The intestinal immune system has the difficult task of protecting a large environmentally exposed single layer of epithelium from pathogens without allowing inappropriate inflammatory responses. ...Unmitigated inflammation drives multiple pathologies, including the development of colorectal cancer. CD4
T cells mediate both the suppression and promotion of intestinal inflammation. They comprise an array of phenotypically and functionally distinct subsets tailored to a specific inflammatory context. This diversity of form and function is relevant to a broad array of pathologic and physiologic processes. The heterogeneity underlying both effector and regulatory T helper cell responses to colorectal cancer, and its impact on disease progression, is reviewed herein. Importantly, T cell responses are dynamic; they exhibit both quantitative and qualitative changes as the inflammatory context shifts. Recent evidence outlines the role of CD4
T cells in colorectal cancer responses and suggests possible mechanisms driving qualitative alterations in anti-cancer immune responses. The heterogeneity of T cells in colorectal cancer, as well as the manner and mechanism by which they change, offer an abundance of opportunities for more specific, and likely effective, interventional strategies.
Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we ...investigated the absence of IL-6 alone, IL-21 alone, or the combined lack of IL-6 and IL-21 on Tfh differentiation and the development of B cell immunity in vivo. C57BL/6 or IL-21(-/-) mice were treated with a neutralizing monoclonal antibody against IL-6 throughout the course of an acute viral infection (lymphocytic choriomeningitis virus, LCMV). The combined absence of IL-6 and IL-21 resulted in reduced Tfh differentiation and reduced Bcl6 protein expression. In addition, we observed that these cytokines had a large impact on antigen-specific B cell responses. IL-6 and IL-21 collaborate in the acute T-dependent antiviral antibody response (90% loss of circulating antiviral IgG in the absence of both cytokines). In contrast, we observed reduced germinal center formation only in the absence of IL-21. Absence of IL-6 had no impact on germinal centers, and combined absence of both IL-21 and IL-6 revealed no synergistic effect on germinal center B cell development. Studying CD4 T cells in vitro, we found that high IL-21 production was not associated with high Bcl6 or CXCR5 expression. TCR stimulation of purified naïve CD4 T cells in the presence of IL-6 also did not result in Tfh differentiation, as determined by Bcl6 or CXCR5 protein expression. Cumulatively, our data indicates that optimal Tfh formation requires IL-21 and IL-6, and that cytokines alone are insufficient to drive Tfh differentiation.
Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate ...transplant rejection. Here, we use TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following PD-1 inhibition. The treatment was associated with a sharp increase in circulating alloreactive CD8
T cell clones, which display a unique transcriptomic signature and were also detected in the rejected kidney but not at tumor sites. Longitudinal and cross-tissue TCR analyses indicate unintended expansion of alloreactive CD8
T cells induced by ICI therapy for cancer, coinciding with ICI-associated organ rejection.
Herpes simplex virus (HSV) is a common cause of viral encephalitis and can result in refractory seizures. Although HSV encephalitis (HSVE) is treated primarily with acyclovir, surgery can play a role ...in medically intractable cases.
To systematically review cases describing surgery for the treatment of severe HSVE. We also present an illustrative case of anterior temporal lobectomy (ATL) for refractory status epilepticus in a patient with unilateral HSVE. This case demonstrates one clinical context in which surgery can be a useful adjunct.
We performed a systematic review using PubMed and Google Scholar, including case reports and series describing surgical interventions for HSVE. Clinical data were extracted from 54 publications that incorporated 67 patient cases.
Surgical decompression occurred at a wide range of times after the onset of illness, although most patients were operated on 4 or more days after HSVE symptoms began. Numerous reports indicated that decompressive craniectomy, temporal lobectomy, and hematoma removal could treat intractably elevated intracranial pressure because of HSVE with favorable long-term outcomes. We describe an additional case in which a 52-year-old woman with HSVE developed refractory right temporal lobe seizures. After ATL, the seizures resolved with significant clinical improvement.
Surgical treatment can be a useful adjunct for treatment of HSVE. There is substantial variability in the timing of surgical decompression in patients with HSVE, which can be necessary up to approximately 3 weeks after illness onset. ATL should be considered for refractory status epilepticus in HSVE with a unilateral seizure focus.
Immunotherapy with oncolytic herpes simplex virus-1 therapy offers an innovative, targeted, less-toxic approach for treating brain tumors. However, a major obstacle in maximizing oncolytic ...virotherapy is a lack of comprehensive understanding of the underlying mechanisms that unfold in CNS tumors/associated microenvironments after infusion of virus. We demonstrate that our multiplex biomarker screening platform comprehensively informs changes in both topographical location and functional states of resident/infiltrating immune cells that play a role in neuropathology after treatment with HSV G207 in a pediatric Phase 1 patient. Using this approach, we identified robust infiltration of CD8
T cells suggesting activation of the immune response following virotherapy; however there was a corresponding upregulation of checkpoint proteins PD-1, PD-L1, CTLA-4, and IDO revealing a potential role for checkpoint inhibitors. Such work may ultimately lead to an understanding of the governing pathobiology of tumors, thereby fostering development of novel therapeutics tailored to produce optimal responses.
We have attempted here to provide an up-to-date review of the collaboration between helper T cells and B cells in response to protein and glycoprotein antigens. This collaboration is essential as it ...not only protects from many pathogens but also contributes to a litany of autoimmune and immune-mediated diseases.
Acting in concert with TGF-β, interleukin-6 (IL-6) signaling induces T helper 17 (T
17) cell development by programming T
17-related genes via signal transducers and activators of transcription 3 ...(STAT3). A role for IL-6 signaling beyond the inductive phase of T
17 cell development has not been defined because IL-23 signaling downstream of T
17 cell induction also activates STAT3 and is thought responsible for T
17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of mouse T
17 cells; IL-6Rα-deficient T
17 cells rapidly lost their T
17 phenotype and did not cause disease in two models of colitis. Cotransfer of wild-type T
17 cells with IL-6Rα-deficient T
17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 expression in the colon promoted classic, or cis, rather than transreceptor signaling that was required for maintenance of T
17 cells. Thus, ongoing classic IL-6 signaling underpins the T
17 program and is required for T
17 cell maintenance and function.
Background:
Ruptured intracranial dermoid cysts are extremely rare. Standard treatment consists of endonasal decompression or craniotomy with evacuation and copious irrigation of subarachnoid spaces ...to remove any disseminated cystic contents. Disseminated fat particles in the subarachnoid space may be the cause of further sequalae, including the subsequent development of chemical meningitis and hydrocephalus. Here, we present a case of ruptured suprasellar dermoid cyst treated with craniotomy for emergent optic nerve decompression, followed by postoperative hydrocephalus successfully treated with lumbar drain.
Case description:
We describe a 30-year-old man with a history of migraines who presented with acute onset of headache, photophobia, nausea, vomiting, and vision loss in the left eye. Head CT and brain MRI demonstrated a ruptured suprasellar dermoid cyst with associated mass effect on the optic nerves and frontal lobes as well as fat attenuation material within the subarachnoid spaces. The patient underwent left frontotemporal craniotomy for cyst resection and developed non-obstructive hydrocephalus on postoperative day 1, refractory to external ventricular drainage. Placement of a lumbar drain cleared the subarachnoid space of debris derived from the ruptured dermoid cyst, and the hydrocephalus resolved. The patient did not require permanent CSF diversion.
Conclusions:
Intracranial dermoid cysts are uncommon, and rupture is a rare event. Standard surgical treatment with craniotomy for evacuation may leave disseminated dermoid contents and fat particles throughout the subarachnoid spaces. We highlight a case of ruptured suprasellar dermoid cyst with postoperative communicating hydrocephalus treated with lumbar drain when external ventricular drain (EVD) was ineffective. Review of the current literature reveals inconsistent findings on the effects of remaining fat particles. In cases with clinical evidence of increased intracranial pressure due to non-obstructive hydrocephalus attributable to chemical meningitis, temporary lumbar drainage is an option to be considered before committing the patient to permanent shunting.
Hemolysis Index and Potassium Reporting DiToro, Daniel F; Conrad, Michael J; Jarolim, Petr
American journal of clinical pathology,
2022-Jun-07, 2022-06-07, 20220607, Letnik:
157, Številka:
6
Journal Article
Recenzirano
In vitro hemolysis generates a spurious increase in potassium. Roche Diagnostics recently revised its recommended guidelines for potassium reporting on cobas analyzers. By dramatically reducing the ...allowable degree of hemolysis, these guidelines would increase specimen rejection rates. We attempted to balance the desire to avoid inaccurate results with the clinical implications of increased specimen rejection rates.
We downloaded hemolytic indices (HI) for 80,795 specimens tested at our institution on cobas chemistry analyzers in 1 month and evaluated potential specimen rejection rates based on the new criteria. We also spiked nonhemolyzed samples with hemolyzed blood to assess the influence of HI values on potassium measurements.
The new recommendations would lead to specimen rejection rates of 76% in the neonatal intensive care unit (NICU), 41% in the emergency department (ED), 16% in inpatient specimens, and 9% in outpatient samples. Our current criteria of reporting potassium concentrations in inpatient and outpatient specimens with HI ≤100 and in NICU and ED specimens with HI ≤300 and additional interpretive guidance for HI values between 100 and 300 reduce unnecessary specimen rejections to 3% in NICU, 2% in ED and inpatients, and less than 1% in outpatients without significantly increasing the number of clinically consequential incorrect results.
The new recommendations would lead to unacceptably high specimen rejection rates. Laboratories should develop context-specific, evidence-based reporting criteria that minimize reporting of inaccurate results without disrupting delivery of care.
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