Different tumor growth pattern of clinically nonfunctioning pituitary neuroendocrine tumor according to sex and age: a longitudinal study.

PURPOSE: Asymptomatic patients with clinically non-functional pituitary neuroendocrine tumors (CNF-PitNETs) are usually followed up. However, the natural course of CNF-PitNETs according to sex and age remains unclear. Therefore, this study assessed growth patterns of CNF-PitNETs according to sex and age. METHODS: In this longitudinal study, we enrolled 431 consecutive patients with CNF-PitNETs who were treated at Seoul National University Hospital from 1997 to 2021. The patients underwent hormone function testing and visual field testing, and were subsequently followed up with imaging over a median duration of 66 months. RESULTS: The median age of the patients was 53.0 years, and 37.1% (n = 160) were men. Men were older and harbored more macroadenomas than women. The annual tumor volume change was higher in men than in women (0.21 vs. 0.04 cm3/year, P < 0.001). The estimated cutoff value of age for significant tumor growth was 51 years. In men, the annual tumor volume change was similar across all age groups. In women, those aged ≤ 50 years showed significantly lower annual tumor volume change than those aged > 50 years (0.01, 0.11, and 0.17 cm3/year, P = 0.001). When comparing sexes within the same age group, the annual tumor volume changes was significantly lower for women than for men, only in patients aged ≤ 50 years (0.01 vs. 0.15 cm3/year, P < 0.001). CONCLUSIONS: Among patients with CNF-PitNET, tumor growth was slower in women aged ≤ 50 years than in men and women aged > 50. These findings may guide the customization of surveillance strategies for CNF-PitNETs according to sex and age.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Study of structural and magnetic properties and heat induction of gadolinium-substituted manganese zinc ferrite nanoparticles for in vitro magnetic fluid hyperthermia.

This article outlines the synthesis of gadolinium (Gd)-doped manganese zinc ferrite magnetic nanoparticles (MNPs) as potential magnetic carriers for magnetic fluid hyperthermia (MFH). MNPs with high specific loss power (SLP; 146 W/g) have been developed and used for an in vitro hyperthermia study. The treatment of MFH is fruitful if there is an adequate number of MNPs in tumor cells with the highest SLP to rapidly generate heat while minimizing thermal injury to surrounding healthy tissue. X-ray diffraction patterns of the studied particles confirm the formation of a cubic spinel structure. Field emission scanning electron micrographs showed homogeneous distributions of particles with some agglomerates with a granular appearance. Transmission electron microscopy analysis showed the presence of agglomerated spherical particles at the surface. The substitution of Gd resulted in superparamagnetism at room temperature as confirmed by vibrating sample magnetometer analysis. The estimated saturation magnetization reduced from 48.6 to 28.2 emu/g with an increase in Gd concentration. However, the coercivity increased from 1093 Oe to 1597 Oe. Field cooled and zero field cooled measurements showed Curie temperatures from 315 to 326 K, as required for MFH applications. Cell viability measurements indicated that the MNPs are nontoxic to A549 cells for the studied concentrations of particle fraction and a contact time of up to 24 h. The interaction of the MNPs with A549 cells was highlighted from an image captured by an inverted microscope. In order to treat cancer in vivo, an in vitro hyperthermia study has initially been carried out with A549 cells.

Staged lengthening and reconstruction for children with a leg-length discrepancy after excision of an osteosarcoma around the knee.

AIMS: Children treated for osteosarcoma around the knee often have a substantial leg-length discrepancy at skeletal maturity. The aim of this study was to investigate the results of staged skeletal reconstruction after a leg lengthening procedure using an external fixator in these patients. PATIENTS AND METHODS: We reviewed 11 patients who underwent staged reconstruction with either an arthroplasty (n = 6) or an arthrodesis (n = 5). A control group of 11 patients who had undergone wide excision and concurrent reconstruction with an arthroplasty were matched for gender, location, and size of tumour. We investigated the change in leg-length discrepancy, function as assessed by the Musculoskeletal Tumor Society Scale (MSTS) score and complications. RESULTS: A mean 5.2 cm (1.7 to 8.9) of lengthening was achieved. The mean MSTS scores significantly improved after staged reconstruction (p = 0.003) but were still worse than those of the control group (p = 0.049). However, the MSTS scores of the arthroplasty subgroup were comparable with those of the controls, although the extensor lag was greater and the range of movement was less. The patient group experienced more complications, but all of these resolved. CONCLUSION: Approximately 5 cm of lengthening and significant functional improvement can be achieved by staged reconstruction and lengthening, without major complications. Although it has limitations, this method of treatment seems to be a satisfactory surgical option for growing children with a significant leg-length discrepancy after excision of an osteosarcoma around the knee. Cite this article: Bone Joint J 2017;99-B:401-8.

The effect of low-volatile organic compounds, water-based paint on aggravation of allergic disease in schoolchildren.

Whether indoor painting aggravates preexisting allergic diseases remains unclear. We aimed to evaluate the impact of new classroom painting on aggravation of asthma, allergic rhinitis (AR), and atopic dermatitis (AD) in children. Studied school was previously painted with conventional water-based paint 20 years ago and had natural ventilation system. We identified a total of 172 children aged 10-12 years with allergic diseases in 17 classrooms, which were allocated to newly painted rooms with low-volatile organic compounds (VOC), water-based paint, or existing rooms. After painting, there was no intervention or internal airflow to influence indoor air environment in both classrooms. We prospectively assessed the symptom severity and serious events of allergic diseases between both classrooms at baseline and after one and eight weeks after painting. At one and eight weeks, there were no significant changes in the Childhood Asthma Control Test scores, the fractional nitric oxide levels, lung function in asthmatic children in either classroom. There were also no significant changes in the severity score of AR or AD, or serious events in all allergic diseases. These findings suggest classroom painting with this new paint at the levels encountered in this study might not be a major aggravating factor for school-aged children with allergic diseases.

Prediction of rebound phenomenon after removal of hemiepiphyseal staples in patients with idiopathic genu valgum deformity.

AIMS: Our aim was to investigate the predictive factors for the development of a rebound phenomenon after temporary hemiepiphysiodesis in children with genu valgum. PATIENTS AND METHODS: We studied 37 limbs with idiopathic genu valgum who were treated with hemiepiphyseal stapling, and with more than six months remaining growth at removal of the staples. All children were followed until skeletal maturity or for more than two years after removal of the staples. RESULTS: On multivariate logistic regression analysis, the rate of correction, body mass index (BMI), age, and initial valgus angle were significantly associated with a rebound phenomenon. With those characteristics, a predictive model for rebound was generated using recursive partitioning analysis. Children with a rapid rate of correction had the most frequent and severe rebound phenomenon (incidence 79%, mean 4°), whereas those with a slow rate of correction had less rebound when they had low BMI (43%, 2°) and none when the BMI was ≥ 21 kg/m(2). CONCLUSION: This is the first study to evaluate a predictive model for a rebound phenomenon after temporary hemiepiphysiodesis in children with idiopathic genu valgum. Cite this article: Bone Joint J 2016;98-B:1270-5.

Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer.

BACKGROUND: The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases. EXPERIMENTAL DESIGN: Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ(2) or Fisher's exact test were used for analysis. RESULTS: We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009). CONCLUSIONS: We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment.

Validity and reliability of the Korean version of the Speech Handicap Index in patients with oral cavity cancer.

The aims of this study were to evaluate the cross-cultural adaptation of the Speech Handicap Index (SHI) for Korean subjects and to determine its reliability and utility in patients with oral cavity cancer. The Korean version of the SHI was administered to 50 healthy subjects and 56 patients with speech problems resulting from treatment for oral cavity cancers. The content and construct validity, internal consistency, and test-retest reliability were examined. Healthy subject and patient group scores were compared, and the Mann-Whitney U-test was used to determine discriminatory ability. The Korean version of the SHI had high internal consistency (Cronbach's alpha=0.99) and test-retest reliability for the total and subscales: total (T) 0.98, speech (S) 0.99, and psychosocial (P) 0.97. Mean scores in the healthy group were 0.5 (T), 0.2 (S), and 0.2 (P), whereas those in the patient group were 34.3 (T), 16.6 (S), and 15.5 (P). The scores differed significantly between the groups (P<0.05). The Korean version of the SHI can be a useful tool to evaluate a patient's self-perception of their speech dysfunction in daily life and to better understand postoperative speech disorders in patients with oral cavity cancer.

Clinical applications of next-generation sequencing-based gene panel in patients with muscular dystrophy: Korean experience.

Muscular dystrophy (MD) is a genetically and clinically heterogeneous group of disorders. Here, we performed targeted sequencing of 18 limb-girdle MD (LGMD)-related genes in 35 patients who were highly suspected of having MD. We identified one or more pathogenic variants in 23 of 35 patients (65.7%), and a genetic diagnosis was performed in 20 patients (57.1%). LGMD2B was the most common LGMD type, followed by LGMD1B, LGMD2A, and LGMD2G. Among the three major LGMD types in this group, LGMD1B was correlated with the lowest creatine kinase (CK) levels and the earliest onset, whereas LGMD2B was correlated with the highest CK levels and the latest onset. Thus, next-generation sequencing-based gene panels can be a helpful tool for the diagnosis of MDs, particularly in young children and those displaying atypical symptoms.

Disseminated mucormycosis with myocardial involvement in a renal transplant recipient.

We report the case of a renal transplant recipient with pulmonary and splenic mucormycosis whose demise was accelerated by a myocardial abscess. Once pulmonary and splenic mucormycosis was diagnosed, liposomal amphotericin B was started and immunosuppressant treatments were discontinued. The pulmonary cavities regressed during treatment, but new myocardial and peri-allograft abscesses developed. The myocardial abscess diffusely infiltrated the left ventricular wall and was associated with akinesia, which led to sudden cardiac arrest. This case demonstrates a rare manifestation of mucormycosis and highlights the fatality and invasiveness of this infection.

Unintentional secondary exogenous corticosteroid exposure and central serous chorioretinopathy.

PURPOSE: The purpose of this study is to describe a possible association between unintentional secondary exogenous corticosteroid exposure and central serous chorioretinpathy (CSCR). METHODS: A retrospective review of three patients diagnosed with CSCR in one or both eyes and a history of possible unintentional secondary corticosteroid exposure. Clinical history, exam findings, optical coherence tomography, fluorescein angiography, and clinical course were reviewed. RESULTS: Three patients, who did not use corticosteroids, reported suspected unintentional secondary corticosteroid exposure from living with family members or partners using dermatologic corticosteroid cream and/or inhalers frequently. Two of the three patients had a history of recurrent CSCR, one patient involving both eyes. After taking precautions to avoid secondary corticosteroid exposure, all three patients had complete resolution of CSCR without further recurrence during follow-up ranging from 2 to 4 years. CONCLUSIONS: Patients with CSCR should be queried for both primary and possible unintentional secondary routes of corticosteroid exposure, which may contribute to this condition.

The prognostic value of the fracture level in the treatment of Gartland type III supracondylar humeral fracture in children.

A small proportion of children with Gartland type III supracondylar humeral fracture (SCHF) experience troubling limited or delayed recovery after operative treatment. We hypothesised that the fracture level relative to the isthmus of the humerus would affect the outcome. We retrospectively reviewed 230 children who underwent closed reduction and percutaneous pinning (CRPP) for their Gartland type III SCHFs between March 2003 and December 2012. There were 144 boys and 86 girls, with the mean age of six years (1.1 to 15.2). The clinico-radiological characteristics and surgical outcomes (recovery of the elbow range of movement, post-operative angulation, and the final Flynn grade) were recorded. Multivariate analysis was employed to identify prognostic factors that influenced outcome, including fracture level. Multivariate analysis revealed that a fracture below the humeral isthmus was significantly associated with poor prognosis in terms of the range of elbow movement (p < 0.001), angulation (p = 0.001) and Flynn grade (p = 0.003). Age over ten years was also a poor prognostic factor for recovery of the range of elbow movement (p = 0.027). This is the first study demonstrating a subclassification system of Gartland III fractures with prognostic significance. This will guide surgeons in peri-operative planning and counselling as well as directing future research aimed at improving outcomes.

Measurement of microelectric potentials in a bioelectrically-active wound care device in the presence of bacteria.

OBJECTIVE: Wound healing is enhanced in the presence of an external electrical field. The purpose of this study was first to investigate whether microelectric potentials (EPs) can be generated when the innovative design of a silver (Ag)- and zinc (Zn)-printed wound care device was exposed to saline solution which is commonly used to clean wound sites; and second to measure the generated EPs while the device was exposed to bacterial culture suspensions to mimic infection. METHOD: An Ag/Zn-printed test specimen as a wound care device was designed to accommodate Ag and Zn half-cell potentials by alternatively printing them on a woven polyester material in a well-characterised dot matrix pattern. A well-calibrated high impedance EPs measuring system was used to measure any EPs generated. Ultrasensitive inductively coupled plasma analysis was performed to determine whether the device induced any increase in trace metals in rabbit blood following implantation for 2-4 weeks. RESULTS: EPs were consistently generated under various conductive solutions at the levels of 120.4±26.3mV (average±standard deviation) on Ag dots and -506.5±76.3mV over Zn dots to form microcircuits with EPs of 626.7±86.3mV between the Ag and Zn metallic elements of the dressing. Interestingly, the patterns of EPs generated with stable polarities were consistent when the device was exposed to bacterial suspensions for mimicking wound infection. Implantation of the device did not cause any increase in Ag or Zn in rabbit blood. CONCLUSION: The Ag/Zn-printed wound device generated sustained EPs successfully in the presence of various conductive fluids without changing EPs including polarities. Consistently generated EPs at each battery couple with Ag/Zn-based wound device would restore disrupted physiologic bioelectric signals on wound sites, which could lead to improved wound healing. DECLARATION OF INTEREST: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army, the US Department of Defense, the Department of Veterans Affairs, or the Henry M. Jackson Foundation for Advancement of Military Medicine. The research was supported by the US Air Force medical support agency (AFMSA), office of the Air Force Surgeon General, USA.

Identification of novel mutations in the VPS33B gene involved in arthrogryposis, renal dysfunction, and cholestasis syndrome.

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B and VIPAS39. Here, we report novel mutations identified in four patients with ARC syndrome. We analyzed the entire coding regions of the VPS33B and VIPAS39 genes by direct sequencing. To detect novel splice site mutations, mRNA transcripts were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. All four patients had compound heterozygous variants in the VPS33B gene. One patient had a previously reported splice site variant with unknown significance, c.239+5G>A, and a novel nonsense mutation, c.621G>A. The other three patients had the c.403+2T>A mutation, and each of them carried one of the splice site variants, c.239+5G>A or c.499-11G>A. c.239+5G>A and c.499-11G>A created novel splice sites which resulted in abnormal transcripts. No significant VIPAS39 mutation was detected in all patients. In patients suspected with ARC syndrome, mutation analysis of the VPS33B gene should be employed as a primary diagnostic test before performing invasive testing procedures such as organ biopsies. Performing mRNA analysis can be useful in predicting the pathogenic phenotype when the mutation seems to affect a normal splicing mechanism.

Effects of combination of rice straw with alfalfa pellet on milk productivity and chewing activity in lactating dairy cows.

An experiment was conducted to determine the effects of diets containing coarse-texture rice straw and small particle size alfalfa pellets as a part of total mixed ration (TMR) on milk productivity and chewing activity in lactating dairy cows. Sixteen multiparous Holstein dairy cows (670±21 kg body weight) in mid-lactation (194.1±13.6 days in milk) were randomly assigned to TMR containing 50% of timothy hay (TH) or TMR containing 20% of rice straw and 30% of alfalfa pellet mixture (RSAP). Geometric mean lengths of TH and RSAP were found to be 5.8 and 3.6, respectively. Dry matter intake, milk yield and milk composition were measured. Moreover, eating and ruminating times were recorded continuously using infrared digital camcorders. Milk yield and milk composition were not detected to have significant differences between TH and RSAP. Dry matter intake (DMI) did not significantly differ for cows fed with TH or RSAP. Although particle size of TH was larger than RSAP, eating, ruminating and total chewing time (min/d or min/kg of DMI) on TH and RSAP were similar. Taken together, our results suggest that using a proper amount of coarse-texture rice straw with high value nutritive alfalfa pellets may stimulate chewing activity in dairy cows without decreasing milk yield and composition even though the quantity of rice straw was 40% of TH.

Wound infections and healing: are they contributing factors for carcinogenesis?

The link between inflammation and tumourisation has long been considered as a key event in clinical cancer development. Inflammation and inflammatory diseases can be caused by many factors including infectious agents, altered genetics and various degrees of injuries from simple cuts to traumatic wounds, such as those suffered in battlefield. Improved management of all wound types is critical in protecting affected individuals against the development of tumourisation cues, which may potentially lead to cancer development. There have been numerous studies on the mechanism of inflammation-induced tumourisation. Thus, in this mini review, we summarised evidence demonstrating the potential link between infectious agents and their moonlight proteins, wounding, trauma, overactive repair mechanisms, and carcinogenesis.

Macular pigment and macular volume in eyes of patients with cystic fibrosis.

BACKGROUND: Because patients with cystic fibrosis (CF) are living longer, chronic malabsorption of carotenoids associated with CF resulting in decreased macular pigment (MP) may affect macular long-term health in later-life pathology. This study compared the macular pigment optical density (MPOD) and corresponding central macular volume (MV) of adult CF subjects and age-matched normal controls subjects to determine whether chronic malabsorption associated with CF could adversely affect macular photoreceptor anatomy. OBJECTIVE: Our aim was to compare MPOD with measurements of central MV in CF patients with age-matched controls. Design. In nine adult CF patients (ages: 29-46) without a history of carotenoid supplementation or known retinal or optic nerve disease MPOD and MV were measured by heterochromatic flicker photometry (HFP) and optical coherence tomography (OCT), respectively, and compared to results obtained from 14 age-matched controls. RESULTS: MPOD was significantly reduced at 15' and 30' eccentricities in CF subjects compared to normal subjects (mean difference -0.21 at 15', -0.25 at 30', p < 0.005). No significant difference, in MV noted at any of the eccentricities tested between CF and normal subjects (CF: normal MV ratios ranged from 0.94 to 1.1 for all eccentricities with p > 0.1 at all eccentricities). Best corrected vision acuity and fundus examination were normal in all subjects. CONCLUSIONS: Unsupplemented CF patients have markedly lower levels of macular carotenoids (e.g., lutein and zeaxanthin), but well-maintained visual function and no significant reductions in central MV primarily composed of macular photoreceptors. Future studies are needed to determine whether the lifelong decrease in protective central retinal carotenoids predisposes CF patients to later-life retinal pathology.

Effect of inhalers on the development of haemoptysis in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: The association of inhaler use with haemoptysis has rarely been reported in patients with non-cystic fibrosis (CF) bronchiectasis. OBJECTIVE: To elucidate the effect of inhaler use on the development of haemoptysis in patients with non-CF bronchiectasis. METHODS: In a case-crossover study of 192 non-CF bronchiectasis patients with a history of haemoptysis and inhaler use, the risk of haemoptysis associated with the use of inhalers was elucidated. Two inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA), one long-acting muscarinic antagonist and one short-acting ß2-agonist (SABA) were evaluated. The case and control periods were defined respectively as 030 and 180210 days before haemoptysis. RESULTS: The risk of haemoptysis during the case period was 3.51 times higher than during the control period with any use of inhalers (95%CI 1.966.28). The results of clinically significant haemoptysis showed good agreement with those of total events. These associations were consistent with the sensitivity analyses. In the sub-analysis according to inhaler type, ICS/LABA and SABA were significantly associated with an increased risk of haemoptysis (aOR 2.62, 95%CI 1.255.45; aOR 2.51, 95%CI 2.235.15). CONCLUSIONS: In patients with non-CF bronchiectasis, the use of inhalers, especially including 2-agonist, was associated with an increased risk of haemoptysis.