A novel infrasound and audible machine-learning approach to the diagnosis of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) outbreak has rapidly spread around the world, causing a global public health and economic crisis. A critical limitation in detecting COVID-19-related pneumonia is that it is often manifested as a "silent pneumonia", i.e. pulmonary auscultation that sounds "normal" using a standard stethoscope. Chest computed tomography is the gold standard for detecting COVID-19 pneumonia; however, radiation exposure, availability and cost preclude its utilisation as a screening tool for COVID-19 pneumonia. In this study we hypothesised that COVID-19 pneumonia, "silent" to the human ear using a standard stethoscope, is detectable using a full-spectrum auscultation device that contains a machine-learning analysis. Methods: Lung sound signals were acquired, using a novel full-spectrum (3-2000 Hz) stethoscope, from 164 COVID-19 pneumonia patients, 61 non-COVID-19 pneumonia patients and 141 healthy subjects. A machine-learning classifier was constructed and the data were classified into three groups: 1) normal lung sounds, 2) COVID-19 pneumonia and 3) non-COVID-19 pneumonia. Results: Standard auscultation found that 72% of the non-COVID-19 pneumonia patients had abnormal lung sounds compared with only 25% of the COVID-19 pneumonia patients. The classifier's sensitivity and specificity for the detection of COVID-19 pneumonia were 97% and 93%, respectively, when analysing the sound and infrasound data, and they were reduced to 93% and 80%, respectively, without the infrasound data (p<0.01 difference in receiver operating characteristic curves with and without infrasound). Conclusions: This study reveals that useful clinical information exists in the infrasound spectrum of COVID-19-related pneumonia and machine-learning analysis applied to the full spectrum of lung sounds is useful in its detection.

A comparison of the power of breathing sounds signals acquired with a smart stethoscope from a cohort of COVID-19 patients at peak disease, and pre-discharge from the hospital.

Objectives: To characterize the frequencies of breathing sounds signals (BS) in COVID-19 patients at peak disease and pre-discharge from hospitalization using a Smart stethoscope. Methods: Prospective cohort study conducted during the first COVID-19 wave (April-August 2020) in Israel. COVID-19 patients (n = 19) were validated by SARS-Cov-2 PCR test. The healthy control group was composed of 153 volunteers who stated that they were healthy. Power of BS was calculated in the frequency ranges of 0-20, 0-200, and 0-2000 Hz. Results: The power calculated over frequency ranges 0-20, 20-200, and 200-2000 Hz contributed approximately 45%, 45%, and 10% to the total power calculated over the range 0-2000 Hz, respectively. Total power calculated from the right side of the back showed an increase of 45-80% during peak disease compared with the healthy controls (p < 0.05). The power calculated over the back, in the infrasound range, 0-20 Hz, and not in the 20-2000 Hz range, was greater for the healthy controls than for patients. Using all 3 ranges of frequencies for distinguishing peak disease from healthy controls resulted in sensitivity and specificity of 84% and 91%, respectively. Omitting the 0-20 Hz range resulted in sensitivity and specificity of 74% and 67%, respectively. Discussion: The BS power acquired from COVID-19 patients at peak disease was significantly greater than that at pre-discharge from the hospital. The infrasound range had a significant contribution to the total power. Although the source of the infrasound is not presently clear, it may serve as an automated diagnostic tool when more clinical experience is gained with this method.

Candida Bloodstream Infection, a Dire Complication in Hospitalized COVID-19 Patients: Three Cases from a Single Center in Northern Israel.

BACKGROUND: Patients with severe coronavirus disease-2019 (COVID-19) are susceptible to superimposed infections. OBJECTIVES: To describe COVID-19 patients who presented with complications due to Candida bloodstream co-infection (candidemia) and their outcome in a single center in northern Israel (Emek Medical Center) during the second outbreak of COVID-19 in Israel (15 June 2020 to 20 September 2020). METHODS: A retrospective study of COVID-19 patients presenting with candidemia was conducted, including clinical and laboratory data. The incidence of candidemia among hospitalized COVID-19 patients was compared to a historical cohort of non-COVID-19 controls. RESULTS: Three COVID-19 patients complicated with candidemia were documented. All three patients died shortly after the detection of candidemia. Three different Candida sp. were isolated from the blood cultures: C. albicans, C. parapsilosis, and C. glabrata. The incidence of candidemia among COVID-19 patients was 0.679 episodes per 1000 hospital days. CONCLUSIONS: Our small sample suggests a much higher incidence of candidemia among COVID-19 patients compared to a historical cohort of non-COVID-19 controls. All clinicians treating COVID-19 patients in GICU should be aware of this complication.

Diplopia from abducens nerve paresis as a presenting symptom of COVID-19: a case report and review of literature.

Neurological manifestations of novel coronavirus disease 3019 (COVID-19) remain unclear. We report the case of a 44-year-old febrile man who presented with double vision and headache 2 d after initial symptoms of fatigue, generalized muscle weakness, and loss of appetite. He was subsequently diagnosed with COVID-19 and transient abducens nerve paresis. He did not present with any respiratory symptoms or additional specific neurological findings. We recommend that with the rising number of cases across the world, physicians develop a greater index of suspicion for COVID-19 in patients with cranial neuropathies, even in those with mild disease without typical respiratory symptoms.

Severe hypercalcemia in a patient with chronic lymphocytic leukemia and non-small cell lung carcinoma: A case report.

RATIONALE: Hypercalcemia is a common finding in patients with advanced-stage cancers. Paraneoplastic hypercalcemia is commonly associated with dismal prognoses, with survival rates of about 3 months. In this paper, we report on a patient with advanced chronic lymphocytic leukemia and non-small cell lung carcinoma who developed severe hypercalcemia and discuss the diagnosis and treatment of this metabolic complication. PATIENT CONCERNS: A 56-year old male with a 2-year history of Rai stage IV chronic lymphocytic leukemia presented with life-threatening hypercalcemia. Positron emission tomography/computed tomography revealed a suspicious lung lesion. A transbronchial biopsy was performed from the upper left lobe. Due to the small size of the specimen, immunohistochemical markers were performed and revealed positive staining for cytokeratin 7 and negative for TTF-1, napsin A and p 40, which were consistent with non-small cell lung carcinoma. DIAGNOSIS: Humoral hypercalcemia of malignancy was diagnosed. INTERVENTION: The patient was treated with saline infusion, calcitonin, intravenous pamidronate, followed with denosumab. OUTCOMES: The hypercalcemia was successfully treated and the patient's calcium levels returned to normal. Further evaluation revealed a non-small cell lung carcinoma as a second primary malignancy. The patient was treated with venetoclax for his refractory CLL and received chemotherapy and immunotherapy for lung adenocarcinoma. Several days after starting venetoclax, he developed Legionella pneumonia and short time after the second course of chemotherapy, a severe sepsis occurred and he passed away. LESSONS: Coexistence of 2 unrelated malignancies, whichever could be a reason for hypercalcemia of malignancy is a rare event. Severe hypercalcemia, which is possible but rare feature of CLL should be a reason for further prompt evaluation.

The Hyper-Inflammatory Response in Adults with Severe COVID-19 Pneumonia Differs from the Cytokine Storm of Hemophagocytic Syndrome.

BACKGROUND: In this review we described the values of commonly available HScore laboratory markers in patients with coronavirus-19 (COVID-19)-pneumonia associated cytokine storm syndrome (CPN-CSS) and compared results with those of other forms cytokine storm syndrome (O-CSS) to determine a pattern for CPN-CSS. Twelve CPN-CSS studies and six O-CSS studies were included. CPN-CSS typically obtained a single HScore value (e.g., aspartate transaminase > 30 U/L) while failing all other HScore criteria. A typical pattern for CPN-CSS was revealed when compared to O-CSS: lymphopenia vs. pancytopenia and increased vs. decreased fibrinogen. Findings, other than HScore commonly found in CPN-CSS studies, showed elevated lactate dehydrogenase, D-dimer, and C-reactive protein. Although CPN-CSS studies describe severely ill patients, the HScore markers are typically less toxic that O-CSS.

Sodium glucose cotransporter2 inhibitor-possible treatment for patients with diabetes, pulmonary disease and CO2 retention.

Chronic pulmonary diseases such as chronic obstructive pulmonary disease, obstructive sleep apnea and obesity hypoventilation syndrome are common conditions which share decreased pulmonary ventilation and CO2 retention. CO2 is an end-product of metabolism of all body cells. When CO2 accumulates, it is recommended to consider measures to reduce its endogenous production. One such measure relates to the sources of energy ingested as nutrition. It is recommended to increase the intake of dietary lipids and reduce carbohydrates, as the former produces less endogenous CO2 when metabolized. Our hypothesis focuses on a different mechanism for reducing the availability of carbohydrates, especially glucose, as a fuel for body cells metabolism. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of oral anti-hyperglycemic agents. Physiologically, glucose filtered through kidney glomeruli is reabsorbed in the proximal convoluted tubule; SGLT2i inhibit this mechanism. Therefore, glucose is secreted in the urine (glucosuria) and as a result glucose serum level is reduced. If glucose serum level is reduced, less glucose is available for metabolism, less CO2 is endogenously produced, and less CO2 must be expelled from the diseased lungs. It is hypothesized that these agents may be beneficial for patients with diabetes and concomitant pulmonary disease who retain CO2.

Beta-blockers in non-surgical patients with type A aortic dissection.

Type A aortic dissection (TAAD) is a catastrophic condition with 24-48% mortality during the first day, if patients are not surgically treated. Due to old age and associated co-morbidities surgeons may be reluctant to operate and patients are administered medical therapy for the end of reducing systolic blood pressure and heart rate. Beta-blockers (BB) are the "medications of choice". Based on physical and physiological considerations, it was hypothesized that BB may actually exacerbate TAAD.

Rare clinical manifestation of community-acquired pneumonia.

A 71-year-old patient was admitted due to fever and persistent (>48 hours) hiccups. History and physical examination were not instructive. Lab tests were not specific, showing an inflammatory response. Chest film did not demonstrate opacities. The patient was treated with chlorpromazine with no relief. Fever and hiccups persisted, and therefore neck and chest CT was performed revealing a right lower lobe infiltrate, a finding consistent with pneumonia. Antibiotics were initiated and within 48 hours fever and hiccups resolved and patient recovered. Although hiccups are rarely described as a clinical manifestation of community acquired pneumonia, one should consider this diagnosis in a patient with unexplained fever.

A novel system for continuous, real-time monitoring of heart motion signals.

BACKGROUND: Understanding cardiac mechanics is important for developing cardiac therapies. Current modalities for assessing cardiac mechanics sample patient's heart at specific heart rate, contractility, preload, and afterload. The objective of this study was to test the feasibility of a novel system composed of intra-cardiac leads equipped with an inertial module chip (3D accelerometers and 3D gyroscopes) in monitoring continuous heart motion. METHODS: In this descriptive study, four healthy pigs were anesthetized and instrumented with motion-sensitive intra-cardiac leads; the temporal correlation between signals from motion sensors and tissue Doppler from the chest wall were studied; changes in real-time heart accelerations (ACC) and angular velocity (ANGV) were reported as percentages of change from baseline. RESULTS: Heart motion signals were sensed continuously from the right ventricular apex (RVa) and coronary sinus (CS). Volume expansion did not produce significant changes in the ACC and ANGV signals. Increasing heart rate increased the peak systolic ACC signal recorded from RVa and CS by 94 and 76%, respectively, and increased both peak systolic (61% RVa and 27% CS) and diastolic ANGV (200% CS vs. 31% RVa). Epinephrine administration increased peak systolic ACC signals at both sites (246% RVa; 331% CS). Peak systolic and diastolic ANGV increased in response to epinephrine (systolic: 198% RVa and 175% CS; diastolic: 723% CS and 89% RVa) (p = 0.125 for all changes expressed in percent). Temporal correlation between the ANGV signal and tissue Doppler signal was detected throughout all interventions. CONCLUSIONS: A novel system for continuously monitoring heart motion signals from within the heart was presented. Heart motion signals in response to physiologic manipulations were characterized.

Speckle tracking technology for quantifying lung sliding.

Ultrasound (US) is gaining recognition as a useful tool for assessing lung physiology and pathology. Yet, currently the skill of performing lung US is taught by experienced operators to novice ones, mainly by recognizing expected patterns. Recognizing the latter may be difficult and subjective. In this hypothesis we propose to apply a well-known and used image processing technology in echocardiography, speckle tracking (ST), to lung sliding - the marker of normal lung function. If implementing ST to lung sliding is technically feasible, several outcomes are expected: (1) Lung sliding will become an objective, operator-independent marker of normal lung function. (2) Subsequently, ST will provide normal values for lung sliding. (3) Lastly, the effects of pulmonary pathologies on lung sliding may be assessed. It is stressed, however, that the preliminary idea suggested here is limited to a single physiological phenomenon (lung sliding). Only when technical feasibility is demonstrated then ST technology may potentially be applied and investigated in other clinical settings of lung diseases.

Transition from sinus rhythm to atrial fibrillation - a mechanism inducing or delaying pulmonary congestion and edema.

Cardiogenic pulmonary edema (PEd) is a life-threatening condition where fluid accumulates in the lungs due to increasing hydrostatic pressure building up in the pulmonary vasculature (PV): veins, venules and capillaries. Atrial fibrillation (AF) is accepted as an arrhythmia which triggers and promotes the pathophysiological processes leading to pulmonary congestion and its final expression: PEd. We propose a different view, where AF is actually a physiological solution temporarily protecting from PEd. We hypothesize that the compliance of the left atrium (LA) increases with the onset of AF. Thus, it is possible that even if the volume of blood within the LA increases due to loss of atrial contraction, the pressure within the LA would still be lower than that prior to AF (because of the increased LA compliance during AF). Decreased LA pressure allows more blood to flow from the PV to the LA, abating the hydrostatic pressure buildup in the PV compartment. The ratio, R, between the LA volume gained from the transition to AF provided by the greater LA compliance, and the volume of blood retained in the LA due to loss of atrial contraction, determines the instant pressure in the LA, as AF begins. If R is >1, then the LA pressure will instantly decrease with the transition to AF and this may be beneficial in delaying PEd.

Two-slope ascending arm of the early trans-mitral flow velocity Doppler wave in patients with heart failure and preserved ejection fraction.

Trans-mitral flow velocity (TMFV) examination is a standard echocardiographic measure for assessing diastolic function of the heart. Typically, the Doppler signal representing the early rapid filling phase of the left ventricle (LV), termed: E wave, is triangular. The ascending arm of the E wave (EWAA) represents blood accelerating into the LV from the left atrium (LA), whereas the descending arm reflects blood decelerating as the LV fills and resists further filling. The slope of EWAA is linear, starting at TMFV of zero cm/s (prior to mitral valve opening) and building to peak E wave value. The physical meaning of a single slope is that blood acceleration is constant with time. Little data exist regarding the significance of the shape of EWAA. It is hypothesized that in heart failure with preserved ejection fraction (HFPEF) the EWAA displays 2 slopes. A first steeper slope followed by a second less steep slope reaching peak E wave. The different slopes represent a change in the composition of driving forces propelling blood from LA to LV. It is hypothesized that the first steeper slope of EWAA represents a set of driving force including a force termed: diastolic suction, whereas in the second slope diastolic suction has already dissipated. This 2-slope phenomenon is not expected in healthy subjects because the assumed underlying mechanism is not operative.