The accuracy of breast MRI radiomic methodologies in predicting pathological complete response to neoadjuvant chemotherapy: A systematic review and network meta-analysis.

BACKGROUND: Achieving pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) improves survival outcomes for breast cancer patients. Currently, conventional histopathological biomarkers predicting such responses are inconsistent. Studies investigating radiomic texture analysis from breast magnetic resonance imaging (MRI) to predict pCR have varied radiomic protocols introducing heterogeneity between results. Thus, the efficacy of radiomic profiles compared to conventional strategies to predict pCR are inconclusive. PURPOSE: Comparing the predictive accuracy of different breast MRI radiomic protocols to identify the optimal strategy in predicting pCR to NAC. MATERIAL AND METHODS: A systematic review and network meta-analysis was performed according to PRISMA guidelines. Four databases were searched up to October 4th, 2021. Nine predictive strategies were compared, including conventional biomarker parameters, MRI radiomic analysis conducted before, during, or after NAC, combination strategies and nomographic methodology. RESULTS: 14 studies included radiomic data from 2,722 breast cancers, of which 994 were used in validation cohorts. All MRI derived radiomic features improved predictive accuracy when compared to biomarkers, except for pre-NAC MRI radiomics (odds ratio [OR]: 0.00; 95 % CI: -0.07-0.08). During-NAC and post-NAC MRI improved predictive accuracy compared to Pre-NAC MRI (OR: 0.14, 95 % CI: 0.02-0.26) and (OR: 0.26, 95 % CI: 0.07-0.45) respectively. Combining multiple MRIs did not improve predictive performance compared to Mid- or Post-NAC MRIs individually. CONCLUSION: Radiomic analysis of breast MRIs improve identification of patients likely to achieve a pCR to NAC. Post-NAC MRI are the most accurate imaging method to extrapolate radiomic data to predict pCR.

Timeliness and completeness of laboratory-based surveillance of COVID-19 cases in England.

OBJECTIVES: The aim of the study was to evaluate completeness and timeliness of the rapidly developed surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in England using patient-level data. STUDY DESIGN: This is an observational study wherein public health surveillance systems are evaluated. METHODS: Data were collected in the Public Health England's Second-Generation Surveillance System through routine laboratory reporting processes, as well as via enhanced testing in collaboration with commercial partners. Three periods were chosen to present developments in disease surveillance around the first pandemic wave in England. Completeness of valid entries for key demographic and epidemiological fields was summarised. Timeliness was assessed using recorded date intervals: from sample collection to the laboratory reporting a positive result, the positive result being received by the national surveillance system and the data being available for epidemiological analysis. RESULTS: In each period, demographic variables were more than 95% complete and enhanced ethnicity more than 85%, allowing a rich understanding of the general characteristics of COVID-19 cases in England. The proportion of cases completing all reporting stages of the national system within 3 days of when the specimen was taken increased from 69.1% in period 1 to 76.6% in period 3. In period 3, the median number of days to complete all reporting stages decreased to 2, from 3 in previous periods. Analysis of each reporting stage offers suggestive evidence that timeliness of the system has improved as reporting has become established over time. CONCLUSIONS: Timely processing of data for epidemiological use was consistent and rapid once received by the national system. Delays in timeliness were most likely to occur in the first stage of the reporting process, before laboratory input to the surveillance platform. Existing national surveillance mechanisms enhanced during the response have succeeded in providing rapid collection and reporting of case data to facilitate epidemiological monitoring and analysis and guide public health policy and strategy.

Vitamin D and bisphosphonate therapy in systemic lupus erythematosus patients who receive glucocorticoids: are we offering the best care?

OBJECTIVE: This study aimed to evaluate management practices for glucocorticoid (GC)-induced osteoporosis (GIOP) in systemic lupus erythematosus (SLE) patients using 2017 American College of Rheumatology guidelines as a gold standard. METHODS: We conducted a retrospective cohort study using a clinical database from the years 2011 to 2016. SLE cases with >90 days continuous prednisone use at doses of ≥7.51 mg daily were identified. Osteoporosis risk factors were assessed via chart review. The Fracture Risk Assessment (FRAX) score was estimated for patients > 40 years of age. Vitamin D, bisphosphonate prescriptions, and osteoporotic (OP) fractures were ascertained through chart review. A classification tree was used to identify the key patient-related predictors of bisphosphonate prescription. RESULTS: A total of 203 SLE patients met the inclusion criteria. The recommended dose of vitamin D supplement was prescribed to 58.9% of patients < 40 years of age and 61.5% of patients ≥ 40 years of age. Among patients aged ≥ 40 years, 25% were prescribed bisphosphonates compared to 36% who met indications for bisphosphonates per the ACR guidelines. Another 10% were prescribed a bisphosphonate, despite not having indication per the ACR guidelines, which was considered as overtreatment. Among patients aged ≥ 40 years, older age and a higher FRAX score for major OP fracture and hip fracture predicted bisphosphonate prescription. In a classification tree analysis, patients with FRAX scores (for major OP fracture) of ≥ 23.5% predicted bisphosphonate prescription in this SLE population. Among patients who had OP fractures in the follow-up period, nine (6.50%) were inpatients receiving appropriate GIOP care versus 12 (13.6%) who were inpatients not receiving ACR-appropriate care (p = 0.098). CONCLUSIONS: In clinical practice, fewer SLE patients with or at risk for GIOP are prescribed vitamin D and bisphosphonates than recommended by the 2017 ACR guidelines. Also, in this study, another 10% were prescribed a bisphosphonate, despite not having an indication per the ACR guidelines. Patients were most likely to receive a bisphosphonate prescription if they had a major OP FRAX score of > 23.5%.

Evaluation of a national microbiological surveillance system to inform automated outbreak detection.

OBJECTIVES: Evaluate data available from a national voluntary reporting system and describe the data processing necessary to enable the development and application of outbreak detection methods in healthcare settings. METHODS: Evaluation was performed on an extract of data reported between March 2007 and May 2012. Reporting delays were calculated and analysed at the trust, regional and national levels. Negative binomial regression analysis was performed to detect any changes in laboratory reporting within this time. RESULTS: 167 hospital laboratories have reported to the voluntary reporting system. 1,705,126 reports were made in the five-year study period. There is large variation in how laboratories report to the system. Under half (44.9%) report in a timely manner, with >90% of infections reported within three weeks of the specimen date. Overall, there was a significant increase of 17.5% in reporting after October 2010 (95% CI 13.8-21.4%, p < 0.001) and an improvement in reporting delay, when new statutory reporting regulations were introduced. CONCLUSIONS: The outbreak detection algorithm used at the national and regional level requires further modification to optimise outbreak detection for individual hospitals. For any prospective outbreak detection system to perform optimally it is imperative that laboratories ensure that the data they submit is complete, consistent and timely.

Comparison of the clinical performance of three digital mammography systems in a breast cancer screening programme.

This study compares the clinical performance of three digital mammography system types in a breast cancer screening programme. 28 digital mammography systems from three different vendors were included in the study. The retrospective analysis included 238 182 screening examinations of females aged between 50 and 64 years over a 3-year period. All images were double read and assigned a result according to a 5-point rating scale to indicate the probability of cancer. Females with a positive result were recalled for further assessment imaging and biopsy if necessary. Clinical performance in terms of cancer detection rate was analysed and the results presented. No statistically significant difference was found between the three different mammography systems in a population-based screening programme, in terms of the overall cancer detection rate or in the detection of invasive cancer and ductal carcinoma in situ. This was shown in both prevalent and subsequent screening examination categories. The results demonstrate comparable cancer detection performance for the three imaging system types operational in the screening programme.

Fine-needle trucut biopsy versus fine-needle aspiration cytology with ultrasound guidance in the abdomen.

Historically, fine-needle aspiration cytology (FNAC) has varying sensitivity, specificity and accuracy in the diagnosis of abdominal lesions with a high insufficient sampling rate. We compared 20-G fine-needle trucut biopsy (FNTB) with FNAC results in the biopsy of solid abdominal tumours. A retrospective review of 171 (128x 20-G FNTB and 43x FNAC) ultrasound-guided biopsies of abdominal tumours on 157 patients (male : female 85:72, mean age 61.25 years) were carried out. One hundred and seventy-one biopsies were carried out: liver 109, pancreas 19, lymph node 10, omentum 5, right iliac fossa mass 6, adrenal 6 and others 16. An average of 2.06 and 1.97 passes (range 1-4) were carried out per FNTB and FNAC, respectively. A definitive diagnosis was made in 122/128 biopsies (95.3%) and 32/43 biopsies (74.4%) for FNTB and FNAC, respectively. Diagnoses consisted of metastatic liver disease (74/171), pancreatic adenocarcinoma (10/171), lymphoma (8/171) and others (33/171) and benign (29/171). No significant complications occurred in either group. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 87, 100, 100, 50, 84.4 and 93.1, 100, 100, 60, 71.4 for FNTB and FNAC, respectively. A greater and more consistent positive diagnosis rate is yielded by 20-G FNTB (95.3%) than FNAC (74.4%). The diagnostic accuracy of FNTB is 84.4% compared with 69.8% for FNAC. A greater insufficient sampling rate occurs with FNAC (25.6%) than with FNTB (4.7%). For abdominal biopsy, 20-G FNTB needles have a much higher yield than FNAC with no increase in complications. FNTB is the preferred choice, particularly where cytological assistance at the time of biopsy is unavailable.

Secretin-assisted CT of the pancreas: improved pancreatic enhancement and tumour conspicuity.

PURPOSE: The primary aim of this prospective pilot study was to determine if the administration of intravenous secretin prior to contrast-enhanced computed tomography (CT) improves pancreatic enhancement and pancreatic tumor conspicuity. The second aim was to determine the optimal timing for secretin administration prior to contrast-enhanced CT. METHODS: Local ethics committee approval was obtained. 35 patients (18 men, 17 women; mean age, 67.6 years; age range; 25 to 86 years) with known or suspected pancreatic malignancy or an abdominal malignancy underwent a helical CT of the pancreas. The pancreas was first localised on an unenhanced scan using 10mm sections. Following 120 ml of intravenous 300 mg/ml of non ionic contrast medium (CM), injected at a rate of 5 ml/s, images of the pancreas (3mm slice thickness) and liver (8mm slice thickness) were obtained at 40 and 70 seconds respectively. A second CT was obtained 1-5 days after the first one using the same CT and intravenous contrast medium injection parameters. However 100 IU of secretin was given as an intravenous bolus between 0 and 5 min prior to intravenous contrast medium administration. Each patient acted as their own control. The attenuation in Hounsfield Units (HU) was recorded on non-contrast, pancreatic phase and portal venous phases for both secretin and non-secretin CTs, in the pancreas and pancreatic tumors (where present). Tumor conspicuity was calculated (in the 19 patients with pancreatic adenocarcinomas) by subtracting pancreatic tumor attenuation from pancreatic attenuation. Statistical evaluation comparing pre and post secretin enhancement was performed using matched paired t-tests. RESULTS: A significant increase in pancreatic enhancement was observed when secretin was injected at 2 to 3 min before contrast material injection (the increase in pancreatic density following secretin at 2 min was 31.5+/-10 HU (29.2%) (p=.035); and at 3 min was 23.2+/-7.8 HU (22.7%) (p=.041). Pancreatic tumor conspicuity in the pancreatic phase was most marked when secretin was injected between 2 to 4 min before contrast medium, with 4 min showing a statistically significant increase in tumor conspicuity, 48.2+/-14.2 HU (p=.04). CONCLUSION: Imaging in the pancreatic phase 2 to 4 min after administration of intravenous secretin leads to greater enhancement of the pancreas with greater tumor conspicuity, than imaging without secretin.

Malignant transformation of a lipomyelocele into a rhabdomyosarcoma?

SUMMARY: We report the unusual transformation of a lipomyelocele to a rhabdomyosarcoma in a 3-year-old boy. A lipomyelocele is not considered pre-malignant, but the possibility of developing such a tumor may represent another reason for close neurological follow-up in patients with spinal dysraphism.

CT of pelvic extraperitoneal spaces: an anatomical study in cadavers.

AIM: To evaluate the pelvic extraperitoneal compartments and communications with abdominal retroperitoneal spaces. MATERIAL AND METHODS: Helical computed tomography (CT) was used to image the abdomen and pelvis after injection of 800 ml of dilute (1 in 25) contrast material into prevesical, perivesical and perirectal spaces in eight embalmed cadavers. Axial images and multiplanar reconstructions were reviewed to determine flow pathways. RESULTS: The prevesical space was injected in four cadavers, the perivesical space in two and the perirectal in two. After the four prevesical space injections, communication was seen with the perivesical (four of four), perirectal (one of four) and abdominal extraperitoneal spaces (posterior pararenal space in all, anterior pararenal space in two of four, and perirenal space in three of four). After the two perivesical injections, communication was seen with the prevesical (two of two), perirectal (two of two) and abdominal extraperitoneal spaces (posterior pararenal in two of two, anterior pararenal in two of two, and perirenal space in two of two). After the two perirectal space injections, communication was seen with the prevesical (two of two), perivesical (one of two) and abdominal extraperitoneal spaces (posterior pararenal in two of two, anterior pararenal in two of two, and perirenal space in one of two). CONCLUSION: The extraperitoneal spaces of the pelvis comprise three communicating compartments: the prevesical space, the perivesical space, and the perirectal space. The perirectal space, previously thought to be separate, communicates with the perivesical and the prevesical spaces. Intercommunication occurs both between the pelvic extraperitoneal spaces and with abdominal retroperitoneal spaces.

Heart failure disease management in an indigent population.

BACKGROUND: Multidisciplinary disease management programs (MDMP) have demonstrated reduced hospitalizations in motivated pretransplant heart failure populations, but little is known about their effectiveness in largely indigent patients who are not transplant candidates. METHODS AND RESULTS: We studied 35 patients with heart failure with left ventricular ejection fraction (EF) /=2 per year (group A) and 21 patients referred by their primary care physicians because they were difficult to manage (group B). Group A patients were New York Heart Association (NYHA) class III or IV, aged 25 to 87 years (mean 57 +/- 17 SD) and had an EF of 15% to 45% (29% +/- 11%). Group B patients were NYHA class II or III, aged 35 to 86 (57 +/- 16) years and had an EF of 20% to 45% (28% +/- 10%). Data were compared for the year before enrollment in the MDMP and the year afterward. In group A hospital admissions decreased from 33 to 3, a 91% reduction, and NYHA class improved to class II-III (P <.001). In group B hospital admissions decreased from 9 to 0, and NYHA class improved to class I-II (P <.001). When hospital and clinic charges were assessed for both groups, the net savings were $162,000 per year or $4600 per patient. CONCLUSIONS: A multidisciplinary heart failure program can improve functional status and reduce hospitalization and net costs compared with conventional care in indigent non-transplant candidate patients.

Hypochlorite oxidation causes cross-linking of Lp(a).

When purified low density lipoprotein (LDL) or lipoprotein(a) (Lp[a]) was oxidized in vitro using concentrations of hypochlorite (50-500 microM) which might be achieved by activated neutrophils in vivo, high molecular weight species were observed on SDS polyacrylamide gels. The reaction was concentration-, temperature- and time-dependent. The high molecular weight apoprotein complexes were resistant to heating in SDS and DTT, suggesting covalent, but non-disulfide bond, cross-linking. Negligible amounts of lower molecular weight degradation products were formed. Bityrosine formation, measured by fluorescence and HPLC analysis, was found to increase with the amount of hypochlorite added. However, the molar concentration of bityrosine could not account for cross-linking, even if it was assumed that every bityrosine was intermolecular. Hypochlorite-oxidized Lp(a) and LDL were both effective as ligands for loading mouse peritoneal macrophages in vitro. We conclude that hypochlorite produced in inflammatory reactions might be important in the generation of atherogenic forms of lipoproteins.

Kinetics of gramicidin channel formation in lipid bilayers: transmembrane monomer association.

Conducting gramicidin channels form predominantly by the transmembrane association of monomers, one from each side of a lipid bilayer. In single-channel experiments in planar bilayers the two gramicidin analogs, [Val1]gramicidin A (gA) and [4,4,4-F3-Val1]gramicidin A (F3gA), form dimeric channels that are structurally equivalent and have characteristically different conductances. When these gramicidins were added asymmetrically, one to each side of a preformed bilayer, the predominant channel type was the hybrid channel, formed between two chemically dissimilar monomers. These channels formed by the association of monomers residing in each half of the membrane. These results also indicate that the hydrophobic gramicidins are surprisingly membrane impermeant, a conclusion that was confirmed in experiments in which gA was added asymmetrically and symmetrically to preformed bilayers.

Formation of an active transcription complex in the Drosophila melanogaster 5S RNA gene is dependent on an upstream region.

We constructed deletion-substitution and linker-scanning mutations in the 5'-flanking region of the Drosophila melanogaster 5S RNA gene. In vitro transcription of these templates in Drosophila and HeLa cell extracts revealed the presence of an essential control region (-30 region) located between nucleotides -39 and -26 upstream of the transcription initiation site: deletion of sequences upstream of nucleotide position -39 had no detectable effect on the wild-type level of in vitro transcription, whereas mutations extending between positions -39 and 1 resulted in templates with decreased transcriptional levels; specifically, deletion and linker-scanning mutations in the -34 to -26 region (-30 region) resulted in loss of transcription. The -30 region is essential for transcription and therefore forms part of the Drosophila 5S RNA gene transcription promoter. Compared with the activity of the wild-type gene, mutant 5S DNAs exhibited no impairment in the ability to sequester limiting transcription factors in a template exclusion competition assay. While we do not know which transcription factor(s) interacts with the -30 region, the possible involvement of RNA polymerase III at this region is discussed.

Isolation of genomic clones coding for the heavy chains of two human cardiac myosins.

A 14 kilo-base pair DNA clone (lambda HCMHC8) was isolated from a human genomic library by hybridization with a complementary DNA coding for a rabbit cardiac myosin heavy chain. lambda HCMHC8 hybridized to RNA isolated from cardiac but not skeletal muscle and formed heteroduplexes with a genomic clone coding for the fast type of rabbit cardiac myosin heavy chain. lambda HCMHC8 represented at least the 3' half of the gene and contained over 11 exons which together spanned 4 kb of the coding region estimated to be 6 kb. Probes made from lambda HCMHC8 were used to rescreen the library in order to isolate overlapping clones and so extend the sequence (estimated to be approximately 25 kb for the whole gene, including introns). In addition, a clone having a different restriction map was isolated suggesting that man, like rat and rabbit, has two cardiac myosin heavy chain genes. These may code for proteins having different ATPase activity and be expressed in different proportions in different cardiac states, including hypertension.

Occurrence of calcium oxalate in karri (Eucalyptus diversicolor F. Muell.) forest ecosystems of south western Australia.

The amount of calcium in Eucalyptus diversicolor (karri) ecosystems is high in comparison with other eucalypt forest ecosystems in Australia. A large proportion of this calcium is present as crystalline Ca oxalate. Whewellite (CaC2O4·H2O) accumulates in leaf tissue of the over- and understorey species. Up to 70% of the calcium in the leaves of karri is stored as whewellite, the highest concentrations occurring in the oldest leaves. Synthesis of Ca oxalate by karri may be related in part to the high levels of exchangeable soil calcium. Oxalate of plant origin is rapidly metabolized on the forest floor during decomposition of leaf litter. About 70% of the whewellite in fresh karri leaf litter is degraded during the first wet season following leaf fall. However, additional oxalate is formed in the soil and litter layer from microbial production of oxalic acid. These crystals are of the dihydrate calcium salt, weddelite (CaC2CO4· 2H2O). Microbial production of oxalate, particularly by ectomycorrhizal fungi, may be an important mechanism for mobilizing of phosphate from the strongly phosphateadsorbing soils on which these forests grow.