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Κυριακή 6 Μαρτίου 2022

PKM2 Is Overexpressed in Glioma Tissues, and Its Inhibition Highly Increases Late Apoptosis in U87MG Cells With Low-density Specificity

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In Vivo. 2022 Mar-Apr;36(2):694-703. doi: 10.21873/invivo.12755.

ABSTRACT

BACKGROUND/AIM: Pyruvate kinase M2 (PKM2) functions as an important rate-limiting enzyme in aerobic glycolysis and is involved in tumor initiation and progression. However, there are few studies on the correlation between PKM2 expression and its role in glioma.

MATERIALS AND METHODS: PKM2 expression was immunohistochemically examined in human brain tumor samples. Furthermore, we studied the effects of two PKM2 inhibitors (shikonin and compound 3K) on the U87MG glioma cell line.

RESULTS: PKM2 was overexpressed in most glioma tissues when compared to controls. Interestingly, glioma-adjacent tissues from showed slight PKM2 overexpression. This suggests that PKM2 overexpression maybe an important trigger factor for glioma tumorigenesis. We found that the PKM2 inhibitor shikonin was effective against U87MG cells at a relatively low dose and was largely dep endent on low cellular density compared to the effects of the anticancer drug vincristine. Shikonin highly increased late-apoptosis of U87MG cells. We also demonstrated that autophagy was involved in the increase in late-apoptosis levels caused by shikonin. Although vincristine treatment led to a high level of G2-phase arrest in U87MG cells, shikonin did not increase G2 arrest. Co-treatment with two PKM2 inhibitors, shikonin and compound 3K, increased the inhibitory effects.

CONCLUSION: Combination therapy with PKM2 inhibitors together might be more effective than combination therapy with anticancer drugs. Our findings encourage the application of PKM2-targeting in gliomas, and lay the foundation for the development of PKM2 inhibitors as promising antitumor agents for glioma.

PMID:35241524 | DOI:10.21873/invivo.12755

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Endonasal Acoustic Doppler Sonography in Predicting the Survival of Nasoseptal Flap Following Previous Irradiation

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Objective

Blood supply to the nasoseptal flap may be compromised in patients who had previous irradiation to the head and neck region, hence, affecting its viability. Here, we evaluate the role of an endonasal acoustic Doppler sonography in predicting the survival of the nasoseptal flap in this group of patients.

Study Design

Retrospective cohort.

Methods

Retrospective review of patients with previous irradiation to the head and neck region who had undergone endoscopic endonasal surgeries requiring nasoseptal flap as reconstruction. Survival rates of nasoseptal flap were compared between groups where endonasal Doppler was used.

Results

A total of 28 patients were identified with previous irradiation to the head and neck region who had undergone endoscopic endonasal surgeries requiring nasoseptal flap as reconstruction. The overall survival rate of nasoseptal flap is 67.8% (19 out of 28). Endonasal acoustic Doppler was used in 17 of these patients, of which 13 patients had a positive signal. The flap survival rate in the Doppler-positive group compared to the non-Doppler group was significantly better at 100% vs 45.4% (P = .003). Among those where the endonasal Doppler was used, the flap survival rate with a negative doppler signal was significantly worse at 25%, compared with 100% flap survival in those with positive doppler signal (P = .006). The positive predictive value of a positive endonasal Doppler signal with flap survival is 100%.

Conclusion

The use of endonasal acoustic Doppler may be useful in predicting the viability of nasoseptal flap in postirradiated patients who need a local mucosal flap coverage.

Level of Evidence

Level 3 Laryngoscope, 2022

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Smoothed Cepstral Peak Analysis

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Childhood and adolescence are essential stages in the development of voice and speech quality; therefore, it is essential to understand the vocal changes that occur during this period. Frequency-based measurement methods like cepstral measurements stand out among the methods described, which are able to identify fo and estimate the periodicity and noise in the acoustic wave without establishing individual cycles of the sound wave.
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Whole‐transcriptome sequencing identifies postzygotic ATP2A2 mutations in a patient misdiagnosed with herpes zoster, confirming the diagnosis of very late‐onset segmental Darier disease

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ABSTRACT

An 82-year-old female patient presented with a recent onset of painful skin lesions in unilateral distribution on the abdominal area following the lines of Blaschko; the initial diagnosis of Varicella-zoster infection was made. However, because the individual lesions appeared as hyperkeratotic papules and were unresponsive to antiviral therapy, a skin biopsy was performed, which revealed hyperkeratosis, suprabasal acantholysis and dyskeratosis with corps ronds and grains, consistent with acantholytic dyskeratotic acanthoma. Since this entity has been associated with Darier disease, whole transcriptome sequencing by RNA-Seq was performed on RNA isolated from a lesion as well as from adjacent normal appearing skin, and a recently developed bioinformatics pipeline that can identify both genomic sequence variants and the presence of any of over 900 viruses was applied. Two pathogenic missense mutations in the ATP2A2 gene were identified in the lesional but not in normal appeari ng skin, and no evidence of Varicella-Zoster infection was obtained. These findings confirm the diagnosis of segmental Darier disease due to postzygotic mutations in the ATP2A2 gene, and attest to the power of a novel single-step application of RNA-Seq in providing correct diagnosis in this rare genodermatosis.

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A Novel 3-Step Tuning Fork Hearing Test; Preliminary Report on Its Clinical Utility

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Abstract

It is pertinent to have a Tuning Fork Hearing Test that stand-alone can detect severities (Mild, Moderate, Severe and Profound) and the types of hearing losses (Conductive, Sensorineural, and Mixed). A novel 3-Step Tuning Fork Hearing Test (3-STFHT) was attempted for the first time that could detect both the types and the severities of hearing losses. The study was aimed to describe the method of the 3-STFHT and evaluate its clinical utility and reliability. Research Design: Hospital-based observational study of a diagnostic tool. Settings: Otorhinolaryngology Department of a tertiary care medical college hospital. Subjects: 108 adult patients (216 ears) who required hearing evaluation. Main Outcome measures: Sensitivity and specificity of novel 3-STFHT were assessed by comparing its results with the reports of pure tone audiometry in detecting the type and severity of hearing loss. The new 3-STFHT was found very effective (100% sensitivity and specificity) in de tecting conductive and profound sensorineural hearing losses. The sensitivity in detecting sensorineural hearing loss was found 97%-100%. The sensitivity was observed relatively low (92%) at detecting mixed hearing loss. The overall sensitivity and specificity of the 3-STFHT in detecting the types of hearing losses was found 97% and 86% respectively. The novel 3-STFHT, which is simple and convenient, was found very effective in detecting the types and severity of hearing losses. The 3-STFHT can be an important tool in otorhinolaryngology practice and in primary care setting for detecting and screening the types and severities of hearing losses.

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Πέμπτη 3 Μαρτίου 2022

Cost of Total Intravenous Anesthesia Versus Inhalation Anesthesia in Obstructive Sleep Apnea Surgery

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ABSTRACT

Objectives

To compare cost and time spent in surgical and postoperative courses in patients with obstructive sleep apnea (OSA) undergoing surgery with either total intravenous anesthesia (TIVA) or inhalational anesthesia.

Study Design

Retrospective chart review.

Methods

Retrospective review on patients undergoing surgery for OSA under general anesthesia from January 2019 to October 2020. Cost per service was acquired for the day of surgery.

Results

A total of 230 patients were included: 95 received TIVA; 135 received inhalation anesthesia. Total cost was significantly higher in the TIVA nasal surgery group by $286 (P = .035). TIVA produced significantly higher pharmacy and operating room costs across all surgeries and OSA severities. These increased costs were offset by significantly lower supply costs in upper airway stimulator (UAS, −$419.50; P = .007) and uvulopalatopharyngoplasty (UPPP, −$115.16; P = .015) patients receiving TIVA. In the TIVA cohort, there was a trend toward lower recovery room costs after UAS (−$111.09; P = .063) and nasal surgery (−$64.45; P = .096) and anesthesia costs after nasal surgery (−$36.67; P = .054). Total recovery time was reduced by 18 minutes (P = .004) for nasal surgery, 25 minutes (P = .043) for UAS, and 27 minutes (P  ;= .147) for UPPP patients receiving TIVA.

Conclusion

When used in an outpatient setting for patients with OSA, TIVA adds to pharmacy and operating room costs, but this is usually offset by lower supply, anesthesia, and recovery room costs. We found decreased recovery times in the TIVA cohort. TIVA has proven benefits in patient outcomes and can be cost-effective in OSA surgery.

Level of Evidence

3 Laryngoscope, 2022

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Limited contribution of indocyanine green (ICG) angiography for the detection of parathyroid glands and their vascularization during total thyroidectomy: A STROBE observational study

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Publication date: Available online 2 March 2022

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): J. Quéré, G. Potard, R. Le Pennec, R. Marianowski, J.-C. Leclere

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Primary Pyomyositis of Levator Scapulae

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This case report describes a young woman who presented with a suspected deep neck space infection who was subsequently found to have an intramuscular abscess in the left levator scapulae muscle.
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Tumor mutational burden and somatic mutation status to predict disease recurrence in advanced melanoma

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Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma. A retrospective review of 85 patients with stage III or IV melanoma whose tumors were analyzed by next-generation sequencing was conducted. Fisher's exact test was used to assess differences in TMB category by somatic mutation status as well as recurrence locations. Kaplan–Meier estimates and Cox-proportional regression model were used for survival analyses. The most frequently detected mutations were TERT (32.9%), CDKN2A (28.2%), KMT2 (25.9%), BRAF V600E (24.7%), and NRAS (24.7%). Patients with TMB-L + BRAFWT status were more likely to have a recurrence [hazard ratio (HR), 3.43; confidence interval (CI), 1.29–9.15; P = 0.01] compared to TMB-H + BRAF WT. Patients with TMB-L + NRASmut were more likely to have a recurrence (HR, 5.29; 95% CI, 1.44–19.45; P = 0.01) compared to TMB-H + NRAS WT. TMB-L tumors were associated with local (P = 0.029) and in-transit (P = 0.004) recurrences. Analysis of TMB alone may be insufficient in understanding the relationship between melanoma's molecular profile and the body's immune system. Classification into BRAFmut, NRASmut, and tumor mutational load groups may aid in identifying patients who are more likely to have disease recurrence in advanced melanoma. Received 9 December 2021 Accepted 13 January 2022 Correspondence to Meghan J. Hotz, BS, Department of Surgical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA, Tel: +1 610 675 6602; fax: +1 215 728 2773; e-mail: mjohannahotz@gmail.com Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Τετάρτη 2 Μαρτίου 2022

How Many Nodes to Take? Lymph Node Ratio Below 1/3 Reduces Papillary Thyroid Cancer Nodal Recurrence

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Introduction

Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid malignancies; risk of PTC recurrence over a 30-year period is approximately 30%, of which 70% occur as nodal metastases. Patients with nodal disease who are treated with therapeutic dissection are at higher risk for recurrence, but optimal nodal yield has not been defined. We aim to determine variables predictive of nodal recurrence of PTC within the first 5 years of surgery, with a focus on lymph node ratio (LNR), to inform clinical decision-making.

Methods

Retrospective chart review identified 41 patients with nodal recurrence of PTC and 284 without nodal recurrence following thyroid surgery from 2000 to 2015. Cohorts were compared with regards to clinical history, surgical findings, and tumor characteristics.

Results

The fraction of the patients who underwent therapeutic central or lateral lymph node dissection was significantly higher in the nodal recurrence cohort. Maximum tumor size, presence of extrathyroidal extension, largest lymph node focus, LNR, postoperative thyroglobulin level, and administration of postoperative radioactive iodine were significantly increased in the PTC nodal recurrence group. LNR greater than 0.3 held the highest level of significance as a binary cutoff and captured the larger proportion of patients in the nodal recurrence cohort (68.3%).

Conclusion

This study demonstrates characteristics to help assess risk of nodal recurrence of PTC and suggests LNR of lower than 0.3 is optimal to reduce risk of recurrence. The next steps include cohort studies to validate findings and weight variable analysis to optimize the extent of surgical therapeutic dissection.

Level of Evidence

4 Laryngoscope, 2022

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Survival of adult patients with solid cancer

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Bull Cancer. 2022 Feb 26:S0007-4551(22)00068-6. doi: 10.1016/j.bulcan.2022.01.010. Online ahead of print.

ABSTRACT

INTRODUCTION: Population-based cancer survival is a major indicator of effectiveness of cancer management. This study is the first population-based study to estimate the net survival (NS) of adult cancer patients in Reunion Island, a French overseas department with distinctive epidemiological, cultural, and sociodemographic characteristics.

METHODS: All adult incident cases (n=23,055) of invasive solid tumors diagnosed between 1998 and 2014 and registered in the Reunion Island Cancer Registry were included in the study. The Pohar-Perme estimator was used to estimate 1-, 3-, 5-, and 10-year NS.

RESULTS: 5-year NS ranged from 7% (liver in women) to 97% (thyroid cancer in women) for cancers diagnosed between 2006 and 2014. For the most common cancers, the age-standardized 5-year NS of women was 81% for breast canc er, 58% for colorectal cancer and 62% for cervical cancer. For men, the age-standardized 5-year NS was 85% for prostate cancer, 12% for lung cancer, and 52% for colorectal cancer. Age-standardized 5-year NS increased slightly with the period of diagnosis (from 1998-2005 to 2006-2014) for prostate, breast, head and neck, lung, colorectal (women), and stomach (men) cancers, remained stable for colorectal (men) cancer, and decreased slightly for cervical and stomach (women) cancers.

DISCUSSION: Overall, NS was lower in Reunion Island than in mainland France. While the epidemiological, cultural, and sociodemographic characteristics of the Reunionese population likely explain some of the observed differences compared to mainland France, site-specific studies are needed to explore the different determinants of survival in Reunion Island.

PMID:35232576 | DOI:10.1016/j.bulcan.2022.01.010

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Thyroid and Parathyroid Conditions: Hyperthyroidism

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FP Essent. 2022 Mar;514:11-17.

ABSTRACT

Hyperthyroidism is an excess in thyroid hormone production caused by such conditions as Graves disease, toxic multinodular goiter, and toxic adenoma. Overt hyperthyroidism is defined as a low or undetectable thyrotropin (TSH) level with elevated triiodothyronine (T3) or thyroxine (T4) values, whereas subclinical hyperthyroidism is defined as low or undetectable TSH with normal T3 and T4 levels. Symp toms of hyperthyroidism include nervousness, heat intolerance, weight loss, and fatigue. The long-term consequences of unmanaged or poorly managed hyperthyroidism include increased risk of all-cause mortality, cardiovascular events, atrial fibrillation, sexual dysfunction, and osteoporosis. Overt and subclinical hyperthyroidism can be managed effectively with antithyroid drugs (eg, propylthiouracil, methimazole) or with definitive therapies (eg, radioactive iodine ablation, thyroidectomy). Subclinical hyperthyroidism is not always treated, although close monitoring is needed to prevent disease complications or progression to overt hyperthyroidism. Treatment for subclinical hyperthyroidism is recommended for patients 65 years or older with TSH levels lower than 0.10 mIU/L. Treatment also is recommended for symptomatic patients or those with cardiac or osteoporotic risk factors. Thyroid storm is a life-threatening complication of unmanaged or inadequately managed hyperthyroidism that warrants urgent treatment in a hospital setting.

PMID:35235281

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