Ultrasound Imaging Offers Promising Alternative to Create 3-D Models for Personalised Auricular Implants

Three-dimensional imaging and advanced manufacturing are being applied in health care research to create novel diagnostic and surgical planning methods, as well as personalised treatments and implants. For ear reconstruction, where a cartilage-shaped implant is embedded underneath the skin to re-create shape and form, volumetric imaging and segmentation processing to capture patient anatomy are particularly challenging. Here, we introduce 3-D ultrasound (US) as an available option for imaging the external ear and underlying auricular cartilage structure, and compare it with computed tomography (CT) and magnetic resonance imaging (MRI) against micro-CT (µCT) as a high-resolution reference (gold standard). US images were segmented to create 3-D models of the auricular cartilage and compared against models generated from µCT to assess accuracy. We found that CT was significantly less accurate than the other methods (root mean square [RMS]: 1.30 ± 0.5 mm) and had the least contrast between tissues. There was no significant difference between MRI (RMS: 0.69 ± 0.2 mm) and US (0.55 ± 0.1 mm). US was also the least expensive imaging method at half the cost of MRI. These results unveil a novel use of ultrasound imaging that has not been presented before, as well as support its more widespread use in biofabrication as a low-cost imaging technique to create patient-specific 3D models and implants.     

Efficacy of early administration of liposomal amphotericin B in patients with septic shock: A nationwide observational study

IntroductionLiposomal amphotericin B (L-AMB), a broad spectrum anti-fungicidal drug, is often administered to treat invasive fungal infections (IFIs). However, the most suitable time to initiate treatment in septic shock patients with IFI is unknown.MethodsPatients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database and were stratified according to L-AMB treatment initiation either at septic shock onset (early L-AMB group) or after the onset (delayed L-AMB group) to determine their survival rates following septic shock onset and the shock cessation period.ResultsWe identified 141 patients administered L-AMB on the day of or after septic shock onset: 60 patients received early treatment, whereas 81 patients received delayed treatment. Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P = 0.197; 6 weeks: 62.2% vs 44.5%, P = 0.061; 12 weeks: 43.4% vs 35.0%, P = 0.168, respectively). The septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0 ± 7.0 days vs 16.5 ± 15.4 days, P < 0.001), with a significant difference confirmed after adjusting for confounding factors with propensity score matching (7.1 ± 7.2 days vs 16.7 ± 14.0 days, P = 0.001).ConclusionEarly L-AMB administration at septic shock onset may be associated with early shock cessation.     

Benchmarking weakly-supervised deep learning pipelines for whole slide classification in computational pathology

Artificial intelligence (AI) can extract visual information from histopathological slides and yield biological insight and clinical biomarkers. Whole slide images are cut into thousands of tiles and classification problems are often weakly-supervised: the ground truth is only known for the slide, not for every single tile. In classical weakly-supervised analysis pipelines, all tiles inherit the slide label while in multiple-instance learning (MIL), only bags of tiles inherit the label. However, it is still unclear how these widely used but markedly different approaches perform relative to each other.We implemented and systematically compared six methods in six clinically relevant end-to-end prediction tasks using data from N=2980 patients for training with rigorous external validation. We tested three classical weakly-supervised approaches with convolutional neural networks and vision transformers (ViT) and three MIL-based approaches with and without an additional attention module. Our results empirically demonstrate that histological tumor subtyping of renal cell carcinoma is an easy task in which all approaches achieve an area under the receiver operating curve (AUROC) of above 0.9. In contrast, we report significant performance differences for clinically relevant tasks of mutation prediction in colorectal, gastric, and bladder cancer. In these mutation prediction tasks, classical weakly-supervised workflows outperformed MIL-based weakly-supervised methods for mutation prediction, which is surprising given their simplicity. This shows that new end-to-end image analysis pipelines in computational pathology should be compared to classical weakly-supervised methods. Also, these findings motivate the development of new methods which combine the elegant assumptions of MIL with the empirically observed higher performance of classical weakly-supervised approaches. We make all source codes publicly available at https://github.com/KatherLab/HIA, allowing easy application of all methods to any similar task.     

Clinical characteristics and prognosis of immunosuppressed inpatients with COVID-19 in Japan

IntroductionWe aimed to analyze the clinical characteristics and outcomes of immunosuppressed inpatients with coronavirus disease 2019 (COVID-19).MethodsIn this observational study, we utilized a large nationwide registry of hospitalized patients with COVID-19 in Japan. Patients’ baseline characteristics and outcomes were compared according to the immunosuppressed states of the patients. The impact of different therapeutic agents on the clinical courses of the patients was evaluated.ResultsData of 14,760 patients were included, and 887 (5.9%) were immunosuppressed. The immunosuppressed state of the patient resulted from solid tumor (43.3%, n = 384), chemotherapy within 3 months (15.6%, n = 138), collagen disease (16.9%, n = 150), use of immunosuppressive agents (16.0%, n = 142), and metastatic solid tumor (13.5%, n = 120). Immunosuppressed patients were older and had a higher severity of illness at admission and during hospitalization than non-immunosuppressed patients. The mortality rates for major diseases causing immunosuppression were as follows: solid tumor, 12.5% (48/384; P < 0.001; relative risk [RR], 3.41); metastatic solid tumor, 31.7% (38/120; P < 0.001; RR, 8.43); leukemia, 23.1% (9/39; P < 0.001; RR, 5.87); lymphoma, 33.3% (20/60; P < 0.001; RR, 8.63); and collagen disease, 15.3% (23/150; P < 0.001; RR 3.97). Underlying diseases with high mortality rates were not necessarily associated with high rates of invasive supportive care.ConclusionsThe prognosis of immunosuppressed COVID-19 inpatients varied according to the different immunosuppressed states. Multiple factors, including the severity of the underlying diseases, might have affected their invasive supportive care indications.     

Physical Activity in Cardiac Implantable Electronic Device Recipients During the COVID-19 Pandemic

ObjectiveTo characterize the physical activity (PA) level in patients with a cardiac implantable electronic device (CIED) during the coronavirus disease 2019 (COVID-19) pandemic and compare PA level during the pandemic in 2020 with the year 2019.MethodsWe performed a retrospective analysis of PA activity in individuals implanted with a CIED enrolled in the BIOTRONIK CERTITUDE Registry. Mean daily and weekly PA from January to August 2020 was compared with 2019.ResultsA total of 21,660 individuals met eligibility criteria, with mean age of 72.6±11.6 years, and 12,411 (57.3)% were males. A significant decline in daily PA was noted following the pandemic declaration in 2020, with a maximum mean reduction of -24.5±36.3 minutes (P<.0001) observed in April 2020 compared with 2019. PA in 2020 increased from April to May (120.6±67.4 to 129.2±70.9 min/d). PA was lower for all months in 2020 compared with 2019. The decrease in PA was observed in all prespecified groups based on age, sex, type of device, and region of the country.ConclusionAfter the declaration of the coronavirus disease 2019 pandemic, a significant decline in daily PA was observed in individuals with a CIED. Future investigation to establish the impact of this reduction on short and long-term cardiovascular outcomes is required.     

A multimodal deep learning model for cardiac resynchronisation therapy response prediction

We present a novel multimodal deep learning framework for cardiac resynchronisation therapy (CRT) response prediction from 2D echocardiography and cardiac magnetic resonance (CMR) data. The proposed method first uses the ‘nnU-Net’ segmentation model to extract segmentations of the heart over the full cardiac cycle from the two modalities. Next, a multimodal deep learning classifier is used for CRT response prediction, which combines the latent spaces of the segmentation models of the two modalities. At test time, this framework can be used with 2D echocardiography data only, whilst taking advantage of the implicit relationship between CMR and echocardiography features learnt from the model. We evaluate our pipeline on a cohort of 50 CRT patients for whom paired echocardiography/CMR data were available, and results show that the proposed multimodal classifier results in a statistically significant improvement in accuracy compared to the baseline approach that uses only 2D echocardiography data. The combination of multimodal data enables CRT response to be predicted with 77.38% accuracy (83.33% sensitivity and 71.43% specificity), which is comparable with the current state-of-the-art in machine learning-based CRT response prediction. Our work represents the first multimodal deep learning approach for CRT response prediction.     

Sex Differences in Outcomes of Patients With Chronic Aortic Regurgitation: Closing the Mortality Gap

ObjectiveTo examine contemporary clinical differences between men and women with hemodynamically significant chronic aortic regurgitation (AR).Patients and MethodsWe retrospectively identified 1072 consecutive patients with moderate to severe or severe AR diagnosed between February 21, 2004, and April 29, 2019. Echocardiographic data, aortic valve surgical intervention (AVS), and all-cause death were analyzed.ResultsAt baseline, the 189 women in the study group were older than the 883 men (mean ± SD age, 64±18 years vs 58±17 years), had more advanced symptoms, and had larger left ventricular end-systolic dimension index (LVESDi) (all P<.001) despite similar AR severity. An LVESDi of greater than 20 mm/m² was noted in 60 of 92 asymptomatic women (65%) vs 225 of 559 asymptomatic men (40%) (P<.001). Median follow-up was 5.6 years (interquartile range, 2.5 to 10.0 years). Female sex was associated with less AVS (P=.009), and overall 10-year survival was better in men (76%±2%) than in women (64%±5%) (P=.004). However, 10-year post-AVS survival was similar between the sexes (P=.86), and women had better left ventricular reverse remodeling than men regarding end-diastolic dimension (P=.02). Multivariable independent predictors of death were age, advanced symptoms, LVESDi, ejection fraction, and AVS (all P≤.03) but not female sex. When compared with the age-matched US population, women exhibited a 1.3-fold increased relative risk of death (P=.0383) while men had similar survival (P=.11).ConclusionIn contemporary practice, women with AR continue to exhibit an overall survival penalty not related to female sex but to late referral markers, including more advanced symptoms, larger LVESDi, and less AVS. Nonetheless, women in our study exhibited outstanding post-AVS left ventricular remodeling and had good post-AVS survival, a step forward toward closing the sex-related mortality gap. The high percentage of LVESDi of 20 mm/m² or greater in asymptomatic women represents a window of opportunity for advanced-symptom prevention and timely AR surgical correction that may close the mortality gap.     

Do Patients With COVID-19 Benefit from Rehabilitation? Functional Outcomes of the First 100 Patients in a COVID-19 Rehabilitation Unit

ObjectiveTo determine the benefits associated with brief inpatient rehabilitation for coronavirus 2019 (COVID-19) patients.DesignRetrospective chart review.SettingA newly created specialized rehabilitation unit in a tertiary care medical center.ParticipantsConsecutive sample of patients (N=100) with COVID-19 infection admitted to rehabilitation.InterventionInpatient rehabilitation for postacute care COVID-19 patients.Main Outcome MeasuresMeasurements at admission and discharge comprised a Barthel Activities of Daily Living Index (including baseline value before COVID-19 infection), time to perform 10 sit-to-stands with associated cardiorespiratory changes, and grip strength (dynamometry). Correlations between these outcomes and the time spent in the intensive care unit (ICU) were explored.ResultsUpon admission to rehabilitation, 66% of the patients were men, the age was 66±22 years, mean delay from symptom onset was 20.4±10.0 days, body mass index was 26.0±5.4 kg/m², 49% had hypertension, 29% had diabetes, and 26% had more than 50% pulmonary damage on computed tomographic scans. The mean length of rehabilitation stay was 9.8±5.6 days. From admission to discharge, the Barthel index increased from 77.3±26.7 to 88.8±24.5 (P<.001), without recovering baseline values (94.5±16.2; P<.001). There was a 37% improvement in sit-to-stand frequency (0.27±0.16 to 0.37±0.16 Hz; P<.001), a 13% decrease in post-test respiratory rate (30.7±12.6 to 26.6±6.1; P=.03), and a 15% increase in grip strength (18.1±9.2 to 20.9±8.9 kg; P<.001). At both admission and discharge, Barthel score correlated with grip strength (ρ=0.39-0.66; P<.01), which negatively correlated with time spent in the ICU (ρ=–0.57 to –0.49; P<.05).ConclusionsInpatient rehabilitation for COVID-19 patients was associated with substantial motor, respiratory, and functional improvement, especially in severe cases, although there remained mild persistent autonomy loss upon discharge. After acute stages, COVID-19, primarily a respiratory disease, might convert into a motor impairment correlated with the time spent in intensive care.     

Effectiveness of betadine-soaked gauze covering umbilical catheter connectors on the outcome of neonates: A randomized control trial

BackgroundNeonatal sepsis is the critical underlying cause of morbidity and mortality among neonates. In Neonatal Intensive Care Unit most commonly umbilical catheters are used for vascular access. However, certain complications are also associated with its use. One of them is Umbilical-catheter related sepsis. To enable safe IV access, a small critical piece of equipment is a connector that connects to the end of the catheter. As the external surface of the connector is exposed and contaminated, it can lead to umbilical catheter connector-related sepsis.ObjectiveThe present study was conducted with an aim to assess the effectiveness of betadine-soaked gauze covering umbilical catheter connectors on the outcome of neonates, admitted to NICU.MethodologyA RCT design was used and a total of 70 neonates were enrolled out of which 7 neonates did not match the inclusion criteria and 5 abstained from participating in the study. Therefore, 58 neonates were then randomized using a computer-assisted method.ResultsThe incidence of sepsis in the experimental group was lower (24.1%) than in the control group (44.8%). However, this difference was found to be statistically non-significant (p = 0.0973). The mean duration of hospitalization in the experimental group was found to be 18.48 ± 9.977 and in the control group 16.38 ± 8.801. The difference was non-significant (p = 0.3989). No neonatal death was recorded in the groups.ConclusionThe study findings conclude that although there was a lower incidence of sepsis in the experimental group as compared to the control group, this difference was found to be statistically non-significant. However, consideration should be given to connector-related infection practices.     

Noninvasive Ventilation in the Management of Respiratory Failure Due to COVID-19 Infection: Experience From a Resource-Limited Setting

ObjectiveTo study the role of noninvasive ventilation (NIV) in Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) related acute respiratory failure (C-ARF).Patients and MethodsPatients with C-ARF managed on NIV were categorized as NIV success or failure (death or intubation). Factors associated with failure were explored using regression analysis and expressed as odds ratio (OR) with 95% CI.ResultsBetween April 1, 2020, and September 15, 2020, a total of 286 patients with a mean ± SD age of 53.1±11.6 years and Acute Physiology and Chronic Health Evaluation II score of 11.1±5.5 were initiated on NIV. Of the 182 patients (63.6%) successfully managed on NIV alone, 118 had moderate or severe acute respiratory distress syndrome. When compared with NIV success, NIV failure was associated with lower admission PaO₂ to fraction of inspired oxygen ratio (P<.001) and higher respiratory rate (P<.001). On penalized logistic regression analysis, NIV failure was associated with higher Acute Physiology and Chronic Health Evaluation II score (OR, 1.12; 95% CI, 1.01 to 1.24), severe acute respiratory distress syndrome (OR, 3.99; 95% CI, 1.24 to 12.9), D-dimer level of 1000 ng/mL DDU (to convert to mg/L, divide by 1000) or greater (OR, 2.60; 95% CI, 1.16 to 5.87), need for inotropes or dialysis (OR, 12.7; 95% CI, 4.3 to 37.7), and nosocomial infections (OR, 13.6; 95% CI, 4.06 to 45.9). Overall mortality was 30.1% (86/286). In patients requiring intubation, time to intubation was longer in nonsurvivors than survivors (median, 5; interquartile range, 3-8 vs 3; interquartile range, 2-3 days; P<.001).ConclusionNoninvasive ventilation can be used successfully in C-ARF. Illness severity and need for non–respiratory organ support predict NIV failure.     

Stability of benzylpenicillin for continuous intravenous infusions: An isotonic formulation for therapeutic use and a low-dose formulation for clinical trial

IntroductionThe objectives of this study were to develop a stability-indicating high performance liquid chromatography (HPLC) assay for benzylpenicillin (BPC) in pharmaceutical fluids, and to investigate the stability of (i) isotonic citrate-buffered BPC solutions at the clinically relevant concentration of 30 mg/mL, and (ii) low concentration citrate-buffered BPC intravenous infusions (5–30 μg/mL).MethodsThe stability of isotonic BPC solutions containing 3.4 or 7.2 mg/mL sodium citrate was compared against contemporary hypertonic solutions. The HPLC assay was shown to be stability-indicating following acidic, alkali, oxidative and elevated temperature stress testing.ResultsAfter 7 d storage at 4 °C and 24 h at 35 °C, the concentrations of isotonic BPC 30 mg/mL solutions containing 3.4 and 7.2 mg/mL sodium citrate were 96% and 95% respectively, compared to day 0. After 3 d at 4 °C and 24 h at room temperature (22 °C), the concentrations of isotonic BPC solutions with 3.4 and 7.2 mg/mL sodium citrate were 99% and 96% respectively, compared to day 0. These data were comparable to the hypertonic solutions and meet pharmacopeial stability requirements. Low concentration BPC infusions showed 0.5% and 2.5% degradation after 24 h storage at 22 °C and 35 °C, respectively.ConclusionsThe isotonic BPC 30 mg/mL formulation is simple to prepare and may offer clinical benefits in settings where hypertonic solutions are problematic. This study provides assurance that high- and low-dose isotonic BPC infusions are stable at room temperature and our findings may be applicable to in vitro studies of BPC.     

Collaboration with an infection control team promoted appropriate antibiotic use for third molar extraction at a Japanese hospital

Oral antibiotic therapy is routinely administered when a third molar (M3) is extracted to prevent infectious complications after surgery. Oral third-generation cephalosporins are frequently used after M3 extraction in Japan but at the expense of an increased risk of antimicrobial resistance. Therefore, the infection control team (ICT) at our institution recommended a reduction in use of these agents after M3 extraction. In this study, we compared the types of antibiotic agents prescribed for patients undergoing M3 extraction before and after this recommendation. We investigated the relationship between type of antibiotic used and the likelihood of infectious complications as well as cost savings in patients who underwent M3 extraction in the 6 months before and after the ICT recommendation in July 2018. There was a marked reduction in use of oral third-generation cephalosporins after M3 extraction (P < 0.0001) and increased use of oral penicillins and first-generation cephalosporins after the ICT recommendation. Moreover, surgical site infection (SSIs) were significantly less common after the ICT recommendation (P = 0.0099); however, the SSI rate was higher in patients who received a third-generation cephalosporin than in those who received penicillin (8.8% vs 0.5%). There was also a significant saving in per-patient antibiotic costs after the ICT recommendation (269.5 ± 282.0 JPY vs 454.7 ± 376.6 JPY; P < 0.0001). These findings suggest that collaboration with an ICT promotes appropriate antibiotic use, decreases the risk of an SSI, and improves the cost-benefit ratio in patients undergoing M3 extraction.     

Right Ventricular Enlargement and Dysfunction Are Associated With Increased All-Cause Mortality in Hypertrophic Cardiomyopathy

ObjectiveTo assess whether right ventricular enlargement (RVE) and right ventricular dysfunction (RVD) adversely affect prognosis in hypertrophic cardiomyopathy (HCM).Patients and MethodsData were retrieved from Mayo Clinic’s prospectively collected HCM registry between January 1, 2000, and September 30, 2012. Right ventricle (RV) size and function were semiquantitatively categorized via echocardiography as normal (RV-Norm) versus abnormal (RV-Abn) (RVE or RVD). All-cause mortality was the primary endpoint.ResultsOf 1878 HCM patients studied (mean age 53±15 years; 41.6% female), only 71 (3.8%) had RV-Abn (24 RVE, 28 RVD, 19 combined RVE and RVD). Compared with HCM patients with RV-Norm, RV-Abn patients were older (57±14 vs 53±15 years, P=.02), more symptomatic (New York Heart Association functional class III-IV in 62.0% vs 48.6%, P=.03), had more atrial fibrillation (53.5% vs 17.3%, P<.001), and more prior implantable cardioverter-defibrillator implantation (23.9% vs 11.3%, P=.02). Median follow-up was 9.4 years with 311 deaths. Patients who were RV-Abn had higher all-cause mortality compared with RV-Norm (log-rank P<.001); 24.1% (95% CI, 15.5% to 35.3%) vs 6.1% (95% CI, 5.1% to 7.3%) at 5 years. In multivariable Cox modeling, RV-Abn (hazard ratio, 1.89; 95% CI, 1.18 to 3.03; P=.008) was associated independently with all-cause mortality after adjusting for age, female sex, New York Heart Association functional class, atrial fibrillation, hypertension, coronary artery disease, implantable cardioverter-defibrillator implantation, beta blocker use, prior septal reduction therapy, resting LV outflow tract gradient, maximal LV wall thickness, and moderate or greater tricuspid regurgitation.ConclusionAlthough perturbations in RV size and function were observed in fewer than 5% of patients with HCM, they were associated with nearly two-fold higher all-cause mortality at long-term follow-up.     

Clinical Outcomes of Adults With Bicuspid Aortic Valve: A European Perspective

ObjectiveTo describe the clinical history of patients with a wide age range diagnosed with bicuspid aortic valve (BAV) and no surgical indication and to evaluate the long-term outcome of patients with BAV referred for elective surgery.Patients and MethodsBetween 2005 and 2017, 350 consecutive patients with no surgical indication (surveillance group, mean age 53±16, 71% men) and 191 with a surgical indication (surgical group, mean age 59±13, 71% men) were prospectively included. Median follow-up was 80 (32 to 115) months.ResultsIn the surveillance group, the 5-year and 10-year survival rates were 93±1% and 89±2%, respectively, with a relative survival of patients with BAV compared with an age- and sex-matched control population of 98.7%. During follow-up, the cumulative 10-year incidence of aortic valve and aorta surgery was high; of 35±4%, the incidence of native valve infective endocarditis (IE) of 0.2% per patient-year, and no cases of aortic dissection were observed. In the surgical group, the 5-year and 10-year survival rates were 97±1% and 89±3%, respectively, with a relative survival of 99.4% compared with the general population. The incidence of IE was 0.4% per patient-year, and no cases of aortic dissection were observed.ConclusionThis regional cohort shows that the 10-year survival rates of patients with BAV and a wide age range, but mostly middle-aged adults, were similar to those of the general population with a very low rate of complications. Adherence to prophylactic surgical indications and younger age might have contributed to this lack of difference.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Population-Based Evaluation of Total Protein in Cerebrospinal Fluid

ObjectivesTo present a normal range of cerebrospinal fluid (CSF) protein levels in a community-based population and to evaluate factors that contribute to CSF protein level variability.Patients and MethodsSamples of CSF protein were obtained from participants aged 32 to 95 years who underwent lumbar puncture (LP) between November 1, 2007, and October 1, 2017, as part of the Mayo Clinic Study of Aging, a longitudinal, population-based study of residents of Olmsted County, Minnesota.ResultsA total of 633 participants (58.1% male; 99.1% White; mean ± SD age, 70.9±11.6 years) underwent LP with recorded CSF protein level. Mean ± SD CSF protein level was 52.2±18.4 mg/dL (to convert to mg/L, multiply by 10), with a 95% reference interval of 24.0 to 93.4 mg/dL (range, 14.0-148.0 mg/dL). Spinal stenosis and arterial hypertension were associated with higher CSF protein levels on univariable analysis (P<.001). Increasing age, male sex, and diabetes were all independently associated with higher CSF protein levels on multivariable analysis (P<.001). In the 66 participants with repeated LPs within 2.5 years, the coefficient of repeatability was 26.1 mg/dL. Eleven participants (16.7%) had a CSF protein level difference of 20 mg/dL or more between serial LPs, and 4 (6.1%) had a difference of 25 mg/dL or more. There was a trend toward greater CSF protein level variability in patients with spinal stenosis (P=.054).ConclusionThis large population-based study showed that CSF protein level can vary significantly among individuals. Elevated CSF protein level was independently associated with older age, male sex, and diabetes and is higher than listed in many laboratories. These findings emphasize the necessity of evidence-based reevaluation and standardization of CSF protein metrics.     

CEUS Versus MRI in Evaluation of the Effect of Microwave Ablation of Breast Cancer

Percutaneous microwave ablation (MWA) is a new minimally invasive technique for breast cancer treatment. The aim of this research was to compare the differences in performance between contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) with respect to the curative effect of MWA in the treatment of breast cancer. Between 2015 and 2019, 26 patients with breast cancer underwent ultrasound-guided MWA. All patients underwent both CEUS and MRI within 3 d after ablation. If either of the two imaging modalities revealed suspicious enhancement of the ablation zone and the ultrasound-guided biopsy confirmed residual tumor in the suspicious area, supplementary MWA was applied. The diagnostic efficacy of CEUS and MRI within 3 d after ablation was evaluated based on a >6-mo follow-up of 26 patients. Two cases were diagnosed with residual tumors by ultrasound that were missed by MRI. Three cases were diagnosed with residual tumors by MRI that were missed by CEUS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the diagnosis of complete ablation were 100%, 40%, 87.5%, 100% and 88.5%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of MRI in the diagnosis of complete ablation were 100%, 60%, 91.3%, 100% and 92.3%, respectively. Within 3 d, both CEUS and MRI can efficiently assess the efficacy of MWA of breast cancer.     

Breast Cancer Mode of Detection in a Population-Based Cohort

ObjectiveTo evaluate how breast cancers come to clinical attention (mode of detection [MOD]) in a population-based cohort, determine the relative frequency of different MODs, and characterize patient and tumor characteristics associated with MOD.Patients and MethodsWe used the Rochester Epidemiology Project to identify women ages 40 to 75 years with a first-time diagnosis of breast cancer from May 9, 2017, to May 9, 2019 (n=500) in a 9-county region in Minnesota. We conducted a retrospective medical record review to ascertain the relative frequency of MODs, evaluating differences between screening mammography vs all other MODs by breast density and cancer characteristics. Multiple logistic regression was conducted to examine the likelihood of MOD for breast density and stage of disease.ResultsIn our population-based cohort, 162 of 500 breast cancers (32.4%) were detected by MODs other than screening mammography, including 124 (24.8%) self-detected cancers. Compared with women with mammography-detected cancers, those with MODs other than screening mammography were more frequently younger than 50 years of age (P=.004) and had higher-grade tumors (P=.007), higher number of positive lymph nodes (P<.001), and larger tumor size (P<.001). Relative to women with mammography-detected cancers, those with MODs other than screening mammography were more likely to have dense breasts (odds ratio, 1.87; 95% CI, 1.20 to 2.92; P=.006) and advanced cancer at diagnosis (odds ratio, 3.58; 95% CI, 2.29 to 5.58; P<.001).ConclusionOne-third of all breast cancers in this population were detected by MODs other than screening mammography. Increased likelihood of nonmammographic MODs was observed among women with dense breasts and advanced cancer.