Comparison of the diagnostic and prognostic abilities of flexible laryngoscopy and dynamic digital radiography for vocal cord paralysis: A prospective observational study.

BACKGROUND: Although flexible laryngoscopy (FL) is the reference modality for diagnosing vocal cord paralysis (VCP), FL involves patient discomfort and insertion intolerance. Dynamic digital radiography (DDR) with high spatial and temporal resolution is easier to use and less invasive when evaluating VCP. METHODS: Seventy-eight patients underwent FL and DDR before and after neck surgery. Qualitative and quantitative vocal cord movement (VCM) evaluations were conducted. Patients with postoperative VCP were followed-up regularly. RESULTS: DDR exhibited diagnostic performance with 67% sensitivity and 100% specificity. The cutoff for VCM was 2.4 mm, with DDR exhibiting 100% sensitivity and 78% specificity. All cords with transient VCP had positive VCM at both 3 weeks and 2 months. Additionally, 50% and 75% of cords with permanent VCP had negative VCM at 3 weeks and 2 months, respectively. CONCLUSIONS: DDR is promising for the diagnosis of postoperative VCP and early prediction of permanent postoperative VCP.

[Relationship Between Psychiatric Nurses' Self-Evaluation of Their Technical Skills and Support From Others in the Hospital].

We conducted a questionnaire survey of psychiatric nurses to clarify the relationship between their self-evaluation of their technical skills and support from others. We obtained valid responses from 578 of these nurses. Factor analysis was used to extract support factors for five types of professionals: supervisors, seniors, peers, juniors, and other professionals in the workplace. The results demonstrated that even in a psychiatric nursing field consisting of nurses of various ages, the structure of support was similar to that in a previous study of young and mid-career employees in the workplace in Japanese companies. The results also showed that the self-evaluation of technical skills was higher for those who received psychological support from their seniors and work support from other professions. The results also revealed that the self-evaluation of technical skills was lower for those who received psychological support from their peers.

Bilateral recurrent laryngeal nerve paralysis diagnosed using dynamic digital radiography during the COVID-19 pandemic.

Dynamic digital radiography (DDR) is a motion-detecting technique with high temporal resolution. Flexible laryngoscopy is a common modality for the observation of the larynx; however, it generates aerosol. DDR is an easy and less risky screening test for the diagnosis of recurrent laryngeal nerve paralysis during the COVID-19 pandemic.

Optimal Preservations of Cytological Materials Using Liquid-Based Cytology Fixatives for Next-Generation Sequencing Analysis.

INTRODUCTION: Molecular targeted therapies have been established for various diseases, including cancers, and there is an increasing need for molecular testing on cytology specimens. The aim of this study was to determine the optimal preservation methods of liquid-based cytology (LBC) materials for molecular testing. METHODS: Cytological samples from 35 surgical resected non-small cell lung carcinoma specimens were obtained between June 2016 and June 2021. The samples were fixed in CytoRich™ red Preservative and stored at 4°C. One week later, three tubes were prepared from each specimen sample and divided into the following groups: the SurePath™ group (continued storage at 4°C), Frozen (Fr) group (stored at -80°C after centrifugation), and LBC-Cell Block (LBC-CB) group (generation of paraffin-embedded CB and storage at 4°C). Samples from 5 patients were used for the time course analysis, and we performed evaluations on these samples at 1, 3, 6, 12, 24, and 36 months. The concentrations and purities of extracted DNA and RNA were measured. The double-stranded DNA (dsDNA) and RNA concentrations were also measured by a fluorometer. The DNA and RNA integrities were quantified by the DNA and RNA integrity number. RESULTS: Evaluation of samples was performed at baseline and the six timepoints. In the LBC-CB group, DNA and dsDNA concentrations were higher rather than those in the other groups. The RNA concentration of the LBC-CB group was relatively high compared with those of the other groups at the 36-month timepoint. The Fr group maintained higher DNA quality compared with the other groups over 3 years. The LBC-CB group maintained a higher RNA quality than the other groups until 24 months. CONCLUSION: LBC-CB preparation is an effective method to maintain DNA/RNA quality and quantity in long-duration preservation for eventual molecular testing. Therefore, LBC-CB may have applications on preanalytical stage for molecular genomic testing such as next-generation sequencing.

Regulatory Single Nucleotide Polymorphism Increases TERT Promoter Activity in Thyroid Carcinoma Cells.

BACKGROUND/AIM: The telomerase reverse transcriptase (TERT) promoter has a regulatory single nucleotide polymorphism (rSNP), rs2853669, and occasionally shows point mutations C228T and C250T. Although C228T and C250T have been well examined to increase TERT promoter activity and are known as risk factors for thyroid carcinoma, the significance of rs2853669 has not been well investigated. This study aimed to clarify the influence of rs2853669 on TERT promoter activity in thyroid carcinoma cells. MATERIALS: Seven of 8 examined thyroid cell lines had rs2853669, 5 had C228T, and 1 had C250T. RESULTS: Three papillary thyroid carcinoma cell lines, harboring both rs2853669 and C228T, showed higher TERT mRNA expression on real-time PCR than the other cell lines. Anaplastic thyroid carcinoma cell lines, in contrast, showed variable TERT mRNA expression depending on the combination of rs2853669, C228T, and C250T. Luciferase assays, performed to compare the influences of rs2853669, C228T, and C250T on TERT promoter activity in thyroid carcinoma, showed that rs2853669, as well as C228T, increased the promoter activity, and the combination of rs2853669 and C228T increased the promoter activity even more strongly than C228T alone. CONCLUSION: We conclude that the presence of rs2853669 within the TERT promoter could be as significant as the C228T mutation in thyroid carcinoma.

Subtyping and EGFR mutation testing from blocks of cytological materials, based on liquid-based cytology for lung cancer at bronchoscopic examinations.

BACKGROUND: Liquid-based cytology (LBC) allows immunohistochemistry (IHC), fluorescence in situ hybridization, and molecular testing to be performed in fixed cell materials. We examined the feasibility of subtyping and EGFR mutation testing of bronchoscopic samples from patients with lung cancer using cell blocks (CB) based on LBC fixation (LBC-CB). METHODS: We included 35 consecutive patients with peripheral lung nodules who underwent endobronchial ultrasonography with a guide sheath in our hospital. Thirty of these patients were diagnosed with lung cancer by obtaining cytological samples. Cytological subtyping was performed with IHC using LBC-CB, and the Cobas EGFR Mutation Test ver. 2 was performed using extracted genomic DNA from the LBC-CB, formalin-fixed paraffin-embedded (FFPE) tissue, and matched plasma. RESULTS: Of the 30 cases, 25 were classified cytomorphologically as adenocarcinoma (ADC, n = 17) and squamous-cell carcinoma (SQCC, n = 8). The remaining five cases were classified by IHC as favor ADC (n = 3) and favor SQCC (n = 2) according to the WHO criteria. In the final ADC group (n = 20), EGFR mutations on the LBC-CB were identified in eight cases (40%; 1 exon 19 deletion, 6 L858R, and 1 L861Q). Mutations in FFPE samples were identified in seven cases (35%) at the same site in each case. Plasma EGFR mutations were identified in four cases (20%) at the same site. The CB detection rate was higher than for FFPE and plasma. CONCLUSION: LBC-CB is suitable for subtyping and EGFR mutation testing in lung cancers.

Effect of single-nucleotide polymorphism in TERT promoter on follicular thyroid tumor development.

Follicular thyroid neoplasm is a common tumor, and consists of follicular thyroid adenoma (FTA) and carcinoma (FTC). The mechanisms of tumor development of FTA and FTC are not well-understood. Single-nucleotide polymorphisms (SNPs) and point mutations in the telomerase reverse transcriptase (TERT) promoter have been associated with tumor development of many cancers. In order to clarify the significance of TERT promoter SNPs and mutations, including rs2853669 (-245T>C), C228T, and C250T, we analyzed 59 FTA patients and 19 FTC patients. Rs2853669 was found in 67.8% (40/59) and 57.9% (11/19) of FTAs and FTCs, respectively, and homozygous rs2853669 (CC) was more frequently found in FTC than in FTA. Furthermore, in FTA, rs2853669 was significantly associated with tumor size greater than 2.0 cm (P < 0.05). C228T was found in 5.1% and 36.8% of FTAs and FTCs, respectively. Frequencies of rs2853669 or/and C228T mutation were 71.2% in FTAs and 73.7%, in FTCs, and were significantly associated with larger tumor sizes in FTAs (P < 0.05). Rs2853669 is considered to be associated with tumor development in FTA and FTC.

A rare post-lobectomy complication of right-to-left shunt via foramen ovale.

BACKGROUND: Various complications can cause hypoxemia after pulmonary resection for lung cancer, but intracardiac shunt that becomes symptomatic and causes severe hypoxemia postoperatively is very rare. We report a case that presented platypnea-orthodeoxia syndrome (POS) due to right-to-left shunt via patent foramen ovale (PFO). CASE: A 71-year-old man with a lung cancer in the left upper lobe was referred to our hospital. Left upper lobectomy was performed. Dyspnea developed postoperatively, which was worsened by sitting or standing and relieved in a recumbent position. Contrast transesophageal echocardiogram (TEE) and right intracardiac catheterization revealed a right-to-left shunt via PFO. Open-heart closure of PFO was performed and the patient was free from POS. CONCLUSIONS: Postoperative intracardiac shunt via PFO can cause severe hypoxemia after lung resection. POS suggests the possibility of intracardiac shunt and careful observation is needed.

Differences in the Impact of Age on Mortality in Well-Differentiated Thyroid Cancer.

INTRODUCTION: Well-differentiated thyroid cancer (WDTC) is unique in that patient age is part of staging. Several studies have shown a need to increase the age threshold in staging for WDTC, but the separate impact of age on prognosis for papillary and follicular carcinomas has not been examined. We hypothesize that age impacts survival differently for papillary and follicular carcinomas. METHODS: Patients with invasive papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) between 2004 and 2013 were identified in the National Cancer Database, and were stratified by histologic type. Overall survival (OS) was analyzed using multivariable Cox regression, and the Youden index was used to find the optimal age threshold for both histologies. RESULTS: A total of 204,139 patients with WDTC were identified. Ninety-two percent had PTC, while 7.7% had FTC. The average age was 48.4 years and OS was 96.3%, with a median follow-up of 52.7 months. When analyzing age in 5-year increments, 10-year mortality increased incrementally by 30-50% per age group for PTC, from age < 35 to ≥ 70 years, without an obvious inflection point. However, FTC patients experienced a more than threefold increase in 10-year mortality from age 40-44 years (2.5%) to age 45-49 years (7.9%). The same pattern was found on multivariable Cox regression. The Youden index found the optimal age thresholds were 58.5 years for PTC and 46.2 years for FTC. CONCLUSION: OS for PTC decreases incrementally with age, but OS for FTC decreases significantly in patients aged 45 years and older. A higher age threshold may inappropriately downstage some high-risk follicular cancer patients.

Interleukin-23 as a therapeutic target for inflammatory myopathy.

Current treatments of polymyositis and dermatomyositis (PM/DM) depend on non-specific immunosuppressants. This study was performed to elucidate the role of interleukin (IL)-23, as their possible therapeutic target. As was reported earlier in PM/DM patients, serum IL-23 levels were elevated in mice with C protein induced-myositis (CIM), a murine model of PM. IL-23 was expressed by macrophages in the PM/DM and CIM muscles and by dendritic cells and macrophages in the lymph nodes from the CIM mice. It was also expressed by macrophages in the chemically injured muscles, but not those recruited into the muscles by footpad injection of Freund's complete adjuvant, demonstrating that IL-23 production should be associated with muscle damage. Genetic deletion of IL-23 as well as preventive and therapeutic administration of blocking antibodies against IL-23p19 subunit suppressed CIM. When lymph node cells from the CIM mice were transferred adoptively into naive wild type or IL-23p19 deficient recipient mice, both recipients developed myositis equally. Thus, elevated IL-23 should promote dendritic cells and macrophages to activate the autoaggressive T cells. Our findings suggest that IL-23 should mediate positive feedback loop from the muscle damage to the T cell activation and be a promising therapeutic target for autoimmune myositis.

[Role of Pharmacists in Completion of Adjuvant Cisplatin-Vinorelbine Chemotherapy in Japanese Patients with Non-small Cell Lung Cancer].

　Adjuvant cisplatin-vinorelbine chemotherapy has been shown to be effective in patients with completely resected non-small cell lung cancer (NSCLC) in several Phase III trials, but not yet in the Japanese population. Pharmacists are expected to assist patients with completion of adjuvant chemotherapy. The aim of this retrospective study was to evaluate the compliance with and safety of adjuvant cisplatin-vinorelbine chemotherapy in Japanese patients and to evaluate the contribution of pharmacists to completion of treatment. Thirty-four patients with NSCLC who received adjuvant cisplatin-vinorelbine chemotherapy at Kyorin University Hospital between January 2006 and June 2015 were reviewed. The treatment schedule comprised cisplatin 80 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks. Four 3-week cycles were planned. A pharmacist provided guidance to all patients and monitored them for adverse effects thereafter. The pharmacist intervened with advice to doctors as necessary. The 4 cycles were administered in 67.6% of cases. There were no treatment-related deaths. The main grade 3 or 4 toxicities were neutropenia (76.5%) and anorexia (38.2%). The most common reason for discontinuation and dose reduction was anorexia. There were 56 instances of pharmacist intervention. In total, 96.4% of the pharmacist interventions were implemented by doctors, which included administration of an antiemetic on 15 occasions and hot fomentation for prevention of vasculitis on 7 occasions. Adjuvant cisplatin-vinorelbine chemotherapy was tolerated by most patients but was discontinued because of adverse events in some. Pharmacist intervention aids completion of planned chemotherapy and management of treatment-related adverse events.

Risk Factors for Chest Pain and Fever in Patients Undergoing Pleurodesis with OK-432.

Objective In Japan, pleurodesis is often performed using OK-432. However, OK-432 may cause severe chest pain and fever. The risk factors for these complications are unclear. The aim of this study was to identify the risk factors for chest pain and fever caused by pleurodesis with OK-432. Methods The clinical data of 94 patients who underwent pleurodesis with OK-432 were retrospectively analyzed. Patients who developed chest pain (indicated by a record of rescue pain medication) and/or fever (a recorded temperature of >38°C) were identified. A logistic regression analysis was performed to determine the risk factors for these complications. Results Rescue medication for chest pain was required by 43.6% of the patients and 40.4% developed pyrexia after pleurodesis with OK-432. The univariate analysis showed that the likelihood of requiring rescue medication for chest pain was significantly increased in patients of <70 years of age (p=0.028) and in those who were not premedicated with a nonsteroidal anti-inflammatory drug (NSAID; p=0.003). Age <70 years (adjusted odds ratio 2.97, 95% confidence interval 1.10-8.00, p=0.031) and a lack of premedication with an NSAID (adjusted odds ratio 4.21, 95% confidence interval 1.47-12.04, p=0.007) remained significant factors in a multivariate analysis. The absence of NSAID premedication was the only statistically significant risk factor for fever in the univariate analysis (p=0.034). The multivariate analysis revealed no significant risk factors for fever. Conclusion The results of the present study suggest that premedication with an NSAID might be useful for preventing the chest pain caused by pleurodesis with OK-432. Furthermore, caution is advised when managing chest pain in adults of <70 years of age. Prospective studies should be performed to further investigate this issue.

Sporadic minute medullary thyroid carcinoma with a double RET mutation: A case report.

We describe a 74-year-old man with a nodular goiter accompanied by an incidental sporadic minute medullary thyroid carcinoma (MTC). Histopathologically, the MTC was a well-defined 1.7 mm tumor in the upper one-third right lobe, with solid cell nests (SCNs) adjacent to the MTC. C-cells were scattered mainly around the SCNs, but C-cell hyperplasia was not evident in the background thyroid. The MTC cell phenotype was immunohistochemically identical to background C-cells, but was completely different from the SCN main cells. Direct DNA analyses of isolated MTC paraffin-embedded specimens revealed two RET proto-oncogene missense point mutations in exon 11 (i.e., C630R and C634W). The non-tumor thyroid tissue did not reveal any mutations. This study reports the smallest case of sporadic MTC with a double RET somatic mutation, substantiating that RET mutations can occur during a very early stage of carcinogenesis. The combined presence of C630R and C634W represent a novel somatic mutation in sporadic MTC. The present case indicates that the sporadic MTC originated from the surrounding C-cells of the SCNs without C-cell hyperplasia and that the SCN main cells may not be able to develop into an MTC.

Discoid Lupus Erythematosus Complicated with Pregnancy-induced Hemophagocytic Syndrome.

A 35-year-old woman with discoid lupus erythematosus (DLE) was admitted at 11 weeks' gestation with a persistent fever. Laboratory studies revealed pancytopenia, elevated liver enzymes, and hyperferritinemia. Bone marrow aspiration confirmed the diagnosis of hemophagocytic syndrome (HPS). She had no findings of infection or active systemic lupus erythematosus. The administration of high-dose corticosteroids resolved the clinical and laboratory findings. She delivered a healthy baby at 35 weeks' gestation. This case suggests that DLE can be a predisposing factor for pregnancy-induced HPS.

Acute Tubulointerstitial Nephritis Associated with Infliximab in a Patient with Crohn's Disease.

We report the findings of a 46-year-old man, who presented with fever and renal dysfunction while undergoing treatment for Crohn's disease with infliximab (IFX). Remittent fever and renal dysfunction with urinary casts developed and lasted for 3 weeks without deterioration of Crohn's disease. Renal biopsy revealed acute tubulointerstitial nephritis (ATIN). After the discontinuation of IFX, his fever and renal abnormalities resolved. We herein report the first known case of ATIN associated with IFX.

Thoracoscopic modified pleural tent for spontaneous pneumothorax.

OBJECTIVES: We developed a modified pleural tent (m-tent) procedure and used it in our hospital in almost 30 consecutive patients with spontaneous pneumothorax. The objective of this study was to clarify the feasibility and effectiveness of a thoracoscopic m-tent for the treatment of spontaneous pneumothorax. METHODS: From July 2013 to November 2014, 107 patients with spontaneous pneumothorax were treated in our institution. Eighty-nine of these patients were analysed retrospectively. The inclusion criteria for thoracoscopic m-tent for spontaneous pneumothorax were multiple and widespread bullae, postoperative relapse and secondary spontaneous pneumothorax. The surgical procedures were usually performed through three ports. After bullectomy, an m-tent is made to strip the parietal pleura off the chest wall from about the level of the fourth or fifth rib to the apex, and two or three ligations are then applied to fix the pleural tent and lung parenchyma. Patients in whom an m-tent was not indicated underwent bullectomy plus coverage using absorbable materials. RESULTS: Twenty-seven patients underwent bullectomy plus m-tent (m-tent group) and 62 underwent bullectomy plus coverage over a staple line using an absorbable material such as a polyglycolic acid sheet or nitrocellulose sheet (coverage group). No severe postoperative complications were observed in either group. The m-tent and coverage groups showed significant differences in operation time (129 vs 86 min, mean), haemorrhage (12.8 vs 7.2 ml), postoperative hospital stay (3.7 vs 2.9 days) and postoperative painkiller intake (8.6 vs 6.8 days). Recurrence was observed in 1 (3.7%) and 2 patients (3.2%), respectively. CONCLUSIONS: The thoracoscopic m-tent procedure requires a longer operation, a longer hospital stay and greater painkiller intake. However, these differences are acceptable, and an m-tent should be considered as an option for pleural reinforcement in spontaneous pneumothorax, especially in patients who are complicated with severe pulmonary emphysema, widespread bullae or recurrent pneumothorax.

Interferon-γ, but Not Interleukin-4, Suppresses Experimental Polymyositis.

OBJECTIVE: C protein-induced myositis (CIM) is a mouse model of polymyositis in which activated antigen-specific CD8+ T cells injure the muscles. Animal models of autoimmunity that have been examined in the past for the effects of the type 1 cytokine interferon-γ (IFNγ) and the type 2 cytokine interleukin-4 (IL-4) are all mediated by pathogenic CD4+ T cells. In those models, the disruption of IFNγ leads to up-regulation of IL-17A, exacerbating the disease with neutrophil infiltration into sites of inflammation. This study was undertaken to investigate the roles of IFNγ and IL-4, as well as IL-17A in the absence of IFNγ, in CD8+ T cell-mediated CIM. METHODS: IFNγ(-/-) mice, anti-IL-17A antibody-treated IFNγ(-/-) mice, IFNγ(-/-) IL-17A(-/-) mice, IL-4(-/-) mice, and wild-type C57BL/6 mice were immunized with skeletal muscle C protein fragments to induce CIM. Muscle tissue specimens were examined histologically. RESULTS: IFNγ(-/-) mice developed myositis at a higher incidence and with greater severity than wild-type mice. Unlike wild-type mice, IFNγ(-/-) mice had infiltration of neutrophils into the endomysial sites of the affected muscles. IFNγ(-/-) mice treated with anti-IL-17A antibodies and IFNγ(-/-) IL-17A(-/-) mice developed myositis with an incidence and severity comparable to those in IFNγ(-/-) mice and showed neutrophil infiltration similar to that in IFNγ(-/-) mice. IL-4(-/-) mice developed CIM comparable to that in wild-type mice. CONCLUSION: Our findings indicate that IFNγ, but not IL-4, plays a suppressive role in the development of CIM. Unlike in CD4+ T cell-mediated autoimmune disease models, IFNγ prevents factors other than IL-17A from exacerbating myositis and neutrophil infiltration in CD8+ T cell-mediated CIM.

A case of relapsing polychondritis initially presenting with bronchial chondritis.

A 51-year-old woman presented with one-month history of fever, productive cough, dyspnea, hoarseness and polyarthritis. Computed tomography (CT) depicted diffuse bronchotracheal stenosis, which deteriorated in exhalation. Three-dimensional CT revealed airway stenosis from the trachea to the lobar bronchi. We made a diagnosis of relapsing polychondritis (RP). Administration of high-dose glucocorticoid and oral cyclophosphamide resolved the symptoms and the bronchial stenosis. It was noteworthy that all features presented were bronchial chondritis and polyarthritis. RP should be considered when patients have polyarthritis with respiratory symptoms. The dynamic expiratory CT and three-dimensional image reconstructions are useful for detecting and following up bronchotracheal involvement.

Diffusion-weighted imaging and positron emission tomography in various cytological subtypes of primary lung adenocarcinoma.

The purpose of the study was to retrospectively characterize diffusion-weighted magnetic resonance imaging (DWI) and positron emission tomography for differentiating among the various cytological subtypes of primary lung adenocarcinomas. The maximum diffusion signal intensities and the maximum standardized uptake value (SUV max) of 31 lesions were analyzed after delineation of regions of interest on the images. Diffusion intensities were 0.934 for Clara type, 0.938 for type II type, 1.473 for nongoblet type, and 1.617 for poorly differentiated adenocarcinoma type based on Shimosato's cytological classification (P=.020). The SUV max values were 4.926, 5.491, 5.709, and 12.132, respectively (P=.044). DWI might reflect some of the cytological characteristics of the tumor cells for differentiating the subtypes of lung adenocarcinomas.

The saw-tooth sign as a clinical clue for intrathoracic central airway obstruction.

BACKGROUND: The saw-tooth sign was first described by Sanders et al in patients with obstructive sleep apnea syndrome as one cause of extrathoracic central airway obstruction. The mechanism of the saw-tooth sign has not been conclusively clarified. The sign has also been described in various extrathoracic central airway diseases, such as in burn victims with thermal injury to the upper airways, Parkinson's disease, tracheobronchomalacia, laryngeal dyskinesia, and pedunculated tumors of the upper airway. CASE PRESENTATION: A 61-year-old man was referred to our hospital with a two-month history of persistent dry cough and dyspnea. He was diagnosed with lung cancer located in an intrathoracic central airway, which was accompanied by the saw-tooth sign on flow-volume loops. This peculiar sign repeatedly improved and deteriorated, in accordance with the waxing and waning of central airway stenosis by anti-cancer treatments. CONCLUSION: This report suggests that the so-called saw-tooth sign may be found even in intrathoracic central airway obstruction due to lung cancer.