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Κυριακή 28 Νοεμβρίου 2021

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review

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Abstract

Given the recent successes of anti-PD-1 immunotherapy, many clinical trials have sought to assess the safety and efficacy of this treatment modality in the neoadjuvant setting. This systematic review provides a comprehensive summary of findings from neoadjuvant head and neck cancer immunotherapy clinical trials with a focus on PD-1/PD-L1 axis blockade. Pubmed, Embase, Cochrane Library, Web of Science, Google Scholar, and clinicaltrials.gov were systematically searched for all eligible neoadjuvant head and neck cancer immunotherapy clinical trials. Eight clinical trials met the inclusion criteria comprising a total of 260 patients. Study drugs included nivolumab, pembrolizumab, ipilimumab, durvalumab, and tremelimumab. The overall mean objective response rate (ORR) was 45.9 ± 5.7% with a 41.5 ± 5.6% single agent mean ORR. There were no deaths due to immune-related toxicities. Neoadjuvant immunotherapy for mucosal head and neck squamous cell cancer has demonstrated favorable response rates with no unexpected immune-related toxicities in phase I/II clinical trials.

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Identifying Barriers in Access to Care for Head and Neck Cancer Patients: A Field Study in Dakar

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Objectives/Hypothesis

To identify barriers in access to care for head and neck cancer (H&NC) patients in low- and middle-income countries (LMICs), specifically within Dakar, Senegal, using both quantitative and qualitative data.

Study Design

Descriptive observational study.

Methods

Patients with H&NC were selected from two independent university hospitals in Dakar, Senegal. A mixed-methods descriptive study was performed using a specifically tailored questionnaire and a focused ethnographic qualitative approach to identify factors that delay patient presentation, referral, and treatment. Quantitative data were analyzed using descriptive statistics and qualitative using a deductive approach based on a systematic review of the literature.

Results

Thirty-three patients with a mean age of 57.8 years were included. Presentation delay was 5.7 months, mainly attributed to cost of consultation (39%), waiting time at doctor's office (15%), and distance to healthcare facility (12%). Referral delay greater than 3 months was observed in 60% of participants, secondary to misdiagnosis and lack of appropriate referral. Treatment delay was associated with limited local treatment capacity and securing cost of treatment. Cost of transportation impacted all delays.

Conclusions

This work used an evidence-based approach to identify barriers in access to care for H&NC patients in sub-Saharan Africa. It suggests the feasibility and transferability of this methodology which combined a quantitative approach based on the literature with a qualitative analysis. Insight provided by this study will be used to guide development of implementation strategies for early detection of H&NC in LMICs.

Level of Evidence

4 Laryngoscope, 2021

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Introducing a modified algorithm for enhanced operator independency in auditory steady-state responses (ASSRs) testing

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Acta Otorhinolaryngol Ital. 2021 Nov 26. doi: 10.14639/0392-100X-N1640. Online ahead of print.

NO ABSTRACT

PMID:34825670 | DOI:10.14639/0392-100X-N1640

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Relationship between Ideal Cardiovascular Health Metrics and Hearing Loss: A 10‐Year Retrospective Cohort Study

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ABSTRACT

Objective

The role of ideal cardiovascular health (CVH) metrics in developing hearing loss remains uncertain. Thus, our objective was to analyze the connection between hearing loss and ideal CVH metrics in a 10-year retrospective cohort.

Study Design

Retrospective cohort study.

Setting

A health management center in Taiwan.

Participants

Participants who underwent the first annual health check-up between 2000 and 2006 and with a follow-up check-up more than ten years later.

Main outcome measures

Hearing thresholds were measured at 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz. Individuals with a best ear pure-tone audiometry four-frequency average of >25 dB HL were defined as having hearing loss. The ideal CVH metrics were classified into 7 categories based on the American Heart Association's definition. The associations of hearing loss with the sum of the ideal CVH metrics and each ideal CVH metric were examined by multiple logistic regression analysis.

Results

The present study consisted of 6,974 participants. The 10-year follow-up showed that the odds ratio (OR) of hearing loss was 0.74 for participants with 5-7 ideal CVH metrics (95% CI, 0.59-0.93, p=0.01) compared to those with 0-2 ideal CVH metrics. Among the CVH metrics, participants with an ideal smoking status might have reduced odds of developing hearing loss; the OR was 0.72 (95% CI, 0.58-0.89, p=0.003).

Conclusions

Participants with an increased number of ideal CVH metrics and better performance on the smoking metric had a significantly protective effect regarding hearing loss development.

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Cochleovestibular involvement in patients with Fabry disease: data from the multicenter cohort FFABRY

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Eur Arch Otorhinolaryngol. 2021 Nov 26. doi: 10.1007/s00405-021-07173-x. Online ahead of print.

ABSTRACT

PURPOSE: Fabry disease (FD) is a lysosomal storage disease responsible for cochleovestibular involvement. Exact prevalence and pathophysiological mechanisms behind ENT affections are still poorly known. Treating FD with enzyme replacement therapy (ERT) does not seem to significantly improve the ENT symptoms, while the impact of migalastat has yet to be determined.

METHODS: We carried out a retrospective multi-centre study on 47 patients from the FFABRY cohort who had an ENT consultation in the context of their FD. The information collected were as follows: clinical examination, videonystagmoscopy, pure-tone speech audiometry, videonystagmography or VHIT (Video Head Impulse Test). Severe hearing loss was defined as greater than 70 dB.

RESULTS: The median age of our cohort was 52 years with a non-negligible proportion of n on-classic variants and female carriers. 72.3% of the patients complained of at least one of the following symptoms: hearing loss, tinnitus or vertigo. Pure-tone audiometry was abnormal in 61.7% of the patients (29/47), while speech audiometry was abnormal for 41.7% of the patients. The age of the patients and hypertrophic cardiomyopathy were significantly associated with the existence of an anomaly in pure-tone audiometry results. Severe hearing loss (> 70 dB) was significantly more common in male patients.

DISCUSSION: Hearing loss is particularly frequent in FD and is not limited to classic phenotypes. Close ENT follow-up is essential for Fabry patients to detect those who might benefit from hearing aid. Further studies are needed to define the impact of migalastat on cochleovestibular symptoms.

PMID:34825971 | DOI:10.1007/s00405-021-07173-x

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An experience with 124 cases of fanconi anemia: clinical spectrum, hematological parameters and chromosomal breakage analysis

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Am J Blood Res. 2021 Oct 15;11(5):498-503. eCollection 2021.

ABSTRACT

BACKGROUND: Fanconi anemia is an inherited bone marrow failure syndrome characterized by somatic abnormalities and an increased predisposition to malignancies.

OBJECTIVE: To determine the clinical spectrum and evaluate the hematological parameters as well as highlight diagnosis by chromosomal breakage analysis of Fanconi anemia patients.

MATERIAL AND METHODS: A total of 124 patients were diagnosed as having Fanconi anemia from August 2014 to May 2020 at Armed Forces Institute of Pathology, Rawalpindi, Pakistan. Clinical details, somatic abnormalities, radiological findings, lab parameters and result of chromosomal breakage analysis were noted and analyzed.

RESULTS: One hundred and twenty four (14.29%) were diagnosed as having Fanconi anemia (FA) on chromosomal breakage test. Median age was 09 years 06 months. Male to female ratio was 1.9:1. Six of t hese patients exhibited mosaicism and were classified as FA mosaic. Somatic abnormalities were detected in 74 (59.7%) patients; the most common being skeletal abnormalities and short stature.

CONCLUSION: Chromosomal breakage analysis is a cost-effective method for diagnosis of Fanconi anemia. Early diagnosis is pertinent for proper treatment and long term prognosis.

PMID:34824882 | PMC:PMC8610795

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Impact of G-CSF administration post-allogeneic hematopoietic stem-cell transplantation on outcomes: a systematic review and meta-analysis

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Am J Blood Res. 2021 Oct 15;11(5):544-563. eCollection 2021.

ABSTRACT

Granulocyte colony-stimulating factors (G-CSFs) have been used post hematopoietic stem cell transplant (HSCT) for earlier neutrophil engraftment. The use of G-CSFs, and their effect on other post-HSCT outcomes remains debatable. In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane library, Google Scholar, and IndMed using a predefined search strategy. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) reporting data on G-CSF administration post-HSCT, published in the English language from their inception until Jan 31, 2021. The primary outcome of this systematic review and meta-analysis was to evaluate the time to neutrophil engraftment (NE). The secondary outcomes were probability of NE, time to platelet engraftment (PE), the incidence of graft-versus-host disease (GVHD), duration of hospital stay (HS), and overall survival (OS). The review is registered with PROSPERO (CRD42020206989). Fourteen studies were extracted (n=9850), of which five were RCTs, and nine were NRSs. As per Egger's test, publication bias was not present for any outcome. After meta-analysis, we found that the duration of NE favouring G-CSF arm from RCTs was -0.94 days (SMD) [(95% CI: -1.38, -0.51); I2=35%], and from NRSs -1.2 days (SMD) [(95% CI: -1.43, -0.96); I2=74%]. For the outcome of GVHD, the relative risks (RR) of incidence for chronic GVHD and overall GVHD were not significant for the RCTs, and these were 1.11 (RR) [(95% CI: 1.00, 1.22); I2=43%] and 1.10 (RR) [(95% CI: 1.03, 1.18); I2=48%], respectively for NRSs. There was no difference in the incidence of GVHD (acute or chronic) in both arms. No significant difference was found between the two arms for the outcomes of PE, HS, and OS. For NE, there was a marginal benefit of around one day with the use of G-CSF. Th e use of G-CSF did not alter time to PE, the incidence of GVHD, HS, and OS in both arms.

PMID:34824887 | PMC:PMC8610798

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The Insula: A Stimulating Island of the Brain

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Brain Sci. 2021 Nov 19;11(11):1533. doi: 10.3390/brainsci11111533.

ABSTRACT

Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and trigger seizures. Clinical responses to insular DCS are frequent and diverse, showing a partial segregation with spatial overlap, including a posterior somatosensory, auditory, and vestibular part, a central olfactory-gustatory region, and an anterior visceral and cognitive-emotional portion. The study of cortico-cortical evoked potentials (CCEPs) has shown that the anterior (resp. posterior) insula has a higher connectivity rate with itself than with the posterior (resp. anterior) insula, and that both the anterior and posterior insula are closely connected, notably between the homologous insula r subdivisions. All insular gyri show extensive and complex ipsilateral and contralateral extra-insular connections, more anteriorly for the anterior insula and more posteriorly for the posterior insula. As a rule, CCEPs propagate first and with a higher probability around the insular DCS site, then to the homologous region, and later to more distal regions with fast cortico-cortical axonal conduction delays. Seizures elicited by insular DCS have rarely been specifically studied, but their rate does not seem to differ from those of other DCS studies. They are mainly provoked from the insular seizure onset zone but can also be triggered by stimulating intra- and extra-insular early propagation zones. Overall, in line with the neuroimaging studies, insular DCS studies converge on the view that the insula is a multimodal functional hub with a fast propagation of information, whose organization helps understand where insular seizures start and how they propagate.

PMID:34827532 | DOI:10.3390/brainsci11111533

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Paraneoplastic acute vestibular syndrome: What, when and how

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Publication date: November–December 2021

Source: Acta Otorrinolaringologica (English Edition), Volume 72, Issue 6

Author(s): Carolina Moreno-de-Jesús, Lucía Prieto-Sánchez-de-Puerta, Irene Mármol-Szombathy, Emilio Domínguez-Durán

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Rare anastomosis between a replaced right hepatic artery and left branch of the proper hepatic artery

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Surg Radiol Anat. 2021 Nov 27. doi: 10.1007/s00276-021-02863-x. Online ahead of print.

ABSTRACT

Appreciation of the potential anatomical variation of the hepatic arterial supply and branches of the abdominal aorta is of paramount importance in pancreatic and hepatobiliary surgery. Here we describe a hitherto un-reported coelio-mesenteric anastomotic connection between a replaced right hepatic artery, originating from the superior mesenteric artery, and the left hepatic branc h of the proper hepatic artery. The embryological origins of the variant anatomy as well as its potential surgical implications are discussed with a view to encourage thorough pre-operative interrogation of available imaging by radiologists and surgeons to successfully identify such variants and take advantage of their potentially useful functionality.

PMID:34837499 | DOI:10.1007/s00276-021-02863-x

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Double‐Barrel Versus Single‐Barrel Fibula Flaps for Mandibular Reconstruction: Safety and Outcomes

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Objectives/Hypothesis

Fibula flaps are routinely used for osseous reconstruction of head and neck defects. However, single-barrel fibula flaps may result in a height discrepancy between native mandible and grafted bone, limiting outcomes from both an aesthetic and dental standpoint. The double-barrel fibula flap aims to resolve this. We present our institution's outcomes comparing both flap designs.

Study Design

Retrospective cohort study.

Methods

We conducted a retrospective review of all patients undergoing free fibula flap mandibular reconstruction at our institution between October 2008 and October 2020. Patients were grouped based on whether they underwent single-barrel or double-barrel reconstruction. Postoperative outcomes data were collected and compared between groups. Differences in categorical and continuous variables were assessed using a Chi-square test or Student's t-test, respectively.

Results

Out of 168 patients, 126 underwent single-barrel and 42 underwent double-barrel reconstruction. There was no significant difference in postoperative morbidity between approaches, including total complications (P = .37), flap-related complications (P = .62), takeback to the operating room (P = .75), flap salvage (P = .66), flap failure (P = .45), and mortality (P = .19). In addition, there was no significant difference in operative time (P = .86) or duration of hospital stay (P = .17). After adjusting for confounders, primary dental implantation was significantly higher in the double-barrel group (odds ratio, 3.02; 95% confidence interval, 1.2–7.6; P = .019).

Conclusion

Double-barrel fibula flap mandibular reconstruction can be performed safely without increased postoperative morbidity or duration of hospital stay relative to single-barrel reconstruction. Moreover, the double-barrel approach is associated with higher odds of primary dental implantation and may warrant further consideration as part of an expanded toolkit for achieving early dental rehabilitation.

Level of Evidence

III Laryngoscope, 2021

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