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Δευτέρα 31 Οκτωβρίου 2022

Higher levels of cerebrospinal fluid and plasma neurofilament light in human immunodeficiency virus-associated distal sensory polyneuropathy

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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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Outcome and associated predictors for non‐surgical management of large cyst‐like periapical lesions: A CBCT‐based prospective cohort study.

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Abstract

Aim

The aim of this cone-beam computed tomography (CBCT) based study was to evaluate the outcome of non-surgical root canal treatment (RCT) performed for the management of large cyst like periapical lesions (LCPL) and to identify the predictive factors affecting healing.

Methodology

54 subjects (77 permanent maxillary anterior teeth) with LCPL (>10mm) of endodontic origin were included. A single operator performed standardised multi-visit RCT. Patients were clinically and radiographically examined at 6,12 months and a CBCT scan was taken at 24 months. Two independent blinded evaluators measured the pre and postoperative volume of periapical lesions on CBCT scans using ITK snap software (version 3.8.0-beta-20181028-win64). The outcome was assessed as a percentage change in lesion volume and dichotomized as success (resolved/reduced) or failure (unchanged/enlarged). Ten pre-operative (gender; age; intraoral draining sinus, soft tissue swelling, tooth discoloration, pulp canal obliteration, open apex, root resorption, cortical bone defect and lesion volume) and four intraoperative (apical extent and density of root filling; number of treatment visits and type of root filling) predictive factors were observed. Bivariate and stepwise multivariable linear regres sion analysis was performed to identify independent predictors affecting treatment outcomes. The significance level was set at 5%.

Results

A recall rate of 88% was achieved. The success rate of RCT was 82.2% (8.9% resolved, 73.3% reduced). Median lesion volume reduction was 75% (IQR 61%-93%). No pre or intra-operative factors were related to treatment failure. However, presence of preoperative cortical bone defect (palatal versus no cortical defect, β= -51.5; 95% CI: -86.9 to -16, p = 0.006) and apical extent of obturation (long versus flush, β= -27.2; 95% CI: -53.8 to -0.6, p = 0.04) were negatively associated with reduction in lesion volume (%).

Conclusion

LCPL may be successfully managed with RCT. Preoperative cortical bone defect and apical extent of obturation may negatively influence osseous healing.

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

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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

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

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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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Comparative analysis and trends in liver transplant hospitalizations with clostridium difficile infections: A 10‐year national cross‐sectional study

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ABSTRACT

Goals and Background

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea in the United States. We aimed to determine comparative trends in inpatient outcomes of liver transplant (LT) patients based on CDI during hospitalizations.

Methods

The national inpatient sample (NIS) database was used to conduct the present retrospective study regarding CDI among the LT hospitalizations from 2009, to 2019. Primary outcomes included ten-year comparative trends of the length of stay (LOS) and mean inpatient charges (MIC). Secondary outcomes included comparative mortality and LT rejection trends.

Results

There was a 14.05% decrease in CDI in LT hospitalizations over the study period (P = 0.05). The trend in LOS did not significantly vary (P = 0.9). MIC increased significantly over last decade in LT hospitalizations with CDI (P < 0.001). LT hospitalizations of autoimmune etiology compared against non-autoimmune did not increase association with CDI, adjusted odds ratio (aOR) 0.97 [95% confidence interval (CI) 0.75-1.26, P = 0.87]. CDI was associated with increased mortality in LT hospitalizations, aOR 1.84 [95% confidence interval (CI) 1.52-2.24, P < 0.001].  In-hospital mortality for LT hospitalizations with CDI decreased by 7.75% over the study period (P = 0.3). CDI increased transplant rejections, aOR 1.3 [95% CI 1.08-1.65, P < 0.001]. There was a declining trend in transplant rejection for LT hospitalization with CDI from 5% to 3% over the study period (P = 0.0048).

Conclusion

CDI prevalence doesnot increase based on autoimmune LT etiology. It increases mortality in LT hospitalizations; however, trend for mortality and transplant rejections has been declining over the last decade.

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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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The evolution of fertility preservation care models in a large pediatric cancer and blood disorders center

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Children and adolescents who receive gonadotoxic treatments are at risk for future infertility. While there is a growing focus on integrating fertility preservation (FP) within pediatric cancer and blood disorder centers, wide variations in care models and methods exist across institutions. The purpose of this work is to describe the evolution of FP care models within a large pediatric hematology/oncology center.

Methods

Models of care and associated timeframes are described, including a pre-FP program model, establishment of a formal FP program, integration of nurse navigators, and the addition of FP consult stratification based on urgency (urgent/nonurgent). The number of patient consults within each model, patient sex, diagnosis (oncologic/hematologic), and consult timing (pre-gonadotoxic treatment/posttreatment completion) were abstracted from the clinical database.

Results

The number of annual consults increased from 24 during the pre-FP program model (2015) to 181 during the current care model (2020). Over time, the proportion of consults for females and patients with nonmalignant hematologic disorders increased. Patient stratification reduced the proportion of consults needing to be completed urgently from 75% at the advent of the FP program to 49% in the current model.

Conclusions

The evolution of care models within our FP program allowed for growth in the number of consults completed, expansion of services to more patients with nonmalignant hematologic disorders, and more consults for female patients. Nurse navigators play a critical role in care facilitating referrals, coordination, and patient education. Urgency stratification has allowed FP team members to manage increasing FP-related encounters.

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Off‐label pharmacological treatment for neuropathic pain: A Delphi study by the Spanish Pain Society Neuropathic Pain Task Force

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Abstract

Objectives

The use of off-label pharmacotherapies for neuropathic pain (NP) is growing relating to the many unmet needs of patients. However, clinical guidelines fail to address it, and the available evidence is sparse and fragmented. We arranged a formal expert consensus to address this controversial issue and provide some guidance on judicious use.

Methods

A two-round standard Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 40-item questionnaire prepared by the authors. Consensus on each statement was defined as at least either 80% endorsement or rejection after the second round.

Results

Forty-three and thirty-seven panelists participated in the first and second round, respectively. Consensus was reached in 34 out of 40 statements. Endorsed alternatives for unresponsive patients include non-gabapentinoid antiepileptics (oxcarbazepine and eslicarbazepine), venlafaxine, intravenous lidocaine (when doses can be optimized), and some vaporized cannabinoids (under appropriate surveillance). In addition, lacosamide, low-dose naltrexone, propofol or ketamine could prove beneficial if subjected to more research. Other options were rejected, and there was controversy about the usefulness of topical preparations.

Discussion

For patients who do not respond to standard NP treatments, some other viable pharmacological options can be attempted before advancing to other therapeutic stages. This may help patients who are reluctant to or have some contraindication for interventional therapies.

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Παρασκευή 28 Οκτωβρίου 2022

Cytosolic DNA Sensors Activation Inhibits HIV Infection of Macrophages

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Abstract

Cytosolic recognition of microbial DNA in macrophages results in the activation of the interferon (IFN) dependent antiviral innate immunity. Here, we examined whether activating DNA sensors in peripheral blood monocyte-derived macrophages (MDMs) can inhibit HIV. We observed that the stimulation of MDMs with poly(dA:dT) or poly(dG:dC) (synthetic ligands for the DNA sensors) inhibited HIV infection and replication. MDMs treated with poly(dA:dT) or poly(dG:dC) expressed higher levels of both type I and type III IFNs than untreated cells. Activation of the DNA sensors in MDMs also induced the expression of the multiple intracellular anti-HIV factors, including IFN-stimulated genes (ISGs: ISG15, ISG56, Viperin, OAS2, GBP5, MxB and Tetherin) and the HIV restriction microRNAs (miR-29c, miR-138, miR-146a, miR-155, miR-198, and miR-223). In addition, the DNA sensor activation of MDM upregulated the expression of the CC chemokines (RANTES, MIP-1α, MIP-1β), the ligan ds for HIV entry coreceptor CCR5. These observations indicate that the cytosolic DNA sensors have a protective role in the macrophage intracellular immunity against HIV and that targeting the DNA sensors has therapeutic potential for immune activation-based anti-HIV treatment.

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Impact of Serial Intralesional Steroid Injections on Idiopathic Subglottic Stenosis

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Objectives

Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea.

Methods

Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan–Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score. Within patients undergoing SILSI, demographics, time from last procedure, and PEF at initiation of SILSI were evaluated to determine the effect on recurrence.

Results

Two hundred and ninety patients were included, 238 undergoing endoscopic dilation alone and 52 undergoing dilation and SILSI. No differences in baseline characteristics were observed. There was no difference in time to recurrence (hazard ratio: 0.64; p = 0.183). There were no differences in PEF or CCQ across the 2.5-year study period. Among 52 patients undergoing SILSI, PEF at the time of starting SILSI did not affect recurrence (χ 2 = 0.09, p = 0.77).

Conclusion

Patients undergoing and not undergoing SILSI had similar times to recurrence, PEF, and CCQ. Factors predicting recurrence among patients undergoing SILSI were not identified. These results support a randomized controlled trial with a uniform SILSI protocol to quantify the effects of SILSI on objective and subjective outcomes and help determine which iSGS patients benefit most.

Level of Evidence

3 Laryngoscope, 2022

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