Flea-Borne Typhus as a COVID-19 Mimic: A Report of Four Cases.

Flea-borne typhus (FBT), due to Rickettsia typhi and R. felis, is an infection causing fever, headache, rash, hepatitis, thrombocytopenia, and diverse organ manifestations. Cough occurs in about 30% of patients with FBT, and chest X-ray abnormalities are seen in 17%. Severe pulmonary manifestations have also been reported in FBT, including adult respiratory distress syndrome and pulmonary embolism. Because of these pulmonary manifestations, FBT can mimic Coronavirus Illness 2019 (COVID-19), a febrile illness with prominent respiratory involvement. Flea-borne typhus and COVID-19 may also have similar laboratory abnormalities, including elevated ferritin, C-reactive protein, and D-dimer. However, elevated transaminase levels, rash, and thrombocytopenia are more common in FBT. Herein, we present four cases of patients with FBT who were initially suspected to have COVID-19. These cases illustrate the problem of availability bias, in which the clinician thinks a particular common condition (COVID-19 in this case) is more prevalent than it actually is.

Flea-Borne Typhus Causing Hemophagocytic Lymphohistiocytosis: An Autopsy Case.

Infection with members of the order Rickettsiales (the genera Rickettsia, Anaplasma, Orientia, and Ehrlichia) is known to cause hemophagocytic lymphohistiocytosis (HLH). The literature is scant on flea-borne typhus (FBT) being implicated in this process. We present a case of autopsy-proven HLH caused by FBT in a 71-year-old diabetic female who was initially suspected of having diabetic ketoacidosis who rapidly suffered decompensated multi-organ failure. Although she was suspected of having FBT and HLH pre-mortem, due to her rapid progression to multi-organ failure, she was transitioned to comfort care by her family five days after admission. A literature search yielded five other cases of HLH secondary to FBT, which are analyzed in this review. The literature on HLH occurring with infection due to other members of the order Rickettsiales is also surveyed.

Angiotensin II Use in Treatment of Refractory Shock Due to Benazepril and Amlodipine Toxic Ingestion.

INTRODUCTION: Calcium channel blockers (CCB) are a leading cause of ingestion-associated fatality. Angiotensin-converting enzyme inhibitor (ACEi) overdose as part of co-ingestion is common and associated with refractory shock. Treatment options to manage this profound vasoplegia are limited. We describe the first case of use of newly formulated Angiotensin II for treatment of severe ACEi and CCB poisoning. CASE REPORT: A 57-year-old man presented after suicide attempt by ingesting 20 tablets each of amlodipine 10 mg and benazepril 20 mg. His hypotension was initially managed with 35 mL/kg of crystalloid, norepinephrine, and hyperinsulinemic euglycemic therapy (HIET). His hemodynamics further deteriorated, and he developed lactic acidosis, electrolyte derangements, and renal dysfunction. Further complications of his ingestion included cardiac arrest, subsequent requirement for emergency cricothyrotomy, and renal replacement therapy. Maximal hemodynamic support with HIET therapy insulin drip 4.4 units/kg/hour, norepinephrine 2 mcg/kg/min, epinephrine 1 mcg/kg/min, vasopressin .06 units/hour, and intravenous lipid emulsion was unsuccessful. Ang II was started and titrated to maximal doses with dramatic improvement in hemodynamics. Within hours of starting Ang II, epinephrine was stopped and norepinephrine decreased by 50%. He was downgraded from the intensive care unit without any ongoing end-organ dysfunction. DISCUSSION: Isolated CCB overdoses have high complication rates and well-established treatments. Therefore, management of CCB and ACEi co-ingestion is typically driven by CCB poisoning algorithm. There are multiple reports of CCB and ACEi co-ingestions causing treatment-refractory shock. Therapeutic options are limited by toxicities and availability of salvage therapies. Ang II is a safe and highly effective option to manage these patients.

Streptococcus pyogenes NAD+-Glycohydrolase Reduces Skeletal Muscle ßNAD+ Levels Independently of Streptolysin O.

Necrotizing soft tissue infections caused by Streptococcus pyogenes (group A streptococcus [GAS]) are characterized by rapid and extensive necrosis of fascia and muscle. Molecular epidemiological studies have demonstrated a positive correlation between GAS isolates that cause invasive infections and the production of S. pyogenes NAD+-glycohydrolase (SPN), an NADase secreted by GAS, but the effect of SPN on muscle cells has not been described. Thus, using standard ßNAD+ and ATP quantification assays, we investigated the effects of SPN on cultured human skeletal muscle cell (SkMC) ßNAD+ and ATP with and without streptolysin O (SLO)-a secreted cholesterol-dependent cytolysin known to act synergistically with SPN. We found that culture supernatants from GAS strains producing SLO and SPN depleted intracellular ßNAD+ and ATP, while exotoxins from a GAS strain producing SLO and an enzymatically-inactive form of SPN had no effect on ßNAD+ or ATP. Addition of purified, enzymatically-active SPN to NADase-negative culture supernatants or sterile media reconstituted ßNAD+ depletion but had no effect ATP levels. Further, SPN-mediated ßNAD+ depletion could be augmented by SLO or the homologous cholesterol-dependent cytolysin, perfringolysin O (PFO). Remarkably, SPN-mediated ßNAD+ depletion was SkMC-specific, as purified SPN had minimal effect on epithelial cell ßNAD+. Taken together, this study identifies a previously unrecognized role for SPN as a major disruptor of skeletal muscle ßNAD+. Such activity could contribute to the rapid and widespread myonecrosis characteristic of severe GAS soft tissue infections.

Comparison of four handheld point-of-care ultrasound devices by expert users.

BACKGROUND: Point-of-care ultrasound (POCUS) is rapidly becoming ubiquitous across healthcare specialties. This is due to several factors including its portability, immediacy of results to guide clinical decision-making, and lack of radiation exposure to patients. The recent growth of handheld ultrasound devices has improved access to ultrasound for many clinicians. Few studies have directly compared different handheld ultrasound devices among themselves or to cart-based ultrasound machines. We conducted a prospective observational study comparing four common handheld ultrasound devices for ease of use, image quality, and overall satisfaction. Twenty-four POCUS experts utilized four handheld devices (Butterfly iQ+™ by Butterfly Network Inc., Kosmos™ by EchoNous, Vscan Air™ by General Electric, and Lumify™ by Philips Healthcare) to obtain three ultrasound views on the same standardized patients using high- and low-frequency probes. RESULTS: Data were collected from 24 POCUS experts using all 4 handheld devices. No single ultrasound device was superior in all categories. For overall ease of use, the Vscan Air™ was rated highest, followed by the Lumify™. For overall image quality, Lumify™ was rated highest, followed by Kosmos™. The Lumify™ device was rated highest for overall satisfaction, while the Vscan Air™ was rated as the most likely to be purchased personally and carried in one's coat pocket. The top 5 characteristics of handheld ultrasound devices rated as being "very important" were image quality, ease of use, portability, total costs, and availability of different probes. CONCLUSIONS: In a comparison of four common handheld ultrasound devices in the United States, no single handheld ultrasound device was perceived to have all desired characteristics. POCUS experts rated the Lumify™ highest for image quality and Vscan Air™ highest for ease of use. Overall satisfaction was highest with the Lumify™ device, while the most likely to be purchased as a pocket device was the Vscan Air™. Image quality was felt to be the most important characteristic in evaluating handheld ultrasound devices.

Developing and Testing a Protocol for Managing Cardiopulmonary Resuscitation of Patients with Suspected or Confirmed COVID-19: In Situ Simulation Study.

BACKGROUND: Resuscitating patients with suspected or confirmed COVID-19 imposes unique challenges to organizations and code blue teams. Studies that applied the American Heart Association (AHA) COVID-19-related Interim Resuscitation Guideline and similar European guidelines are scarce. OBJECTIVE: This study aimed to develop and test a cardiopulmonary resuscitation protocol based on the AHA COVID-19-related Interim Resuscitation Guideline. METHODS: The study was conducted as an in situ simulation in a medical intensive care unit. The COVID-19 cardiopulmonary resuscitation protocol was created and validated by 11 health care team members and tested using 4 simulation sessions where 46 code blue team members participated. During the simulation, we observed role clarity, the effectiveness of communication, team dynamics, infection control measures, and the availability of essential supplies and equipment. RESULTS: The main issues identified in each simulation session were debriefed to the code blue teams and used to further revise the protocol. These include the assignment of tasks, availability of equipment and supplies, and failure of communication between the in-room and out-of-room teams. Solutions included changes in the placement of team members and roles and responsibilities; the creation of an isolation code medication package, a respiratory therapy kit, and an isolation code blue bag; and the use of two-way radios and N-95 masks with eye goggles to enhance communication between the teams. CONCLUSIONS: This study shed light on the challenges to implement the AHA COVID-19-related Interim Resuscitation Guideline. The in situ simulation was an effective approach for rapid training, identifying unreliable equipment and ineffective and inefficient workflow, and managing the complexity of the physical environment.

Parinaud's Oculoglandular Syndrome: A Case in an Adult with Flea-Borne Typhus and a Review.

Parinaud's oculoglandular syndrome (POGS) is defined as unilateral granulomatous conjunctivitis and facial lymphadenopathy. The aims of the current study are to describe a case of POGS with uveitis due to flea-borne typhus (FBT) and to present a diagnostic and therapeutic approach to POGS. The patient, a 38-year old man, presented with persistent unilateral eye pain, fever, rash, preauricular and submandibular lymphadenopathy, and laboratory findings of FBT: hyponatremia, elevated transaminase and lactate dehydrogenase levels, thrombocytopenia, and hypoalbuminemia. His condition rapidly improved after starting doxycycline. Soon after hospitalization, he was diagnosed with uveitis, which responded to topical prednisolone. To derive a diagnostic and empiric therapeutic approach to POGS, we reviewed the cases of POGS from its various causes since 1976 to discern epidemiologic clues and determine successful diagnostic techniques and therapies; we found multiple cases due to cat scratch disease (CSD; due to Bartonella henselae) (twelve), tularemia (ten), sporotrichosis (three), Rickettsia conorii (three), R. typhi/felis (two), and herpes simplex virus (two) and single cases due to tuberculosis, paracoccidioidomycosis, Yersinia enterocolitica, Pasteurella multocida, Chlamydia trachomatis, Epstein-Barr virus, and Nocardia brasiliensis. Preauricular lymphadenopathy is a common clinical clue for POGS and is unusual in viral and bacterial conjunctivitis. For POGS, the major etiological consideration is B. henselae, which is usually diagnosed by the indirect immunofluorescence serologic technique. Although CSD POGS is usually self-limited, oral azithromycin may hasten resolution. However, other possible etiologies of POGS may also arise from cat or cat flea contact: sporotrichosis, tularemia, Pasteurella multocida, or FBT. If there is no cat contact, other epidemiologic and clinical findings should be sought, because several of these conditions, such as tularemia, paracoccidioidomycosis, and tuberculosis, may have grave systemic complications. Although there are usually no long-term ocular sequelae if POGS is properly diagnosed, it still may cause prolonged ocular discomfort and require multiple physician contacts.

Enrichment of Antigen-Specific Class-Switched B Cells from Individuals Naturally Immunized by Infection with Group A Streptococcus.

The low frequency of circulating antigen-specific memory B cells is a considerable obstacle in the discovery and development of human monoclonal antibodies for therapeutic application. Here, we evaluate two solid-phase isolation methods to enrich the number of antigen-specific B cells from individuals naturally immunized against streptolysin O (SLO), a key virulence factor and known immunogen of group A streptococcus (GAS). Class-switched B cells obtained from individuals with a history of GAS infection were separated from peripheral blood mononuclear cells (PBMCs) by immunomagnetic methods. SLO-specific B cells were further enriched directly by binding to SLO monomers and captured by streptavidin-coated magnetic microbeads or indirectly by binding a fluorescently labeled SLO-streptavidin tetramer and captured by anti-fluorophore immunomagnetic microbeads. SLO-bound B cells were quantitated by flow cytometry and/or expanded in batch culture to determine IgG specificity. From individuals who have suffered a GAS infection ≥2 years prior, only the direct method enriched SLO-specific B cells, as determined by flow cytometry. Likewise, in batch culture, B cells isolated by the direct method resulted in an average of 375-fold enrichment in anti-SLO IgG, while no enrichment was observed for B cells isolated by the indirect method. The direct method established here provides a simple approach to increase low-frequency antigen-specific B cell populations supporting many downstream applications, such as immortalization of B cells, cloning of immunoglobulin genes, or purification of antibodies from supernatant for future study. Overall, this process is efficient, is inexpensive, and can be applied to many naturally immunogenic antigens.IMPORTANCE Bacteria called group A streptococci can cause a variety of skin and soft tissue infections ranging from mild pharyngitis ("strep throat") to deadly necrotizing fasciitis (sometimes called "flesh-eating" disease). In each case, the development of disease and the degree of tissue damage are mediated by toxins released from the bacteria during infection. Consequently, novel therapies aimed at clearing bacterial toxins are greatly needed. One promising new treatment is the utilization of monoclonal antibodies delivered as an immunotherapeutic for toxin neutralization. However, current methods of antibody development are laborious and costly. Here, we report a method to enrich and increase the detection of highly desirable antigen-specific memory B cells from individuals previously exposed to GAS using a cost-effective and less-time-intensive strategy. We envision that this method will be incorporated into many applications supporting the development of immunotherapeutics.

Case Report: Early Doxycycline Therapy for Potential Rickettsiosis in Critically Ill Patients in Flea-Borne Typhus-Endemic Areas.

Flea-borne typhus (FBT), although usually perceived as a self-resolving febrile illness, actually encompasses a wide spectrum of disease severity, including fulminant sepsis with multi-organ failure. In endemic Texas and California, the incidence of FBT has more than doubled over the last decade. Clinicians remain unfamiliar with severe septic presentations of FBT when considering the etiologies of acute undifferentiated febrile syndromes. The diagnostic challenges of FBT include the nonspecific and variable nature of both history and physical examination and the lack of diagnostic testing that can provide clinically relevant information early in the course of infection. These barriers perpetuate misdiagnoses in critically ill patients and lead to delay in initiating appropriate antibiotics, which may contribute to preventable morbidity and mortality. This case series describes the clinical and diagnostic trajectories of three patients who developed FBT-associated multi-organ dysfunction. These patients achieved resolution of infection after receiving doxycycline in the context of a high clinical suspicion. Patients residing in FBT-endemic areas presenting with a febrile illness of unknown etiology with a suggestive constellation of hyponatremia, elevated transaminase levels, and thrombocytopenia should be suspected of having FBT. Clinicians should proceed to serologic testing with early doxycycline therapy for potential rickettsiosis. Familiarizing clinicians with the presentation of rickettsiosis-associated septic syndromes and its early and appropriate antibiotic treatment can provide lifesaving care and reduce health-care costs through prevention of the morbidity associated with FBT.

Staged Implementation of Awakening and Breathing, Coordination, Delirium Monitoring and Management, and Early Mobilization Bundle Improves Patient Outcomes and Reduces Hospital Costs.

OBJECTIVES: To measure the impact of staged implementation of full versus partial ABCDE bundle on mechanical ventilation duration, ICU and hospital lengths of stay, and cost. DESIGN: Prospective cohort study. SETTING: Two medical ICUs within Montefiore Healthcare Center (Bronx, NY). PATIENTS: One thousand eight hundred fifty-five mechanically ventilated patients admitted to ICUs between July 2011 and July 2014. INTERVENTIONS: At baseline, spontaneous (B)reathing trials (B) were ongoing in both ICUs; in period 1, (A)wakening and (D)elirium (AD) were implemented in both full and partial bundle ICUs; in period 2, (E)arly mobilization and structured bundle (C)oordination (EC) were implemented in the full bundle (B-AD-EC) but not the partial bundle ICU (B-AD). MEASUREMENTS AND MAIN RESULTS: In the full bundle ICU, 95% patient days were spent in bed before EC (period 1). After EC was implemented (period 2), 65% of patients stood, 54% walked at least once during their ICU stay, and ICU-acquired pressure ulcers and physical restraint use decreased (period 1 vs 2: 39% vs 23% of patients; 30% vs 26% patient days, respectively; p < 0.001 for both). After adjustment for patient-level covariates, implementation of the full (B-AD-EC) versus partial (B-AD) bundle was associated with reduced mechanical ventilation duration (-22.3%; 95% CI, -22.5% to -22.0%; p < 0.001), ICU length of stay (-10.3%; 95% CI, -15.6% to -4.7%; p = 0.028), and hospital length of stay (-7.8%; 95% CI, -8.7% to -6.9%; p = 0.006). Total ICU and hospital cost were also reduced by 24.2% (95% CI, -41.4% to -2.0%; p = 0.03) and 30.2% (95% CI, -46.1% to -9.5%; p = 0.007), respectively. CONCLUSIONS: In a clinical practice setting, the addition of (E)arly mobilization and structured (C)oordination of ABCDE bundle components to a spontaneous (B)reathing, (A)wakening, and (D) elirium management background led to substantial reductions in the duration of mechanical ventilation, length of stay, and cost.

Case Report: Fulminant Murine Typhus Presenting with Status Epilepticus and Multi-Organ Failure: an Autopsy Case and a Review of the Neurologic Presentations of Murine Typhus.

Murine typhus (MT) is an important cause of febrile illness in endemic areas, and there is an epidemiologic resurgence of this infection currently transpiring in Texas and California. Fatal cases and severe neurological complications are rare. A fatal case of MT in a middle-aged man is reported with a course culminating in multi-organ failure and refractory status epilepticus. An autopsy revealed hemorrhagic pneumonia, acute tubular necrosis, and ischemic necrosis in the liver, adrenals, and brain. We have also reviewed the neurologic complications of MT.

Integrated plan to augment surge capacity.

INTRODUCTION: Surge capacity is defined as a healthcare system's ability to rapidly expand beyond normal services to meet the increased demand for appropriate space, qualified personnel, medical care, and public health in the event ofbioterrorism, disaster, or other large-scale, public health emergencies. There are many individuals and agencies, including policy makers, planners, administrators, and staff at the federal, state, and local level, involved in the process of planning for and executing policy in respect to a surge in the medical requirements of a population. They are responsible to ensure there is sufficient surge capacity within their own jurisdiction. PROBLEM: The [US] federal government has required New York State to create a system of hospital bed surge capacity that provides for 500 adult and pediatric patients per 1 million population, which has been estimated to be an increase of 15-20% in bed availability. In response, the New York City Department of Health and Mental Hygiene (NYC DOH) has requested that area hospitals take an inventory of available beds and set a goal to provide for a 20% surge capacity to be available during a mass-casualty event or other conditions calling for increased inpatient bed availability. METHODS: In 2003, under the auspices of the NYC DOH, the New York Institute of All Hazard Preparedness (NYIHP) was formed from four unaffiliated, healthcare facilities in Central Brooklyn to address this and other goals. RESULTS: The NYIHP hospitals have developed a surge capacity plan to provide necessary space and utilities. As these plans have been applied, a bed surge capacity of approximately 25% was identified and created for Central Brooklyn to provide for the increased demand on the medical care system that may accompany a disaster. Through the process of developing an integrated plan that would engage a public health incident, the facilities of NYIHP demonstrate that a model of cooperation may be applied to an inherently fractioned medical system.