A Prospective, Longitudinal Evaluation of SARS-CoV-2 COVID-19 Exposure, Use of Protective Equipment and Social Distancing in a Group of Community Physicians.

INTRODUCTION: Healthcare workers experience a significant risk of exposure to and infection from SARS-CoV-2, COVID-19. Nonetheless, little research has focused on physicians' use of personal protective equipment (PPE), their concerns about becoming infected and their social distancing maneuvers. METHODS: All staff physicians at Advocate Lutheran General Hospital were invited to participate. Their COVID-19 IgG antibody level was measured and an online questionnaire was completed. The questionnaire assessed the risk of COVID-19 exposure, PPE usage, concern for contracting COVID-19, the performance of high-risk procedures, work in high-risk settings, and social distancing practices. Testing was performed in September (T0), and December 2020 (T1) at the height of the global pandemic. RESULTS: A total of 481 (26.7%) of 1800 AGLH physicians were enrolled at T0 and 458 (95% of the original group) at T1. A total of 21 (4.3%) and 39 (8.5%) participants had antibodies at T0 and T1. A total of 63 (13.8%) worked in high-risk settings and 111 (24.2%) performed high-risk procedures. Participants working in high-risk settings had increased exposure to COVID-19 infected patients (OR = 4.464 CI = 2.522-8.459, p < 0.001). Participants were highly adherent to the use of PPE and social distancing practices including mask-wearing in public (86%, 82.1%), avoiding crowds (85.1%, 85.6%), six feet distancing (83.8%, 83.4%), and avoiding public transportation (78%, 83.8%). A total of 251 (55.4%) participants expressed moderate to extreme concern about becoming infected with COVID-19. CONCLUSIONS AND RELEVANCE: Among a group of community physicians, consistent PPE use and social distancing practices were common. These practices were associated with a low level of initial acquisition of COVID-19 infections and a relatively low longitudinal risk of infection.

Strategies for vaccine-product innovation: Creating an enabling environment for product development to uptake in low- and middle-income countries.

Vaccine-product innovations that address barriers to immunization are urgently needed to achieve equitable vaccine coverage, as articulated in the new Immunization Agenda 2030 and the Gavi 5.0 strategy. In 2020, the Vaccine Innovation Prioritisation Strategy (VIPS) prioritized three innovations, namely microarray patches (MAPs), heat-stable and controlled-temperature chain (CTC) enabled liquid vaccine formulations and barcodes on primary packaging. These innovations were prioritized based on the priority immunization barriers that they may help overcome in resource constrained contexts, as well as by considering their potential impact on health, coverage and equity, safety, economic costs and their technical readiness and commercial feasibility. VIPS is now working to accelerate the development and lay the foundation for future uptake of the three priority vaccine-product innovations, with the long term-goal to ensure equitable vaccine coverage and increased impact of vaccines in low- and middle- income countries. To inform our strategic planning, we analyzed four commercially available vaccine product-innovations and conducted interviews with individuals from 17 immunization organizations, and/or independent immunization experts. The findings are synthesized into an 'innovation conundrum' that describes the challenges encountered in developing vaccine-product innovations and a vaccine-product innovation 'theory of change', which highlights actions that should be undertaken in parallel to product development to incentivize sustainable investment and prepare the pathway for uptake and impact.

Percutaneous Endoscopic Jejunostomy Tube Placement for Treatment of Severe Hyperemesis Gravidarum in Pregnancy.

Hyperemesis gravidarum is a common disease. Most patients are effectively treated with conservative measures, but gastric feeding and, rarely, post-pyloric feeding can be necessary. A 27-year-old woman, G3P2002, with a history of refractory hyperemesis in previous pregnancies, required placement of a nasojejunal tube but was removed due to an oropharyngeal ulcer. Endoscopic placement of a percutaneous endoscopic transgastric-jejunostomy (PEG-J) tube caused resolution of her symptoms. Twelve days after placement, the distal tube became dislodged and was endoscopically replaced with hemoclip anchoring in the jejunum. PEG-J tube placement is a safe and effective option for nutritional support in refractory hyperemesis gravidarum.

A Case of Idiopathic Non-Cirrhotic Portal Hypertension in a Patient With a Left Ventricular Assist Device.

Idiopathic non-cirrhotic portal hypertension is a rare diagnosis caused by an unknown etiology with elevated intrahepatic portal pressures in the absence of underlying liver disease. We present a unique case of a 57-year-old male with a left ventricular assist device and preserved right ventricular function that was found to have an elevated hepatic venous pressure gradient and sequelae of portal hypertension without underlying liver disease. There is limited treatment available as management is primarily aimed toward preventing complications of the disease. This case highlights the need for further investigative research of this disease entity and its pathogenesis.

Calciphylaxis in the Setting of Alcoholic Cirrhosis: Case Report and Literature Review.

Calciphylaxis can be a severe life-threatening dermatologic disease that is a known complication associated with end-stage renal disease. However, multiple non-uremic etiologies that are not yet well studied can cause calciphylaxis. We report a rare care of a 40-year-old female with history of alcoholic cirrhosis without any evidence of renal dysfunction who presents with calciphylaxis.

Mirrizi Syndrome and Markedly Elevated Levels of Carbohydrate Antigen 19-9 in the Absence of Malignant Disease.

Elevated carbohydrate antigen 19-9 (CA19-9) beyond 1000 U/L occurs in nonneoplastic conditions which is causing questioning of the use of CA19-9 as a marker for screening. We report a case where a 51-year-old male with Mirrizi Syndrome (MS) presented with markedly increased CA19-9 level (4,618 U/mL). MS is a rare complication characterized by compression of the common bile or hepatic duct caused by an impacted gallstone in the cystic duct or neck of the gallbladder. Biliary epithelial cells secrete CA19-9: it is hypothesized that increased proliferation of such cells caused by inflammation leads to increased secretion. CA19-9 should not be used as a diagnostic tool, but rather for surveillance.

Racial Disparities in Colorectal Carcinoma Incidence, Severity and Survival Times Over 10 Years: A Retrospective Single Center Study.

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Although studies have been performed on malignancy behavior in African Americans and Caucasians, scant data are present on other minority racial groups. METHODS: A retrospective single center study was performed where 1,860 patient charts with a diagnosis of CRC from January 1, 2004 to December 31, 2014 were reviewed. Data collected on each patient included age, gender, ethnicity, primary site and histological stage at the time of diagnosis. Survival time over the course of 5 years was documented for patients from January 1, 2004 to December 31, 2009. Comparisons were made amongst different racial groups for the above mentioned factors. RESULTS: Study population consisted of 27.09% African Americans, 65.61% Caucasians, 3.86% Hispanics, 0.54% South Asians, 1.03% Arabs, 0.54% Asians and 0.22% American Indians. Mean age of CRC presentation was found to be significantly different (P < 0.05) between the three largest racial groups: 71 years for Caucasians, 69 years for African Americans, and 61 years for Hispanics. African Americans (27.09%) and Hispanics (28.79%) presented predominantly at stage IV in comparison to other racial groups. Caucasians presented predominantly at stage III (24.84%). The rectum was the most common site of CRC across all racial groups with the exception of Asians, where sigmoid colon was the predominant site (30%). Adenocarcinoma remained the predominant cancer type in all groups. Hispanics had relatively higher incidence rate of carcinoid tumor (12.68%). Survival time analysis showed that Caucasians tend to have better survival probability over 5 years after initial diagnosis as compared to African Americans and Hispanic (P < 0.05). CONCLUSION: There is lack of studies performed on minority racial groups in North America. Our study highlighted some important clinical differences of CRC presentation in different racial groups which are not well studied and can be used to formulate future multi-center studies to assess disease behavior.

Sterile Seroma after Drainage of Purulent Muscle Abscess in Crohn's Disease: Two Cases.

Purulent skeletal muscle abscesses can occur in Crohn's disease. We report a case of a sterile seroma complicating percutaneous drainage of a purulent skeletal muscle abscess in Crohn's ileitis. We compare and contrast this case with a similar case we published earlier. We emphasize the importance of recognition and differentiation from a septic purulent abscess.

Markedly Elevated Liver Enzymes in Choledocholithiasis in the absence of Hepatocellular Disease: Case Series and Literature Review.

Liver enzyme levels are commonly obtained in the evaluation of many conditions. Elevated alanine transaminase and aspartate transaminase have traditionally been considered a "hepatocellular" pattern concerning for ischemic, viral, or toxic hepatitis. Elevations in these levels pose a diagnostic dilemma in patients without a clinical picture consistent with liver disease. On the other hand, elevated alkaline phosphatase historically represents a "cholestatic" pattern concerning for gallbladder and biliary tract disease. Often, patients present with a "mixed" picture of elevation in all 3 liver enzymes, further confounding the clinical scenario. We present 4 cases of women with severe upper abdominal pain and markedly elevated transaminases. Three of the patients had accompanying jaundice. A higher rise in enzyme levels was seen in those who had greater bile duct dilation. All patients saw a rapid decrease in transaminases after biliary decompression, along with a fall in alkaline phosphatase and total bilirubin levels. No evidence of liver disease was found, nor were there any signs of hepatocellular disease on imaging. The patients were ultimately found to have choledocholithiasis on endoscopic retrograde cholangiopancreatography with no hepatocellular disease. Furthermore, our cases show that severe abdominal pain in the setting of elevated liver enzymes is likely associated with biliary disease rather than a primary hepatic process. Recognition of this rare pattern of markedly elevated transaminases in isolated biliary disease can aid in avoiding unnecessary evaluation of primary hepatic disease and invasive surgical interventions such as liver biopsy.

Molecular dynamic simulations reveal the structural determinants of Fatty Acid binding to oxy-myoglobin.

The mechanism(s) by which fatty acids are sequestered and transported in muscle have not been fully elucidated. A potential key player in this process is the protein myoglobin (Mb). Indeed, there is a catalogue of empirical evidence supporting direct interaction of globins with fatty acid metabolites; however, the binding pocket and regulation of the interaction remains to be established. In this study, we employed a computational strategy to elucidate the structural determinants of fatty acids (palmitic & oleic acid) binding to Mb. Sequence analysis and docking simulations with a horse (Equus caballus) structural Mb reference reveals a fatty acid-binding site in the hydrophobic cleft near the heme region in Mb. Both palmitic acid and oleic acid attain a "U" shaped structure similar to their conformation in pockets of other fatty acid-binding proteins. Specifically, we found that the carboxyl head group of palmitic acid coordinates with the amino group of Lys45, whereas the carboxyl group of oleic acid coordinates with both the amino groups of Lys45 and Lys63. The alkyl tails of both fatty acids are supported by surrounding hydrophobic residues Leu29, Leu32, Phe33, Phe43, Phe46, Val67, Val68 and Ile107. In the saturated palmitic acid, the hydrophobic tail moves freely and occasionally penetrates deeper inside the hydrophobic cleft, making additional contacts with Val28, Leu69, Leu72 and Ile111. Our simulations reveal a dynamic and stable binding pocket in which the oxygen molecule and heme group in Mb are required for additional hydrophobic interactions. Taken together, these findings support a mechanism in which Mb acts as a muscle transporter for fatty acid when it is in the oxygenated state and releases fatty acid when Mb converts to deoxygenated state.

Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy.

We combine diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) to noninvasively monitor early hemodynamic response to neoadjuvant chemotherapy in a breast cancer patient. The potential for early treatment monitoring is demonstrated. Within the first week of treatment (day 7) DOS revealed significant changes in tumor/normal contrast compared to pretreatment (day 0) tissue concentrations of deoxyhemoglobin (rctHHbT/N=69+/-21%), oxyhemoglobin (rctO2HbT/N=73+/-25%), total hemoglobin (rctTHbT/N=72+/-17%), and lipid concentration (rctLipidT/N=116+/-13%). Similarly, DCS found significant changes in tumor/normal blood flow contrast (rBFT/N=75+/-7% on day 7 with respect to day 0). Our observations suggest the combination of DCS and DOS enhances treatment monitoring compared to either technique alone. The hybrid approach also enables construction of indices reflecting tissue metabolic rate of oxygen, which may provide new insights about therapy mechanisms.

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy.

Diffuse optical spectroscopy (DOS) and imaging are emerging diagnostic techniques that quantitatively measure the concentration of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctO(2)Hb), water (ctH(2)O), and lipid in cm-thick tissues. In early-stage clinical studies, diffuse optical imaging and DOS have been used to characterize breast tumor biochemical composition and monitor therapeutic response in stage II/III neoadjuvant chemotherapy patients. We investigated whether DOS measurements obtained before and 1 week into a 3-month adriamycin/cytoxan neoadjuvant chemotherapy regimen can predict final, postsurgical pathological response. Baseline DOS measurements of 11 patients before therapy revealed significant increases in tumor ctHHb, ctO(2)Hb, ctH(2)O, and spectral scattering slope, and decreases in bulk lipids, relative to normal breast tissue. Tumor concentrations of ctHHb, ctO(2)Hb, and ctH(2)O dropped 27 +/- 15%, 33 +/- 7%, and 11 +/- 15%, respectively, within 1 week (6.5 +/- 1.4 days) of the first treatment for pathology-confirmed responders (n = 6), whereas nonresponders (n = 5) and normal side controls showed no significant changes in these parameters. The best single predictor of therapeutic response 1 week posttreatment was ctHHb (83% sensitivity, 100% specificity), while discrimination analysis based on combined ctHHb and ctH(2)O changes classified responders vs. nonresponders with 100% sensitivity and specificity. In addition, the pretreatment tumor-to-normal ctO(2)Hb ratio was significantly higher in responders (2.82 +/- 0.44) vs. nonresponders (1.82 +/- 0.49). These results highlight DOS sensitivity to tumor cellular metabolism and biochemical composition and demonstrate its potential for predicting and monitoring an individual's response to treatment.

In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy.

Diffuse optical imaging (DOI) may be a beneficial diagnostic method for women with mammographically dense breast tissue. In order to evaluate the utility of DOI, we are developing broadband diffuse optical spectroscopy (DOS) to characterize the functional origins of optical signals in breast cancer patients. Broadband DOS combines multifrequency intensity-modulated and continuous-wave near-infrared light to quantify tissue absorption and scattering spectra from 650 to 1000 nm. Values of intrinsic physiological properties (oxy- and deoxy-hemoglobin, water, lipid, and scatter power) derived from absorption and scattering spectra provide detailed information on breast physiology. We present the results of clinical studies of 58 stage II/III malignant breast tumors using a noninvasive, handheld, broadband DOS probe. On average, eight positions were scanned over tumor and contralateral normal breast for each subject. Intrinsic physiological properties were statistically significantly different for malignant vs. normal tissues for all subjects, without patient age or tumor size/type stratification. Breast tissues containing malignant tumors displayed reduced lipid content ( approximately 20%) and increased water, deoxy-, and oxy-hemoglobin (>50% each) compared to normal breast tissues. Functional perturbations by the tumor were significantly larger than functional variations in normal tissues. A tissue optical index (TOI) derived from intrinsic physiological properties yielded an average two-fold contrast difference between malignant tumors and intrinsic tissue properties. Our results demonstrate that intrinsic optical signals can be influenced by functional perturbations characteristic of malignant transformation; cellular metabolism, extracellular matrix composition, and angiogenesis. Our findings further underscore the importance of broadband measurements and patient age stratification in breast cancer DOI.

Combined diffuse optical spectroscopy and contrast-enhanced magnetic resonance imaging for monitoring breast cancer neoadjuvant chemotherapy: a case study.

Monitoring tumor response to therapy can enable assessment of treatment efficacy, maximizing patient outcome and survival. We employ a noninvasive, handheld laser breast scanner (LBS) based on broadband diffuse optical spectroscopy (DOS) in conjunction with contrast-enhanced magnetic resonance imaging (cMRI) to assess tumor response to presurgical neoadjuvant chemotherapy. DOS and cMRI scans are performed after the first and fourth cycles of a doxorubicin/cyclophosphamide regimen in a patient with invasive ductal carcinoma. DOS measurements are used to quantify bulk tissue optical and physiological parameters, which are mapped to T2- and T1-weighted cMRI images. Initial DOS measurements show high tumor/normal contrast in total hemoglobin concentration (THC, 56+/-7 versus 27+/-4 microM) and water fraction (81.4+/-1% versus 24+/-3%) colocalized with regions of strongly enhancing T2-weighted and cMRI signals. After the fourth cycle of chemotherapy, we observe decreases in peak MRI contrast-enhancement values (37.6%) and apparent lesion volume (21.9 versus 13.7 cm3), which corresponds to physiological changes measured by DOS, including a 20 to 25% reduction in the spatial extent of the tumor and a 38.7% drop in mean total hemoglobin content (THC, 41.6 versus 23.4 microM). These data provide in vivo validation of the accuracy of broadband DOS and the sensitivity of optical methods to changes in tumor physiology.

Coregistration of dynamic contrast enhanced MRI and broadband diffuse optical spectroscopy for characterizing breast cancer.

A hand-held scanning probe based on broadband Diffuse Optical Spectroscopy (DOS) was used in combination with dynamic contrast enhanced MRI (DCE-MRI) to quantitatively characterize locally-advanced breast cancers in six patients. Measurements were performed sequentially using external fiducial markers for co-registration. Tumor patterns were categorized according to MRI morphological data, and 3D DCE-MRI slices were converted into a volumetric matrix with isotropic voxels to generate views that coincided with the DOS scanning plane. Tumor volume and depth at each DOS measurement site were determined, and a tissue optical index (TOI) that reflects both angiogenic and stromal characteristics was derived from broadband DOS data. In all six cases, optical scans showed significant TOI contrast corresponding to MRI morphological information. Sharp TOI peaks were recovered for well-circumscribed masses. A reduction in TOI was found inside a tumor with a necrotic center. A broadened peak was observed for a diffuse tumor pattern, and an inflammatory septal case provided two TOI peaks that correlated qualitatively with MRI enhancement. These results provide qualitative confirmation of the common signal origin and complementary information content that can be achieved by combining optical and MR imaging for breast cancer detection and clinical management.

Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy.

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are non-invasive diagnostic techniques that employ near-infrared (NIR) light to quantitatively characterize the optical properties of centimeter-thick, multiple-scattering tissues. Although NIR was first applied to breast diaphanography more than 70 years ago, quantitative optical methods employing time- or frequency-domain 'photon migration' technologies have only recently been used for breast imaging. Because their performance is not limited by mammographic density, optical methods can provide new insight regarding tissue functional changes associated with the appearance, progression, and treatment of breast cancer, particularly for younger women and high-risk subjects who may not benefit from conventional imaging methods. This paper reviews the principles of diffuse optics and describes the development of broadband DOS for quantitatively measuring the optical and physiological properties of thick tissues. Clinical results are shown highlighting the sensitivity of diffuse optics to malignant breast tumors in 12 pre-menopausal subjects ranging in age from 30 to 39 years and a patient undergoing neoadjuvant chemotherapy for locally advanced breast cancer. Significant contrast was observed between normal and tumor regions of tissue for deoxy-hemoglobin (p = 0.005), oxy-hemoglobin (p = 0.002), water (p = 0.014), and lipids (p = 0.0003). Tissue hemoglobin saturation was not found to be a reliable parameter for distinguishing between tumor and normal tissues. Optical data were converted into a tissue optical index that decreased 50% within 1 week in response to neoadjuvant chemotherapy. These results suggest a potential role for diffuse optics as a bedside monitoring tool that could aid the development of new strategies for individualized patient care.

Spatial variations in optical and physiological properties of healthy breast tissue.

Near-infrared (NIR) diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration (FDPM) instrument. Wavelength-dependent absorption and reduced scattering parameters (micro(a) and micro(s'), respectively) were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy-(HbO(2)) and deoxy-(Hb-R) hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal (PRE) women (20 to 30 microM) is approximately two-fold higher than for postmenopausal (POST) subjects at all positions. POST women have approximately 50% higher lipid content (50 to 60%) than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects (30 to 40%) than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration (THC), 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale (3 cm) changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for micro(a) and 5 to 12% for micro(s'). Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering (674 nm) within an individual.

Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study.

Presurgical chemotherapy is widely used in the treatment of locally advanced breast cancer. Monitoring the response to therapy can improve survival and reduce morbidity. We employ a noninvasive, near-infrared method based on diffuse optical spectroscopy (DOS) to quantitatively monitor tumor response to neoadjuvant chemotherapy. DOS was used to monitor tumor response in one patient with locally advanced breast cancer throughout the course of her therapy. Measurements were performed prior to doxorubicin-cyclophosphamide therapy and at several time points over the course of three treatment cycles (68 days). Our results show strong tumor to normal (T/N) tissue contrast in total hemoglobin concentration (T/N=2.4), water fraction (T/N=6.9), tissue hemoglobin oxygen saturation, S(t)O(2) (T/N=0.9), and lipid fraction (T/N=0.7) prior to treatment. Over a 10-week period, the peak total hemoglobin and water dropped 56 and 67%, respectively. Lipid content nearly returned to baseline (T/N =0.9) while S(t)O(2) exceeded pretreatment levels (T/N =1.5). Approximately half of the hemoglobin and water changes occurred within 5 days of treatment (26 and 37%, respectively). These data suggest that noninvasive, quantitative optical methods that characterize tumor physiology may be useful in assessing and optimizing individual response to neoadjuvant chemotherapy.