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Δευτέρα 31 Οκτωβρίου 2022

Recurrence of symptoms following cryptococcal meningitis - characterizing a diagnostic conundrum with multiple etiologies

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies and outcomes among persons with second-episode symptomatic recurrence.
Methods
We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, ART and cryptococcosis histories, clinical outcomes, and CSF analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as 1: microbiological relapse, 2: paradoxical Immune Reconstitution Inflammatory Syndrome (IRIS), 3: persistent elevated intracranial pressure (ICP) only, or 4: persistent symptoms only; along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal Wallis tests as appropriate.
Results
724 participants wer e included (n = 607 primary episode, n = 81 relapse, n = 28 paradoxical IRIS, n = 2 persistently elevated ICP, n = 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/mcL, IQR 9-76) and lower CSF WBC (4 cells/mcL, IQR 4-85) counts than paradoxical IRIS (CD4 78 cells/mcL, IQR 47-142 and WBC 45 cells/mcL, IQR 8-128). Among those with CSF WBC <5 cells/mcL, 86% (43/50) had relapse. Among those with CD4 counts < 50 cells/mcL, 91% (39/43) had relapse. 18-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS.
Conclusions
Poor immune reconstitution was noted more often in relapse compared to IRIS as evidenced by lower CSF WBC counts and blood CD4 counts. These easily obtained lab values should prompt initiation of antifungal treatment while awaiting culture results.
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Higher levels of cerebrospinal fluid and plasma neurofilament light in human immunodeficiency virus-associated distal sensory polyneuropathy

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Neurofilament light chain (NFL) concentrations, reflecting axonal damage, are seen in several polyneuropathies, but have not been studied in HIV distal sensory polyneuropathy (DSP). We evaluated NFL in CSF and plasma in relation to DSP in people with HIV (PWH) from two independent cohorts, and in people without HIV (PWoH).
Methods
Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2.
Results
Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% black, 49.6% white, current CD4+ T-cells (median, IQR) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤ 50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1, but also 51 PWoH, t ogether age 58.4 ± 6.68 years, 41.2% female, 18.0% black, Hispanic, non-Hispanic white 52.0%, 6.00% white. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds.
Conclusions
Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.
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Acute hepatitis associated with an echovirus 9 infection in a heart transplant recipient

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Abstract

We report a case of severe acute hepatitis due to echovirus 9 in a heart transplant patient treated with conventional immunosuppressive therapy. This case supports the importance of testing for enteroviruses in any type of infectious presentation in immunocompromised populations.

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Post‐COVID‐19 vaccination arm pain diagnosed as complex regional pain syndrome: a case report

alexandrossfakianakis shared this article with you from Inoreader

Abstract

As the vaccination efforts against the coronavirus disease-2019 (COVID-19) continue, more patients are likely to present with complications related to COVID-19 vaccination. We describe the first reported case of complex regional pain syndrome (CRPS), involving the upper extremities, that occurred after COVID-19 vaccination. The patient presented with acute-onset severe arm pain and swelling following vaccine administration. Based on the clinical, electrodiagnostic, and radionuclide three-phase bone scan findings, the patient was diagnosed with postvaccination CRPS. The COVID-19 vaccine possibly elicited an immune-mediated inflammatory response to the injected antigen in the patient, who was predisposed to CRPS due to inflammatory immunity. The COVID-19 vaccine elicited an immune-mediated inflammatory response to the injected antigen, resulting in CRPS following COVID-19 vaccination.

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Total calcium, dairy foods and risk of colorectal cancer: a prospective cohort study of younger US women

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Although colorectal cancer (CRC) incidence is declining among adults aged ≥65 years, CRC incidence in younger adults has been rising. The protective role of calcium in colorectal carcinogenesis has been well established, but evidence is lacking on whether the association varies by age at diagnosis. We investigated the association between total calcium intake and risk of overall CRC and CRC before age 55 years.
Methods
In the Nurses' Health Study II (1991–2015), 94 205 women aged 25–42 years at baseline were included in the analysis. Diet was assessed every 4 years through validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) and 95% CIs for CRC were estimated using the Cox proportional hazards model.
Results
We documented 349 incident CRC cases during 2 202 604 person-years of follow-up. Higher total calcium intake was associated with a reduced risk of CRC. Compared with those with <750 mg/day of total calcium intake, the HR of CRC was 0.61 (95% CI, 0.38–0.97) for those who consumed ≥1500 mg/day (P for trend = 0.01). The HR per 300 mg/day increase was 0.85 (95% CI, 0.76–0.95). There was a suggestive inverse association between total calcium intake and CRC before age 55 years (HR per 300 mg/day increase, 0.87; 95% CI, 0.75–1.00), suggesting the importance of calcium intake in the younger population.
Conclusions
In a cohort of younger women, which reflects the birth cohorts, time periods and age ranges paralleling the recent rise in CRC, higher calcium intake was associated with a decreased risk of CRC.
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Κυριακή 30 Οκτωβρίου 2022

Spindle Cell Carcinoma of the Head and Neck: Clinical Characteristics and Molecular Signatures

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Spindle Cell Carcinoma of the Head and Neck: Clinical Characteristics and Molecular Signatures

Spindle cell carcinoma arising from a previously irradiated field is a predictor of dismal survival. Both genetic and microenvironmental factors contribute to this highly invasive tumor.


Objective/Hypothesis

Spindle cell carcinoma of the head and neck (HNSpCC) is a rare variant of head and neck squamous cell carcinoma (HNSCC). This study evaluated the clinical characteristics and molecular signatures of such tumors.

Study Design

Retrospective analysis.

Methods

Medical records of patients diagnosed with HNSpCC from 1996 to 2018 were reviewed. The clinicopathologic features, treatment modalities, and survival status were carefully recorded. Whole exome sequencing (WES) was performed to evaluate the genetic signatures of HNSpCC.

Results

We found that among all 71 patients included in this study, the majority of them were male, with tumors developing predominantly in the oral cavity. The 1-, 3-, and 5-year disease-specific survival (DSS) rates were 64.6%, 49.5%, and 43.9%, respectively. A high local recurrence (LR) and distant metastasis (DM) rate (47.9%–25.3%, respectively) were observed. A significant proportion (28.2%) of patients with the worst prognosis had history of previous head and neck cancer (HNC) and had been treated with radiotherapy (RT). WES revealed that those post-RT SpCC shared common mutations with their previous HNC (pre-RT SCC), but gained additional genetic traits, such as hypoxia and cell-ECM interaction that were favorable for survival in an irradiated microenvironment. Distinct genetic landscapes in primary and post-RT SpCC were also found.

Conclusions

This study demonstrates that HNSpCC is a unique entity with more aggressive behavior than conventional HNSCC. HNSpCC arising from a previously irradiated field is a predictor of dismal survival. Both genetic and microenvironmental factors contribute to this highly invasive tumor.

Level of Evidence

Level 4 Laryngoscope, 2022

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Diagnostic efficacy of positron emission computerized tomography scans in suspicious laryngeal findings postorgan preservation treatment

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Larynx preservation protocols (LPP) for glottic primary squamous cell carcinoma has gained popularity worldwide. Direct laryngoscopy (DL) with biopsy is mandated when recurrence is suspected. The efficacy of 18Fluoro-deoxy-glucose positron emission computerized tomography (PET-CT) as alternative first-line diagnostic investigation in suspected recurrence was evaluated.

Methods

A retrospective study of patients with suspicious fiber-optic findings at more than 12 weeks after LPP. Sensitivity, specificity, and the negative predictive value (NPV) of DL and PET-CT were compared.

Results

Seventy-two patients presenting 105 cases of suspicious events were included in this study. Fifty-two events were initially investigated by DL and 53 events by PET-CT. The sensitivity of DL and PET-CT was 56.25% and 100%, respectively. The NPV was 84% for DL and 100% for PET-CT (p = 0.015).

Conclusion

Negative PET scans after LPP are highly accurate in ruling out recurrent/persistent disease and may spare the patient from negative biopsies.

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Postoperative analysis of osseous midface reconstructions: The value of imaging and a novel scoring system for complexity and operative success

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Few standardized methods exist for evaluating the postoperative outcomes of osteocutaneous free flaps. We propose an anatomic-based scoring system for midface free flap reconstruction.

Methods

One hundred and twelve patients across four institutions underwent osteocutaneous reconstruction of the midface. Postoperative scans were scored based on the number of independent osseous subunits reconstructed (Subunit Score), the number of different bony appositions with bony contact (Contact Score), and the number of osseous segments in anatomic position (Position Score). These were added together to create a Total Score.

Results

Osteocutaneous radial forearm flaps had the lowest Subunit Score (p = 0.001). Fibula flaps had the highest Contact Score (p = 0.0008) and Position Score (p = 0.001). Virtual surgical planning was associated with an increased Subunit Score (p = 0.02) and Total Score (p = 0.04).

Conclusions

We propose a novel scoring system for osseous midface reconstruction based on postoperative imaging scans. This can help guide management decisions and create a common language to compare outcomes.

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The emerging roles of IFIT3 in antiviral innate immunity and cellular biology

alexandrossfakianakis shared this article with you from Inoreader

Abstract

The interferon inducible protein with tetrapeptide repeats 3 (IFIT3) is one of the most important members in both the IFIT family and interferon stimulated genes (ISGs) family. IFIT3 has typical features of the IFIT family in terms of gene and protein structures, and is able to be activated through the classical PRRs-IFN-JAK/STAT pathway. A variety of viruses can induce the expression of IFIT3, which in turn inhibits the replication of viruses, with the underlying mechanism showing its crucial role in antiviral innate immunity. Emerging studies have also identified that IFIT3 is involved in cellular biology changes, including cell proliferation, apoptosis, differentiation and cancer development. In this review, we summarize the characteristics of IFIT3 with respect to molecular structure and regulatory pathways, highlighting the role of IFIT3 in antiviral innate immunity, as well as its diverse biological roles. We also discuss the potential of IFIT3 as a bi omarker in disease diagnosis and therapy.

This article is protected by copyright. All rights reserved.

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Cidofovir‐induced anterior uveitis in an allogeneic stem cell transplant recipient

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Anterior uveitis is a reported complication of intravenous cidofovir, almost exclusively described in human immunodeficiency virus (HIV) infected patients treated for cytomegalovirus retinitis. In this study, we report the case of an allogeneic stem cell transplant recipient with significant visual impairment and hypotony following administration of high-dose intravenous cidofovir for hemorrhagic cystitis due to BK virus.

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The Use of Dissemination and Implementation to Improve Multimodal Analgesia in Head and Neck Surgery

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The Use of Dissemination and Implementation to Improve Multimodal Analgesia in Head and Neck Surgery

The use of a multimodal analgesia approach in a Randomized Clinical Trial including acetaminophen, ketorolac, gabapentin, and a neurogenic extremity block in patients undergoing major head and neck ablative and reconstructive surgery significantly reduced the need for opioids in the immediate postoperative period of a seven-day hospital stay. Coordination of care and reducing variability in pain medication administration were highly dependent on dissemination and implementation processes put in place for perioperative phases of care.


Objectives

To optimize the delivery of multimodal analgesia to patients undergoing major head and neck oncologic surgeries.

Methods

Pilot study included patients enrolled to receive either scheduled acetaminophen and as-needed opioids (control group) or scheduled acetaminophen, gabapentin, ketorolac, and as-needed opioids (experimental group). RCT, a hybrid type 1 effectiveness-implementation pragmatic trial, was designed to test the effectiveness of the intervention. Arm A received scheduled acetaminophen and as-needed opioids. Arm B received scheduled gabapentin, ketorolac, a regional nerve block at the free tissue donor site, scheduled acetaminophen and as-needed opioids.

Results

Pilot: Thirty-one patients undergoing major head and neck surgery were enrolled. Mean MMEs administered in control group (n = 15) was 251.60 mg (SD = 224.57 mg); mean MMEs in Experimental group (n = 16) was 195.78 mg (SD = 131.08 mg), p = 0.401. LOS was 8.0 days in control versus 7.0 days in experimental group (p = 0.054).

RCT: Interim analysis for safety and futility was planned during trial's design after 30 patients (n = 14 Arm A, and n = 16 Arm B). Mean MMEs administered were 135.1 mg in Arm A, (SD = 86.0 mg) versus mean MME of 51.3 mg in Arm B (SD = 43.3 mg, (p < 0.05)). Given clear superiority results, the trial was prematurely terminated. Functional pain scores, LOS, and complications were similar between the arms (p > 0.05). Variability of mean MME was compared before and after implementation of the management protocols: SD in RCT#1 was 181.46 mg versus 124.6 mg in RCT#2.

Conclusion

Multimodal analgesia significantly reduced the need for opioids in patients undergoing major head and neck surgery.

Level of Evidence

1, Randomized Clinical Trial Laryngoscope, 2022

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