Additively manufactured plastic cartridges and low-cost optical reader system to successfully det... more Additively manufactured plastic cartridges and low-cost optical reader system to successfully detect the SARS-CoV-2 virus from saliva samples within 30 min.
Blood stream infections (BSIs) cause high mortality, and their rapid detection remains a signific... more Blood stream infections (BSIs) cause high mortality, and their rapid detection remains a significant diagnostic challenge. Timely and informed administration of antibiotics can significantly improve patient outcomes. However, blood culture, which takes up to 5 d for a negative result, followed by PCR remains the gold standard in diagnosing BSI. Here, we introduce a new approach to blood-based diagnostics where large blood volumes can be rapidly dried, resulting in inactivation of the inhibitory components in blood. Further thermal treatments then generate a physical microscale and nanoscale fluidic network inside the dried matrix to allow access to target nucleic acid. The amplification enzymes and primers initiate the reaction within the dried blood matrix through these networks, precluding any need for conventional nucleic acid purification. High heme background is confined to the solid phase, while amplicons are enriched in the clear supernatant (liquid phase), giving fluorescenc...
A 53-year-old male presented to the emergency room with chest pain, shortness of breath, and back... more A 53-year-old male presented to the emergency room with chest pain, shortness of breath, and back pain. He had recently recovered from COVID-19 infection and returned home on room air. Chest imaging showed bilateral hydropneumothoraces that were not present on the imaging performed during his prior admission three weeks ago. e patient was treated with bilateral chest tube drainage and oxygen support and responded well to treatment. is case represents a unique occurrence of spontaneous loculated bilateral hydropneumothoraces in the context of recent clinical recovery from COVID-19 infection requiring inpatient treatment. is case highlights the importance of an awareness of a potential sequela of COVID-19 that may occur even after presumed clinical recovery.
Additively manufactured plastic cartridges and low-cost optical reader system to successfully det... more Additively manufactured plastic cartridges and low-cost optical reader system to successfully detect the SARS-CoV-2 virus from saliva samples within 30 min.
Learning Objectives: Sepsis is a syndrome defined as a lifethreatening organ dysfunction caused b... more Learning Objectives: Sepsis is a syndrome defined as a lifethreatening organ dysfunction caused by a dysregulated host response triggered by an infection. To date, numerous clinical studies have captured aspects of the host response by measuring biomarkers pertinent to sepsis. Historically, the aim of these studies has been to demonstrate potential diagnostic/prognostic value of a set of biomarkers as opposed to specifically characterizing the degree of dysregulation of the host response. In our study, we sought to quantify the degree of dysregulation of the host response in a clinically relevant population in an intuitive and unbiased manner. Methods: We specifically hypothesized that a multi-dimensional measure of time-dependent abnormality could serve as a useful surrogate for quantifying dysregulation. In a cohort of 252 patients suspected of infection, we measured 4 biomarkers (IL-6, PCT, Pentraxin3, nCD64) spanning various aspects of the host response as a function of time per...
Sepsis, a potentially life-threatening complication of an infection, has the highest burden of de... more Sepsis, a potentially life-threatening complication of an infection, has the highest burden of death and medical expenses in hospitals worldwide. Leukocyte count and CD64 expression on neutrophils (nCD64) are known to correlate strongly with improved sensitivity and specificity of sepsis diagnosis at its onset. A major challenge is the lack of a rapid and accurate point-of-care (PoC) device that can perform these measurements from a minute blood sample. Here, we report a PoC microfluidic biochip to enumerate leukocytes and quantify nCD64 levels from 10 ml of whole blood without any manual processing. Biochip measurements have shown excellent correlation with the results from flow cytometer. In clinical studies, we have used PoC biochip to monitor leukocyte counts and nCD64 levels from patients' blood at different times of their stay in the hospital. Furthermore, we have shown the biochip's utility for improved sepsis diagnosis by combining these measurements with electronic medical record (EMR).
The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diag... more The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diagnostic platforms. Although several PCR-based techniques have been rapidly developed to meet the growing testing needs, such techniques often need samples collected through a swab, the use of RNA extraction kits, and expensive thermocyclers in order to successfully perform the test. Isothermal amplification-based approaches have also been recently demonstrated for rapid SARS-CoV-2 detection by minimizing sample preparation while also reducing the instrumentation and reaction complexity. There are limited reports of saliva as the sample source and some of these indicate inferior sensitivity when comparing RT-LAMP with PCR-based techniques. In this paper, we demonstrate an improved sensitivity assay to test saliva using a 2-step RT-LAMP assay, where a short 10-minute RT step is performed with only B3 and BIP primers before the final reaction. We show that while the 1-step RT-LAMP demonstrat...
The case highlights an unusual presentation of sweet’s syndrome in a previously healthy male. Acu... more The case highlights an unusual presentation of sweet’s syndrome in a previously healthy male. Acute febrile neutrophilic dermatosis (Sweet’s syndrome) is characterized by pyrexia, neutrophilia, and the abrupt appearance of erythematous, painful, cutaneous plaques, primarily on the upper extremities, head, and neck [1]. Histologically, the salient feature is a dense neutrophilic dermal infiltrate. Approximately 10 to 15 percent of published cases of Sweet’s syndrome occurred in patients with cancer [2]. Response to systemic steroids is dramatic in virtually all patients, regardless of the presence of malignancy [2].
WMJ : official publication of the State Medical Society of Wisconsin, 2019
Renal cell carcinoma is well-known for its propensity to present in unusual ways, and renal cell ... more Renal cell carcinoma is well-known for its propensity to present in unusual ways, and renal cell carcinoma presenting as pleural effusion is extremely rare. Pleural effusion secondary to renal cell carcinoma constitutes only about 1% to 2% of all malignant pleural effusions. We report the case of a 34-year-old man with no significant past medical or surgical history who presented in the Emergency Department with dyspnea. Chest x-ray demonstrated right-sided pleural effusion; computed tomography (CT) reported right-sided effusion in the pleura with suspicious mass in the upper border of left kidney. CT-guided pleural tap was performed and cytology was positive for vimentin and common acute lymphocytic leukemia antigen (CD10), leading to the diagnosis of primary renal cell carcinoma presenting as unilateral pleural effusion. While lungs are the common site of metastasis, the presentation of renal cell carcinoma as pleural effusion or pleural metastasis without lung involvement is rare.
Methods: The CFH diabetes team consisted of endocrinologists, a nurse practitioner, nurse diabete... more Methods: The CFH diabetes team consisted of endocrinologists, a nurse practitioner, nurse diabetes educators, and a registered dietitian providing coordinated diabetes management during a patient’s hospital admission. The team conducted a prospective, nine-month study of its impact on both hospital and ambulatory glycemic control for patients with a primary or secondary diagnosis of diabetes mellitus admitted to the Internal Medicine, Family Practice, and General Surgery services.
Paraneoplastic cerebellar degeneration is a rare neurological complication triggered by certain u... more Paraneoplastic cerebellar degeneration is a rare neurological complication triggered by certain underlying malignancies secondary to antibodies against cerebellar antigens. We describe the case of a 71-year-old female who presented with vertigo and ataxic gait. Initial imaging reported schwannoma, but it did not explain the reason for vertigo. Initial lab investigations and MRI Brain were unremarkable. Full body CT scan revealed a large heterogenous pelvic mass. Paraneoplastic panel was positive for anti-Yo antibodies. The patient underwent treatment for her ovarian cancer with surgery and chemotherapy. She had some improvement in her neurological symptoms.
The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diag... more The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diagnostics platforms. Although several polymerase chain reaction (PCR)-based techniques have been rapidly developed to meet the growing testing needs, such techniques often need samples collected through a swab, the use of RNA extraction kits, and expensive thermocyclers in order to successfully perform the test. Isothermal amplification-based approaches have also been recently demonstrated for rapid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by minimizing sample preparation while also reducing the instrumentation and reaction complexity. In addition, there are limited reports of saliva as the sample source, and some of these indicate inferior sensitivity when comparing reverse transcription loop-mediated isothermal amplification (RT-LAMP) with PCR-based techniques. In this paper, we demonstrate an improved sensitivity assay from saliva using a two-step RT-LAMP assay, where a short 10 min RT step is performed with only B3 and backward inner primers before the final reaction. We show that while the one-step RT-LAMP demonstrates satisfactory results, the optimized two-step approach allows detection of only few molecules per reaction and performs significantly better than the one-step RT-LAMP and conventional two-step RT-LAMP approaches with all primers included in the RT step. We show control measurements with RT-PCR, and importantly, we demonstrate RNA extraction-free RT-LAMP-based assays for detection of SARS-CoV-2 from viral transport media and saliva clinical samples.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Additively manufactured plastic cartridges and low-cost optical reader system to successfully det... more Additively manufactured plastic cartridges and low-cost optical reader system to successfully detect the SARS-CoV-2 virus from saliva samples within 30 min.
Blood stream infections (BSIs) cause high mortality, and their rapid detection remains a signific... more Blood stream infections (BSIs) cause high mortality, and their rapid detection remains a significant diagnostic challenge. Timely and informed administration of antibiotics can significantly improve patient outcomes. However, blood culture, which takes up to 5 d for a negative result, followed by PCR remains the gold standard in diagnosing BSI. Here, we introduce a new approach to blood-based diagnostics where large blood volumes can be rapidly dried, resulting in inactivation of the inhibitory components in blood. Further thermal treatments then generate a physical microscale and nanoscale fluidic network inside the dried matrix to allow access to target nucleic acid. The amplification enzymes and primers initiate the reaction within the dried blood matrix through these networks, precluding any need for conventional nucleic acid purification. High heme background is confined to the solid phase, while amplicons are enriched in the clear supernatant (liquid phase), giving fluorescenc...
A 53-year-old male presented to the emergency room with chest pain, shortness of breath, and back... more A 53-year-old male presented to the emergency room with chest pain, shortness of breath, and back pain. He had recently recovered from COVID-19 infection and returned home on room air. Chest imaging showed bilateral hydropneumothoraces that were not present on the imaging performed during his prior admission three weeks ago. e patient was treated with bilateral chest tube drainage and oxygen support and responded well to treatment. is case represents a unique occurrence of spontaneous loculated bilateral hydropneumothoraces in the context of recent clinical recovery from COVID-19 infection requiring inpatient treatment. is case highlights the importance of an awareness of a potential sequela of COVID-19 that may occur even after presumed clinical recovery.
Additively manufactured plastic cartridges and low-cost optical reader system to successfully det... more Additively manufactured plastic cartridges and low-cost optical reader system to successfully detect the SARS-CoV-2 virus from saliva samples within 30 min.
Learning Objectives: Sepsis is a syndrome defined as a lifethreatening organ dysfunction caused b... more Learning Objectives: Sepsis is a syndrome defined as a lifethreatening organ dysfunction caused by a dysregulated host response triggered by an infection. To date, numerous clinical studies have captured aspects of the host response by measuring biomarkers pertinent to sepsis. Historically, the aim of these studies has been to demonstrate potential diagnostic/prognostic value of a set of biomarkers as opposed to specifically characterizing the degree of dysregulation of the host response. In our study, we sought to quantify the degree of dysregulation of the host response in a clinically relevant population in an intuitive and unbiased manner. Methods: We specifically hypothesized that a multi-dimensional measure of time-dependent abnormality could serve as a useful surrogate for quantifying dysregulation. In a cohort of 252 patients suspected of infection, we measured 4 biomarkers (IL-6, PCT, Pentraxin3, nCD64) spanning various aspects of the host response as a function of time per...
Sepsis, a potentially life-threatening complication of an infection, has the highest burden of de... more Sepsis, a potentially life-threatening complication of an infection, has the highest burden of death and medical expenses in hospitals worldwide. Leukocyte count and CD64 expression on neutrophils (nCD64) are known to correlate strongly with improved sensitivity and specificity of sepsis diagnosis at its onset. A major challenge is the lack of a rapid and accurate point-of-care (PoC) device that can perform these measurements from a minute blood sample. Here, we report a PoC microfluidic biochip to enumerate leukocytes and quantify nCD64 levels from 10 ml of whole blood without any manual processing. Biochip measurements have shown excellent correlation with the results from flow cytometer. In clinical studies, we have used PoC biochip to monitor leukocyte counts and nCD64 levels from patients' blood at different times of their stay in the hospital. Furthermore, we have shown the biochip's utility for improved sepsis diagnosis by combining these measurements with electronic medical record (EMR).
The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diag... more The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diagnostic platforms. Although several PCR-based techniques have been rapidly developed to meet the growing testing needs, such techniques often need samples collected through a swab, the use of RNA extraction kits, and expensive thermocyclers in order to successfully perform the test. Isothermal amplification-based approaches have also been recently demonstrated for rapid SARS-CoV-2 detection by minimizing sample preparation while also reducing the instrumentation and reaction complexity. There are limited reports of saliva as the sample source and some of these indicate inferior sensitivity when comparing RT-LAMP with PCR-based techniques. In this paper, we demonstrate an improved sensitivity assay to test saliva using a 2-step RT-LAMP assay, where a short 10-minute RT step is performed with only B3 and BIP primers before the final reaction. We show that while the 1-step RT-LAMP demonstrat...
The case highlights an unusual presentation of sweet’s syndrome in a previously healthy male. Acu... more The case highlights an unusual presentation of sweet’s syndrome in a previously healthy male. Acute febrile neutrophilic dermatosis (Sweet’s syndrome) is characterized by pyrexia, neutrophilia, and the abrupt appearance of erythematous, painful, cutaneous plaques, primarily on the upper extremities, head, and neck [1]. Histologically, the salient feature is a dense neutrophilic dermal infiltrate. Approximately 10 to 15 percent of published cases of Sweet’s syndrome occurred in patients with cancer [2]. Response to systemic steroids is dramatic in virtually all patients, regardless of the presence of malignancy [2].
WMJ : official publication of the State Medical Society of Wisconsin, 2019
Renal cell carcinoma is well-known for its propensity to present in unusual ways, and renal cell ... more Renal cell carcinoma is well-known for its propensity to present in unusual ways, and renal cell carcinoma presenting as pleural effusion is extremely rare. Pleural effusion secondary to renal cell carcinoma constitutes only about 1% to 2% of all malignant pleural effusions. We report the case of a 34-year-old man with no significant past medical or surgical history who presented in the Emergency Department with dyspnea. Chest x-ray demonstrated right-sided pleural effusion; computed tomography (CT) reported right-sided effusion in the pleura with suspicious mass in the upper border of left kidney. CT-guided pleural tap was performed and cytology was positive for vimentin and common acute lymphocytic leukemia antigen (CD10), leading to the diagnosis of primary renal cell carcinoma presenting as unilateral pleural effusion. While lungs are the common site of metastasis, the presentation of renal cell carcinoma as pleural effusion or pleural metastasis without lung involvement is rare.
Methods: The CFH diabetes team consisted of endocrinologists, a nurse practitioner, nurse diabete... more Methods: The CFH diabetes team consisted of endocrinologists, a nurse practitioner, nurse diabetes educators, and a registered dietitian providing coordinated diabetes management during a patient’s hospital admission. The team conducted a prospective, nine-month study of its impact on both hospital and ambulatory glycemic control for patients with a primary or secondary diagnosis of diabetes mellitus admitted to the Internal Medicine, Family Practice, and General Surgery services.
Paraneoplastic cerebellar degeneration is a rare neurological complication triggered by certain u... more Paraneoplastic cerebellar degeneration is a rare neurological complication triggered by certain underlying malignancies secondary to antibodies against cerebellar antigens. We describe the case of a 71-year-old female who presented with vertigo and ataxic gait. Initial imaging reported schwannoma, but it did not explain the reason for vertigo. Initial lab investigations and MRI Brain were unremarkable. Full body CT scan revealed a large heterogenous pelvic mass. Paraneoplastic panel was positive for anti-Yo antibodies. The patient underwent treatment for her ovarian cancer with surgery and chemotherapy. She had some improvement in her neurological symptoms.
The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diag... more The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diagnostics platforms. Although several polymerase chain reaction (PCR)-based techniques have been rapidly developed to meet the growing testing needs, such techniques often need samples collected through a swab, the use of RNA extraction kits, and expensive thermocyclers in order to successfully perform the test. Isothermal amplification-based approaches have also been recently demonstrated for rapid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by minimizing sample preparation while also reducing the instrumentation and reaction complexity. In addition, there are limited reports of saliva as the sample source, and some of these indicate inferior sensitivity when comparing reverse transcription loop-mediated isothermal amplification (RT-LAMP) with PCR-based techniques. In this paper, we demonstrate an improved sensitivity assay from saliva using a two-step RT-LAMP assay, where a short 10 min RT step is performed with only B3 and backward inner primers before the final reaction. We show that while the one-step RT-LAMP demonstrates satisfactory results, the optimized two-step approach allows detection of only few molecules per reaction and performs significantly better than the one-step RT-LAMP and conventional two-step RT-LAMP approaches with all primers included in the RT step. We show control measurements with RT-PCR, and importantly, we demonstrate RNA extraction-free RT-LAMP-based assays for detection of SARS-CoV-2 from viral transport media and saliva clinical samples.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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