The history of urea as a hyperosmolar agent to decrease brain swelling

In 1919, it was observed that intravascular osmolar shifts could collapse the thecal sac and diminish the ability to withdraw CSF from the lumbar cistern. This led to the notion that hyperosmolar compounds could ameliorate brain swelling. Since then, various therapeutic interventions have been used for the reduction of intracranial pressure and brain volume. Urea was first used as an osmotic agent for the reduction of brain volume in 1950. It was associated with greater efficacy and consistency than alternatives such as hyperosmolar glucose. Its use became the standard of clinical practice by 1957, in both the intensive care unit and operating room, to reduce intracranial pressure and brain bulk and was the first hyperosmolar compound to have widespread use. However, the prime of urea was rather short lived. Reports of side effects and complications associated with urea emerged. These included coagulopathy, hemoglobinuria, electrocardiography changes, tissue necrosis with extravasation, and a significant potential for rebound intracranial hypertension. Mannitol was introduced in 1961 as a comparable and potentially superior alternative to urea. However, mannitol was initially purported to be less effective at rapidly reducing intracranial pressure. The debate over the two compounds continued for a decade until mannitol eventually replaced urea by the late 1960s and early 1970s as the hyperosmolar agent of choice due to the ease of preparation, chemical stability, and decreased side effect profile. Although urea is not currently the standard of care today, its rise and eventual replacement by mannitol played a seminal role in both our understanding of cerebral edema and the establishment of strategies for its management.

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Non-Invasive Biomarkers for Earlier Detection of Pancreatic Cancer—A Comprehensive Review

Cancers ◽

10.3390/cancers13112722 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2722

Author(s):

Greta Brezgyte ◽

Vinay Shah ◽

Daria Jach ◽

Tatjana Crnogorac-Jurcevic

Keyword(s):

Clinical Setting ◽

Selection Index ◽

Reporting Quality ◽

Standard Of Care ◽

Therapeutic Interventions ◽

Ductal Adenocarcinoma ◽

Index Test ◽

Delayed Presentation ◽

Non Invasive ◽

Study Selection

Pancreatic ductal adenocarcinoma (PDAC) carries a deadly diagnosis, due in large part to delayed presentation when the disease is already at an advanced stage. CA19-9 is currently the most commonly utilized biomarker for PDAC; however, it lacks the necessary accuracy to detect precursor lesions or stage I PDAC. Novel biomarkers that could detect this malignancy with improved sensitivity (SN) and specificity (SP) would likely result in more curative resections and more effective therapeutic interventions, changing thus the present dismal survival figures. The aim of this study was to systematically and comprehensively review the scientific literature on non-invasive biomarkers in biofluids such as blood, urine and saliva that were attempting earlier PDAC detection. The search performed covered a period of 10 years (January 2010—August 2020). Data were extracted using keywords search in the three databases: MEDLINE, Web of Science and Embase. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was applied for study selection based on establishing the risk of bias and applicability concerns in Patient Selection, Index test (biomarker assay) and Reference Standard (standard-of-care diagnostic test). Out of initially over 4000 published reports, 49 relevant studies were selected and reviewed in more detail. In addition, we discuss the present challenges and complexities in the path of translating the discovered biomarkers into the clinical setting. Our systematic review highlighted several promising biomarkers that could, either alone or in combination with CA19-9, potentially improve earlier detection of PDAC. Overall, reviewed biomarker studies should aim to improve methodological and reporting quality, and novel candidate biomarkers should be investigated further in order to demonstrate their clinical usefulness. However, challenges and complexities in the path of translating the discovered biomarkers from the research laboratory to the clinical setting remain and would have to be addressed before a more realistic breakthrough in earlier detection of PDAC is achieved.

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1268. Dalbavancin for the Treatment of Infections due to Staphylococcus aureus

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1452 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S650-S651

Author(s):

Amber C Streifel ◽

Ellie Sukerman ◽

Monica Sikka ◽

Jina Makadia ◽

James Lewis ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Clinical Outcomes ◽

Adverse Drug Events ◽

Joint Infection ◽

Standard Of Care ◽

Clinical Endpoints ◽

History Of ◽

Antibiotic Failure ◽

Iv Drug Use ◽

Infection Recurrence

Abstract Background Dalbavancin is a lipoglycopeptide antibiotic active against gram-positive organisms. Its extended half-life allows for weekly dosing that can last 4 to 6 weeks with 2 doses. Although approved for treating skin and soft tissue infections, use for more complicated infections is appealing, particularly when daily intravenous antibiotics are impractical. S aureus is the most common cause of complex infections for which dalbavancin is considered at our institution, so we sought to better understand its use. Methods We conducted a retrospective study to describe dalbavancin use at our institution for infections caused by Staphylococcus aureus. We identified all patients ≥18 years who received ≥1 dose of dalbavancin. Infectious disease faculty reviewed charts for clinical characteristics and outcomes of the infections. Results Fifty-two patients with S. aureus infections (60% MRSA) were treated with at least a partial course of dalbavancin. Twenty-seven (52%) had a history of IV drug use (IDU) and the most common infections were bone and joint infection in 51% and bacteremia in 40% (Table 1). The most common dosing regimen was 1500 mg x 1 in 55% or 1500 mg weekly x 2 in 25% (Table 2). The most common reasons for use of dalbavancin were history of IDU in 48% and lack of a safe home environment in 21%. Suppressive oral antibiotics for the primary infection were prescribed to 3 patients after completing dalbavancin (2 received for other indications). Clinical outcomes include 15% of patients lost to follow-up, readmission due to infection recurrence or dalbavancin adverse effects in 12%, and overall infection recurrence or relapse by day 90 in 31% (Table 3). There were no severe dalbavancin-related adverse drug events. Table 1. Patient and Disease Characteristics Table 2. Dalbavancin Use Characteristics Table 3. Clinical Endpoints Conclusion While our results suggest dalbavancin is well tolerated, questions about relapse rates in the treatment of complicated S. aureus infections remain. Further research is needed to evaluate clinical outcomes for dalbavancin compared to standard of care antibiotics and to better elucidate whether relapses were related to true antibiotic failure versus other complexities of the S. aureus infections. Disclosures All Authors: No reported disclosures

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Effect of stimulation of the medullary reticular formation on cerebral vasomotor tonus and intracranial pressure

Journal of Neurosurgery ◽

10.3171/jns.1987.66.4.0548 ◽

1987 ◽

Vol 66 (4) ◽

pp. 548-554 ◽

Cited By ~ 8

Author(s):

Seigo Nagao ◽

Tsukasa Nishiura ◽

Hideyuki Kuyama ◽

Masakazu Suga ◽

Takenobu Murota

Keyword(s):

Intracranial Pressure ◽

Reticular Formation ◽

Cerebral Blood Volume ◽

Systemic Arterial Pressure ◽

Brain Swelling ◽

Dorsomedial Nucleus ◽

Medullary Reticular Formation ◽

Content Type ◽

Fine Print ◽

Stimulation Of

✓ The authors report the results of a study to evaluate the effect of stimulation of the medullary reticular formation on cerebral vasomotor tonus and intracranial pressure (ICP) after the hypothalamic dorsomedial nucleus and midbrain reticular formation were destroyed. Systemic arterial pressure (BP), ICP, and local cerebral blood volume (CBV) were continuously recorded in 32 cats. To assess the changes in the cerebral vasomotor tonus, the vasomotor index defined by the increase in ICP per unit change in BP was calculated. In 29 of the 32 animals, BP, ICP, and CBV increased simultaneously immediately after stimulation. The increase in ICP was not secondary to the increase in BP, because the vasomotor index during stimulation was significantly higher than the vasomotor index after administration of angiotensin II. The vasomotor index was high during stimulation of the area around the nucleus reticularis parvocellularis. In animals with the spinal cord transected at the C-2 vertebral level, ICP increased without a change in BP. These findings indicate that the areas stimulated in the medullary reticular formation play an important role in decreasing cerebral vasomotor tonus. This effect was not influenced by bilateral superior cervical ganglionectomy, indicating that there is an intrinsic neural pathway that regulates cerebral vasomotor tonus directly. In three animals, marked biphasic or progressive increases in ICP up to 100 mm Hg were evoked by stimulation. The reduction of cerebral vasomotor tonus and concomitant vasopressor response induced by stimulation of the medullary reticular formation may be one of the causes of acute brain swelling.

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Identification of Risk Factors to Predict the Occurrences of Relapses in Individuals with Schizophrenia Spectrum Disorder in Iran

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18020546 ◽

2021 ◽

Vol 18 (2) ◽

pp. 546

Author(s):

Omran Davarinejad ◽

Tahereh Mohammadi Majd ◽

Farzaneh Golmohammadi ◽

Payam Mohammadi ◽

Farnaz Radmehr ◽

...

Keyword(s):

Risk Factors ◽

Suicide Attempts ◽

Disease Onset ◽

Sudden Onset ◽

Spectrum Disorder ◽

Therapeutic Interventions ◽

Schizophrenia Spectrum Disorder ◽

Schizophrenia Spectrum ◽

History Of ◽

Log Normal

Schizophrenia Spectrum Disorder (SSD) is a chronic psychiatric disorder with a modest treatment outcome. In addition, relapses are commonplace. Here, we sought to identify factors that predict relapse latency and frequency. To this end, we retrospectively analyzed data for individuals with SSD. Medical records of 401 individuals with SSD were analyzed (mean age: 25.51 years; 63.6% males) covering a five-year period. Univariate and multivariate Penalized Likelihood Models with Shared Log-Normal Frailty were used to determine the correlation between discharge time and relapse and to identify risk factors. A total of 683 relapses were observed in males, and 422 relapses in females. The Relapse Hazard Ratio (RHR) decreased with age (RHR = 0.99, CI: (0.98–0.998)) and with participants’ adherence to pharmacological treatment (HR = 0.71, CI: 0.58–0.86). In contrast, RHR increased with a history of suicide attempts (HR = 1.32, CI: 1.09–1.60), and a gradual compared to a sudden onset of disease (HR = 1.45, CI: 1.02–2.05). Gender was not predictive. Data indicate that preventive and therapeutic interventions may be particularly important for individuals who are younger at disease onset, have a history of suicide attempts, have experienced a gradual onset of disease, and have difficulties adhering to medication.

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Pleuroscopy early experience in the exudative pleural effusion of unknown etiology

Current Respiratory Medicine Reviews ◽

10.2174/2211556010666210728125810 ◽

2021 ◽

Vol 17 ◽

Author(s):

Atefeh Fakharian ◽

Hamidreza Jabbardarjani ◽

Mohamad Reza Masjedi ◽

Masoud Shamaei

Keyword(s):

Pleural Effusion ◽

Previous History ◽

Invasive Procedure ◽

Therapeutic Interventions ◽

Unknown Etiology ◽

Safe Procedure ◽

Pathologic Diagnosis ◽

Medical Thoracoscopy ◽

History Of ◽

Exudative Pleural Effusion

Background: Pleuroscopy (medical thoracoscopy) is a minimally invasive procedure to inspect and perform a biopsy of the pleural space as well as to perform therapeutic interventions; pleural fluid drainage and pleurodesis. Material and Methods: In a retrospective study in Kasra Hospital, Tehran-Iran, the patients with exudative pleural effusion of unknown etiology who underwent pleuroscopy, were evaluated. These patients had negative smear and culture for infective agents. Also, the cytological review was negative for malignancy. Results: 62 patients had undergone pleuroscopy, of which 29 (46.7) were men. After the final evaluation, 47 patients (75.8%) had a definite pathologic diagnosis, of which 39 (82.9%) were cancer. Through these 39 cases, 18 cases (46.1%) had a history of the previously confirmed cancer, in which pleural pathology was consistent with the initial diagnosis. In 21 cases (53.9%), metastatic cancers were detected without a previous history. From a total of 47 cases with definite pathologic diagnosis, 8 cases (17%) had histopathologic evidence of granulomatous lesions consistent with tuberculosis and 15 patients (24%) showed non-specific inflammatory lesions. There was no morbidity and mortality among these patients. Discussion: Considering that pleuroscopy is a safe procedure with high diagnostic accuracy, malignancy is the most finding in the exudative pleural effusion of unknown etiology. This increases the importance of this procedure in these cases to prevent wasting the time and smear-negative anti-TB treatment.

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BRAF in Melanoma: Pathogenesis, Diagnosis, Inhibition, and Resistance

Journal of Skin Cancer ◽

10.1155/2011/423239 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 23

Author(s):

Ryan J. Sullivan ◽

Keith T. Flaherty

Keyword(s):

Standard Of Care ◽

Diagnostic Techniques ◽

Therapeutic Interventions ◽

Molecular Testing ◽

Braf Inhibitors ◽

Testing Methods ◽

Braf Mutations ◽

Initial Discovery ◽

Braf Mutant ◽

Mutant Braf

Since the initial discovery that a subset of patients with cutaneous melanoma harbor BRAF mutations, substantial research has been focused on determining the pathologic consequences of BRAF mutations, optimizing diagnostic techniques to identify these mutations, and developing therapeutic interventions to inhibit the function of this target in mutation-bearing tumors. Recently, advances have been made which are revolutionizing the standard of care for patients with BRAF mutant melanoma. This paper provides an overview on the pathogenic ramifications of mutant BRAF signaling, the latest molecular testing methods to detect BRAF mutations, and the most recent clinical data of BRAF pathway inhibitors in patients with melanoma and BRAF mutations. Finally, emerging mechanisms of resistance to BRAF inhibitors and ways of overcoming this resistance are discussed.

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Case series of sixteen patients with nummular headache

Cephalalgia ◽

10.1177/0333102410368445 ◽

2010 ◽

Vol 30 (12) ◽

pp. 1527-1530 ◽

Cited By ~ 20

Author(s):

Justin Moon ◽

Kamran Ahmed ◽

Ivan Garza

Keyword(s):

Medication Overuse ◽

Age Of Onset ◽

Medication Overuse Headache ◽

Case Series ◽

Primary Headache ◽

Headache Disorder ◽

Therapeutic Interventions ◽

Nummular Headache ◽

Primary Headache Disorder ◽

History Of

Introduction: Nummular headache is a rare primary headache disorder described by a focal circumscribed area of pain (2–6 cm in diameter). Literature on this disorder is sparse. Patients and methods: Here, we describe a case series of 16 patients (6 men, 10 women) seen at the Mayo Clinic. Results: Mean age of onset was 50 years (range, 19–79 years) and mean duration of headache was 7.9 years (range, 0.33–40 years). Location of headache varied and was found to be an average of 3.9 cm in diameter (range, 2–10 cm). Headache was episodic (<15 days/month) in four patients and chronic (>15 days/month) in 12 patients. Attention was paid to therapeutic interventions. Resolution was seen in 38% of patients. Migraine was present in the history of 56% of patients and medication overuse headache was found in 25%. Conclusions: Our series results support previous findings. In our population, no specific therapy was identified to be effective in more than one patient.

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Epigenetic dysregulation in myeloid malignancies

Blood ◽

10.1182/blood.2019004262 ◽

2021 ◽

Author(s):

Hsuan-Ting Huang ◽

Maria Eugenia Figueroa

Keyword(s):

Standard Of Care ◽

Cytotoxic Agents ◽

Therapeutic Interventions ◽

Myeloid Malignancies ◽

Sequencing Studies ◽

Aberrant Dna Methylation ◽

Relapsed Disease ◽

Mouse Modeling ◽

Generation Sequencing ◽

General Standard

Epigenetic deregulation is now a well-recognized -though not yet fully understood- mechanism that contributes to the development and progression of myeloid malignancies. In the past 15 years, next generation sequencing studies have revealed patterns of aberrant DNA methylation, altered chromatin states, and mutations in chromatin modifiers across the spectrum of myeloid malignancies. Studies into the mechanisms that drive these diseases through mouse modeling have helped identify new avenues for therapeutic interventions, from initial treatment to resistant, relapsed disease. This is particularly significant when chemotherapy with cytotoxic agents remains the general standard of care. In this review, we will discuss some of the recent findings of epigenetic mechanisms and how these are informing the development of more targeted strategies for therapeutic intervention in myeloid malignancies.

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