Simultaneous treatment of two lung cancer lesions with stereotactic MR-guided adaptive radiation therapy: A case report.

RATIONALE: Lung cancer is 1 of the most prevalent cancers globally. Definitive stereotactic ablative radiotherapy (SABR) is suggested for those who are unfit for or refuse surgical intervention. Here we present a patient with 2 lung cancer lesions who received SABR simultaneously with magnetic resonance Linear accelerator (Linac)-magnetic resonance (MR). PATIENT CONCERNS: A 46-years-old man had history of left lower lung cancer post lobectomy in 2018. Two recurrent tumors were found 2 years following, then became enlarged 4 months later. DIAGNOSES: The recurrent tumors were found by computed tomography. INTERVENTIONS: SABR was indicated due to inoperability and small size. Simulation was done both by computed tomography and MR scan with ViewRay MRIdian Linac, with the prescription dose being 50 gray in 4 fractions performed every other day within 2 weeks. The 2 lesions were irradiated at the same time with a single isocenter with mean treatment time was 78 minutes. OUTCOMES: No acute side effect was noted. Follow-up chest computed tomography scan 14 months after SABR showed mild consolidation and pneumonitis over the upper irradiated site favoring radiation-related reasons, while pneumonitis was resolved over the lower irradiated site. Positron emission tomography showed no definite evidence of FDG-avid recurrence. The patient has survived over 18 months following SABR and more than 4 years from the first diagnosis of lung cancer without significant adverse effects. LESSONS: Simultaneous SABR for multiple lung lesions is quite challenging because tumor motion by breathing can increase the risk of missing the target. With help by MR-Linac, simultaneous SABR to multiple lung lesions can be performed safely with efficacy.

Histones of Neutrophil Extracellular Traps Directly Disrupt the Permeability and Integrity of the Intestinal Epithelial Barrier.

BACKGROUND: Increased neutrophil extracellular trap (NET) formation and abundant NET-associated proteins are frequently found in the inflamed colon of patients with inflammatory bowel disease. Peptidyl arginine deiminase 4 (PAD4) activation is essential for the generation of NET and NET-mediated pathogenesis. However, the role of PAD4-dependent NET formation in murine inflammatory bowel disease models and the molecular mechanisms responsible for the altered gut barrier function are unknown. METHODS: Wild-type and Pad4 knockout (Pad4-/-) mice were administrated 3% dextran sulfate sodium (DSS) in their drinking water. Caco-2 monolayers were used to test the effect of NETs on intestinal barrier function and cytotoxicity. Histones were intrarectally administrated to wild-type mice to determine their effects on intestinal barrier function and cytotoxicity in vivo. RESULTS: PAD4 deficiency reduced the severity of DSS-induced colitis with decreased intestinal NET formation and enhanced gut barrier function and integrity in mice. NETs disrupted the barrier function in intestinal epithelial Caco-2 monolayers through their protein, rather than DNA, components. Pretreatment of NETs with histone inhibitors abrogated the effects on epithelial permeability. Consistent with these observations, adding purified histone proteins to Caco-2 monolayers significantly damaged epithelial barrier function, which was associated with the abnormal distribution and integrity of tight junctions as well as with increased cell death. Furthermore, intrarectal administration of histones damaged the intestinal barrier integrity and induced cytotoxicity in the mouse colon epithelium. CONCLUSIONS: PAD4-mediated NET formation has a detrimental role in acute colitis. NET-associated histones directly inhibit intestinal barrier function, resulting in cytotoxicity in vitro and in vivo.

Peptidyl arginine deiminase 4­dependent neutrophil extracellular trap formation is detrimental to intestinal barrier function in acute colitis. Neutrophil extracellular trap­associated histones altered the integrity of tight junction and adherens junction proteins as well as induced intestinal epithelial cell death that resulted in increased gut epithelium permeability.

The prognostic significance of pretreatment squamous cell carcinoma antigen levels in cervical cancer patients treated by concurrent chemoradiation therapy and a comparison of dosimetric outcomes and clinical toxicities between tomotherapy and volumetric modulated arc therapy.

BACKGROUND: To analyze the prognostic factors associated with stage IB-IVA cervical cancer in patients who underwent concurrent chemoradiation therapy (CCRT) and to compare the clinical toxicities and dosimetric parameters of organs at risk between the different radiotherapy techniques. METHODS: This retrospective study enrolled 93 patients with stage IB-IVA cervical cancer who underwent definitive CCRT between April 2009 and December 2017. Nine patients (9.7%) received 3DCRT, 43 patients (46.2%) underwent VMAT, and 41 patients (44.1%) received tomotherapy, and all of them followed by brachytherapy using a 2D planning technique. The treatment outcomes and related prognostic factors were analyzed. We also compared the clinical toxicities and dosimetric parameters between the different techniques used for the last 30 patients. RESULTS: With a median follow-up of 52.0 months, the 5-year overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS) were analyzed. In a Cox proportional hazards regression model, pretreatment SCC Ag > 10 ng/mL was a significant prognostic factor for PFS (hazard ratio [HR] 2.20; 95% confidence interval [CI] 1.03-4.70; P = 0.041), LRRFS (HR, 3.48; 95% CI 1.07-11.26; P = 0.038), and DMFS (HR 2.80; 95% CI 1.02-7.67; P = 0.045). Increasing the rectal volume receiving a radiation dose exceeding 30 Gy (V30 of rectum; odds ratio [OR] 1.15; 95% CI 1.10-1.30; P = 0.03) was associated with a higher possibility of ≥ Grade 2 acute radiation therapy (RT)-related diarrhea. The median rectal V30 values were 56.4%, 97.5%, and 86.5% for tomotherapy, 3-dimensional conformal radiation therapy (3DCRT), and volumetric modulated arc therapy (VMAT), respectively (P < 0.001). In addition, the chance of experiencing ≥ Grade 2 acute diarrhea were 10.0%, 66.7%, and 54.5% for tomotherapy, 3DCRT, and VMAT, respectively (P = 0.029). CONCLUSIONS: Patients with pretreatment SCC Ag ≤ 10 ng/mL have better PFS, LRRFS, and DMFS than those with pretreatment SCC Ag > 10 ng/mL. The rectal V30 is a significant predictor of severe acute diarrhea. Tomotherapy significantly decreased the rectal V30, reducing the severity of acute RT-related diarrhea during external beam RT. Trial registration This study was approved by the institutional review board at Kaohsiung Medical University Hospital. The registration number is KMUHIRB-E(I)-20190054 and retrospectively registered on 2019/3.

Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis.

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

Five-year survival outcomes of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) using forward IMRT or Tomotherapy for breast cancer.

Intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) reduces overall treatment duration and results in less radiotherapy (RT)-induced dermatitis. However, the use of traditional sequential approach or IMRT-SIB is still under debate since there is not enough evidence of long-term clinical outcomes. The present study investigated 216 patients who underwent breast conserving surgery (BCS) between 2010 and 2013. The median age was 51 years (range, 21-81 years). All patients received IMRT-SIB, 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Among 216 patients, 175 patients received post-operative RT with forward IMRT and 41 patients had Tomotherapy. The median follow-up was 6.4 years. Forty patients (97.6%) in the Tomotherapy arm and 147 patients (84%) in the IMRT arm developed grade 0-1 skin toxicity (P = 0.021). For the entire cohort, the 5-year and 7-year overall survival (OS) rates were 94.4% and 93.1% respectively. The 7-year distant metastasis-free survival rates were 100% vs 89.1% in the Tomotherapy and IMRT arm respectively (P = 0.028). In conclusion, Tomotherapy improved acute skin toxicity compared with forward IMRT-SIB. Chronic skin complication was 1.9%. IMRT-SIB resulted in good long-term survival.

Humoral and cytokine responses in giant groupers after vaccination and challenge with betanodavirus.

Giant groupers were immunized with two dosages (Vhigh and Vlow) of inactivated nervous necrosis virus (NNV) and subsequently challenged with NNV at 4 weeks post vaccination (wpv). Several indicators were used to analyze the protective effects of the NNV vaccine. The neutralizing antibody titer of fish serum mostly corresponded to the survival rate of immunized fish in the NNV challenge test. Extravascular IgM+ cells were detected in the brains of both NNV-infected and noninfected groupers. After NNV infection, CD8α and IgM gene expression increased in the brains, indicating CD8α+ and IgM+ lymphocyte infiltration. Moreover, the NNV load was not the highest in dead grouper brains, suggesting that this load in the brain was not the key factor for the death of groupers. However, the brains of dead fish showed the highest expression of the interleukin (IL)-1ß gene, a neurotoxic factor in the brain. Therefore, IL-1ß overexpression is likely to be associated with the death of NNV-infected groupers.

Separation, purification, and α-glucosidase inhibition of polysaccharides from Coriolus versicolor LH1 mycelia.

Intracellular polysaccharides (iPs) were separated and purified from Coriolus versicolor LH1 mycelia and characterized for their α-glucosidase inhibitory properties. Three iP fractions (iPL-F5-2-1, iPL-F5-4-1, and iPL-F5-5-1) were extracted, separated, and purified from LH1 mycelia using microwave extraction technology, a DEAE-Sepharose CL-6B column, a Diaion HP20 macroporous adsorption column, and a Sephadex™ G-50 gel-permeation column. The principal constituents of iPL-F5-2-1, iPL-F5-4-1, and iPL-F5-5-1 were saponins and polyphenoic compound mixtures. The enzyme inhibition activity, IC(50) values, of these three fractions were 1.7, 1.8, and 0.8 mg/mL, respectively. The α-glucosidase inhibitory properties were related to the presence of α-(1,4) glycosidic linkages in the polysaccharide structure and the total relative percentage of d-glucose and d-galactose in the structure of polysaccharides, other than triterpenoids.

Applications of Hadamard transform-gas chromatography/mass spectrometry for the detection of hexamethyldisiloxane in a wafer cleanroom.

The Hadamard transform-gas chromatography/mass spectrometry (HT-GC/MS) technique was successfully employed for the detection of hexamethyldisiloxane (HMDSO, C(6)H(18)OSi(2)) at the sub-nL/L level in a semiconductor wafer cleanroom. Indoor air samples were collected from the room, according to EPA Method TO-17 using a Tedlar bag where the air samples were allowed to pass through an absorption tube for 24 h. The condensed components were then heated and simultaneously injected into a GC column through a Hadamard-injector, which was operated in accordance with the Hadamard codes. Compared to the single injection used in most GC/MS systems, the signal-to-noise (S/N) ratios were substantially improved after the inverse Hadamard transformation of the encoded chromatogram. Under optimized conditions, when cyclic S-matrix orders of 255, 1023 and 2047 were used, the S/N ratios of the HMDSO signals were substantially improved by 7.4-, 15.1- and 20.1-fold, respectively. These improvements are in good agreement with theoretically calculated values (8.0-, 16.0- and 22.6-fold, respectively). We found that when the HT-GC/MS technique was applied, HMDSO could be detected at the 0.1 nL/L level.

Applications of Hadamard transform-gas chromatography/mass spectrometry to online detection of exhaled breath after drinking or smoking.

A Hadamard transform-gas chromatography/mass spectrometry (HT-GC/MS) technique was employed for the online detection of ethanol or toluene in exhaled breath after drinking or smoking, respectively. Exhaled breath samples, collected from volunteers, were directly injected into the GC inlet by a Hadamard-injector without any pretreatment. In the case of breath from a drinker, using a conventional single injection, a small ion peak (corresponding to approximately 0.1 ng of ethanol), the intensity of which was approximately equal to or less than the limit of detection. When the HT technique was applied, the signal-to-noise (S/N) ratio was dramatically improved. Furthermore, in the case of breath from a smoker, using conventional injection, a weak ion peak (corresponding to approximately 0.7 pg of toluene) was marginally detected. However, the HT technique led to an improvement in the S/N ratio, with the peak corresponding to the limit of detection. In both cases, the HT technique permitted specific components in exhaled breath to be determined, without the need for any extraction procedures.

Upper aerodigestive tract sequelae in severe enterovirus 71 infection: predictors and outcome.

OBJECTIVE: Enterovirus 71 (EV71) infection sequelae can be severe and life-threatening, and long-term follow-up outcomes remain unknown. Therefore, we conducted a retrospective follow-up study to review airway and neurological sequelae development in patients with severe EV71 infection. We also studied the incidence and risk factors for tracheotomy and gastrostomy requirement. PATIENTS AND METHODS: We investigated 202 EV71-infected children according to their disease stage. Seventy-two of them were diagnosed to have EV71 encephalitis, which was characterized by myoclonus, ataxia, nystagmus, oculomotor palsy and bulbar palsy or combinations of these conditions. All the 72 patients required endotracheal intubation due to respiratory failure or ventilator dependence; among these, 14 underwent tracheostomy and 10 underwent gastrostomy. All patients were followed-up for at least 3 years after discharge. Predictors of tracheostomy and gastrostomy requirement were age <2 years, body weight <10th percentile, pulmonary hemorrhage or edema, meningeal symptoms and magnetic resonance imaging (MRI) findings of upper spinal cord and brainstem. We determined outcome based on persistent tracheostomy or gastrostomy requirement and whether patients developed positive neurological sequelae. RESULTS: Significant tracheostomy and gastrostomy predictors were age <2 years, pulmonary edema or hemorrhage, hypotension, hemiparesis and positive MRI findings. Statistical analysis revealed pulmonary edema and hypotension as index predictors of tracheostomy requirement and pulmonary edema as the significant risk factor for gastrostomy. CONCLUSIONS: Long-term neuropsychological impact was observed on children who present the signs of the pulmonary edema or hypotension in the early onset of the EV71 infection. EV71-infected patients who develop neurological pulmonary edema or hypotension should be hemodynamically stabilized and undergo early tracheostomy to prevent further complications. This may improve the decannulation success rate after the brainstem function recovers.

Increased prevalence of interleukin-1 receptor antagonist gene polymorphism in patients with chronic rhinosinusitis.

OBJECTIVE: To assess the association of the interleukin (IL)-1beta and the IL-1 receptor antagonist (IL-1Ra) gene polymorphisms with chronic rhinosinusitis (CRS). DESIGN: Genotyping of the 2 IL-1beta gene (IL1B) polymorphisms (promoter and exon) and the IL-1Ra gene (IL1RN) polymorphism (intron 2) was performed using polymerase chain reaction and restriction length fragment polymorphism analyses. SETTING: Prospective study, tertiary medical center. PATIENTS: The study population comprised 88 consecutive adult Taiwan-Chinese patients who met stringent criteria for CRS and received endoscopic sinus surgery and 103 healthy volunteers of the same ethnicity and similar age range. Of the 88 patients, 61 had CRS with nasal polyps, while the other 27 had CRS without nasal polyps. RESULTS: There were significant differences in the distribution of the IL1RN polymorphism between the control subjects and patients with CRS (P<.05). The II allele of IL1RN occurred more frequently in the CRS patient group, and the odds ratio for subjects with I/II genotype was 3.39 (95% confidence interval, 1.25-9.18). In the case of CRS without nasal polyps, the odds ratio for subjects with I/II genotype was further increased to 4.75 (1.39-16.25). There was no association between the other 2 polymorphisms of IL1B and CRS. CONCLUSION: Increased prevalence of IL1RN polymorphism in patients with CRS suggests that this polymorphism, or a polymorphism in linkage disequilibrium with it, may be involved in the development of CRS.

Altered expression profile of superoxide dismutase isoforms in nasal polyps from nonallergic patients.

OBJECTIVE/HYPOTHESIS: Nasal polyposis (NP) is a chronic inflammatory disease of the upper respiratory tract. The pathophysiology is unknown but has been shown to be multifactorial. Free radical-mediated damage has been implicated in the pathogenesis of NP. Superoxide dismutases (SODs) are the first and the most important line of antioxidant enzyme defense against reactive oxygen species. Moreover, isozymes of the SOD family are critical for modulating the activity of nitric oxide, a gaseous free radical that is believed to play roles in the physiology and pathology of respiratory tracts. However, the expression profile of SOD isoforms in NP remains unclear. We aimed to investigate the expression profile of the SOD isoforms in nasal polyps from nonallergic patients. STUDY DESIGN: Prospective study. METHODS: Nasal polyp tissues were obtained from eight nonallergic patients who underwent elective polypectomy; mucosal specimens from the middle turbinates were acquired from eight subjects without NP as control tissues. The expression profile of SOD isoenzymes, SOD1, SOD2, and SOD3, in the nasal tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting (WB). RESULTS: NP in all eight of the NP patients manifested as severe or recurrent sinonasal polyposis clinically. The expression pattern of SOD isoenzymes evaluated by RT-PCR analysis indicated that the mean levels of SOD1 mRNA and, to a greater extent, SOD3 mRNA were higher in polyp tissues than in control tissues. There was no significant difference in the expression levels of SOD2 mRNA between the two groups. The data from ELISA and WB analysis showed that there were increased expressions of SOD1 and SOD3 protein in polyp tissues compared with the control tissues, but there was no difference in the expression of SOD2 protein between the two groups. The results from RT-PCR, ELISA, and WB were paralleled and revealed that the expressions of SOD1 and, to a greater extent, SOD3 were higher in polyp tissues than in the control group. CONCLUSIONS: The expressions of SOD3 and SOD1 were higher in polyp tissues. These results are consistent with previously reported data and support the hypothesis that there is increased oxidative stress in NP. Our data also suggest that the SODs might be important in the pathogenesis of NP; however, the roles these SOD isoforms, especially SOD3, play in both normal nasal mucosa and NP require further clarification.

Middle ear effusion in intensive care unit patients with prolonged endotracheal intubation.

OBJECTIVES: The purpose of this study is to explore the factors related to the occurrence of middle ear effusion (MEE) in prolonged endotracheal intubation patients in the intensive care unit (ICU). METHODS: Information about the age, sex, duration of endotracheal intubation, level of consciousness, and placement of nasogastric tube was retrospectively collected from medical charts of 20 prolonged endotracheal intubation (>7 days) patients in the ICU. All patients received otoscopic examination, tympanometry studies, and spectral gradient acoustic reflectometry for evidence of MEE. RESULTS: Among the 40 ears examined in this study, 20 ears had MEE (50%), 14 ears were normal (35%), and 6 ears had negative pressure in the middle ear (15%). In addition, patients with conscious disturbance and those who had been intubated for 14 days had a significantly higher incidence of MEE. Nasogastric tube was not implicated in MEE in this study. No episodes of acute otitis media or systemic infection were encountered in this study. CONCLUSIONS: Prolonged endotracheal intubation (>7 days) in adult ICU patients contributed to the high incidence of MEE (50%). Moreover, conscious disturbance and endotracheal intubation for 14 days were also significant contributing factors of MEE.

Small B cell lymphocytic lymphoma presenting as obstructive sleep apnea.

BACKGROUND: Most lymphomas that involve the tonsil are large B cell lymphomas. Large B-cell lymphoma is a high grade malignancy which progresses rapidly. Tonsillar lymphoma usually presents as either a unilaterally enlarged palatine tonsil or as an ulcerative and fungating lesion over the tonsillar area. Small lymphocytic lymphomas (SLL) of the Waldeyer's ring are uncommon. CASE PRESENTATION: We report a 41-year-old male who presented with a ten-year history of snoring. Physical examination revealed smooth bilateral symmetrically enlarged tonsils without abnormal surface change or cervical lymphadenopathy. Palatal redundancy and a narrowed oropharyngeal airway were also noted. The respiratory disturbance index (RDI) was 66 per hour, and severe obstruction sleep apnea (OSA) was suspected. No B symptoms, sore throat, odynophagia or dysphagia was found. We performed uvulopalatopharyngoplasty (UPPP) and pathological examination revealed incidental small B-cell lymphocytic lymphoma (SLL). CONCLUSION: It is uncommon for lymphoma to initially present as OSA. SLL is an indolent malignancy and is not easy to detect in the early stage. We conclude that SLL may be a contributing factor of OSA in the present case.

Deep neck infection in children.

OBJECTIVES: Deep neck infection is a potentially life-threatening disease and rarely seen in children. Because of the obscure complaints and symptoms, the diagnosis of deep neck infection may be delayed, which may result in inappropriate treatment. This retrospective study was aimed at analyzing the occurrence of complications, diagnostic methods and proper managements of deep neck infection in children. METHODS: A retrospective study was performed on 30 children with deep neck infection treated from October 1999 through October 2003. The etiology, clinical symptoms, laboratory examination, radiological examination, bacteriology, and treatments were retrospectively analyzed. RESULTS: The most common predisposing factors were tonsillitis and upper respiratory tract infection. The most common symptoms were fever (93.3%) and painful swelling of the neck (70.0%). Both peritonsillar (24.3%) and parapharyngeal space infections (24.3%) were the most common, followed by submandibular space infections (18.9%). The most common pathogens isolated were Staphylococcus aureus (27.3%) and viridans streptococci (22.7%). The mean duration of hospitalization was 7.9 days, with a range from 2 to 18 days. Complications occurred in 2 patients, including recurrence and pulmonary edema. CONCLUSIONS: Deep neck infection should be suspected in a child who presents with fever and painful swelling of the neck. Staphylococcus aureus and viridans streptococci were the most common pathogens. Computed tomography scan should be performed in time and infections in peritonsillar and ,parapharyngeal spaces were the most common.

Endoscopic survey of post-extubation stridor in children.

Endotracheal intubation is an important airway procedure in the management of neonates and infants. Prolonged intubation may result in severe laryngeal injury which may lead to chronic laryngeal disability. The nature and causes of post-extubation airway obstruction were evaluated with videoendoscopy. From June 1998 to September 2000, detailed videoendoscopic examination of pediatric airway was performed in 30 children who had persistent stridor after endotracheal extubation or failure of elective extubation. Common locations of post-extubation lesion are the posterior glottis and subglottis. Retrospective analysis of the causes of stridor included: (1) isolated intubation laryngotracheitis (n = 19); (2) intubation laryngotracheitis with neuromuscular dysfunction which resulted in tongue drop, laryngotracheal incoordination, saliva pooling over the larynx or poor cough reflex(n = 5); and (3) specific airway problems such as laryngomalacia, subglottic stenosis or vocal paralysis(n = 6). We favored the term of "intubation laryngotracheitis" instead of "intubation injury" or 'intubation trauma". Although most cases of intubation laryngotracheitis heal, leaving a normal or near-normal larynx, some of them still suffer from airway obstruction after endotracheal extubation. Specific airway problems such as severe laryngomalacia or vocal cords paralysis and neurogenic defects should also be taken into consideration.

Subglottic leiomyoma: report of a case.

Subglottic leiomyoma is a rare disease. We encountered such a tumor in a 7-year-old boy who was transferred to our hospital with respiratory distress and hoarseness of 2 week's duration. Stridor was noted and flexible fiberoscopy revealed a huge mass over the subglottis. The tumor was removed endoscopically. Pathologic examination disclosed a leiomyoma. The patient recovered well and no recurrence was noted during 17 months of follow-up. Although subglottic leiomyoma is rare, it should be included in the differential diagnosis of a subglottic tumor.