Sustaining Mammography Image Quality With a Technologist Coaching Program in the Era of the Enhancing Quality Using the Inspection Program (EQUIP).

OBJECTIVE: To evaluate the ability of a long-term technologist coaching program to sustain gains in mammography quality made by a previously implemented quality improvement (QI) initiative. METHODS: Mammography quality metrics from July 2014 to June 2020 were reviewed. Numbers of screening mammograms performed/audited, monthly average mammogram overall quality pass rates, changes in facilities/staffing, and technical recall rates were evaluated. Performance metrics at baseline (July 2013), during the improvement (July 2014 to January 2015), postimprovement (February 2015 to August 2015), and sustained coaching periods (after initiation of the technologist coaching model, from September 2015 to June 2020) were compared. RESULTS: During the postimprovement and sustained coaching periods, 93% (501/541) and 90% (8902/9929) of audited mammograms, respectively, met overall passing criteria, achieving or exceeding the QI goal of 90%, and results for both periods were significantly higher than that during the improvement period (74%, 1098/1489), at P < 0.0001 and P < 0.0001, respectively. The technical recall rates during the improvement and postimprovement periods were 2.6% (85/3321) and 1.7% (54/3236), respectively; the rate during the sustained coaching period was significantly lower than these, at 1.2% (489/40 440) (P < 0.0001 and P = 0.0232, respectively). Sustained quality passing rates and lower technical recall rates were observed despite statistically significantly increases in screening volumes. CONCLUSION: A technologist coaching program resulted in sustained high mammographic quality for almost 5 years.

Tumor volume doubling time estimated from digital breast tomosynthesis mammograms distinguishes invasive breast cancers from benign lesions.

OBJECTIVES: The aim of this study was to determine whether lesion size metrics on consecutive screening mammograms could predict malignant invasive carcinoma versus benign lesion outcome. METHODS: We retrospectively reviewed suspicious screen-detected lesions confirmed by biopsy to be invasive breast cancers or benign that were visible on current and in-retrospect prior screening mammograms performed with digital breast tomosynthesis from 2017 to 2020. Four experienced radiologists recorded mammogram dates, breast density, lesion type, lesion diameter, and morphology on current and prior exams. We used logistic regression models to evaluate the association of invasive breast cancer outcome with lesion size metrics such as maximum dimension, average dimension, volume, and tumor volume doubling time (TVDT). RESULTS: Twenty-eight patients with invasive ductal carcinoma or invasive lobular carcinoma and 40 patients with benign lesions were identified. The mean TVDT was significantly shorter for invasive breast cancers compared to benign lesions (0.84 vs. 2.5 years; p = 0.0025). Patients with a TVDT of less than 1 year were shown to have an odds ratio of invasive cancer of 6.33 (95% confidence interval, 2.18-18.43). Logistic regression adjusted for age, lesion maximum dimension, and lesion volume demonstrated that shorter TVDT was the size variable significantly associated with invasive cancer outcome. CONCLUSION: Invasive breast cancers detected on current and in-retrospect prior screening mammograms are associated with shorter TVDT compared to benign lesions. If confirmed to be sufficiently predictive of benignity in larger studies, lesions visible on mammograms which in comparison to prior exams have longer TVDTs could potentially avoid additional imaging and/or biopsy. KEY POINTS: • We propose tumor volume doubling time as a measure to distinguish benign from invasive breast cancer lesions. • Logistic regression results summarized the utility of the odds ratio in retrospective clinical mammography data.

Perfusion-only imaging in pregnant women: A comparative reader study with implications for practice patterns.

This study seeks to understand the value of ventilation imaging in pregnant patients imaged for suspected pulmonary embolism (PE). Ventilation-perfusion (VQ) scans in this high-risk population were compared to ventilation-only scans. We hypothesize that in this relatively healthy population, the exclusion of ventilation scans will not impact the rate of scans interpreted as positive. This retrospective blinded comparative reader study on collated VQ scans performed on pregnant patients in the course of routine clinical care in a > 5 year period (03/2012 to 07/2017). Each set of VQ and perfusion only (Q) studies were reviewed by 8 readers (4 nuclear radiology fellows and 4 nuclear medicine faculty) in random order; the Q scans simply omitted the ventilation images. Readers recorded each study as PE, no PE, or non-diagnostic (prospective investigative study of acute PE diagnosis classifications). Logistic mixed effects models were used to test the association between scan type (VQ vs Q). 203 pairs of studies in 197 patients were included (6 patients had 2 scans). Subjects ranged from 14 to 45 years of age, with a median 28 years. A significant association between scan type and positive/negative classification. Q-scans received more positive classifications than VQ-scans (median of 7.6% vs 6.7%). No association was seen between scan type and positive/indeterminate classification, nor between scan type and negative/indeterminate classification. The exclusion of ventilation images in VQ-scans was associated with a higher rate of positive studies, but this difference was small (<1%). Given the overwhelmingly normal percentage of Q-exams (>90% in our study), and the benefits of omitting ventilation imaging, perfusion-only imaging should be considered a reasonable option for imaging the pregnant patient to exclude PE.

Preoperative breast MR imaging in newly diagnosed breast cancer: Comparison of outcomes based on mammographic modality, breast density and breast parenchymal enhancement.

PURPOSE: To compare the role of MR for assessment of extent of disease in women newly diagnosed with breast cancer imaged with digital mammography (DM) alone versus digital breast tomosynthesis (DBT). METHODS: Retrospective review was conducted of 401 consecutive breast MR exams (10/1/2013-7/31/2015) from women who underwent preoperative MR for newly diagnosed breast cancer by either DM or DBT, leaving 388 exams (201 DM and 187 DBT). MR detection of additional, otherwise occult, disease was stratified by modality, breast density, and background parenchymal enhancement. A true-positive finding was defined as malignancy in the ipsilateral-breast >2 cm away from the index-lesion or in the contralateral breast. RESULTS: 50 additional malignancies were detected in 388 exams (12.9%), 37 ipsilateral and 13 contralateral. There was no difference in the MR detection of additional disease in women imaged by either DM versus DBT (p = 0.53). In patients with DM, there was no significant difference in the rate of MR additional cancer detection in dense versus non-dense breasts (p = 0.790). However, in patients with DBT, MR detected significantly more additional sites of malignancy in dense compared to non-dense breasts (p = 0.017). There was no difference in false-positive MR exams (p = 0.470) for DM versus DBT. For both DM and DBT cohorts, higher MR background parenchymal enhancement was associated with higher false-positive (p = 0.040) but no significant difference in true-positive exams. CONCLUSIONS: Among patients with DBT imaging at cancer diagnosis, women with dense breasts appear to benefit more from preoperative MR than non-dense women. In women imaged only with DM, MR finds additional malignancy across all breast densities.

Baseline Gut Microbiota Composition Is Associated with Major Infections Early after Hematopoietic Cell Transplantation.

Infection is a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Gut microbiota (GM) composition and metabolites provide colonization resistance against dominance of potential pathogens, and GM dysbiosis following HCT can be deleterious to immune reconstitution. Little is known about the composition, diversity, and evolution of GM communities in HCT patients and their association with subsequent febrile neutropenia (FN) and infection. Identification of markers before HCT that predict subsequent infection could be useful in developing individualized antimicrobial strategies. Fecal samples were collected prospectively from 33 HCT recipients at serial time points: baseline, post-conditioning regimen, neutropenia onset, FN onset (if present), and hematologic recovery. GM was assessed by 16S rRNA sequencing. FN and major infections (ie, bloodstream infection, typhlitis, invasive fungal infection, pneumonia, and Clostridium difficile enterocolitis) were identified. Significant shifts in GM composition and diversity were observed during HCT, with the largest alterations occurring after initiation of antibiotics. Loss of diversity persisted without a return to baseline at hematologic recovery. GM in patients with FN was enriched in Mogibacterium, Bacteroides fragilis, and Parabacteroides distasonis, whereas increased abundance of Prevotella, Ruminococcus, Dorea, Blautia, and Collinsella was observed in patients without fever. A baseline protective GM profile (BPGMP) was predictive of protection from major infection. The BPGMP was associated with subsequent major infections with 77% accuracy and an area under the curve of 79%, with sensitivity, specificity, and positive and negative predictive values of 0.71, 0.91, 0.77, and 0.87, respectively. Our data show that large shifts in GM composition occur early after HCT, and differences in baseline GM composition are associated with the development of subsequent major infections.

A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma.

Immunologic responses to anti-PD-1 therapy in melanoma patients occur rapidly with pharmacodynamic T cell responses detectable in blood by 3 weeks. It is unclear, however, whether these early blood-based observations translate to the tumor microenvironment. We conducted a study of neoadjuvant/adjuvant anti-PD-1 therapy in stage III/IV melanoma. We hypothesized that immune reinvigoration in the tumor would be detectable at 3 weeks and that this response would correlate with disease-free survival. We identified a rapid and potent anti-tumor response, with 8 of 27 patients experiencing a complete or major pathological response after a single dose of anti-PD-1, all of whom remain disease free. These rapid pathologic and clinical responses were associated with accumulation of exhausted CD8 T cells in the tumor at 3 weeks, with reinvigoration in the blood observed as early as 1 week. Transcriptional analysis demonstrated a pretreatment immune signature (neoadjuvant response signature) that was associated with clinical benefit. In contrast, patients with disease recurrence displayed mechanisms of resistance including immune suppression, mutational escape, and/or tumor evolution. Neoadjuvant anti-PD-1 treatment is effective in high-risk resectable stage III/IV melanoma. Pathological response and immunological analyses after a single neoadjuvant dose can be used to predict clinical outcome and to dissect underlying mechanisms in checkpoint blockade.

Comparison of Helminth Infection among the Native Populations of the Arctic and Subarctic Areas in Western Siberia Throughout History: Parasitological Researches on Contemporary and the Archaeological Resources.

The aim of this parasitological study is examining contemporary (the late 20th century) specimens of the arctic or subarctic areas in Western Siberia and comparing them with the information acquired from archaeological samples from the same area. In the contemporary specimens, we observed the parasite eggs of 3 different species: Opisthochis felineus, Ascaris lumbricoides, and Enterobius vermicularis. Meanwhile, in archaeoparasitological results of Vesakoyakha, Kikki-Akki, and Nyamboyto I burial grounds, the eggs of Diphyllobothrium and Taenia spp. were found while no nematode (soil-transmitted) eggs were observed in the same samples. In this study, we concluded helminth infection pattern among the arctic and subarctic peoples of Western Siberia throughout history as follows: the raw fish-eating tradition did not undergo radical change in the area at least since the 18th century; and A. lumbricoides or E. vermicularis did not infect the inhabitants of this area before 20th century. With respect to the Western Siberia, we caught glimpse of the parasite infection pattern prevalent therein via investigations on contemporary and archaeoparasitological specimens.

Molecular Identification of Bacteria in Intra-abdominal Abscesses Using Deep Sequencing.

BACKGROUND: Intra-abdominal abscesses are localized collections of pus, which generally arise from a breach in the normal mucosal defense barrier that allows bacteria from gastrointestinal tract, and less commonly from the gynecologic or urinary tract, to induce inflammation, resulting in an infection. The microbiology of these abscesses is usually polymicrobial, associated with the primary disease process. However, the microbial identity, diversity and richness in intra-abdominal abscesses have not been well characterized, due in part to the difficulty in cultivating commensal organisms using standard culture-based techniques. METHODS: We used culture-independent 16S rRNA Illumina sequencing to characterize bacterial communities in intra-abdominal abscesses collected by percutaneous drainage. A total of 43 abscess samples, including 19 (44.2%) Gram stain and culture-negative specimens, were analyzed and compared with results from conventional microbiologic cultures. RESULTS: Microbial composition was determined in 8 of 19 culture-negative samples and 18 of 24 culture-positive samples, identifying a total of 221 bacterial taxa or operational taxonomic units (OTUs) and averaging 13.1 OTUs per sample (interquartile range, 8-16.5 OTUs). Microbial richness for monomicrobial and polymicrobial samples was significantly higher than culture-negative samples (17 and 15.2 OTUs vs 8 OTUs, respectively), with a trend toward a higher microbial diversity (Shannon diversity index of 0.87 and 1.18 vs 0.58, respectively). CONCLUSIONS: The bacterial consortia identified by cultures correlated poorly with the microbial composition determined by 16S rRNA sequencing, and in most cases, the cultured isolates were minority constituents of the overall abscess microbiome. Intra-abdominal abscesses were generally polymicrobial with a surprisingly high microbial diversity, but standard culture-based techniques failed to reveal this diversity. These data suggest that molecular-based approaches may be helpful for documenting the presence of bacteria in intra-abdominal abscesses where standard cultures are unrevealing, particularly in the setting of prior antibiotic exposure.

An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

Secular trends in average height and age at menarche of ethnic Russians and Komi-Permyaks of the Permsky Krai, Russia.

The aim was to describe the changes in body size and age at menarche in anthropologically distinct ethnic groups - Komi-Permyaks (KP) and Russians (RU) - of Permsky Krai that occurred in the last century, with a special concern to the urban-rural differences. The comparison of the 1861 - 1865 and 1990 birth cohorts (BiCo) revealed following results. In RU rural males the increase in stature (ST) was 10.8 cm (p < 0.001). The chest circumference has increased by 5.9 cm, but it is unsubstantial 0.25 % when measured in relative to ST values. In RU urban males the overall increase in ST was 10.8 cm (p < 0.001), chest circumference increased by 10.5 cm. The peak increase in ST (+1.36 cm per decade) was attained between the 1964 and the 1990 BiCo. The data on body dimensions of RU females available only from the 1960s to 1990. The ST of rural females has not changed, but the absolute and the relative (to ST) values of pelvic width of the 1980 - 1989 BiCo are significantly (p < 0.05) lower than in the 1966 - 1975 and 1965 BiCo. The RU urban females of the 1985 BiCo are 3.6 cm taller than 1964 BiCo (p < 0.001), but over the next 5 years the ST decreased by 2 cm (p = 0.06). The relative pelvic width has decreased from 17.57 % (BiCo 1965 - 1969) to 17.18 % (BiCo 1980 - 1989; p < 0.05). Menarcheal age of Perm females declined from 14.5 yrs in the 1930 - 1939 BiCo to 13.3 yrs in 1950 - 1965 BiCo, then ceased to change. The changes across generations in rural KP were weak. The rural males born in 1885 were 2.1 cm taller than BiCo 1861 - 1865. From the 1925 to 1975 BiCo the average ST increased by 6.2 cm (1.24 cm/decade). KP rural females became 6.4 cm taller from the 1885 to 1985 BiCo. Pelvic width in the 1985 BiCo (27.4 cm) is significantly bigger (p < 0.05) than in the 1975 BiCo (26.9 cm). The changes in ST of urban KP females were more obvious than in rural groups. The 1985 BiCo of urban KP females (ST 161.8 cm) are taller than those born in 1965 (159.4 cm; p < 0.05), but their pelvic width does not differ. In urban and rural KP females age at menarche is earlier in the 1976 - 1985 than in the 1966 - 1975 BiCo (p < 0.01). In all the KP cohorts, urban females have earlier menarche than rural (p < 0.05).

Vitamin D status of northern indigenous people of Russia leading traditional and "modernized" way of life.

BACKGROUND: Vitamin D status in groups of northern indigenous people of Russia leading close to traditional (seminomadic reindeer herding), post-traditional (in settlements) or "modernized" (in towns) way of life was analysed. DESIGN: The survey study groups consisted of 178 Nenets and Komi aged 18-60 living in the Arctic (66-67°N). Urban Komi, Udmurts and Komi-Permiaks (n=150) living in a non-Arctic area (57-61°N) formed a control group. The concentration of serum 25-hydroxyvitamin D (25OHD), as a transport form of vitamin D, was assessed by enzyme immunoassay analysis. RESULTS: The group average 25OHD levels in both rural and urban Arctic residents are within the range of values seen in the non-Arctic urban subjects adjusted for season: 39.7-47.7 nmol/l. Abandoning traditional lifestyle associates with lower vitamin D levels in indigenous Arctic people. Mean±standard deviation 25OHD values among Nenets were lower in those living in the administrative centre (a big settlement) with a population of 1,460 (32.2±12.90 nmol/l) than in the residents of small settlements (39.6±14.08 nmol/l), and in reindeer herders (42.4±13.45 nmol/l; p<0.05 in both cases). Komi townspeople had lower 25OHD concentrations (47.7±12.00 nmol/l) than Komi reindeer herders (68.7±25.20; p<0.01). CONCLUSION: The transition from seminomadic to post-traditional and "modernized" way of life has led to a decrease in the consumption of traditional foods among the indigenous people of the Russian Arctic. Our data support the notion that the traditional northern diet promotes healthy vitamin D levels, while adherence to the "western" type of diet correlates with a lower 25OHD concentration.

Direct inhibitory and indirect stimulatory effects of RAGE ligand S100 on sRANKL-induced osteoclastogenesis.

Diabetes results in increased fracture risk, and advance glycation endproducts (AGEs) have been implicated in this pathophysiology. S100 proteins are ligands for the receptor of AGEs (RAGE). An intracellular role of the S100 family member S100A4 (Mts1) to suppress mineralization has been described in pre-osteoblastic MC3T3-E1 cells. However, S100 proteins could have additional effects on bone. The goal of the current study was to determine effects of increased extracellular S100 on osteoclastogenesis. We first determined the direct effects of S100 on pre-osteoclast proliferation and osteoclastic differentiation. RANKL-treated RAW 264.7 cell proliferation and TRAP activity were significantly inhibited by S100, and the number and size of TRAP-positive multinucleated cells were decreased. We then determined whether S100 could affect osteoclastogenesis by an indirect process by examining effects of conditioned media from S100-treated MC3T3-E1 cells on osteoclastogenesis. In contrast to the direct inhibitory effect of S100, the conditioned media promoted RAW 264.7 cell proliferation and TRAP activity, with a trend toward increased TRAP-positive multinucleated cells. S100 treatment of the MC3T3-E1 cells for 14 days did not significantly affect alkaline phosphatase, M-CSF, or OPG gene expression. RANKL was undetectable in both untreated and treated cells. The treatment slightly decreased MC3T3-E1 cell proliferation. Interestingly, S100 treatment increased expression of RAGE by the MC3T3-E1 cells. This suggested the possibility that S100 could increase soluble RAGE, which acts as a decoy receptor for S100. This decrease in availability of S100, an inhibitor of pre-osteoclast proliferation, could contribute to osteoclastogenesis, ultimately resulting in increased bone resorption.

Northwest Siberian Khanty and Mansi in the junction of West and East Eurasian gene pools as revealed by uniparental markers.

Northwest Siberia is geographically remote territory, which has been settled by indigenous human populations probably since the Upper Paleolithic. To investigate the genetic landscape of Northwest Siberians, we have analyzed mitochondrial and Y chromosome DNA polymorphisms of 169 unrelated individuals from Khanty and Mansi ethnic groups in Northwest Siberia. In addition, HVS-I sequences (N = 3522) and Y chromosome SNP data (N = 2175), obtained from the literature, were used to elucidate the genetic relationships among the North Eurasian populations. The results show clinal distributions of mtDNA and Y chromosome haplogroups along East-West axis of Northern Eurasia. In this context, the Ugric-speaking Khanty and Mansi appear as unique intermediate populations carrying Upper Paleolithic and more recent haplotypes typical for both West and East Eurasian gene pools. This admixture indicates that the Khanty and Mansi populations have resided in the contact zone of genetically distinguishable eastern and western Eurasia.

Genes related to the metabolism of nutrients in the Kola Sami population.

OBJECTIVES: The environmental and life-style conditions of the Kola Sami could have influenced the population-specific frequencies of the AGXTProIILeu allele, and certain alleles of APOE and LCT genes, involved respectively, in the metabolism of animal proteins, lipids and milk sugar. Study Design. DNA samples were collected from the Sami population of Lovozero settlement (Murmansk Region) in 2005. METHODS: The analysis of the traditional diet of the Kola Sami was made using the data of ethnographic studies conducted in the nineteenth and beginning of the twentieth centuries. Frequencies of the AGXT ProllLeu, APOE*e4 alleles and LCT gene CC w9 genotype were defined by molecular-genetic analysis. RESULTS: The specificity of the Kola Sami gene pool is in the lower frequency of APOE*e4 allele compared with the Sami of Finland (0.205 and 0.310, respectively) and when compared with other groups (except the Skolt) in the higher frequency of hypolactasia conditioned by the CC(-13910) genotype of the LCT gene (0.484). CONCLUSIONS: The high prevalence of the AGXT allele T bearers among Kola Sami (0.273) does not contradict the hypothesis of the adaptive role this allele plays in populations with a traditionally high intake of meat.

Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans.

A single-nucleotide variant, C/T(-13910), located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T(-13910) variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T(-13910) H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T(-13910) H98 allele (approximately 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (approximately 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T(-13910) allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.