Background. Salivary alpha-amylase (sAA) and salivary immunoglobulin A (sIgA) have been proposed as biomarkers for research on the mucosal immune system and on stress. Expression of both sAA and sIgA has been described to follow opposing diurnal patterns. This knowledge is crucial for the interpretation of studies using these biomarkers. Aim. It was hypothesized that sAA and sIgA display diurnal patterns in children and that this is independent of food intake or demographic factors. Methods. Whole saliva was collected from 78 healthy children (15-39 months old) in the morning and evening for two random nonconsecutive days. The samples have been analysed for sAA and sIgA. The total daily energy, fat, saturated fat, protein, carbohydrate and fibre, mineral, and vitamin consumption were analysed based on the two-day weighed food records collected by the parents. Results. It was demonstrated that most young children followed the diurnal pattern when sAA increased and sIgA decreased from morning to evening. No correlation was observed between the intake of any of the nutrients and morning or evening values for both salivary proteins. The morning and evening values of sAA and sIgA did not correlate with age, sex, Asian ethnicity, and BMI of the children. Conclusion. Diurnal patterns of sAA and sIgA exist in healthy young children and are not affected by their nutrient intake, sex, Asian ethnicity, and BMI. Scientists including sIgA and sAA in their research must consider the diurnal pattern that these markers exhibit and design the study accordingly.
http://bit.ly/2QO7IMh
Κυριακή 13 Ιανουαρίου 2019
Young Children Display Diurnal Patterns of Salivary IgA and Alpha-Amylase Expression Which Are Independent of Food Intake and Demographic Factors
Allergic contact dermatitis from topical ophthalmic medications
Liesbeth Gilissen Lana Dedecker Toon Hulshagen An Goossens
First published: 10 January 2019 https://doi.org/10.1111/cod.13209
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cod.13209.
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Abstract
Background
Allergic contact dermatitis (ACD) from topical ophthalmic medications is often overlooked.
Objectives
To study the demographic characteristics, lesion locations, and associated medical conditions of the patients with ACD from ophthalmic drugs, and to identify the most common allergenic culprits, as well as trends in frequencies over the years.
Methods
From January 1990 until December 2016, 16 065 patients were investigated in our clinic; all patients with a positive patch‐test reaction to eye medication or its ingredient(s) having caused ACD were studied. For each allergen identified, the number of positive test results compared with the total number of those in the total population, as well as trends across three periods, namely 1990‐1998, 1999‐2007, and 2008‐2016 were studied.
Results
118 patients (0.7%) presented with positive patch‐test results to ingredients of, and/or topical ophthalmic medications. Aminoglycoside antibiotics, followed by corticosteroids, as pharmacologically active ingredients, as well as wool alcohols, thiomersal and benzalkonium chloride, as excipients were the most frequent culprits. Particularly chloramphenicol showed a decreasing trend in positive reactions over time, whereas reactions tobramycin were increasing.
Conclusion
ACD from eye medication is mainly due to active principles, but other excipient ingredients, beside the products "as is", should be tested as well.
https://onlinelibrary.wiley.com/doi/10.1111/cod.13209
The combination of lanolin alcohol and Amerchol L101 is effective in patch testing for diagnosing lanolin contact allergy
Jannet Knijp Derk P. Bruynzeel Thomas Rustemeyer
First published: 09 January 2019 https://doi.org/10.1111/cod.13210
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cod.13210.
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Summary
Background
The prevalence of lanolin contact allergy in dermatitis patients varies from 1.2% to 6.9%. Different lanolin derivatives are used in patch testing.
Objectives
To determine which combination of lanolin derivatives is most effective in patch testing for diagnosing lanolin contact allergy.
Methods
A retrospective analysis of patients patch tested between 2016 and 2017 was performed. Patients were eligible if tested with lanolin alcohol 30% pet., Amerchol L101 50% pet. and a supplementary series containing other lanolin derivatives. Lanolin alcohol and Amerchol L101 were tested in duplicate.
Results
Out of 594 patients, 28.6% (95% confidence interval [CI]: 25.1%‐32.3%) had a positive patch test reaction to at least one lanolin derivative. Reactions were common to lanolin alcohol (14.7%, 95% CI: 11.3%‐18.2%) and Amerchol L101 (15.0%, 95% CI: 11.5%‐18.5%) in the routinely tested series. Reactions to other test preparations were significantly less frequent (P < 0.05). The addition of Amerchol L101 to lanolin alcohol significantly increased the number of positive cases (odds ratio 1.79, P < 0.001).
Conclusions
The combination of lanolin alcohol and Amerchol L101 is effective in patch testing for diagnosing lanolin contact allergy. Routinely testing with other lanolin derivatives may not be worthwhile as it detects only few additional patients.
https://onlinelibrary.wiley.com/doi/10.1111/cod.13210
Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy
Abstract
Purpose of Review
Therapeutic hypothermia reduces death or disability in term and near-term infants with moderate-severe hypoxic-ischemic encephalopathy. Nevertheless, many infants still survive with disability, despite hypothermia, supporting further research in to ways to further improve neurologic outcomes.
Recent Findings
Recent clinical and experimental studies have refined our understanding of the key parameters for hypothermic neuroprotection, including timing of initiation, depth, and duration of hypothermia, and subsequent rewarming rate. However, important knowledge gaps remain. There is encouraging clinical evidence from a small phase II trial that combined treatment of hypothermia with recombinant erythropoietin further reduces risk of disability but definitive studies are still needed.
Summary
In conclusion, recent studies suggest that current protocols for therapeutic hypothermia are near-optimal, and that the key to better neurodevelopmental outcomes is earlier diagnosis and initiation of hypothermia after birth. Further research is essential to find and evaluate ways to further improve outcomes after hypoxic-ischemic encephalopathy, including add-on therapies for therapeutic hypothermia and preventing pyrexia during labor and delivery.
http://bit.ly/2VQgYD5
CSF Biomarkers for Early Diagnosis of Synucleinopathies: Focus on Idiopathic RBD
Abstract
Purpose of Review
Idiopathic REM sleep behavior disorder (iRBD) is one of the most significant prodromal manifestations of synucleinopathies. Different predictive biomarkers for iRBD conversion have been investigated, but scarce data are present in literature about the predictive role of cerebrospinal fluid (CSF) biomarkers. In this review, we focus on CSF biomarkers in patients with both iRBD and RBD associated with synucleinopathies to explore their potential predictive power.
Recent Findings
Recent studies revealed that CSF α-synuclein levels are higher in Parkinson's disease (PD) patients with RBD compared to those without RBD, even if α-synuclein does not seem to predict conversion of iRBD into PD. In the Parkinson Progression Marker Initiative (PPMI) cohort, early PD patients with RBD show lower CSF Aβ42 levels, which predict faster cognitive decline. CSF prion protein and inflammatory biomarkers have been also investigated in RBD and synucleinopathies with controversial results.
Summary
A variety of CSF biomarkers are promising candidate for predicting iRBD conversion into synucleinopathies. Further studies are needed in iRBD patients followed for several years in order to observe the phenoconversion in synucleinopathies and to elucidate the possible role of CSF biomarkers as predictive biomarkers of conversion.
http://bit.ly/2QJREuU
STAT3 inhibition specifically in human monocytes and macrophages by CD163-targeted corosolic acid-containing liposomes
Abstract
Tumor-associated macrophages (TAMs) are of major importance in cancer-related immune suppression, and tumor infiltration by CD163pos TAMs is associated with poor outcome in most human cancers. Therefore, therapeutic strategies for reprogramming TAMs from a tumor-supporting (M2-like) phenotype towards a tumoricidal (M1-like) phenotype are of great interest. Activation of the transcription factor STAT3 within the tumor microenvironment is associated with worse prognosis, and STAT3 activation promotes the immunosuppressive phenotype of TAMs. Therefore, we aimed to develop a drug for inhibition of STAT3 specifically within human TAMs by targeting the endocytic CD163 scavenger receptor, which is highly expressed on TAMs. Here, we report the first data on a CD163-targeted STAT3-inhibitory drug consisting of corosolic acid (CA) packaged within long-circulating liposomes (LCLs), which are CD163-targeted by modification with monoclonal anti-CD163 antibodies (αCD163)—CA-LCL-αCD163. We show, that activation of STAT3 (by phosphorylation) was inhibited by CA-LCL-αCD163 specifically within CD163pos cells, with minor effect on CD163neg cells. Furthermore, CA-LCL-αCD163 inhibited STAT3-regulated gene expression of IL-10, and increased expression of TNFα, thus indicating a pro-inflammatory effect of the drug on human macrophages. This M1-like reprogramming at the mRNA level was confirmed by significantly elevated levels of pro-inflammatory cytokines (IFNγ, IL-12, TNFα, IL-2) in the culture medium. Since liposomes are attractive vehicles for novel anti-cancer drugs, and since direct TAM-targeting may decrease adverse effects of systemic inhibition of STAT3, the present results encourage future investigation of CA-LCL-αCD163 in the in vivo setting.
http://bit.ly/2RKg6ki
Impaired antimicrobial response and mucosal protection induced by ibuprofen
Impaired antimicrobial response and mucosal protection induced by ibuprofen in the immature human intestine
Emanuela Ferretti, Eric Tremblay, Marie-Pierre Thibault, Sepideh Fallah, David Grynspan, Karolina M. Burghardt, Marcos Bettolli, Corentin Babakissa, Emile Levy & Jean-François Beaulieu
Pediatric Researchvolume 84, pages813–820 (2018) | Download Citation
Abstract
Background
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (INDO) and ibuprofen (IBU) has been shown to be an effective therapy for the closure of patent ductus arteriosus (PDA). However, this treatment has been associated with an increased risk of developing enteropathies in neonates. Whether the use of IBU is safer than INDO for the immature intestine remains to be elucidated.
Methods
The direct impact of IBU on the human immature intestinal transcriptome was investigated using serum-free organ culture. Differentially expressed genes were analyzed with Ingenuity Pathway Analysis software and compared with those previously reported with INDO. Validation of differentially expressed genes was confirmed by qPCR.
Results
We identified several biological processes that were significantly modulated by IBU at similar levels to what had previously been observed with INDO, while the expression of genes involved in "antimicrobial response" and "mucus production" was significantly decreased exclusively by IBU in the immature intestine.
Conclusions
Our findings indicate that IBU has a harmful influence on the immature intestine. In addition to exerting many of the INDO observed deleterious effects, IBU alters pathways regulating microbial colonization and intestinal epithelial defense.
https://www.nature.com/articles/s41390-018-0201-y
Pediatric sinonasal rhabdomyosarcoma (RMS)
Clinicopathologic traits and prognostic factors associated with pediatric sinonasal rhabdomyosarcoma
Sana H. Siddiqui BA Emaad Siddiqui BS Rich D. Bavier BA Nirali M. Patel BA Suat Kiliç MD Soly Baredes MD, FACS Wayne D. Hsueh MD Jean Anderson Eloy MD, FACS, FARS
First published: 10 January 2019 https://doi.org/10.1002/alr.22267
Potential conflict of interest: None provided.
Presented orally at the 64th Annual Meeting of the American Rhinologic Society, Atlanta, GA, October 5‐6, 2018.
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Abstract
Background
Pediatric sinonasal rhabdomyosarcoma (RMS) is an aggressive and rare malignancy. This is the first multi‐institutional study on the prognostic factors associated with outcomes in this population.
Methods
The National Cancer Database was queried for the period from 2004 to 2013 for all cases of malignant sinonasal RMS in the pediatric population. The impact of patients' demographics, tumor characteristics, and Intergroup Rhabdomyosarcoma Study Group (IRSG) staging on survival was assessed using chi‐square test, Fisher's exact test, Kaplan‐Meier test, and Cox regression analyses.
Results
A total of 157 cases of pediatric sinonasal RMS were identified. Mean age at diagnosis was 9.38 years and male patients comprised 48.4% of the cohort. The nasal cavity (31.8%) and maxillary sinus (30.6%) were the most common primary sites. Alveolar was the most common histology (49.7%), followed by embryonal type (32.5%). The majority of patients received solely chemoradiation (52.9%), followed by surgery with adjuvant chemoradiation (30.6%). Five‐year overall survival (OS) was 55.2% (±4.5%). Metastatic disease was associated with a poorer 5‐year OS rate (24.4% vs 61.5%; p = 0.010). Maxillary sinus site was associated with an improved survival (71.8% vs 47.6%; p = 0.009). On multivariate analysis, chemoradiation with or without surgery was an additional prognostic factor. Although IRSG clinical stages did not correlate with survival, high‐risk patients in the IRSG clinical risk groups were associated with poorer survival on multivariate analysis (hazard ratio [HR], 2.005; 95% confidence interval, 1.007‐3.993; p = 0.048).
Conclusion
To date, this is the largest study on pediatric sinonasal RMS. IRSG clinical risk groups may be useful in stratifying high‐risk patients with poor prognosis.
https://onlinelibrary.wiley.com/doi/10.1002/alr.22267
Formation of papillary mucosa folds and enhancement of epithelial barrier in odontogenic sinusitis
Formation of papillary mucosa folds and enhancement of epithelial barrier in odontogenic sinusitis
Yuan Zhang MD, PhD Feng Lan MD, PhD Ying Li BS Chengshuo Wang MD, PhD Luo Zhang MD, PhD
First published: 08 January 2019 https://doi.org/10.1002/alr.22277
Funding sources for the study: National Key R&D Program of China (2016YFC20160905200); the National Natural Science Foundation of China (81570895, 81420108009, 81400444, 81470678, and 81630023); Changjiang Scholars and Innovative Research Team (IRT13082); Special Fund of Capital Health Development (2011‐1017‐06, 2011‐1017‐02); Special Fund of Sanitation Elite Reconstruction of Beijing (2009‐2‐007); Beijing Health Bureau Program for High Level Talents (2011‐3‐043); Beijing Municipal Administration of Hospitals' Mission Plan (SML20150203); Capital Citizenry Health Program (z161100000116062).
Potential conflict of interest: None provided.
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Abstract
Background
Odontogenic sinusitis (OS) presents more satisfactory therapeutic effect after endoscopic surgery compared with chronic rhinosinusitis (CRS) of other origin. The aim of the present study was to investigate the clinical characteristics, morphological features, and epithelial barrier function of sinus mucosa of OS and discuss the possible relationship with good prognosis.
Methods
A total of 25 subjects with OS, 7 CRS without nasal polyps (CRSsNP), 10 CRS with nasal polyps (CRSwNP), and 9 control subjects were recruited. The biopsy specimens were stained with hematoxylin and eosin for general observation of cytomorphologic features. Epithelial tight junctions (TJs) protein claudin‐4 expression was determined to evaluate the epithelial barrier integrity by using immunofluorescence and Image‐Pro Plus software analysis. The representative cytokine profiles regarding T helper 1 (Th1) (interferon [IFN]‐γ), Th2 (interleukin [IL]‐5), and Th17 (IL‐17) were examined by reverse transcription–polymerase chain reaction (RT‐PCR).
Results
Extensively small papillary protrusions could be seen in the maxillary sinus mucosa of OS patients under nasal endoscopy, similar to the morphological behavior, which also presented as papillary folds in the surface of the epithelium. The epithelium in OS kept an increased claudin‐4 expression compared with that seen in CRSsNP, CRSwNP, and control subjects. The inflammatory pattern analysis demonstrated that OS belonged to the lymphocyte and plasma cell‐dominant cellular phenotypes, whereas IL‐17 was dominant compared with IFN‐γ as well as IL‐5.
Conclusion
The odontogenic infections might induce the formation of papillary mucosa folds and enhance the epithelial TJ barrier function. OS exhibited as lymphocyte and plasma cell–dominant cellular phenotypes and Th17 cytokine profiles.
https://onlinelibrary.wiley.com/doi/10.1002/alr.22277
Broncho‐Vaxom(R) (OM‐85 BV) soluble components stimulate sinonasal innate immunity
Broncho‐Vaxom® (OM‐85 BV) soluble components stimulate sinonasal innate immunity
Vasiliki Triantafillou BS Alan D. Workman MD Neil N. Patel BA, BS Ivy W. Maina BA Charles C. L. Tong MD Edward C. Kuan MD, MBA David W. Kennedy MD … See all authors
First published: 07 January 2019 https://doi.org/10.1002/alr.22276
Funding sources for the study: National Institutes of Health (National Institute on Deafness and Other Communication Disorders [NIDCD] R01DC013588 to N.A.C.); Veterans Affairs Merit Review (CX001617 to N.A.C.).
Potential conflict of interest: None provided.
Presented orally at the ARS Meeting at the annual Combined Otolaryngology Spring Meetings (COSM) on April 18‐22, 2018, National Harbor, MD.
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Abstract
Background
Broncho‐Vaxom® (OM‐85 BV) is an extract of infectious respiratory bacteria that is used as an immunostimulant outside of the United States for the prevention and treatment of bronchitis and rhinosinusitis. Prior studies have shown that use of OM‐85 BV is associated with reduction in frequency of respiratory infection and decreased duration of antibiotic usage. However, the effects of OM‐85 BV on respiratory mucosal innate immunity are unknown.
Methods
Human sinonasal epithelial cells were grown at an air‐liquid interface (ALI). Ciliary beat frequency (CBF) and nitric oxide (NO) production in response to stimulation with OM‐85 BV was measured in vitro. Pharmacologic inhibitors of bitter taste receptor (T2R) signaling were used to determine if this pathway was taste‐receptor–mediated.
Results
Apical application of OM‐85 BV resulted in an NO‐mediated increase in CBF (p < 0.05) and increased NO production (p < 0.0001) when compared to saline‐stimulated control cultures. ALI pretreatment with taste receptor pathway inhibitors blocked OM‐85 BV–induced increases in NO.
Conclusion
OM‐85 BV has ciliostimulatory and immunogenic properties that may be partially responsible for its observed efficacy as a respiratory therapeutic. These responses were NO‐dependent and consistent with T2R activation. Further work is necessary to elucidate specific component‐receptor signaling relationships.
https://onlinelibrary.wiley.com/doi/10.1002/alr.22276
One-year survival and admission to hospital for cardiovascular events among older residents of long-term care facilities who were prescribed intensive- and moderate-dose statins [Research]
BACKGROUND:
Guidance from randomized clinical trials about the ongoing benefits of statin therapies in residents of long-term care facilities is lacking. We sought to examine the effect of statin dose on 1-year survival and admission to hospital for cardiovascular events in this setting.
METHODS:We conducted a retrospective cohort study using population-based administrative data from Ontario, Canada. We identified 21 808 residents in long-term care facilities who were 76 years of age and older and were prevalent statin users on the date of a full clinical assessment between April 2013 and March 2014, and categorized residents as intensive- or moderate-dose users. Treatment groups were matched on age, sex, admission to hospital for atherosclerotic cardiovascular disease, resident frailty and propensity score. Differences in 1-year survival and admission to hospital for cardiovascular events were measured using Cox proportional and subdistribution hazard models, respectively.
RESULTS:Using propensity-score matching, we included 4577 well-balanced pairs of residents who were taking intensive- and moderate-dose statins. After 1 year, there were 1210 (26.4%) deaths and 524 (11.5%) admissions to hospital for cardiovascular events among residents using moderate-dose statins compared with 1173 (25.6%) deaths and 522 (11.4%) admissions to hospital for cardiovascular events among those taking intensive-dose statins. We found no significant association between prevalent use of intensive-dose statins and 1-year survival (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.90 to 1.05) or 1-year admission to hospital for cardiovascular events (HR 0.99, 95% CI 0.88 to 1.12) compared with use of moderate-dose statins.
INTERPRETATION:The rates of mortality and admission to hospital for cardiovascular events at 1 year were similar between residents in long-term care taking intensive-dose statins compared with those taking moderate-dose statins. This lack of benefit should be considered when prescribing statins to vulnerable residents of long-term care facilities who are at potentially increased risk of statin-related adverse events.
http://bit.ly/2Cmz1I7
Phenotypic spectrum of NDE1‐related disorders: from microlissencephaly to microhydranencephaly
Biallelic variants in the NDE1 gene have been shown to occur in extreme microcephaly. Most of the patients displayed microlissencephaly but one with microhydranencephaly. We report on three sibs in which the brain MRI and CT scans demonstrated variable degree of reduced volume of cerebral hemispheres and ventriculomegaly. Further, they had agenesis of corpus callosum, cerebellar, and brainstem hypoplasia. Fetal ultrasound at 32 weeks' gestation of the third sib revealed severe micrencephaly with extensive hydranencephaly and an anomaly consistent with non cleaved (fused) thalami. Because of the fused thalami, the STIL gene was targeted initially but showed negative results. His postnatal MRI showed that the cerebral hemispheres are markedly reduced in size (with no definite frontal, parietal, or occipital lobes) and replaced by a large sac filled with CSF. An intact falx cerebri was identified. This extensive hydarencephaly led us to consider the NDE1 and to identify a novel homozygous nonsense variant (c.54G>A, p.W18*). The variability of the degree of brain malformations and the apparent fusion of the thalami were illusive and delayed the recognition of the genetic etiology. Our results provide the first antenatal description of this rare syndrome. Further, we expand the genetic architecture and the neuroradiologic phenotype of NDE1‐related disorders.
http://bit.ly/2CmYbXd
Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature
Abstract
Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype‐up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50–90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome.
http://bit.ly/2Rpr92V
Abnormal bone mineral content and density in people with tetrasomy 18p
Tetrasomy 18p is a rare chromosomal abnormality, resulting from an additional iso‐chromosome composed of two copies of the short arm. It is characterized by craniofacial abnormalities, neuromuscular dysfunction, and developmental delay. The Chromosome 18 Clinical Research Center has established the largest cohort of individuals with this rare genetic condition. Here, we describe a case series of 21 individuals with tetrasomy 18p who have a previously unreported clinical finding: low bone mineral density. Most individuals met criteria for osteopenia despite being relatively young (mean age of 21 years). Clinicians providing care to individuals affected by Tetrasomy 18p should be aware of their increased risk for decreased bone density and pathological fractures.
http://bit.ly/2Cv8FnB
The incidence of anxiety symptoms in boys with 47,XXY (Klinefelter syndrome) and the possible impact of timing of diagnosis and hormonal replacement therapy
47,XXY (Klinefelter syndrome) is the most common X and Y chromosomal variation (1:660 males). The incidence of anxiety disorders and the impact of hormonal replacement therapy (HRT) is not well understood. Child Behavior Checklist and Screen for Childhood Anxiety Related Emotional Disorders were completed by parents of 80 boys with 47,XXY. Forty received HRT prior to 10 years of age while 40 did not. HRT (22.5%) received early hormonal treatment prior to 18 months. About 32.5% received hormone booster treatment between 5 and 10 years. The remaining 42.5% received both. There were fewer reported social (p = .015), thought (p = .012), and affective problems (p = .048) in treated boys when compared to untreated. Boys with both treatments demonstrated fewer symptoms on anxious/depressed scale (p = .001) compared to those with early treatment only. Within the treated group, prenatally diagnosed showed fewer indications of anxiety problems (p = .02) than their postnatal counterparts. This comparative, cross‐sectional study expands previous findings on the possible positive effect of HRT in boys with 47,XXY. Anxiety disorders appear to be a penetrant aspect of the 47,XXY phenotype. Further investigation is warranted to explore the relationship between biological treatment and individual responses to HRT to develop more personalized and precise medicine.
http://bit.ly/2RrfyAC
Solid tumor screening recommendations in trisomy 18
The purpose of this study was to determine whether trisomy 18 patients are at an increased risk of tumor development and require formal tumor screening recommendations. A literature search of trisomy 18 patients with reports of tumors or malignancies, and compilation of all previously reported as well as new unreported cases was performed. 67 patients with trisomy 18 were found to have documented malignancies. 44 patients had hepatoblastomas, 21 patients had Wilms tumors, one patient had a functional neurogenic neoplasia, and one patient had Hodgkins lymphoma. The increasing numbers of reported malignancies in patients with trisomy 18 supports the indication for an early screening process. Specific screening recommendations are outlined consisting of imaging exams and laboratory values performed at specific intervals.
http://bit.ly/2CmyYMr
Combined photodynamic therapy with systemic chemotherapy for unresectable cholangiocarcinoma
Summary
Background
Chemotherapy with gemcitabine and cisplatin is the current standard for patients with unresectable cholangiocarcinoma. Local photodynamic therapy has also demonstrated benefit in patients with extrahepatic cholangiocarcinoma.
Aim
To evaluate the benefit of photodynamic therapy in combination with systemic chemotherapy in advanced extrahepatic cholangiocarcinoma.
Methods
Three hundred and fifty‐three patients diagnosed with cholangiocarcinoma between 2004 and 2016 were treated at the University Hospital of Bonn, Germany. Of these, 96 suffering from unresectable extrahepatic cholangiocarcinoma were included. Patients were stratified according to treatment: combination photodynamic therapy and chemotherapy (36 patients), photodynamic therapy alone (34 patients), and chemotherapy alone (26 patients).
Results
Combined photodynamic therapy with chemotherapy resulted in significantly longer overall survival than chemotherapy alone (P = 0.022). Median survival was 20 months in the combination group (95% CI: 16.38‐23.62), 15 months in the photodynamic alone group (95% CI: 10.02‐19.98) and 10 months in the chemotherapy alone group (95% CI: 8.45‐11.55). In multivariate analysis, combination therapy and photodynamic therapy alone (HR: 0.41, 95% CI: 0.22‐0.77, P = 0.006), metal stenting, and radiofrequency ablation were independent predictors of longer survival.
Conclusions
Combination photodynamic therapy and chemotherapy was well tolerated and resulted in significantly longer survival than chemotherapy alone. Application of photodynamic therapy significantly correlated with longer survival, demonstrating benefit in advanced cholangiocarcinoma. Thus, photodynamic therapy should be considered during therapeutic decision making in advanced cholangiocarcinoma.
http://bit.ly/2FxDcnF
Factors associated with an adverse work outcome in breast cancer survivors 5–10 years after diagnosis: a cross-sectional study
Abstract
Purpose
To identify which factors are associated with adverse work outcome 5–10 years after diagnosis.
Methods
In this cross-sectional study, breast cancer survivors, treated between 2003 and 2008, completed a questionnaire 5–10 years after diagnosis. Adverse work outcome was defined as not having paid employment or working > 20% less compared to prediagnosis. Logistic regression analyses were conducted.
Results
Of 906 participants, 326 (36%) had an adverse work outcome. In multivariable analyses, the probability of an adverse work outcome increased with age (OR, 1.03; 95% CI, 1.00–1.07), time since diagnosis (OR, 1.19; 95% CI, 1.03–1.37), and was higher among women who stated that work had become less important (OR, 2.99; 95% CI, 1.94–4.62). Factors associated with a lower probability of an adverse work outcome were having sufficient financial resources (OR, 0.23; 95% CI, 0.08–0.66), higher total work ability (OR, 0.61; 95% CI, 0.54–0.69), feeling supported at work (OR, 0.52; 95% CI, 0.33–0.80), and, prior to diagnosis, having more children to take care of (OR, 0.65; 95% CI, 0.54–0.79), being able to adjust working hours (OR, 0.55; 95% CI, 0.36–0.83) and not desiring to work less hours if that were to be financially feasible (OR, 1.8; 95% CI, 1.0–3.2).
Conclusions
Predominantly, work-related factors are associated with adverse work outcomes 5–10 years after diagnosis, whereas clinical factors are not. Our results need validation in prospective cohort studies, after which supportive interventions could be developed.
Implications for Cancer Survivors
Work-related factors should be considered in future interventions to prevent adverse work outcome 5–10 years after diagnosis.
http://bit.ly/2Fv5qiR
Cost-Effectiveness of Treatment Options for Neuropathic Pain: a Systematic Review
Abstract
Background
Neuropathic pain significantly reduces an individual's quality of life and places a significant economic burden on society. As such, many cost-effectiveness analyses (CEAs) have been published for treatments available for neuropathic pain.
Objectives
The primary objective of this systematic review was to provide a detailed summary of the estimates of cost-effectiveness from published CEAs comparing available treatments for neuropathic pain. The secondary objectives were to identify the key drivers of cost-effectiveness and to assess the quality of published CEAs in neuropathic pain.
Methods
We searched Embase, MEDLINE, Cochrane CENTRAL and seven other databases to identify CEAs reporting the costs, health benefits (e.g., quality-adjusted life-years or disability-adjusted life-years) and summary statistics, such as incremental cost-effectiveness ratios, of treatments for neuropathic pain. We excluded studies reporting diseases other than neuropathic pain, those for which the full text was not available (e.g., conference abstracts), studies not written in English or not published in peer-reviewed journals, and narrative reviews, editorials and opinion papers. Titles and abstract reviews, full-text reviews, and data extraction were all performed by two independent reviewers, with disagreement resolved by a third reviewer. Mean costs, health benefits, and summary statistics were reported and qualitatively compared across studies, stratified by time horizon. Drivers of cost-effectiveness were assessed using reported one-way sensitivity analyses. The quality of all included studies was evaluated using the Tufts CEA Registry Quality Score and study reporting using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklist.
Results
A total of 22 studies were identified and included in this systematic review. Included studies were heterogeneous in the treatments compared, methodology and design, perspectives, and time horizons considered, making cross-study comparisons difficult. No single treatment was consistently the most cost-effective across all studies, but tricyclic antidepressants were the preferred treatment at a willingness-to-pay threshold of $US50,000 per quality-adjusted life-year in several studies with a short time horizon and a US payer perspective. Among the 14 studies reporting one-way sensitivity analyses, drivers of cost-effectiveness included utility values for health states and the likelihood of pain relief with treatment. The quality of the identified CEAs was moderate to high, and overall reporting largely met CHEERS recommendations.
Limitations
To assess drivers of cost-effectiveness and quality, we only included studies with the full text available and thus excluded some CEAs that reported cost-effectiveness results. The heterogeneity of the included studies meant that the study results could not be synthesized and comparison across studies was limited.
Conclusions
Though many pulished studies have evaluated the cost-effectiveness of treatments for neuropathic pain, significant heterogeneity between CEAs prevented synthesis of the results. Standardized methodology and improved reporting would allow for more reliable comparisons across studies.
http://bit.ly/2Fu4fjO
Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer
Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer
Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer, Published online: 14 January 2019; doi:10.1038/s41416-018-0360-y
Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer
https://go.nature.com/2VYiK5k
Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours
Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours
Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours, Published online: 14 January 2019; doi:10.1038/s41416-018-0367-4
Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours
https://go.nature.com/2Cj4pqV
The frequency and predictors of persistent amenorrhea in premenopausal women with colorectal cancer who received adjuvant chemotherapy
http://bit.ly/2FoWZXk
Long-term therapy with bevacizumab in a young patient affected by NF-2: a case report and review of the literature
http://bit.ly/2FtXOxa
Cardamonin inhibits the proliferation and metastasis of non-small-cell lung cancer cells by suppressing the PI3K/Akt/mTOR pathway
http://bit.ly/2FrgvCh
Cotreatment with sorafenib and oleanolic acid induces reactive oxygen species-dependent and mitochondrial-mediated apoptotic cell death in hepatocellular carcinoma cells
http://bit.ly/2FxvN86
Rectovaginal fistula during treatment with axitinib in a patient with renal cell carcinoma: a case report and review of the literature
http://bit.ly/2FqoQXc
Leadership in American Surgery: Women are Rising to the Top
Objective: To celebrate the increasing representation of women as leaders in American surgery and provide suggestions for increasing diversity in leadership. Background: Women were barred from entering the practice of medicine or surgery until the mid 1800's when Elizabeth Blackwell led the way as the first woman admitted to medical school. Although the numbers of women practicing medicine and surgery have increased exponentially since Dr Blackwell graduated, the number of women in leadership positions has remained low until recently. Methods: An analysis of the literature on the history of women in surgery and the websites of the major surgical societies. Results: More women are now rising to leadership positions in surgery, both in academics and within surgical organizations. The American College of Surgeons and many other surgical societies, as well as an increasing number of academic departments of surgery have realized that women can be inspiring and capable leaders. However, increasing the number of under-represented minority women in leadership positions remains an opportunity for improvement. Conclusions: Great progress has been made in the advancement of women into leadership positions in surgery. To continue this trend and increase the number of under-represented minority women in surgery will require attention to recruitment, mentorship, and sponsorship.http://bit.ly/2ACgtn7
Exploring the Effects of Spaceflight on Mouse Physiology using the Open Access NASA GeneLab Platform
The NASA GeneLab platform provides unfettered access to precious omics data from biological spaceflight experiments. We describe how a typical mouse experiment is conducted in space and how data from such experiments can be accessed and analyzed.
http://bit.ly/2HbAFls
Bring ‘Em All: Chaos. Care. Stories from Medicine's Front Line
Abstract
Bring 'Em All is intended to provide a combined visual and printed introduction to Emergency Medicine including pioneers of the field, new trainees, EMS providers, nurses and technicians. The book uses black and white photos capturing the chaos, emotion and connections forged within the hectic environment of the ED, as well as interviews with the emergency providers themselves. It is modeled after the structure of a shift with vignettes of different patients and experiences.
This article is protected by copyright. All rights reserved.
http://bit.ly/2QJR9Rm
The Birth of a Return to Work Policy for New Resident Parents in Emergency Medicine
Abstract
Objective
With the rising number of female physicians, there will be more children than ever born in residency and the current system is inadequate to handle this increase in new resident parents. Residency is stressful and rigorous in isolation, let alone when pregnant or with a new child. Policies that ease these stressful transitions are generally either insufficient or do not exist. Therefore, we created a comprehensive Return to Work Policy for resident parents and piloted its implementation. Our policy aims to: 1) establish a clear, shared understanding of the regulatory and training requirements as they pertain to parental leave, 2) facilitate a smooth transition for new parents returning back to work, and 3) summarize the local and institutional resources available for both males and females during residency training.
Method
In Fall 2017, a task force was convened to draft a Return to Work Policy for New Resident Parents. The task force included 9 key stakeholders (i.e., residents, faculty, and administration) at our institution and was made up of 3 Graduate Medical Education (GME) Program Directors, a Vice Chair of Education, a Designated Institutional Official (DIO), a Chief Resident, and 3 members of our academic department's Faculty Affairs Committee. The task force was selected because of individual expertise in gender equity issues, mentorship of resident parents, GME, and departmental administration.
Results
After development, the policy was piloted from November 2017 to June 2018. Our pilot implementation period included 7 new resident parents. All of these residents received schedules that met the return to work scheduling terms of our Return to Work Policy including no overnight shifts, no sick call, no more than 3 shifts in a row. Of equal importance, throughout our pilot, the emergency department schedules at all of our clinical sites remained fully staffed and our sick call pool was unaffected.
Conclusion
Our Return to Work Policy for New Resident Parents provides a comprehensive guide to training requirements and family leave policies, an overview of available resources, and a scheduling framework that makes for a smooth transition back to clinical duties.
This article is protected by copyright. All rights reserved.
http://bit.ly/2VSFQdg
Gender Differences in Faculty Rank Among Academic Emergency Physicians in the United States
Abstract
Background
The purpose of this study was to complete a comprehensive analysis of gender differences in faculty rank among United States (U.S.) emergency physicians that reflected all academic emergency physicians.
Methods
We assembled a comprehensive list of academic emergency medicine physicians with U.S. medical school faculty appointments from Doximity. com linked to detailed information on physician gender, age, years since residency completion, scientific authorship, National Institutes of Health (NIH) research funding, and participation in clinical trials. To estimate gender differences in faculty rank, multivariable logistic regression models were used that adjusted for these factors.
Results
Our study included 3600 academic physicians (28%, or 1016, female). Female emergency physicians were younger than their male colleagues [mean age, years (+SD), was 43.8 (+ 8.7) for females and 47.4 (+ 9.9) for males (p<0.001)], had fewer years since residency completion (12.4 vs. 15.6 years, p<0.001), had fewer total and first/last author publications [4.7 vs. 8.6 total publications, p<0.001; 4.3 vs. 7.1 first or last author publications, p<0.001], and were less likely to be principal investigators on NIH grants [1.2% vs. 2.9%, p=0.002] or clinical trials [1.8% vs. 4.4%, p<0.001]. In unadjusted analysis, male physicians were more likely than female physicians to hold the rank of Associate or Full Professor vs. Assistant Professor [13.7 percentage point difference, p<0.001], a relationship that persisted after multivariable adjustment [5.5 percentage point difference, p=0.001].
Conclusions
Female academic emergency medicine physicians are less likely to hold the rank of Associate or Full Professor compared to male physicians even after detailed adjustment for other factors that may influence faculty rank.
This article is protected by copyright. All rights reserved.
http://bit.ly/2QJR8Ni
Changes in Pain Score Associated with Clinically Meaningful Outcomes in Children with Acute Pain
Abstract
Background
Identifying changes in pain score associated with clinically meaningful outcomes is necessary when using self‐report measures to assess pain in children. We aimed to determine the changes in pain score associated with a minimum clinically significant difference (MCSD), ideal clinically significant difference (ICSD), and patient‐perceived adequate analgesia (PPAA), and to evaluate for differences based on initial pain intensity and patient characteristics.
Methods
Cross‐sectional study of children 6‐17 and 4‐17 years old who were assessed using the Verbal Numerical Rating Scale (VNRS) and Faces Pain Scale‐Revised (FPS‐R), respectively. Children qualitatively described any endorsed change in pain score; those who received an analgesic were asked if they wanted additional analgesics to decrease their pain intensity. We used a receiver operating characteristic curve‐based methodology to identify changes in pain score associated with "a little less" and "much less" pain (MCSD and ICSD, respectively) and patients declining additional analgesics because of adequate analgesia (PPAA).
Results
We enrolled 431 children with painful conditions. For the VNRS, raw change and percent reductions in pain scores associated with MCSD, ICSD, and PPAA were 2/10 and 20%, 3/10 and 44%, and 2/10 and 29%, respectively; for the FPS‐R, 2/10 and 33%, 4/10 and 60%, and 4/10 and 40%, respectively. Raw change in pain scores increased with increasing initial pain intensity, but percent reductions remained stable. There were no significant differences based on patient characteristics such as age, sex, and race/ethnicity.
Conclusion
Our findings provide patient‐centered outcomes in children that are suitable for designing trials and are generalizable across patient characteristics.
This article is protected by copyright. All rights reserved.
http://bit.ly/2VQ1wa8
Point‐of‐Care Ocular Ultrasound for the Diagnosis of Retinal Detachment: A Systematic Review and Meta‐Analysis
Abstract
Background
Ocular complaints are common presentations to the Emergency Department (ED). Among these, retinal detachment can cause significant vision loss if not rapidly diagnosed and referred for appropriate treatment. Point‐of‐care ultrasound has been suggested to identify the diagnosis rapidly when the ocular examination is limited or the ophthalmology service is not readily available. However, prior studies were limited by small sample sizes, resulting in wide ranges of potential accuracy. The primary outcome for this review was to determine the test characteristics of point‐of‐care ocular ultrasound for the diagnosis of retinal detachment.
Methods
PubMed, CINAHL, Scopus, LILACS, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and bibliographies of selected articles were assessed for all prospective and randomized controlled trials assessing the accuracy of point‐of‐care ultrasound for identifying retinal detachment. Data were dual extracted into a predefined worksheet and quality analysis was performed using the QUADAS‐2 tool. Data were summarized and a meta‐analysis was performed with planned subgroup analyses by location and provider specialty. This review was registered with PROSPERO [blinded for peer review]. There was no funding for this review.
Results
Eleven studies (n=844 patients) were identified. Overall, ultrasound was 94.2% (95% CI 78.4% to 98.6%) sensitive and 96.3% (95% CI 89.2% to 98.8%) specific for the diagnosis of retinal detachment with a LR+ of 25.2 (95% CI 8.1 to 78.0) and a LR‐ of 0.06 (95% CI 0.01 to 0.25). Subgroup analysis found that ultrasound was more accurate among ED patients, but was not significantly different when performed by ED or non‐ED providers.
Conclusions
Point‐of‐care ocular ultrasound is sensitive and specific for the diagnosis of retinal detachment. Future studies should determine the ideal training protocol and the influence of color Doppler and contrast‐enhanced ultrasound on diagnostic accuracy.
This article is protected by copyright. All rights reserved.
http://bit.ly/2QJR6VG
Four or 6 implants in the maxillary posterior region to support an overdenture: 5‐year results from a randomized controlled trial
Abstract
Objective
To compare clinical and patient‐reported outcomes when providing maxillary overdentures on 4‐bar and 6‐bar connected implants placed in the posterior region during a 5‐year follow‐up period.
Materials and methods
Sixty‐six fully edentulous patients with functional maxillary denture complaints and insufficient bone volume to allow implant placement were scheduled for a maxillary sinus floor elevation procedure with bone from the anterior iliac crest and randomized to receive either 4 or 6 implants in the posterior maxilla and 4 implants in the mandible. After 3 months of osseointegration, a bar‐supported overdenture was constructed. Maxillary implant survival, overdenture survival, clinical scores, peri‐implant bone height changes and patient satisfaction were assessed.
Results
Sixty patients completed the 5‐year follow‐up. Implant survival was 100% in the 4‐implants group and 99.5% in the 6‐implants group. No new overdentures had to be made in the 4‐implants group, three new overdentures were made in the 6‐implants group due to excessive wear of the denture base and teeth (90.9% overdenture survival). Clinical parameters did not differ significantly between groups. Mean marginal bone loss compared to baseline was 0.58±0.51 mm in the 4‐implants group and 0.60±0.58 mm in the 6‐implants group, respectively. Overall, patient satisfaction improved significantly, but did not differ between groups.
Conclusion
Following a bilateral maxillary sinus floor elevation procedure, a bar‐supported overdenture on 4 implants in the posterior maxillary region is not inferior to an overdenture supported by 6 implants after a 5‐year evaluation period in patients with functional maxillary denture complaints and marked posterior resorption.
This article is protected by copyright. All rights reserved.
http://bit.ly/2AIRVcl
Bone Response to Porous Tantalum Implants in a Gap Healing Model
Abstract
Objectives
The objective of this study was to determine the relative osteogenic behavior of titanium implants with or without a porous tantalum modification when placed with a gap between the implant and existing bone.
Materials and Methods
A gap‐healing model in the rabbit tibia was used for placement of titanium implants. Forty‐eight rabbits received 96 implants, with 48 of the implants containing a porous tantalum middle section and the remaining 48 implants were composed of solid titanium. After 4, 8 and 12 weeks of healing, biomechanical stability was measured with removal torque testing, implant‐adherent cells were isolated for analysis of osteogenic gene expression, and histomorphometric analysis was performed on sections of the implants and surrounding bone.
Results
Increased osteogenic activity at 4 weeks was demonstrated by upregulation of key osteogenic genes at implants containing porous tantalum which was accompanied by greater bone‐implant contact at 4, 8 and 12 weeks and significantly greater removal torque at 8 and 12 weeks.
Conclusions
Implants containing porous tantalum demonstrated increased peri‐implant bone formation within this gap‐healing model as shown by significant differences in biomechanical and histomorphometric outcomes. Such implants may represent an alternative to influence bone healing in surgical sites with an existing gap.
This article is protected by copyright. All rights reserved.
http://bit.ly/2SRb2b3
High-grade serous ovarian carcinoma with mucinous differentiation: report of a rare and unique case suggesting transition from the “SET” feature of high-grade serous carcinoma to the “STEM” feature
High-grade serous carcinoma, a representative high-grade ovarian carcinoma, is believed to be closely associated with a TP53 mutation. Recently, this category of ovarian carcinoma has gained increasing attention ...
http://bit.ly/2Fv6DGR
Neonatal Mortality in Hospitalized Chinese Population: A Meta-Analysis
Objective. In this meta-analysis, we aim to investigate the neonatal mortality in hospitalized Chinese population in the recent 20 years in China, which may provide basis for decreasing the neonatal mortality. Methods. The merged mortality was estimated based on the random effect model, and subgroup analysis was performed for the gender, publication year, gestational age, and birth weight. Sensitivity analysis was utilized to evaluate the effects of research type and research quality on the effects. Results. The neonatal mortality in eastern China was lower than that of the central and western China (2.3% versus 2.9; 2.3% versus 26.%). The mortality in neonates with a gestational age of 28-32 weeks (0.6%) was significantly higher than that of 42 weeks (0.1%). The mortality in those with a body weight of 1.0-2.5 kg (0.3%) was significantly higher than that of 2.5-4.0 kg (0.2%) and >4.0 kg (0.0%). Sensitivity analysis revealed that the findings of meta-analysis were stable. The major causes for neonatal death included asphyxia, respiratory distress syndrome, and infection. Conclusions. The hospitalized neonatal mortality showed a tendency of decrease, which differed based on gender, region, gestational age, and birth weight.
http://bit.ly/2Fv2Jhb
Integrated Analysis of lncRNA and mRNA Transcriptomes Reveals New Regulators of Ubiquitination and the Immune Response in Silica-Induced Pulmonary Fibrosis
Objectives. As an epigenetic player, long noncoding RNAs (LncRNAs) have been reported to participate in multiple biological processes; however, their biological functions in silica-induced pulmonary fibrosis (SIPF) occurrence and development remain incompletely understood. Methods. Five case/control pairs were used to perform integrated transcriptomes analysis of lncRNA and mRNA. Prediction of lncRNA and mRNA functions was aided by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Additionally, we constructed a coexpression network of lncRNAs and mRNAs to identify targets of regulation. Results. In total, 1069 differentially expressed mRNAs and 366 lncRNAs were identified with the changes more than 2 times (p2 (p
http://bit.ly/2FqxFAa
Cervical spondylotic myelopathy
Degenerative cervical myeloradiculopathy
Cervical spondylotic myelopathy
Spondylotic cervical myelopathy
Ossification of the posterior longitudinal ligament
The median labio-mandibulo-glossotomy approach to the upper cervical spine
| : A personal series and tips and pearls | p. 92 |
| K Venugopal Menon, Hood Al Saqri, Renjit Kumar, Maruti Kambali DOI:10.4103/isj.isj_8_18 Background: Wide exposure to the anterior part of the upper cervical spine is difficult due to anatomical constraints. The Labio-Mandibulo-Glossotomy (LMG) approach is considered a difficult approach with high morbidity. The objective of this study is to describe the authors experience with the approach and it's outcomes in six cases and offer tips and pearls to the surgical access. Methods: This is a retrospective review of a small series of six cases that were operated for upper cervical lesions by the LMG approach. Two had mandible fractures that needed fixation and in the others osteotomy of the mandible was performed. The patients were followed up for minimum two years or death (in malignancy). We specifically looked for cosmetic or functional problems related to osteotomy, glossotomy, and, hospital and ICU stay duration. Surgical access is described in detail. Results: The hospital stay was similar to other major spine trauma or tumour surgeries at our center (median 14 days) and mean ICU stay 2.8 days. There were no long-term issues related to the access. Several tips and tricks are offered to minimize intra and post-operative problems. Conclusions: The LMG approach, though apparently formidable, is quite a safe and simple procedure with few residual complications.  |
Spine
| EDITORIALS | ||
Publish or perish  | p. 1 | |
| Anil K Jain, Manish Chadha DOI:10.4103/isj.isj_74_18 | ||
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| Symposium on cervical spondylo-myelopathy | p. 4 | |
| T Ajoy Prasad Shetty, Ankur Nanda DOI:10.4103/isj.isj_71_18 | ||
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| SYMPOSIUM - CERVICAL SPONDYLOMYELOPATHY |  | |
| Natural history, prevalence, and pathophysiology of cervical spondylotic myelopathy | p. 5 | |
| Gomatam Raghavan Vijay Kumar, Dibyendu Kumar Ray, Rupant Kumar Das DOI:10.4103/isj.isj_48_18 This study is a narrative review performed to summarize the current knowledge about the epidemiology, natural history and pathogenesis of cervical spondylotic myelopathy (CSM). A comprehensive search was undertaken to look at all available articles between January 1, 1956 to May 1, 2018, on PubMed and the Cochrane Collaboration Library. The natural history of CSM is variable. The main determinants of the clinical course of CSM are the extent of neurological impairment, age, cervical instability, abnormalities of cord conduction, canal diameter, congenitally stenotic spinal canal and the extent of involvement and tract disruption on diffusion tensor imaging (DTI) imaging. There is little data on the true incidence and prevalence of CSM across the globe and none from India. The pathoanatomic basis of CSM is cord compression, either dynamic or static. The biological events that are thought to play a significant role in the development of CSM are ischemia, derangement of the blood-spinal cord barrier, chronic neuronal inflammation, and apoptosis. Emerging knowledge about the molecular biology holds promise for potential intervention, both for prevention and for cure, of this common and debilitating condition. | ||
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| Clinical spectrum and importance of evaluation systems in degenerative cervical myeloradiculopathy | p. 13 | |
| Ganesh Swaminathan, Vetrivel Muralidharan, Baylis Vivek Joseph DOI:10.4103/isj.isj_61_18 Degenerative cervical myelopathy includes facet joint arthropathy and/or intervertebral disc prolapse, as well as aberration (hypertrophy, calcification, or ossification) in the ligamentum flavum, and/or posterior longitudinal ligament. Cervical spondylotic myelopathy and ossification of posterior longitudinal ligament are two major conditions under this spectrum. Patients with degenerative changes of the cervical spine can present with wide spectrum of symptoms and signs ranging from axial neck pain, radiculopathy or myelopathy. A combination of history, physical examination, and provocative tests such as Spurling's sign, shoulder abduction test, neck distraction test, Valsalva maneuver, Elvey's upper limb tension/brachial plexus tension test increase the likelihood of diagnosis of cervical radiculopathy. Myelopathy can manifest in the early stage as subtle changes in the upper limb dexterity or mild walking difficulty and in late stage with severe spasticity and flexor spasms. Clinicians are increasingly using quantitative or semi-quantitative scales of neurological impairment. However, there is no gold standard evaluation systems that can reliably assess disease severity. | ||
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  | Imaging in cervical myelopathy | p. 20 |
| Rajavelu Rajesh, Shanmuganathan Rajasekaran, Sri Vijayanand DOI:10.4103/isj.isj_63_18 This is a narrative review. The objective of this study is to provide an overview on the imaging modalities and their utilization in cervical myelopathy (CM). Using PubMed, studies published on the "imaging modalities in CM," "cervical spondylotic myelopathy (CSM) imaging," "computed tomography (CT) and magnetic resonance imaging (MRI) in CM," "imaging in ossified posterior longitudinal ligament (OPLL)," "dural ossification in OPLL," "diffusion tensor imaging (DTI) in CSM," and "dynamic MRI, functional MRI, and magnetic resonance spectroscopy (MRS) in CSM" were evaluated. The review addresses the evaluation of CM with various imaging modalities ranging from radiographs, CT, and MRI to advanced imaging techniques such as DTI and MRS. Each investigation contributes specific detail to the disease process in a different dimension. Specific parameters for CSM and OPLL, and their influence on outcome are discussed. Imaging in CM plays an important role in analyzing the cause of myelopathy, defining the level of the lesion, parameters to assess the time of intervention and to predict the outcome. | ||
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 | Anterior surgical options for cervical spondylotic myelopathy | p. 33 |
| Andrei Fernandes Joaquim, John Alex Sielatycki, K Daniel Riew DOI:10.4103/isj.isj_39_18 Cervical spondylotic myelopathy (CSM) is one of the most common among causes of spinal cord dysfunction worldwide. In this article, we provide a broad narrative review of the options to treat CSM from an anterior approach to the cervical spine. Anterior procedures are effective and safe, especially for one or two level disease (although can be used up to 7-8 levels). This approach can be used in patients with lordotic, neutral, or kyphotic cervical spine alignment and provide excellent access for direct neural decompression. The most common adverse effects of anterior cervical operations are dysphagia and dysphonia, but fortunately, these are mild and transient in the majority of cases. Severe complications, such as vertebral arterial injury, spinal cord injury or airway compromise, are rare but must be taken into consideration, especially when additional risk factors are present (multilevel procedures, revision surgeries, older, and infirm patients). The primary anterior cervical procedures for treating CSM are anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), oblique cervical corpectomy, and cervical disc arthroplasty. A combination (hybrid) of ACDF and ACCF is also utilized as an option to allow for wide decompression, deformity correction, and provide more surface area of exposed, and bleeding cancellous bone. More recently, the senior author (KDR) has utilized a hemi-corpectomy and fusion hybrid technique which will be described in this text. Advantages and disadvantages of each of these options are discussed in detail, as well as the need for posterior instrumentation supplementation in selected patients; such as those with concomitant cervical deformity, poor bone quality, or those at risk for pseudarthrosis following multilevel arthrodeses. The management of patients with cervical spinal cord compression without myelopathy or with mild symptoms is also discussed. | ||
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 | Posterior surgical options for spondylotic cervical myelopathy | p. 42 |
| Shankar Acharya, Nikhil Jain DOI:10.4103/isj.isj_57_18 Cervical spondylotic myelopathy (CSM) is a common presentation in the middle-aged to elderly population. The cause of myelopathy is multifactorial, and cervical spondylosis is the most common cause. This review looks into the treatment options, timing of the surgery, and the advantages and disadvantages of the various posterior approaches for multilevel spondylotic myelopathy. CSM is a disabling disorder that should be addressed in its early phases. There are limited surgical options available, and each procedure has its advantages and disadvantages. Since the neurological and functional outcomes are the same for all well-performed decompressions, the choice of surgical approach depends on various other factors. Posterior approaches are good for multilevel disease as they make the surgery simpler, shorter and with reduced complications in comparison to multilevel anterior surgeries. | ||
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 | Ossification of the posterior longitudinal ligament: Etiology, prevalence, progression, and surgical strategies | p. 52 |
| Yoshiharu Kawaguchi DOI:10.4103/isj.isj_41_18 Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of the ligamentous tissue by ectopic new bone formation. OPLL often causes narrowing of the spinal canal and has been recognized as a cause of cervical myelopathy and/or radiculopathy. Although a clear inheritance of OPLL has not been identified, there is a strong genetic background for OPLL. A recent genome-wide association study using all Japan cohort reported that there were 6 susceptible loci for OPLL. In addition, there were several studies to seek the biomarkers of OPLL. OPLL is frequently found in the cervical spine. However, 53.4% had OPLL not only in the cervical spine, but also in other spinal regions in patients with cervical OPLL. Further, 65.2% with cervical OPLL had ossification of the ligamentum flavum (OLF) especially at the levels of the thoracic and the lumbar spine. There is no effective conservative treatment. Surgical decompression is considered in patients with severe and/or progressive myelopathy. Early surgical decompression of the spinal cord is recommended in patients with apparent myelopathy. Operative methods are divided into two procedures, anterior decompressive surgery and posterior decompressive surgery. The choice of the surgical procedure is determined according to several factors, such as local pathology of OPLL and spinal alignment. | ||
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 | Clinical predictors of complications and outcomes in degenerative cervical myeloradiculopathy | p. 59 |
| Jamie R F Wilson, Fan Jiang, Michael G Fehlings DOI:10.4103/isj.isj_60_18 Degenerative cervical myelopathy (DCM) is the leading cause of adult spinal cord dysfunction worldwide, and surgical decompression remains the mainstay treatment to arrest the progression of neurological deterioration. A number of clinical factors can predict and influence the outcomes of surgery, including patient demographics, baseline myelopathy severity, duration of symptoms, imaging characteristics, and types of surgical approach. Understanding the influence and relationship of these factors on surgical outcomes allows the treating clinician the ability to provide the patient with realistic expectations when discussing surgical intervention for DCM. | ||
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 | The spine clinics – Cervical spondylotic myelopathy – Clinical scenarios | p. 68 |
| Ankur Nanda, KR Renjith, Abhinandan Mallepally, C S Vishnu Prasath, Ajoy P Shetty DOI:10.4103/isj.isj_67_18 This section of the symposium deals with different case scenarios related to cervical spondylotic myelopathy (CSM) which in our daily clinical practice not only act as diagnostic challenges but also test our decision-making abilities. These cases have been handled by different experts and hence help the readers in providing a wider perspective to the problem of cervical myelopathy and its management. This section ends with comments by the authors on key takeaway points from each case scenario, and some literature supported recommendations for the management of CSM. | ||
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| REVIEW ARTICLE | | |
 | Cell-based treatment strategies for intervertebral disc degeneration: An overview on potentials and shortcomings | p. 81 |
| Prasanthi Sampara, Rajkiran Reddy Banala, Satish Kumar Vemurit, AV Gurava Reddy, G P V Subbaiah DOI:10.4103/isj.isj_21_17 The intervertebral discs (IVDs) are the cushioning pads of fibrocartilage, which are immeasurably vital for the uprightness of vertebral column and for its function. IVD provides flexibility, tensile strength to the spine, and also cope up with varied types of biomechanical stresses. IVD degeneration (IVDD) is one of the musculoskeletal disorders mostly seen in older population, and it is the foremost cause of low back pain and consequences of IVDD are disc herniation, spinal stenosis, and degenerative lumbar scoliosis. Yet the therapeutic options are restricted and the treatments given remain unsatisfactory putting more economical burden on world's population. IVDD is considered as a multifactorial disorder, due to the involvement of factors such as genetic inheritance, alterations in cellular composition, and anabolic and catabolic reactions, which could initiate degenerative process in the IVD. However, our conception on IVD genesis and the etiopathology of IVDD have given us an opportunity for exploring and formulate appropriate therapies to tackle IVDD. The cell therapy gives scope for sustained matrix synthesis, controlled inflammation, and prevention of osteophyte formation in IVD. The present review focuses on the existing issues related to current therapeutic approaches and about latest evidence on cell therapy-based regeneration of IVD and maintaining the microenvironment of cellular matrix which holds a promise for future therapeutic applications. | ||
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| ORIGINAL ARTICLES | | |
 | The median labio-mandibulo-glossotomy approach to the upper cervical spine: A personal series and tips and pearls | p. 92 |
| K Venugopal Menon, Hood Al Saqri, Renjit Kumar, Maruti Kambali DOI:10.4103/isj.isj_8_18 Background: Wide exposure to the anterior part of the upper cervical spine is difficult due to anatomical constraints. The Labio-Mandibulo-Glossotomy (LMG) approach is considered a difficult approach with high morbidity. The objective of this study is to describe the authors experience with the approach and it's outcomes in six cases and offer tips and pearls to the surgical access. Methods: This is a retrospective review of a small series of six cases that were operated for upper cervical lesions by the LMG approach. Two had mandible fractures that needed fixation and in the others osteotomy of the mandible was performed. The patients were followed up for minimum two years or death (in malignancy). We specifically looked for cosmetic or functional problems related to osteotomy, glossotomy, and, hospital and ICU stay duration. Surgical access is described in detail. Results: The hospital stay was similar to other major spine trauma or tumour surgeries at our center (median 14 days) and mean ICU stay 2.8 days. There were no long-term issues related to the access. Several tips and tricks are offered to minimize intra and post-operative problems. Conclusions: The LMG approach, though apparently formidable, is quite a safe and simple procedure with few residual complications. | ||
| [ABSTRACT] [HTML Full text] [PDF] [Mobile Full text] [EPub] [Sword Plugin for Repository]Beta | ||
| CASE REPORTS | | |
 | A novel surgical technique for hydatid cyst involving cervicothoracic anterior epidural space | p. 99 |
| Bharat R Dave, Degulmadi Devanand, Ganesh Deshmukh DOI:10.4103/isj.isj_17_18 Spinal hydatid cyst comprises <1% of the total cases of hydatid disease. There is very little literature on the involvement of anterior epidural space by hydatid cyst and its management. This report presents a unique presentation of spinal hydatidosis in cervicothoracic anterior epidural space and a novel technique in surgical management. | ||
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 | Sacral chordoma with degenerative spondylolisthesis and upper lumbar disc herniation | p. 102 |
| Shakti A Goel, Hitesh N Modi, Yatin J Desai, Bhavin Patel DOI:10.4103/isj.isj_24_17 Sacral chordoma is a rare condition requiring multidisciplinary approach for management. Here, we report a 72-year-old male patient who was diagnosed with sacral chordoma with L2–L3 disc herniation and L5–S1 degenerative spondylolisthesis and L1 body fracture. The patient was first managed by discectomy L2–L3 with D12–L3 decompression and fixation. Sacral chordoma excision was done 10 months later. The chordoma was excised by anterior laparoscopic resection and mobilization of tissues from the tumor followed by posterior sacrectomy with L5–S1 decompression and extension of fixation in a single stage. Proline mesh was used to support the colon posteriorly. This was further complicated by proximal junction fracture due to fall which was further managed by proximal extension of the rod-screw construct. The patient became symptom free without any radiotherapy or chemotherapy and is able to walk independently, two years following the primary surgery without recurrence of tumor. | ||
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 | Lumbar disc herniation in ochronosis | p. 108 |
| Subbiah Jayakumar, Sathish Devadoss, Annamalai Devadoss DOI:10.4103/isj.isj_40_18 Alkaptonuria is a rare metabolic, autosomal recessive disorder caused by the deficiency of homogentisic acid oxidase and it is characterized by bluish-black discoloration of cartilages, skin (Ochronosis), degenerative changes in the articular, extra-articular cartilages, intervertebral disc, other tissues causing pain in the joints and spinal column. Although intervertebral disc degeneration is common in these patients, those presenting with symptoms severe enough to warrant surgery are rare. Only a few patients have been treated surgically. We present a case of alkaptonuria presenting with radiculopathy and lumbar disc herniation. The case presented demonstrates that although lumbar disc herniation is rare in alkaptonuria, it should be sought in such patients and surgical treatment yields good functional outcome. | ||
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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