with 3D reconstruction was proposed as an aid in the diagnosis of skeletal dysplasias.
To describe our experience with 3D-CT imaging for the evaluation of suspected skeletal dysplasias.
The study group comprised 20 pregnant women carrying 22 fetuses, referred for further evaluation by CT following sonographic suspicion of fetal skeletal dysplasia at 17-39 weeks of gestation. Examinations were performed using various CT protocols. Radiation exposure was decreased during the study period, with eventual lowering of the dose to 1-3 mSv. Meticulous review of the skeleton and long bone measurements were performed on 3D reconstructions. For cases of pregnancy termination, the postmortem diagnosis was compared retrospectively with the CT findings.
Very low dose CT protocols provided excellent diagnostic images. Of 22 fetuses suspected of having skeletal dysplasia on ultrasound, 8 were found by CT to be dysplastic and in 7 the pregnancy was terminated. Postmortem findings, when available, concurred with the CT diagnosis. The remaining 14 fetuses within this cohort were found to be normal according to CT and were carried to term.
3D-CT may be a valuable complimentary imaging tool to ultrasound for the diagnosis of skeletal dysplasias. With low dose protocols, this examination is relatively safe, and in the appropriate clinical context may assist in making difficult decisions prenatally.
The two main branches of bionanotechnology involve the self-assembly of either peptides or DNA. Peptide scaffolds offer chemical versatility, architectural flexibility and structural complexity, but ...they lack the precise base pairing and molecular recognition available with nucleic acid assemblies. Here, inspired by the ability of aromatic dipeptides to form ordered nanostructures with unique physical properties, we explore the assembly of peptide nucleic acids (PNAs), which are short DNA mimics that have an amide backbone. All 16 combinations of the very short di-PNA building blocks were synthesized and assayed for their ability to self-associate. Only three guanine-containing di-PNAs-CG, GC and GG-could form ordered assemblies, as observed by electron microscopy, and these di-PNAs efficiently assembled into discrete architectures within a few minutes. The X-ray crystal structure of the GC di-PNA showed the occurrence of both stacking interactions and Watson-Crick base pairing. The assemblies were also found to exhibit optical properties including voltage-dependent electroluminescence and wide-range excitation-dependent fluorescence in the visible region.
Abstract
Background
Preventing medical errors is crucial, especially during crises like the COVID-19 pandemic. Failure Modes and Effects Analysis (FMEA) is the most widely used prospective hazard ...analysis in healthcare. FMEA relies on brainstorming by multi-disciplinary teams to identify hazards. This approach has two major weaknesses: significant time and human resource investments, and lack of complete and error-free results.
Objectives
To introduce the algorithmic prediction of failure modes in healthcare (APFMH) and to examine whether APFMH is leaner in resource allocation in comparison to the traditional FMEA and whether it ensures the complete identification of hazards.
Methods
The patient identification during imaging process at the emergency department of Sheba Medical Center was analyzed by FMEA and APFMH, independently and separately. We compared between the hazards predicted by APFMH method and the hazards predicted by FMEA method; the total participants’ working hours invested in each process and the adverse events, categorized as ‘patient identification’, before and after the recommendations resulted from the above processes were implemented.
Results
APFMH is more effective in identifying hazards (P < 0.0001) and is leaner in resources than the traditional FMEA: the former used 21 h whereas the latter required 63 h. Following the implementation of the recommendations, the adverse events decreased by 44% annually (P = 0.0026). Most adverse events were preventable, had all recommendations been fully implemented.
Conclusion
In light of our initial and limited-size study, APFMH is more effective in identifying hazards (P < 0.0001) and is leaner in resources than the traditional FMEA. APFMH is suggested as an alternative to FMEA since it is leaner in time and human resources, ensures more complete hazard identification and is especially valuable during crisis time, when new protocols are often adopted, such as in the current days of the COVID-19 pandemic.
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