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Article ; Online: Addressing the Needs of Preclinical Student Researchers in the SCI Community to Advance Communication and Education.

Singh, Shayna / Weinberger, Jeremy / O'Reilly, Micaela / Borisyuk, Andrey

2023 Volume 10, Issue 5

MeSH term(s)	Humans ; Students ; Communication ; Spinal Cord Injuries
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0040-23.2023
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Article ; Online: Sprouting of afferent and efferent inputs to pelvic organs after spinal cord injury.

Zhao, Shunyi / Tang, Chuanxi / Weinberger, Jeremy / Gao, Dianshuai / Hou, Shaoping

Journal of neuropathology and experimental neurology

2023 Volume 83, Issue 1, Page(s) 20–29

Abstract: Neural plasticity occurs within the central and peripheral nervous systems after spinal cord injury (SCI). Although central alterations have extensively been studied, it is largely unknown whether afferent and efferent fibers in pelvic viscera undergo ... ...

Abstract	Neural plasticity occurs within the central and peripheral nervous systems after spinal cord injury (SCI). Although central alterations have extensively been studied, it is largely unknown whether afferent and efferent fibers in pelvic viscera undergo similar morphological changes. Using a rat spinal cord transection model, we conducted immunohistochemistry to investigate afferent and efferent innervations to the kidney, colon, and bladder. Approximately 3-4 weeks after injury, immunostaining demonstrated that tyrosine hydroxylase (TH)-labeled postganglionic sympathetic fibers and calcitonin gene-related peptide (CGRP)-immunoreactive sensory terminals sprout in the renal pelvis and colon. Morphologically, sprouted afferent or efferent projections showed a disorganized structure. In the bladder, however, denser CGRP-positive primary sensory fibers emerged in rats with SCI, whereas TH-positive sympathetic efferent fibers did not change. Numerous CGRP-positive afferents were observed in the muscle layer and the lamina propria of the bladder following SCI. TH-positive efferent inputs displayed hypertrophy with large diameters, but their innervation patterns were sustained. Collectively, afferent or efferent inputs sprout widely in the pelvic organs after SCI, which may be one of the morphological bases underlying functional adaptation or maladaptation.
MeSH term(s)	Rats ; Animals ; Calcitonin Gene-Related Peptide ; Viscera ; Spinal Cord Injuries/complications ; Immunohistochemistry ; Spinal Cord ; Afferent Pathways
Chemical Substances	Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
Language	English
Publishing date	2023-12-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nlad108
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Article: Delivery of the 5-HT

DeFinis, Jaclyn H / Weinberger, Jeremy / Hou, Shaoping

Biology

2021 Volume 10, Issue 1

Abstract: Traumatic spinal cord injury (SCI) interrupts spinobulbospinal micturition reflex pathways and results in urinary dysfunction. Over time, an involuntary bladder reflex is established due to the reorganization of spinal circuitry. Previous studies show ... ...

Abstract	Traumatic spinal cord injury (SCI) interrupts spinobulbospinal micturition reflex pathways and results in urinary dysfunction. Over time, an involuntary bladder reflex is established due to the reorganization of spinal circuitry. Previous studies show that manipulation of serotonin 2A (5-HT
Language	English
Publishing date	2021-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10010068
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Article ; Online: Incidence, Characteristics, and Outcomes of Ventilator-associated Events during the COVID-19 Pandemic.

Weinberger, Jeremy / Rhee, Chanu / Klompas, Michael

Annals of the American Thoracic Society

2021 Volume 19, Issue 1, Page(s) 82–89

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Adult ; COVID-19 ; Humans ; Incidence ; Pandemics ; Pneumonia, Ventilator-Associated/epidemiology ; Respiration, Artificial ; Retrospective Studies ; SARS-CoV-2 ; Ventilators, Mechanical/adverse effects
Language	English
Publishing date	2021-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2717461-X
ISSN	2325-6621 ; 1943-5665 ; 2325-6621
ISSN (online)	2325-6621 ; 1943-5665
ISSN	2325-6621
DOI	10.1513/AnnalsATS.202103-364OC
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Article ; Online: Changes in the epidemiology of ventilator-associated events over the course of the coronavirus disease 2019 (COVID-19) pandemic.

Weinberger, Jeremy F / Rhee, Chanu / Klompas, Michael

Infection control and hospital epidemiology

2021 Volume 44, Issue 2, Page(s) 305–307

Abstract: Management of critically ill coronavirus disease 2019 (COVID-19) patients has evolved considerably during the pandemic. We investigated rates and causes of ventilator-associated events (VAEs) in COVID-19 patients in the late versus early waves in 4 ... ...

Abstract	Management of critically ill coronavirus disease 2019 (COVID-19) patients has evolved considerably during the pandemic. We investigated rates and causes of ventilator-associated events (VAEs) in COVID-19 patients in the late versus early waves in 4 Massachusetts hospitals. VAE rates per episode decreased, rates per ventilator day were stable, and most cases were caused by acute respiratory distress syndrome (ARDS).
MeSH term(s)	Humans ; Respiration, Artificial/adverse effects ; Pneumonia, Ventilator-Associated/epidemiology ; Pandemics ; COVID-19/epidemiology ; COVID-19/etiology ; Ventilators, Mechanical/adverse effects
Language	English
Publishing date	2021-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1017/ice.2021.459
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Article ; Online: Ventilator-Associated Events: Epidemiology, Risk Factors, and Prevention.

Weinberger, Jeremy / Cocoros, Noelle / Klompas, Michael

Infectious disease clinics of North America

2021 Volume 35, Issue 4, Page(s) 871–899

Abstract: The Centers for Disease Control and Prevention shifted the focus of safety surveillance in mechanically ventilated patients from ventilator-associated pneumonia to ventilator-associated events in 2013 to increase the objectivity and reproducibility of ... ...

Abstract	The Centers for Disease Control and Prevention shifted the focus of safety surveillance in mechanically ventilated patients from ventilator-associated pneumonia to ventilator-associated events in 2013 to increase the objectivity and reproducibility of surveillance and to encourage quality improvement programs to focus on preventing a broader array of complications. Ventilator-associated events are associated with a doubling of the risk of dying. Prospective studies have found that minimizing sedation, increasing spontaneous awakening and breathing trials, and conservative fluid management can decrease event rates and the duration of ventilation. Multifaceted interventions to enhance these practices can decrease ventilator-associated event rates.
MeSH term(s)	Cross Infection/prevention & control ; Humans ; Infection Control ; Pneumonia, Ventilator-Associated/prevention & control ; Quality Improvement ; Respiration, Artificial/adverse effects ; Respiratory Insufficiency/therapy ; Risk Factors ; United States ; Ventilator-Induced Lung Injury ; Ventilators, Mechanical
Language	English
Publishing date	2021-11-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1077676-x
ISSN	1557-9824 ; 0891-5520
ISSN (online)	1557-9824
ISSN	0891-5520
DOI	10.1016/j.idc.2021.07.005
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Article ; Online: What Is the Utility of Measuring Lactate Levels in Patients with Sepsis and Septic Shock?

Weinberger, Jeremy / Klompas, Michael / Rhee, Chanu

Seminars in respiratory and critical care medicine

2021 Volume 42, Issue 5, Page(s) 650–661

Abstract: Elevations in blood lactate concentrations have been studied in sepsis and other disease states for decades and are well known to be associated with increased mortality. Many studies have also demonstrated the prognostic accuracy of serial lactate levels, ...

Abstract	Elevations in blood lactate concentrations have been studied in sepsis and other disease states for decades and are well known to be associated with increased mortality. Many studies have also demonstrated the prognostic accuracy of serial lactate levels, and some have suggested that lactate clearance may be a useful therapeutic target for resuscitation. Lactate measurements have therefore gained an increasingly prominent role in sepsis definitions, screening protocols, management guidelines, and quality measures over the past two decades. The heavy emphasis on lactate monitoring, however, has also generated controversy and concerns. Lactate is not specific to infection and its frequent use for sepsis screening and diagnosis may therefore trigger unnecessary broad-spectrum antibiotic use in some patients. Because hyperlactatemia does not always reflect fluid-responsive hypoperfusion, titrating resuscitation to lactate clearance can also lead to unnecessary fluid and volume overload. More broadly, there is a lack of high-quality evidence demonstrating that initial and serial lactate monitoring leads to better patient-centered outcomes. Indeed, a recent randomized controlled trial comparing resuscitation strategies based on lactate clearance versus normalizing capillary refill time showed no benefit and potential harm with lactate-guided therapy. In this article, we review the basic pathobiology of lactate metabolism and delineate why the traditional paradigm that hyperlactatemia reflects tissue hypoxia is overly simplistic and incomplete. We then review the evidence behind the diagnostic, prognostic, and therapeutic uses of lactate monitoring and place this in the context of evolving sepsis diagnosis and management guidelines.
MeSH term(s)	Humans ; Hyperlactatemia/diagnosis ; Lactic Acid ; Resuscitation ; Sepsis/diagnosis ; Sepsis/therapy ; Shock, Septic/diagnosis ; Shock, Septic/therapy
Chemical Substances	Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2021-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1183617-9
ISSN	1098-9048 ; 1069-3424
ISSN (online)	1098-9048
ISSN	1069-3424
DOI	10.1055/s-0041-1733915
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Article ; Online: Delivery of the 5-HT 2A Receptor Agonist, DOI, Enhances Activity of the Sphincter Muscle during the Micturition Reflex in Rats after Spinal Cord Injury

Jaclyn H. DeFinis / Jeremy Weinberger / Shaoping Hou

Biology, Vol 10, Iss 1, p

2021 Volume 68

Abstract	Traumatic spinal cord injury (SCI) interrupts spinobulbospinal micturition reflex pathways and results in urinary dysfunction. Over time, an involuntary bladder reflex is established due to the reorganization of spinal circuitry. Previous studies show that manipulation of serotonin 2A (5-HT 2A ) receptors affects recovered bladder function, but it remains unclear if this receptor regulates the activity of the external urethral sphincter (EUS) following SCI. To elucidate how central and peripheral serotonergic machinery acts on the lower urinary tract (LUT) system, we employed bladder cystometry and EUS electromyography recordings combined with intravenous or intrathecal pharmacological interventions of 5-HT 2A receptors in female SCI rats. Three to four weeks after a T10 spinal transection, systemic and central blockage of 5-HT 2A receptors with MDL only slightly influenced the micturition reflex. However, delivery of the 5-HT 2A receptor agonist, DOI, increased EUS tonic activity and elicited bursting during voiding. Additionally, subcutaneous administration of DOI verified the enhancement of continence and voiding capability during spontaneous micturition in metabolic cage assays. Although spinal 5HT 2A receptors may not be actively involved in the recovered micturition reflex, stimulating this receptor subtype enhances EUS function and the synergistic activity between the detrusor and sphincter to improve the micturition reflex in rats with SCI.
Keywords	micturition ; external urethral sphincter ; spinal cord injury ; serotonin ; electromyogram ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: A Critical Analysis of the Literature on Time-to-Antibiotics in Suspected Sepsis.

Weinberger, Jeremy / Rhee, Chanu / Klompas, Michael

The Journal of infectious diseases

2020 Volume 222, Issue Suppl 2, Page(s) S110–S118

Abstract: The Surviving Sepsis Campaign recommends immediate antibiotics for all patients with suspected sepsis and septic shock, ideally within 1 hour of recognition. Immediate antibiotic treatment is lifesaving for some patients, but a substantial fraction of ... ...

Abstract	The Surviving Sepsis Campaign recommends immediate antibiotics for all patients with suspected sepsis and septic shock, ideally within 1 hour of recognition. Immediate antibiotic treatment is lifesaving for some patients, but a substantial fraction of patients initially diagnosed with sepsis have noninfectious conditions. Aggressive time-to-antibiotic targets risk promoting antibiotic overuse and antibiotic-associated harms for this subset of the population. An accurate understanding of the precise relationship between time-to-antibiotics and mortality for patients with possible sepsis is therefore critical to finding the best balance between assuring immediate antibiotics for those patients who truly need them versus allowing clinicians some time for rapid investigation to minimize the risk of overtreatment and antibiotic-associated harms for patients who are not infected. More than 30 papers have been published assessing the relationship between time-to-antibiotics and outcomes, almost all of which are observational cohort studies. Most report significant associations but all have important limitations. Key limitations include focusing just on the sickest subset of patients (only patients requiring intensive care and/or patients with septic shock), blending together mortality estimates from patients with very long intervals until antibiotics with patients with shorter intervals and reporting a single blended (and thus inflated) estimate for the average increase in mortality associated with each hour until antibiotics, and failure to control for large potential confounders including patients' presenting signs and symptoms and granular measures of comorbidities and severity of illness. In this study, we elaborate on these potential sources of bias and try to distill a better understanding of what the true relationship between time-to-antibiotics and mortality may be for patients with suspected sepsis or septic shock.
MeSH term(s)	Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/therapeutic use ; Humans ; Sepsis/drug therapy ; Sepsis/mortality ; Time-to-Treatment
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2020-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiaa146
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Article ; Online: The susceptibility of cardiac arrhythmias after spinal cord crush injury in rats.

Fernandes, Silvia / Oatman, Emily / Weinberger, Jeremy / Dixon, Alethia / Osei-Owusu, Patrick / Hou, Shaoping

Experimental neurology

2022 Volume 357, Page(s) 114200

Abstract: High-level spinal cord injury (SCI) often interrupts supraspinal regulation of sympathetic input to the heart. Although it is known that dysregulated autonomic control increases the risk for cardiac disorders, the mechanisms mediating SCI-induced ... ...

Abstract	High-level spinal cord injury (SCI) often interrupts supraspinal regulation of sympathetic input to the heart. Although it is known that dysregulated autonomic control increases the risk for cardiac disorders, the mechanisms mediating SCI-induced arrhythmias are poorly understood. Here, we employed a rat model of complete spinal cord crush injury at the 2nd/3rd thoracic (T2/3) level to investigate cardiac rhythm disorders resulting from SCI. Rats with T9 injury and naïve animals served as two controls. Four weeks after SCI, rats were implanted with a radio-telemetric device for electrocardiogram and blood pressure monitoring. During 24-h recordings, heart rate variability in rats with T2/3 but not T9 injury exhibited a significant reduction in the time domain, and a decrease in power at low frequency but increased power at high frequency in the frequency domain which indicates reduced sympathetic and increased parasympathetic outflow to the heart. Pharmacological blockade of the sympathetic or parasympathetic branches confirmed the imbalance of cardiac autonomic control. Activation of sympatho-vagal input during the induction of autonomic dysreflexia by colorectal distention triggered various severe arrhythmic events in T2/3 injured rats. Meanwhile, intravenous infusion of the β1-adrenergic receptor agonist, dobutamine, caused greater incidence of arrhythmias in rats with T2/3 injury than naïve and T9 injured controls. Together, the results indicate that high-level SCI increases the susceptibility to developing cardiac arrhythmias likely owing to compromised autonomic homeostasis. The T2/3 crush model is appropriate for studying abnormal cardiac electrophysiology resulting from SCI.
MeSH term(s)	Animals ; Arrhythmias, Cardiac/complications ; Autonomic Dysreflexia/etiology ; Blood Pressure/physiology ; Crush Injuries/complications ; Rats ; Spinal Cord ; Spinal Cord Injuries/complications
Language	English
Publishing date	2022-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2022.114200
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