Microarray analysis in pregnancies with isolated echogenic bowel.

Early Hum Dev. 2018 Mar 06;119:25-28

Authors: Singer A, Maya I, Koifman A, Nasser Samra N, Baris HN, Falik-Zaccai T, Ben Shachar S, Sagi-Dain L

Abstract
INTRODUCTION: Fetal echogenic bowel is a frequent sonographic finding, demonstrated in about 1% of pregnancies. The advised evaluation of fetal echogenic bowel includes maternal serology, genetic testing for cystic fibrosis, detailed sonographic anatomic survey, and invasive prenatal testing for fetal chromosomal aberrations. The objective of our study was to evaluate the risk for clinically significant chromosomal microarray analysis (CMA) findings in pregnancies with isolated echogenic bowel.
METHODS: Data from all CMA analyses performed due to isolated echogenic bowel reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained. Risk estimation was performed comparing the rate of abnormal microarray findings to the control population, based on a systematic review of 9272 pregnancies and a large local cohort of 5541 fetuses with normal ultrasound, undergoing CMA testing due to maternal request.
RESULTS: Of 103 CMA analyses performed due to isolated echogenic bowel, two (1.94%) pathogenic findings were detected (47,XYY and 16p11.2 duplication). This risk was not significantly elevated compared to the control groups. In addition, three variants of unknown significance were demonstrated.
CONCLUSIONS: To our best knowledge, our study is the first report describing the rate of clinically significant copy number variants in pregnancies with isolated echogenic bowel. According to our results, it seems that pregnancies with isolated echogenic bowel do not have an increased risk for abnormal CMA compared to fetuses with no evidence of sonographic anomalies. Our findings suggest that the consideration to perform CMA analysis in such pregnancies should not differ from any pregnancy with normal ultrasound.

PMID: 29522884 [PubMed - as supplied by publisher]

Fluctuations in airway bacterial communities associated with clinical states and disease stages in cystic fibrosis.

PLoS One. 2018;13(3):e0194060

Authors: Carmody LA, Caverly LJ, Foster BK, Rogers MAM, Kalikin LM, Simon RH, VanDevanter DR, LiPuma JJ

Abstract
Bacteria that infect the airways of persons with cystic fibrosis (CF) include a group of well-described opportunistic pathogens as well as numerous, mainly obligate or facultative anaerobic species typically not reported by standard sputum culture. We sequenced the V3-V5 hypervariable region of the bacterial 16S rRNA gene in DNA derived from 631 sputum specimens collected from 111 CF patients over 10 years. We describe fluctuations in the relative abundances of typical CF pathogens, as well as anaerobic species, in relation to changes in patients' clinical state and lung disease stage. Both bacterial community diversity and the relative abundance of anaerobes increased during exacerbation of symptoms (prior to antibiotic treatment), although this trend was not observed uniformly across disease stages. Community diversity and the relative abundance of anaerobic species decreased during antibiotic treatment. These results support current hypotheses regarding the role of anaerobes in CF pulmonary exacerbations and lung disease progression.

PMID: 29522532 [PubMed - in process]

Biological Activity of Trans-Membrane Anion Carriers.

Curr Med Chem. 2018 Mar 08;:

Authors: Tosolini M, Pengo P, Tecilla P

Abstract
Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter the cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article an overview of the recent results on the study of anion-transporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived by dysregulation of natural anion channels.

PMID: 29521206 [PubMed - as supplied by publisher]

Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis.

Front Med. 2018 Mar 09;:

Authors: Qiu L, Yang F, He Y, Yuan H, Zhou J

Abstract
Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.

PMID: 29520692 [PubMed - as supplied by publisher]

A 24-Year-Old Woman With Precipitous Respiratory Failure After Lung Transplantation.

Chest. 2018 Mar;153(3):e53-e56

Authors: Warren WA, Franco-Palacios D, King CS, Shlobin OA, Nathan SD, Katugaha SB, Mani H, Brown AW

Abstract
CASE PRESENTATION: A 24-year-old woman with ΔF508/Y1092X cystic fibrosis (CF) complicated by severe obstructive lung disease (FEV1 of 30% predicted) was admitted for IV antibiotics for planned sinus surgery resulting from severe chronic sinusitis causing frequent exacerbations and declining lung function. She had persistent airway infection with multidrug-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and growth of a fungus presumed to be an airway colonizer, identified as Stephanoascus ciferrii 1 year before presentation. Two days after surgery, she developed acute respiratory failure requiring mechanical ventilation. On day 4 of mechanical ventilation, venovenous-extracorporeal membrane oxygenation (VV-ECMO) was initiated for refractory respiratory failure. The following day, she was listed for bilateral lung transplant and was transplanted 4 days later. Following transplantation, she was decannulated from ECMO; however, over the next 12 hours, oxygenation deteriorated requiring reinstitution of VV-ECMO for presumed severe primary graft dysfunction. Despite treatment with broad spectrum antimicrobial coverage with piperacillin/tazobactam, ciprofloxacin, linezolid, micafungin, voriconazole, and ganciclovir, she failed to improve and developed complex bilateral pleural effusions.

PMID: 29519311 [PubMed - in process]

Antibacterial and Antifungal Activities of Poloxamer Micelles Containing Ceragenin CSA-131 on Ciliated Tissues.

Molecules. 2018 Mar 07;23(3):

Authors: Hashemi MM, Holden BS, Taylor MF, Wilson J, Coburn J, Hilton B, Nance T, Gubler S, Genberg C, Deng S, Savage PB

Abstract
Ceragenins were designed as non-peptide mimics of endogenous antimicrobial peptides, and they display broad-spectrum antibacterial and antifungal activities, including the ability to eradicate established biofilms. These features of ceragenins make them attractive potential therapeutics for persistent infections in the lung, including those associated with cystic fibrosis. A characteristic of an optimal therapeutic for use in the lungs and trachea is the exertion of potent antimicrobial activities without damaging the cilia that play a critical role in these tissues. In previous work, potent antimicrobial activities of ceragenin CSA-131 have been reported; however, we found in ex vivo studies that this ceragenin, at concentrations necessary to eradicate established biofilms, also causes loss of cilia function. By formulating CSA-131 in poloxamer micelles, cilia damage was eliminated and antimicrobial activity was unaffected. The ability of CSA-131, formulated with a poloxamer, to reduce the populations of fungal pathogens in tracheal and lung tissue was also observed in ex vivo studies. These findings suggest that CSA-131, formulated in micelles, may act as a potential therapeutic for polymicrobial and biofilm-related infections in the lung and trachea.

PMID: 29518893 [PubMed - in process]

Exome-wide somatic mutation characterization of small bowel adenocarcinoma.

PLoS Genet. 2018 Mar 09;14(3):e1007200

Authors: Hänninen UA, Katainen R, Tanskanen T, Plaketti RM, Laine R, Hamberg J, Ristimäki A, Pukkala E, Taipale M, Mecklin JP, Forsström LM, Pitkänen E, Palin K, Välimäki N, Mäkinen N, Aaltonen LA

Abstract
Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (AI) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.

PMID: 29522538 [PubMed - as supplied by publisher]

Morphogenetic defects underlie Superior Coloboma, a newly identified closure disorder of the dorsal eye.

PLoS Genet. 2018 Mar 09;14(3):e1007246

Authors: Hocking JC, Famulski JK, Yoon KH, Widen SA, Bernstein CS, Koch S, Weiss O, FORGE Canada Consortium, Agarwala S, Inbal A, Lehmann OJ, Waskiewicz AJ

Abstract
The eye primordium arises as a lateral outgrowth of the forebrain, with a transient fissure on the inferior side of the optic cup providing an entry point for developing blood vessels. Incomplete closure of the inferior ocular fissure results in coloboma, a disease characterized by gaps in the inferior eye and recognized as a significant cause of pediatric blindness. Here, we identify eight patients with defects in tissues of the superior eye, a congenital disorder that we term superior coloboma. The embryonic origin of superior coloboma could not be explained by conventional models of eye development, leading us to reanalyze morphogenesis of the dorsal eye. Our studies revealed the presence of the superior ocular sulcus (SOS), a transient division of the dorsal eye conserved across fish, chick, and mouse. Exome sequencing of superior coloboma patients identified rare variants in a Bone Morphogenetic Protein (Bmp) receptor (BMPR1A) and T-box transcription factor (TBX2). Consistent with this, we find sulcus closure defects in zebrafish lacking Bmp signaling or Tbx2b. In addition, loss of dorsal ocular Bmp is rescued by concomitant suppression of the ventral-specific Hedgehog pathway, arguing that sulcus closure is dependent on dorsal-ventral eye patterning cues. The superior ocular sulcus acts as a conduit for blood vessels, with altered sulcus closure resulting in inappropriate connections between the hyaloid and superficial vascular systems. Together, our findings explain the existence of superior coloboma, a congenital ocular anomaly resulting from aberrant morphogenesis of a developmental structure.

PMID: 29522511 [PubMed - as supplied by publisher]

RSRC1 mutation affects intellect and behaviour through aberrant splicing and transcription, downregulating IGFBP3.

Brain. 2018 Mar 07;:

Authors: Perez Y, Menascu S, Cohen I, Kadir R, Basha O, Shorer Z, Romi H, Meiri G, Rabinski T, Ofir R, Yeger-Lotem E, Birk OS

Abstract
RSRC1, whose polymorphism is associated with altered brain function in schizophrenia, is a member of the serine and arginine rich-related protein family. Through homozygosity mapping and whole exome sequencing we show that RSRC1 mutation causes an autosomal recessive syndrome of intellectual disability, aberrant behaviour, hypotonia and mild facial dysmorphism with normal brain MRI. Further, we show that RSRC1 is ubiquitously expressed, and that the RSRC1 mutation triggers nonsense-mediated mRNA decay of the RSRC1 transcript in patients' fibroblasts. Short hairpin RNA (shRNA)-mediated lentiviral silencing and overexpression of RSRC1 in SH-SY5Y cells demonstrated that RSRC1 has a role in alternative splicing and transcription regulation. Transcriptome profiling of RSRC1-silenced cells unravelled specific differentially expressed genes previously associated with intellectual disability, hypotonia and schizophrenia, relevant to the disease phenotype. Protein-protein interaction network modelling suggested possible intermediate interactions by which RSRC1 affects gene-specific differential expression. Patient-derived induced pluripotent stem cells, differentiated into neural progenitor cells, showed expression dynamics similar to the RSRC1-silenced SH-SY5Y model. Notably, patient neural progenitor cells had 9.6-fold downregulated expression of IGFBP3, whose brain expression is affected by MECP2, aberrant in Rett syndrome. Interestingly, Igfbp3-null mice have behavioural impairment, abnormal synaptic function and monoaminergic neurotransmission, likely correlating with the disease phenotype.

PMID: 29522154 [PubMed - as supplied by publisher]

Coincident myelomeningocele and gastroschisis: report of 2 cases.

J Neurosurg Pediatr. 2018 Mar 09;:1-4

Authors: Hauptman JS, Bollo R, Damerla R, Gibbs B, Lo C, Katz A, Greene S

Abstract
Myelomeningocele and gastroschisis, on their own, are both relatively common entities encountered in pediatric surgical care. Coexistence of these pathologies, however, is exceedingly rare. The authors report on 2 patients who presented with myelomeningocele and gastroschisis at birth. They obtained blood for whole-exome analysis for one of the patients and identified 3 mutations that could be related to the underlying anomalies: homozygous mutations in FAM171B and ABCA1 and a hemizygous (X-linked) mutation in COL4A5. Of these, FAM171B and ABCA1 both have function that may be related to the underlying disease.

PMID: 29521606 [PubMed - as supplied by publisher]

Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis.

Front Med. 2018 Mar 09;:

Authors: Qiu L, Yang F, He Y, Yuan H, Zhou J

Abstract
Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.

PMID: 29520692 [PubMed - as supplied by publisher]

De novo HDAC8 mutation causes Rett-related disorder with distinctive facial features and multiple congenital anomalies.

Brain Dev. 2018 Mar 05;:

Authors: Saikusa T, Hara M, Iwama K, Yuge K, Ohba C, Okada JI, Hisano T, Yamashita Y, Okamoto N, Saitsu H, Matsumoto N, Matsuishi T

Abstract
We present a unique 11-year-old girl showing clinical features of Rett-related disorder with distinctive facial features and multiple congenital anomalies including ocular hypertelorism, arched eyebrows, a broad nose, dental anomalies, congenital heart disease, truncal obesity, and epilepsy. A novel de novo mutation in histone deacetylase 8 (HDAC8) (c.652G > T, p.Gly218Cys) was confirmed by whole exome sequencing and Sanger sequencing. X-chromosome inactivation analysis on DNA isolated from peripheral blood lymphocytes revealed a completely skewed pattern associated with an inactive maternal allele. Late clinical loss of acquired purposeful hand movements and psychomotor deterioration may be a feature of Rett-related disorder, while distinctive facial features and multiple congenital anomalies are reminiscent of Cornelia de Lange syndrome.

PMID: 29519750 [PubMed - as supplied by publisher]

[DARS mutations responsible for hypomyelination with brain stem and spinal cord involvement and leg spasticity: report of two cases and review of literature].

Zhonghua Er Ke Za Zhi. 2018 Mar 02;56(3):211-215

Authors: Zhang J, Liu M, Zhou L, Zhang ZB, Wang JM, Jiang YW, Wu Y

Abstract
Objective: To analyze the clinical and imaging features of hypomyelination with brain stem and spinal cord involvement and leg spasticity (HBSL) due to mutations in DARS, and to identify DARS mutations responsible for HBSL. Methods: Data on 2 HBSL patients who were admitted to the pediatric department of Peking University First Hospital from January 2009 through December 2016 were reviewed and the 2 patients were followed up. Targeted next generation sequencing, whole exome sequencing and Sanger sequencing were employed to identify potential genetic variations of the children and their parents. The clinical manifestations, MRI features and genotypic characteristics of two patients were reviewed, and the literature was reviewed. HBSL reported cases were searched with"leukoencephalopathies, DARS"on databases of PubMed, Wanfang, China National Knowledge Infrastructure and VIP from 1975 to 2017. The clinical manifestations and molecular features were analyzed. Results: Both patients showed delayed motor development, but had normal cognitive development. At the age of 8 years, case 1 reached the most significant motor development milestone of only standing with help during the last follow-up. At the age of 9, case 2 could walk independently during the last follow-up. On physical examination, both showed leg spastcity, active tendon reflex, positive Babinski sign. Both patients had brain MRI findings of high T2WI signal in bilateral deep cerebral white matter, slightly lower T1WI, and no abnormal DWI signal. Lesions of case 1 were relatively extensive and involved subcortical white matter, corpus callosum and internal capsule. Spinal MRI scans for both patients showed no abnormal signals. Novel mutations in DARS gene-namely, c.1498_1499insTCA (p.500_501insIle) and c.1210A>G (p.Met404Val) , c.1432A>G (p.Met478Val) and c.1210A>G (p.Met404Val) were identified in case 1 and case 2 respectively. On the database, 2 reports involving 13 foreign patients were retrieved. The age of disease onset was from 4 months to 18 years, and their initial symptoms were development delay or regression. Most of them presented with progressive lower extremity spasm, and the brain magnetic resonance imaging was characterized by hypomyelination in white matter. Clinical phenotypes of different age groups were significantly different. Conclusion: We have reported two patients with HBSL in China, and 3 novel mutations in DARS, which is helpful for the diagnosis and genetic counseling of HBSL.

PMID: 29518832 [PubMed - in process]

Identification of a novel functional JAK1 S646P mutation in acute lymphoblastic leukemia.

Oncotarget. 2017 May 23;8(21):34687-34697

Authors: Li Q, Li B, Hu L, Ning H, Jiang M, Wang D, Liu T, Zhang B, Chen H

Abstract
The survival rate of childhood acute lymphoblastic leukemia (ALL) is approaching 90%, while the prognosis of adults remains poor due to the limited therapeutic approaches. In order to identify new targets for ALL, we performed whole-exome sequencing on four adults with B-ALL and discovered a somatic JAK1 S646P mutation. Sanger sequencing of JAK1 was conducted on 53 ALL patients, and two cases exhibited A639G and P960S mutations separately. Functional studies demonstrated that only JAK1 S646P mutation could activate multiple signaling pathways, drive cytokine-independent cell growth, and promote proliferation of malignant cells in nude mice. Moreover, a high sensitivity to the JAK1/2 inhibitor ruxolitinib was observed in S646P mutant model. Exploration in a total of 209 ALL cases showed that JAK1 mutations occur at a frequency of 10.5% in T-ALL (2/19) and 1.6% in B-ALL (3/190). Collectively, our results suggested that JAK1 S646P is an activating mutation in vitro and in vivo. JAK-STAT pathway might represent a promising therapeutic target for ALL.

PMID: 28410228 [PubMed - indexed for MEDLINE]

Selenium - a fascinating antioxidant of protective properties.

Adv Clin Exp Med. 2018 Feb;27(2):245-255

Authors: Kiełczykowska M, Kocot J, Paździor M, Musik I

Abstract
Selenium is a trace element which fulfils important functions in the organism. Its deficit may cause acute disorders, but an overdose can also lead to severe consequences. The functions of selenium in the organism are mainly connected with its antioxidant properties, as it is an essential part of important antioxidant enzymes. Disturbances of oxidant balance have been found to be involved in the activity of numerous harmful factors as well as in the pathogenesis of diverse illnesses. Selenium administration has proved to be effective against the toxicity of many agents and the side effects of drugs. However, the narrow range between therapeutic and toxic doses of selenium, as well as the dependence of its effect on the applied form, dose and method of treatment, makes the choice of the most effective supplement a very complex issue. Divergent forms of selenium are still being studied, including both inorganic and organic compounds as well as Se-enriched natural products. The newest research has also involved selenium nanoparticles. The aim of this review is to present the great potential of selenium for protecting the organism against a wide variety of environmental pollutants, drugs and physical factors.

PMID: 29521069 [PubMed - in process]

Recurrent dysphasia due to nivolumab-induced encephalopathy with presence of Hu autoantibody.

Lung Cancer. 2017 Jul;109:74-77

Authors: Raskin J, Masrori P, Cant A, Snoeckx A, Hiddinga B, Kohl S, Janssens A, Cras P, Van Meerbeeck JP

Abstract
A 58-year-old man was being treated for squamous non-small-cell lung cancer with nivolumab. At the 17th of biweekly administrations he presented with global dysphasia, dysarthria and myoclonus in the right upper extremity. MRI showed multiple T2/FLAIR hyperintense lesions in the left hemisphere; lumbar puncture showed lymphocytic pleiocytosis in the CSF without identifiable pathogens. Hu antibodies were present in serum and CSF. Nivolumab was discontinued and corticosteroids were administered. The neurological symptoms gradually improved; MRI showed complete remission of cerebral lesions. After rechallenge with nivolumab his symptoms and cerebral lesions recurred, proving the causal relationship with nivolumab. After tapering of corticosteroids, a second relapse occurred.

PMID: 28577954 [PubMed - indexed for MEDLINE]

Vitiligo in a patient with lung adenocarcinoma treated with nivolumab: A case report.

Lung Cancer. 2017 Jul;109:42-44

Authors: Uenami T, Hosono Y, Ishijima M, Kanazu M, Akazawa Y, Yano Y, Mori M, Yamaguchi T, Yokota S

Abstract
Nivolumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for treating patients with late-stage non-small-cell lung cancer. Immune checkpoint inhibitors such as nivolumab induce various kinds of immune-related adverse events, including vitiligo. Vitiligo has been reported in patients with melanoma but not lung cancer. We describe a 75-year-old man with lung adenocarcinoma, stage 4 with pleural and pericardial effusion, that progressed after first-line chemotherapy. Subsequently, he was treated with nivolumab as second-line therapy. After 6days of administering nivolumab, he developed vitiligo suddenly on the trunk of his body. Except for vitiligo, his physical examination was normal, and treatment with nivolumab was well tolerated. Therefore, this treatment was continued without further development or expansion of vitiligo. A computed tomography scan showed a reduction in the size of the lung nodule and stabilization of the pleural and pericardial effusion. This is the first case of vitiligo associated with the use of nivolumab in a patient with lung adenocarcinoma.

PMID: 28577948 [PubMed - indexed for MEDLINE]

Venous thromboembolism in hospitalized patients receiving chemotherapy for malignancies at Japanese community hospital: prospective observational study.

BMC Cancer. 2017 May 19;17(1):351

Authors: Kitayama H, Kondo T, Sugiyama J, Kurimoto K, Nishino Y, Hirayama M, Tsuji Y

Abstract
BACKGROUND: Although Asian population was recognized to have a lower risk of venous thromboembolism (VTE), its increasing prevalence and incidence remain unclear in patients with malignancies. We attempted to predict VTE development using activation markers of coagulation and fibrinolysis.
METHODS: We enrolled patients with malignancy admitted to Tonan Hospital between April and December 2014 to receive a new-for-them chemotherapy regimen. All patients were examined for VTE by computed tomography and whole-leg compression ultrasonography before chemotherapy and three months later. We also examined plasma levels of thrombin-antithrombin complex (TAT) and plasmin α2-plasmin inhibitor complex (PIC) before chemotherapy. The cut off values of TAT and PIC were set at 2.1 ng/mL and 1.8 μg/mL, respectively.
RESULTS: Of 97 patients, the majority (67%) had distant metastases. The most common malignancies were colorectal (26%), breast (23%), and stomach (19%) cancer. VTE was detected in 29 patients (31%); all were asymptomatic. VTE was newly developed in 12 patients in the three-month observation period, which means the incidence was 49 per 1000 person-years. Non-increased PIC with increased TAT was the only significant risk factor for both VTE prevalence and incidence in multivariate analysis, and the odds ratios were 3.0 (95% confidence interval, 1.1-8.2; P = 0.034) and 9.4 (95% confidence interval, 1.7-51.9; P = 0.011), respectively.
CONCLUSIONS: The prevalence and incidence of VTE were high in hospitalized Japanese patients receiving chemotherapy for malignancies. Non-increased PIC with increased levels of TAT may be an independent risk factor for VTE development.

PMID: 28525975 [PubMed - indexed for MEDLINE]

Exploring consumer opinions on the presentation of side-effects information in Australian Consumer Medicine Information leaflets.

Health Expect. 2016 Jun;19(3):543-56

Authors: Tong V, Raynor DK, Blalock SJ, Aslani P

Abstract
BACKGROUND: Consumer Medicine Information (CMI) is a brand-specific and standardized source of written medicine information available in Australia for all prescription medicines. Side-effect information is poorly presented in CMI and may not adequately address consumer information needs.
OBJECTIVE: To explore consumer opinions on (i) the presentation of side-effect information in existing Australian CMI leaflets and alternative study-designed CMIs and (ii) side-effect risk information and its impact on treatment decision making.
DESIGN: Fuzzy trace, affect heuristic, frequency hypothesis and cognitive-experiential theories were applied when revising existing CMI side-effects sections. Together with good information design, functional linguistics and medicine information expertise, alternative ramipril and clopidogrel CMI versions were proposed. Focus groups were then conducted to address the study objectives.
PARTICIPANTS AND SETTING: Three focus groups (n = 18) were conducted in Sydney, Australia. Mean consumer age was 58 years (range 50-65 years), with equal number of males and females.
RESULTS: All consumers preferred the alternative CMIs developed as part of the study, with unequivocal preference for the side-effects presented in a simple tabular format, as it allowed quick and easy access to information. Consumer misunderstandings reflected literacy and numeracy issues inherent in consumer risk appraisal. Many preferred no numerical information and a large proportion preferred natural frequencies.
CONCLUSIONS: One single method of risk presentation in CMI is unable to cater for all consumers. Consumer misunderstandings are indicative of possible health literacy and numeracy factors that influence consumer risk appraisal, which should be explored further.

PMID: 24905668 [PubMed - indexed for MEDLINE]