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Τετάρτη 3 Αυγούστου 2022

Constitutive programmed death ligand 1 expression protects gastric G‐cells from Helicobacter pylori–induced inflammation

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Abstract

Introduction

Gastric intestinal metaplasia (GIM) is a premalignant lesion, highly associated with Helicobacter pylori infection. Previous studies have shown that H. pylori is able to induce the expression of programmed death ligand 1 (PD-L1), an inhibitory immune modulator, in gastric cells. Our aim was to investigate whether tissues from GIM patients may exploit PD-L1 expression upon H. pylori infection to evade immunosurveillance.

Methods

Immunohistochemistry was performed for PD-L1 and enteroendocrine markers somatostatin and gastrin on samples derived from a cohort of patients with known GIM, both before and after H. pylori eradication. To determine the identity of any observed PD-L1-positive cells, we performed multiplex immunofluorescent staining and analysis of single-cell sequencing data.

Results

GIM tissue was rarely positive for PD-L1. In normal glands from GIM patients, PD-L1 was mainly expressed by gastrin-positive G-cells. While the D-cell and G-cell compartments were both diminished 2-fold (p = .015 and p = .01, respectively) during H. pylori infection in the normal antral tissue of GIM patients, they were restored 1 year after eradication. The total number of PD-L1-positive cells was not affected by H. pylori, but the percentage of PD-L1-positive G-cells was 30% higher in infected subjects (p = .011), suggesting that these cells are preferentially rescued from destruction.

Conclusions

Antral G-cells frequently express PD-L1 during homeostasis. G-cells seem to be protected from H. pylori-induced immune destruction by PD-L1 expression. GIM itself does not express PD-L1 and is unlikely to escape immunosurveillance via expression of PD-L1.

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Effectiveness of root resection techniques compared with root canal retreatment or apical surgery for the treatment of apical periodontitis and tooth survival: A systematic review

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Abstract

Background

To manage apical periodontitis in root filled maxillary and mandibular molars, root resection techniques may be employed to avoid the loss of the tooth.

Objectives

To systematically analyse the effectiveness of root resection techniques (root resection/crown resection/root amputation) for the management of apical periodontitis with non-surgical root canal retreatment or apical surgery by the evaluation of clinical and patient-related outcomes (PROMS), in human experimental studies and longitudinal studies.

Methods

An electronic literature search in PubMed, MEDLINE via OVID interface, EMBASE, and Cochrane Central, supplemented by a manual hand search of the grey literature, was performed up to 25th September 2021. Randomised controlled trials, comparative clinical trials, and observational studies reporting on the outcome (tooth survival and patient-reported outcome measures with a minimum follow-up of one year) of root resection techniques for treating apical periodontitis were identified. The risk of bias was evaluated using the Newcastle-Ottawa scale.

Results

From a total of 2098 reports, 36 were considered for further screening. Three retrospective studies, published between 2018 and 2020, were included in this systematic review. A high heterogeneity in terms of protocols, study design and the reported outcomes were observed. The risk of bias was scored as low to moderate. These three studies consisted of data from 305 resected teeth, from 254 patients, with a follow-up period of 1-16.8 years. Overall, 151 teeth were extracted during the follow-up period. In these studies, root resection treatment was carried out on 42 teeth exclusively for endodontic reasons. One of these studies reported 12 out of 23 teeth lost at follow-up. None of the studies reported on PROMS.

Discussion

Although root resection techniques may be used for treating teeth with apical periodontitis, the data are limited. Furthermore, the studies are very heterogeneous and associated with high risk of bias.

Conclusions

Given the current level of available evidence, it is not possible to recommend, or dismiss, root resection techniques for managing apical periodontitis.

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Seroprevalence of Kaposi’s Sarcoma‐Associated Herpesvirus and Risk Factors in Jiuquan area, China

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Abstract

The seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) is high in Xinjiang, China. But the seroprevalence of KSHV and risk factors are still unknown in Gansu which is adjacent to Xinjiang. 678 serum samples of general population and 87 serum samples of syphilis patients from Jiuquan, Gansu were tested for antibodies against KSHV including one latent protein (ORF73) and two lytic proteins (ORF65 and K8.1) using the ELISA. The total KSHV-seropositive rate was 15.9% in 678 serum samples of Jiuquan area, the KSHV-seropositive rate of males was higher than females (18.0% VS 14.6%, P > 0.05). The Uygur, Kazakh, Hui, Manchu and Mongolian population had a higher seroprevalence of KSHV than the Han population (43.8%, 40.0%, 34.5%, 30.3%, 35.0% VS 11.0%, respectively) among the ethnic groups in Jiuquan. Compared to the Han, Uygur, Kazak, Hui, Manchu and Mongolian people had an increase in the risk of KSHV of 528.9%, 439.1%, 325.6%, 251.6%, 335. 4% (P < 0.001, P < 0.001, P < 0.001, P = 0.002, P = 0.003, respectively). The serum prevalence of KSHV in subjects aged < 20 years, 20-50 years and > 50 years was 13.8%, 14.7% and 20.1%, respectively. Compared to the subjects aged < 20 years, 20-50 years and > 50 years had an increase in the risk of KSHV of 7.4% and 56.9% (P = 0.829 and P = 0.204, respectively). Compared to the positive rate of KSHV in the general population of Anhui, the positive rate of KSHV was significantly higher in the general population of Jiuquan area (15.9% VS 9%, P < 0.01). There was no significant difference in the positive rate of KSHV between the Han population of Jiuquan and the Han population of Anhui (P > 0.05). In the population of syphilis patients of Jiuquan area, the positive rate of KSHV was 30.7%, which was higher than that of the general population in Gansu area (P < 0.05). This study indicates that Gansu has a high seroprevalence of KSHV. Ethnicity and syphilis are risk factors for KSHV infection.

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The effect of clinical interventions on the oral health‐related quality of life in older adults

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Abstract

This paper reviews the literature to assess the effectiveness of oral health interventions in influencing oral health-related quality of life (OHRQoL) in older adults. Clinical studies published in 2010 onwards reporting oral health interventions in older adults and subsequent changes in OHRQoL were systematically searched in Medline, Web of Science and EMBASE databases. Reporting followed Preferred Reporting Items for Systematic Review and Meta-Analysis criteria. Eligibility evaluation and data abstraction from eligible studies were guided by predefined PICO questions and bias assessment by the Quality in Prognosis Studies tool. The search retrieved 144 articles. Of the 20 articles that met the eligibility criteria, 45% (9) reported a statistically significant improvement in OHRQoL. The majority of studies were conducted in adults with complete edentulism (70%) and mainly focused on implant provision to support a removable prosthesis (30%). The search indicates the limited scope of current literature on geriatric dental interventions, focusing mainly on denture realignments, denture fabrication and implant placement. Although the majority of the oral health interventions focused on edentulism and removable prostheses, there are many areas of oral health interventions and their potential impact on OHRQoL in this demographic group that have yet to be explored.

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Τρίτη 2 Αυγούστου 2022

First Demonstration Project of Long-Acting Injectable Antiretroviral Therapy for Persons With and Without Detectable HIV Viremia in an Urban HIV Clinic

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Abstract
Background
Long-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naïve or experienced people living with HIV (PLWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PLWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART.
Methods
Ward 86 is a large HIV clinic in San Francisco that serves publicly insured or underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method. Descriptive statistics evaluated program outcomes.
Results
Between June 2021-April 2022, 51 patients initiated LAI-ART, with 39 receiving at least two follow-up injections by database closure (median age 46; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients initiating injections with viral suppression (median CD4 706), 100% (95% CI 86-100%) maintained viral suppression. Of 15 patients initiating injections with detectable viremia (median CD4 99, mean log10 viral load 4.67 SD 1.16), 12 (80%; 95% CI 55-93%) achieved viral suppression and the other 3 had a 2-log viral load decline by a median of 22 days.
Conclusions
This small demo nstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.
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Spatiotemporal trends in norovirus outbreaks in the United States, 2009–2019

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Abstract
Background
Globally, noroviruses cause infections year-round but have recognized winter seasonality in the northern hemisphere and yearly variations in incidence. With candidate norovirus vaccines in development, understanding temporal and geographic trends in norovirus disease is important to inform potential vaccination strategies and evaluate vaccine impact.
Methods
We analyzed data from the National Outbreak Reporting System (NORS) and CaliciNet on single-state norovirus outbreaks that occurred from August 2009–July 2019 in the contiguous United States. We defined norovirus season onset and offset as the weeks by which 10% and 90% of norovirus outbreaks in a surveillance year occurred, respectively, and duration as the difference in weeks between onset and offset. We compared norovirus seasons across surveillance years and geographic regions.
Results
During August 2009–July 2019, 24,995 single-state norovirus outbreaks were reported to NORS and/or CaliciNet. Nationally, median norovirus season duration was 24 weeks, with onset occurring between October–December and offset occurring between April–May. Across all years combined, we observed a west-to-east trend in seasonality, with the earliest onset (October) and latest offset (May) occurring in western regions and the latest onset (December) and earliest offset (April) occurring in northeastern regions.
Conclusions
Timing and duration of the US norovi rus season varied annually, but generally occurred during October–May. Norovirus wintertime seasonality was less distinct in western regions and was progressively more pronounced moving east. Further understanding the drivers of spatiotemporal dynamics of norovirus could provide insights into factors promoting virus transmission and help guide future interventions.
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The management of metastatic neck nodes following induction chemotherapy in N2/3 classification hypopharyngeal carcinoma

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Abstract

Background

For patients with less chemosensitive neck nodes, poor prognosis after chemoradiotherapy (CRT) could be predicted and neck dissection is needed.

Methods

Ninety-two N2/3 hypopharyngeal carcinoma patients were retrospectively studied. According to response after induction chemotherapy (ICT), patients were treated with neck dissection followed by concurrent CRT (CCRT) (group 1), surgery plus postoperative CRT (group 2), or CCRT for primary and regional sites (group 3).

Results

Overall survival and disease-free survival rates of group 1 were significantly higher than group 2 (p = 0.038, p = 0.031) and group 3 (both p = 0.018). Regional control rate of group 1 was significantly higher than group 3 (p = 0.041). There were no significant differences between groups 1 and 2 regarding local and regional control (p = 0.746, p = 0.302).

Conclusions

Neck dissection followed by CCRT is the best choice for patients with responsive primary but nonresponsive nodes.

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Association between body composition and survival in head and neck cancer patients undergoing radiotherapy

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Body composition may influence the prognosis of head and neck cancer (HNC) patients. To find out the most crucial factors in this relationship, we explored the association between body composition and survival.

Methods

In this prospective longitudinal study, HNC patients who underwent radiotherapy (RT) from March 2017 to December 2018 were recruited. The association between body composition and survival was analyzed using Cox proportional hazard regression.

Results

Final analysis included 316 patients, with a median follow-up of 34.4 months. Multivariable analysis revealed that weight loss 6 months before RT and body composition changes during RT did not affect the survival outcome. However, patients with low appendicular skeletal muscle mass index (ASMI) before RT exhibited poor overall survival (OS). ASMI before RT was an independent prognostic factor for OS.

Conclusions

Body composition loss was common during RT, and ASMI before RT independently influenced the survival outcomes of HNC patients.

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Recurrence risk stratification and treatment strategies of patients with stage IVa‐b hypopharyngeal squamous cell carcinoma

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Abstract

Background

Optimal treatment strategies for patients with stage IVa-b hypopharyngeal squamous cell carcinoma (HSCC) remain controversial. This study aimed to examine the high-risk factors of postoperative tumor recurrence after surgical resection of HSCC and devise individualized postoperative adjuvant treatment (POAT).

Methods

Overall, 218 patients with stage IVa-b HSCC who received surgery as initial treatment and with negative surgical margins were evaluated. Independent risk factors of recurrence were identified, and survival outcomes were compared according to recurrence risk and POAT use.

Results

POAT significantly improved recurrence-free survival (RFS) and overall survival (OS) only in the high-risk patients (p = 0.003 and 0.018, respectively). Compared with postoperative radiotherapy alone, postoperative chemoradiotherapy (pCRT) achieved significantly better RFS (p = 0.035) and OS (p = 0.048).

Conclusions

POATs are recommended for high-risk patients with stage Iva-b HSCC, with pCRT achieving superior outcomes. Regular re-examination after tumor resection is sufficient for low-risk patients.

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Prediction of R Status in Resections for Pancreatic Cancer Using Simplified Radiological Criteria

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imageObjective: Predicting R status before surgery for pancreatic cancer (PDAC) patients with upfront surgery and neoadjuvant therapy. Summary Background Data: Negative surgical margins (R0) are a key predictor of long-term outcomes in PDAC. Methods: Patients undergoing pancreatic resection with curative intent for PDAC were identified. Using the CT scans from the time of diagnosis, the 2019 NCCN borderline resectability criteria were compared to novel criteria: presence of any alteration of the superior mesenteric-portal vein (SMPV) and perivascular stranding of the superior mesenteric artery (SMA). Accuracy of predicting R status was evaluated for both criteria. Patient baseline characteristics, surgical, histopathological parameters, and long-term overall survival (OS) after resection were evaluated. Results: A total of 593 patients undergoing pancreatic resections for PDAC between 2010 and 2018 were identified. Three hundred and twenty-five (54.8%) patients underwent upfront surgery, whereas 268 (45.2%) received neoadjuvant therapy. In upfront resected patients, positive SMA stranding was associated with 56% margin positive resection rates, whereas positive SMA stranding and SMPV alterations together showed a margin positive resection rate of 75%. In contrast to these criteria, the 2019 NCCN borderline criteria failed to predict margin status. In patients undergoing neoadjuvant therapy, only perivascular SMA stranding remained a predictor of margin positive resection, leading to a rate of 33% R+ resections. Perivascular SMA stranding was related to higher clinical T stage (P = 0.003) and clinical N stage (P = 0.043) as well as perineural invasion (P = 0.022). SMA stranding was associated with worse survival in both patients undergoing upfront surgery (36 vs 22 months, P = 0.002) and neoa djuvant therapy (47 vs 34 months, P = 0.050). Conclusions: The novel criteria were accurate predictors of R status in PDAC patients undergoing upfront resection. After neoadjuvant treatment, likelihood of positive resection margins is approximately halved, and only perivascular SMA stranding remained a predictive factor.
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