Αρχειοθήκη ιστολογίου

Σάββατο 15 Δεκεμβρίου 2018

Initiation of methotrexate with or without a test dose: a retrospective toxicity study



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Guselkumab in the Treatment of Hidradenitis Suppurativa: A Retrospective Chart Review



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Flush technique to minimize adverse reactions from syringe lubricant (silicone oil)



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British Association of Dermatologists guidelines for the management of hidradenitis suppurativa (acne inversa) 2018

Abstract

The overall objective of the guideline is to provide up‐to‐date, evidence‐based recommendations for the management of hidradenitis suppurativa (HS). The document aims to:.

offer an appraisal of all relevant literature up to July 2018, focusing on any key developments.

address important, practical clinical questions relating to the primary guideline objective.

provide guideline recommendations and if appropriate research recommendations.

This article is protected by copyright. All rights reserved.



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Effect of radiotherapy on the chemical composition of root dentin

Abstract

Background

The radiotherapy can directly affect the bond strength of the adhesive materials, interfering in the prognosis of restorative treatments, which may be caused by chemical changes in dentin structure.

Methods

Twenty inferior homologues premolars were distributed in 2 groups (in vitro study) (n = 10): nonirradiated and irradiated. The specimens were submitted to the analysis of phosphate (ν1PO43−2PO43−4PO43−), carbonate (ν3CO32−), amide I, CH2, amide III, and amide I/III ratio by confocal Raman spectroscopy. Data were submitted to statistical analysis (T test, P < .05).

Results

In intracanal dentin, the irradiated group had lower ν4PO43− values (1.23 ± 0.06) compared to nonirradiated group (1.40 ± 0.18) (P < .05), with no difference for ν1PO43− and ν2PO43 peaks (P > .05). The irradiated (1.56 ± 0.06) had lower carbonate, amide III (1.05 ± 0.19), and amide I/III ratio values (0.19 ± 0.06) compared to nonirradiated group (1.42 ± 0.10, 1.28 ± 0.24, and 0.31 ± 0.10, respectively) (P < .05). For medium dentin irradiated group (1.30 ± 0.12) had lower phosphate values compared to nonirradiated group (1.48 ± 0.22) (P < .05). In cementum, there was no statistical difference between the groups.

Conclusion

The radiotherapy was able to cause changes in ν4PO43−, carbonate, and amide III peaks of root dentin.



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Salivary gland tumors: Molecular characterization and therapeutic advances for metastatic disease

Abstract

Salivary gland cancers represent a rare group of tumors composed by over 20 histological subtypes. Initially treated as one single disease, its diagnosis, prognosis, and treatment are currently being stratified based on morphology. More recently, insight has been provided on the molecular characterization of each subtype, further improving diagnostic accuracy and paving the way for personalized therapy. In this article, we provide a comprehensive review of recent breakthroughs, preliminary results of novel therapy, and future directions on the treatment of these complex malignancies.



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Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: Impact on outcomes of intensity‐modulated radiation therapy

Abstract

Background

Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment.

Methods

p16/epidermal growth factor receptor (EGFR)/cluster of differentiation‐44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients.

Results

In the entire group and the p16 negative cohort, better 3‐year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16−, EGFR+/p16−, and EGFR+/CD44+ groups and in the EGFR+/CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup.

Conclusion

Our study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.



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Reply to Letter to the Editor regarding “Carbon Dioxide Embolism during Transoral Robotic Thyroidectomy: A Case Report”



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Receptor tyrosine kinase MET as potential target of multi‐kinase inhibitor and radiosensitizer sorafenib in HNSCC

Abstract

Background

The multi‐kinase inhibitor sorafenib displays antitumoral effects in head and neck squamous cell carcinoma (HNSCC); however, the targeted kinases are unknown. Here we aimed to identify those kinases to determine the mechanism of sorafenib‐mediated effects and establish candidate biomarkers for patient stratification.

Methods

The effects of sorafenib and MET inhibitors crizotinib and SU11274 were analyzed using a slide‐based antibody array, Western blotting, proliferation, and survival assays. X‐rays were used for irradiations.

Results

Sorafenib inhibited auto‐phosphorylation of epidermal growth factor receptor and MET, which has not been described previously. MET expression in HNSCC cells was not always associated with activity/phosphorylation. Furthermore, sorafenib‐dependent cell kill and radiosensitization was not associated with MET level. Although MET inhibitors blocked proliferation, they caused only mild cytotoxicity and no radiosensitization.

Conclusion

We identified MET as a new potential target of sorafenib. However, MET inhibition is not the cause for sorafenib‐mediated cytotoxicity or radiosensitization.



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Prospective instrumental evaluation of swallowing, tongue function, and QOL measures following transoral robotic surgery alone without adjuvant therapy

Abstract

Background

Transoral robotic surgery (TORS) has been utilized to deintensify treatment. No studies have measured swallow safety and efficiency, nor assessed the functional impact of TORS alone.

Methods

This prospective cohort underwent baseline and 1‐month postsurgery assessments including modified barium swallow evaluation, using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) rating system, tongue range of motion assessment, the Performance Status Scale (PSS), and quality of life with the MD Anderson Dysphagia Inventory (MDADI).

Results

All DIGEST safety scores were 0 (normal) at both time points. DIGEST efficiency scores were mildly impaired in 2 of 10 patients postsurgery. PSS scores revealed all patients were on regular diets, were 100% understandable, and were eating in public at both time points. Tongue Range of Motion scores were 100 of 100 at both time points. MDADI scores were not significantly different across time points.

Conclusions

Careful identification of patients can result in excellent outcomes following TORS. Future studies will examine longer follow‐up of speech, swallowing, and tongue function in patients undergoing TORS surgery.



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Prognostic value of C‐reactive protein/albumin ratio for patients with hypopharyngeal and laryngeal cancer undergoing invasive surgery involving laryngectomy

Abstract

Background

The C‐reactive protein/albumin (CRP/Alb) ratio has been recently established as a prognostic indicator in various cancer types. However, few reports regarding the prognostic value of the CRP/Alb ratio in head and neck cancer exist. This study aimed to investigate the significance of the CRP/Alb ratio in clinical outcomes after invasive surgery involving laryngectomy for hypopharyngeal and laryngeal cancer.

Methods

We evaluated 56 patients who underwent total laryngectomy or total pharyngolaryngectomy between 2003 and 2012. Univariate and multivariate analyses were retrospectively performed to examine the prognostic value of the CRP/Alb ratio in these patients.

Results

The optimal cutoff value of the CRP/Alb ratio was 0.32. Multivariate analysis showed that the CRP/Alb ratio was a significant and independent predictor of poor overall and disease‐free survival.

Conclusion

The CRP/Alb ratio may be a novel and useful indicator for predicting postoperative outcomes in patients with hypopharyngeal and laryngeal cancer.



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Influence of comorbidity on therapeutic decision making and impact on outcomes in patients with head and neck squamous cell cancers: Results from a prospective cohort study

Abstract

Background

High prevalence of comorbidity in head and neck squamous cell carcinoma (HNSCC) often lead to suboptimal treatment. The presence study aims to evaluate the presence of comorbidity, its impact on therapeutic decision making, treatment compliance, and overall survival in HNSCC.

Methods

Five hundred eighteen patients with nonmetastatic HNSCC, elder than 18 years of age, without any prior history of cancer or anticancer treatment in the last 5 years were evaluated using Adult Comorbidity Evaluation 27 (ACE 27) index.

Results

Two hundred ninety three (56.6%) patients had comorbidity, and 20.6% had deviation from the ideal treatment plan. Higher grade of comorbidity led to less likely completion of guideline‐concordant therapy (moderate ACE 27 vs none: odds ratio [OR] 0.46, 95% confidence interval [CI] 0.26‐0.82, P < .01*; severe ACE 27 vs none: OR 0.23, 95% CI 0.08‐0.57, P < .01*). Patients who completed guideline‐concordant treatment had the best outcomes as compared to those who could not (median survival: not reached vs 9.56 months, hazard ratio 3.66, 95% CI: 2.8‐4.79; P < .01*).

Conclusion

Presence of increasing severity of comorbidity in HNSCC influences therapeutic decision making. Survival outcomes are poorer in patients receiving guideline‐discordant treatment.



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Masticatory function and related factors after oral oncological treatment: a 5‐year prospective study

Abstract

Background

Chewing ability is often compromised in patients with oral cancer. The aim of this study was to identify which factors affect masticatory performance in these patients.

Methods

Patients with primary oral cancer were assessed for up to 5 years after primary treatment. Healthy controls were assessed once. A mixed‐model analysis was performed, with masticatory performance as outcome measure.

Results

A total of 123 patients were included in the study. Factors positively associated with masticatory performance were number of occlusal units (OU), having functional dentures, and maximum mouth opening (MMO). The impact of tumor location and maximum bite force (MBF) differed per assessment moment. Masticatory performance declined for up to 1 year but recovered at 5 years after treatment.

Conclusion

Masticatory performance in patients treated for oral cancer is affected by MBF, MMO, number of OU, and dental status. These should be the focus of posttreatment therapy.



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Smoking and papillomavirus DNA in patients with p16‐positive N3 oropharyngeal squamous cell carcinoma

Abstract

Background

We investigated the survival of patients with a p16‐positive N3 oropharyngeal squamous cell carcinoma (OPSCC) and the prognostic significance of patient, tumor, and treatment characteristics.

Methods

We retrospectively reviewed the data of patients treated at our Cancer Center for a p16‐positive N3 OPSCC between 2003 and 2016. End points were overall survival (OS) and progression‐free survival (PFS).

Results

A total of 29 patients were included. The 5‐year OS and PFS were 67.5% and 59.1%, respectively. Smoking history above 10 pack‐years and the absence of human papillomavirus DNA were associated with worse OS (P = .02 and P = .03, respectively) and PFS (P = .02 and P = .02, respectively). Induction chemotherapy or radical neck dissection were not associated with different treatment outcomes.

Conclusion

Patients with an N3 p16‐positive oropharyngeal cancer in our series had a 5‐year OS rate of 67.5%. Smoking history and viral DNA were prognostic factors associated with survival.



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Regression of human immunodeficiency virus‐associated oral Kaposi sarcoma with combined antiretroviral therapy: A case report and literature review

Abstract

Background

Kaposi's sarcoma (KS) is the most prevalent malignant neoplasia in human immunodeficiency virus positive (HIV+) patients for which the primary mode of management was chemotherapy.

Methods

We have presented the case of a newly diagnosed HIV+ male patient who was diagnosed with a pedunculated nodule in the anterior region of the hard palate, measuring 3.5 cm in diameter and with 2 months of evolution.

Results

Histopathological examination confirmed the clinical hypothesis of KS. Soon after the diagnosis, the patient started using combined antiretroviral therapy (Biovir and Kaletra), presenting a significant reduction of the lesion after 4 weeks. With 1.5 cm in diameter, the lesion was surgically removed. The patient was followed‐up for 10 years without any recurrence.

Conclusion

In antiretroviral‐naive patients with a well‐preserved immune system, the use of cART may be efficient in reducing the progression of the KS lesions, thus avoiding the use of chemotherapeutic agents.



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The DAHANCA 32 study: Electrochemotherapy for recurrent mucosal head and neck cancer

Abstract

Background

Electrochemotherapy is an established treatment for cutaneous tumors. This study aimed at determining efficacy of electrochemotherapy in recurrent head and neck cancer.

Methods

Phase II clinical trial in patients with recurrent head and neck carcinomas with no curative treatment options. Electrochemotherapy was performed under general anesthesia. Primary endpoint was tumor response (CT scanning) evaluated at week 8. Secondary endpoints included biopsy results, MRI and fluorodeoxyglucose‐positron emission tomography scanning, safety, toxicity, pain score, and quality‐of‐life questionnaires.

Results

Of 26 patients treated, 5 (19%) achieved complete response, 10 (39%) partial response, resulting in an objective response of 58%. Two responders remain without recurrence. No serious adverse events occurred during treatment. Four events occurred posttreatment: one bleeding episode, two episodes with mucosal swelling, and one patient died due to disease progression.

Conclusion

Electrochemotherapy is efficient against local recurrence of head and neck cancer with an overall response rate of 58%.



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Tobacco smoking, alcohol drinking, betel quid chewing, and the risk of head and neck cancer in an East Asian population

Abstract

Background

The smoking prevalence among men in China is high, but the head and neck cancer incidence rates are low. This study's purpose was to investigate the impact of tobacco, betel quid, and alcohol on head and neck cancer risk in East Asia.

Methods

A multicenter case‐control study (921 patients with head and neck cancer and 806 controls) in East Asia was conducted. The odds ratio (OR) and 95% confidence interval (CI) were estimated using logistic regression.

Results

Head and neck cancer risks were elevated for tobacco (OR = 1.58), betel quid (OR = 8.23), and alcohol (OR = 2.29). The total attributable risk of tobacco and/or alcohol was 47.2%. Tobacco/alcohol appeared to account for a small proportion of head and neck cancer among women (attributable risk of 2.2%). Betel quid chewing alone accounted for 28.7% of head and neck cancer.

Conclusions

Betel quid chewing is the strongest risk factor for oral cavity cancer in this Chinese population. Alcohol may play a larger role for head and neck cancer in this population than in European or U.S. populations.



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Radiographic nodal prognostic factors in stage I HPV‐related oropharyngeal squamous cell carcinoma

Abstract

Background

The updated AJCC Cancer Staging Manual groups all p16‐positive oropharyngeal squamous cell carcinoma (OPSCC) with unilateral nodal involvement within 6 cm into the new clinical N1 classification, consolidating a heterogeneous group of disease with varying radiographic findings.

Methods

A central radiological review was conducted identifying 233 patients with stage I node‐positive (cT1‐2N1) disease who underwent definitive concurrent chemoradiation. Factors evaluated included lymph node size, low‐neck lymphadenopathy, retropharyngeal lymphadenopathy, overt radiographic extracapsular extension, and matted lymphadenopathy.

Results

On multivariate analysis adjusted for age, smoking history, and chemotherapy regimen, low‐neck lymphadenopathy (hazard ratio (HR) = 6.55; P < .001) and retropharyngeal lymphadenopathy (HR = 3.36; P = .009) predicted for inferior progression‐free survival (PFS). low‐neck lymphadenopathy (HR = 6.38; P = .001) and retropharyngeal lymphadenopathy (HR = 3.32; P = .02) also predicted for inferior overall survival (OS). All other radiographic characteristics showed no prognostic impact for PFS or OS.

Conclusions

This analysis suggests that caution should be advised against de‐intensification efforts among patients with stage I node‐positive p16‐positive OPSCC with low‐neck lymphadenopathy or retropharyngeal lymphadenopathy.



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Three prognostic indexes as predictors of response to adjuvant chemoradiotherapy in patients with oral squamous cell carcinoma after radical surgery: A large‐scale prospective study

Abstract

Background

To develop and validate practical prognostic indexes (PIs) for predicting the prognosis and response to postoperative adjuvant therapy in patients with oral squamous cell carcinoma (OSCC).

Methods

A large cohort of 1071 OSCC patients were randomized to either training set (N = 708) or validation set (N = 363). Three types of PIs were developed according to the nomogram scores, β coefficients and excess hazard ratios, respectively. Restricted cubic spline was used to demonstrate the relationship between PIs and the risks of death.

Results

First, a nomogram was developed incorporating age at diagnosis, smoking status, clinical stage, tumor differentiation, lymph node status, comorbidity, and neutrophil to lymphocyte ratio levels. Then, three PIs were established with high survival predictive ability, and were superior to AJCC staging system (all P < .05). The risks of death were escalated continuously with the increasing number of PIs. Interestingly, adjuvant chemoradiotherapy was positively associated with poor overall survival in patients with low PIs, but exerted a beneficial effect on patients with high PIs.

Conclusion

Combined nomogram with further established PIs not only predicts the survival probability of OSCC patients, but also continuously quantifies the risk of death. High PIs could predict a beneficial response to adjuvant chemoradiotherapy, whereas low PIs indicate an unfavorable response.



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Pancreatic carcinoma underlying a complex presentation in late pregnancy: a case report

Gestational diabetes mellitus is strongly related to the risk of pancreatic cancer in pregnant women, but gestational diabetes can precede a diagnosis of pancreatic cancer by many years. Women with a history o...

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Efficacy of allergen-blocker mechanical barrier gel on symptoms and quality of life in patients with allergic rhinitis

Abstract

Propose

Allergic rhinitis (AR) is a very common, chronic and global health problem. In the last two decades, the efficiency of barrier-enforcing measures in AR has been investigated. In this study, we aimed to evaluate the effect of allergen-blocker mechanical barrier gel (MBG) (AlerjiSTOP®) treatment on symptoms and quality of life score (QoLS) in patients with seasonal and perennial allergic rhinitis.

Methods

A single-center, prospective study was conducted between January 2017 and May 2018. Patients diagnosed with allergic rhinitis with a visual analogue scale (VAS) of 5 or higher (moderate/severe) were enrolled in the study. Patients were evaluated in terms of VAS, nasal symptom score (NSS), ocular symptom score (OSS), total symptom score (TSS) and QoLS at baseline, 1 week and 1 month of MBG treatment.

Results

A total of 83 patients with AR were enrolled in the study. Clinical and laboratory examinations showed that 50 (60.2%) patients were mono-sensitized. Allergen-blocker mechanical barrier gel treatment was performed as monotherapy in 22 (26.5%) patients. Median VAS, NSS, OSS and TSS decreased from 7 to 4, 8 to 3, 4 to 0 and 12 to 4, respectively (p < 0.0001). Correlation analysis revealed positive correlations between lower pediatric rhinoconjunctivitis quality of life questionnaire scores for patients under 12 years of age and decrease in VAS, NSS and TSS (r = 0.380, p = 0.008; r = 0.544, p < 0.0001; r = 0.543, p < 0.0001). Positive correlations were detected between lower rhinoconjunctivitis quality of life questionnaire (self-administered) scores for patients ≥ 12 years of age and decrease in VAS, NSS, OSS and TSS (r = 0.703, p < 0.0001; r = 0.465, p = 0.005; r = 0.526, p = 0.001; r = 0.624, p < 0.0001).

Conclusion

In conclusion, we found significant decrease in all symptom scores and improvement in QoLS of patients treated with MBG as monotherapy and combination therapy.



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Influence of patient-specific anatomy on medical computed tomography and risk evaluation of minimally invasive surgery at the otobasis

Abstract

Purpose

With the increasing use of new minimally invasive approaches in temporal bone surgery, the need arises for evaluation of the risk of injury to sensitive anatomical structures. The factors that influence the measurement uncertainty (variation in representation of position and shape of anatomical structures) of imaging are of relevance. We investigate the effect of patients' anatomy on the measurement uncertainty of medical CT.

Methods

Six formalin-fixed temporal bones were used, fiducial markers were bone-implanted, and 20 CT scans of each temporal bone were generated. Surgically threatened anatomical structures of importance were defined. Manual segmentation was performed to create 3D surface models, and different Gaussian filters were applied. Analysis points were established along the border of the superior semicircular canal to determine the deviation between the 3D images of the labyrinth. The standard uncertainty was calculated, and one-way analysis of variance was performed (significance level = 5%) to evaluate the effect of certain factors (patient, side, Gaussian filter) on the measurement uncertainty.

Results

The influence of patient-specific anatomy on the measurement uncertainty of medical CT (p = 0.049) was demonstrated for the first time. The applied Gaussian filter (p = 0.622) and the patient's side (p = 0.341) showed no significant effect.

Conclusion

The applied method and the results of the statistical analysis suggest that the patient's individual anatomical conditions affect the measurement uncertainty of medical CT. Thus, the patient's anatomy must be considered as an important influencing factor during risk evaluation concerning minimally invasive and image-guided surgery.



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An internal carotid artery pseudoaneurysm with neck hematoma: A rare cause of a life-threatening neck mass mimicking an abscess

Publication date: Available online 14 December 2018

Source: Auris Nasus Larynx

Author(s): Ana Penezić, Luka Ljubešić, Tomislav Gregurić, Krešo Zurak, Davor Vagić, Dijana Zadravec

Abstract

A neck mass has a broad and complex differential diagnosis, generally divided into neoplastic, congenital and inflammatory categories. An internal carotid artery hemorrhage with pseudoaneurysm formation is a very rare entity that may resemble other common conditions in the differential diagnosis. Large, expanding or symptomatic pseudoaneurysm is critical to efficiently diagnose and manage, due to risk of life-threatening hemorrhage. We present a case of an adult male patient with clinical and laboratory signs of severe neck cellulitis and a large gradually increasing neck mass, primarily suggestive of an abscess. Neck CT and MRI imaging revealed the presence of a disruption of the internal carotid artery resulting in a large hematoma and formation of pseudoaneurysm. A multidisciplinary team of interventional radiologists and ENT surgeons successfully treated the patient by endovascular placement of stents and subsequent surgical drainage. Awareness of such a rare, life-threatening condition and efficient multidisciplinary teamwork are essential for patient management.



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Polymorphisms associated with oral clefts as potential susceptibility markers for oral and breast cancer

Publication date: Available online 14 December 2018

Source: Archives of Oral Biology

Author(s): Edimilson Martins de Freitas, Renato Assis Machado, Edilmar de Moura Santos, Felipe Rodrigues de Matos, Hébel Cavalcanti Galvão, Priscila Bernardina Miranda Soares, Roseana de Almeida Freitas, Hercílio Martelli

ABSTRACT
Objective

To evaluate the association of single nucleotide polymorphisms (SNPs) in genes/loci consistently altered in nonsyndromic oral clefts in patients with oral and breast cancer in a Brazilian population.

Design

This case-control study evaluated the association of SNPs in IRF6 (rs642961), WNT3A (rs708111), GSK3β (rs9879992), 8q24 (rs987525) and WNT11 (rs1533767), representing regions consistently identified as of susceptibility for oral clefts, with oral cancer (oral squamous cell carcinoma) and breast cancer. Logistic regression analyses were used for confounding adjustments, and p values ≤0.01 were considered statistically significant (Bonferroni correction = 0.05 / 5 polymorphic markers).

Results

The minor G allele of rs9879992 in GSK3β was associated with oral cancer risk (p = 0.02), whereas rs1533767 in WNT11 showed a protective effect against it (p = 0.04). Several SNP-SNP interactions containing GSK3β rs9879992 were significantly associated with oral cancer after 1,000 permutation test. To breast cancer, the A allele of rs987525 was associated with increase risk in early stage (p = 0.02) and SNP-SNP interactions involving the 5 SNPs were significantly observed, with the most significant interaction among rs708111, rs1533767, rs9879992 and rs642961 (p1000permutation<0.001).

Conclusion

Our results reveal associations of SNPs consistently altered in oral cleft with oral and breast cancer risk, raising interesting possibilities to identify risk markers for those tumors.



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Comparison of 3 Indices for Assessing the Severity of Bronchial Asthma Exacerbations in Children

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 215-220, December 2018.


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Angiopoietin-1, Angiopoietin-2, and Periostin Levels in Children with Recurrent Wheeze

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 230-235, December 2018.


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Relationship Between Health Literacy in Parents and Asthma Control in Their Children: A Prospective Study in a Diverse Suburban Population

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 221-225, December 2018.


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Making the Case for Sesame: A Major U.S. Food Allergen

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 241-242, December 2018.


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Pediatric Spontaneous Pneumothorax: Our Experience and a Review of the Literature

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 208-214, December 2018.


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Looking Towards the Future

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 207-207, December 2018.


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Role of the Airway Microbiome in Respiratory Infections and Asthma in Children

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 236-240, December 2018.


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Direct Observed Therapy of Inhaled Corticosteroids for Asthma at School or Daycare

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 226-229, December 2018.


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Highlights from the U.S. Asthma Summit 2018

Pediatric Allergy, Immunology, and Pulmonology, Volume 31, Issue 4, Page 243-244, December 2018.


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Intestinal absorption of the wheat allergen gliadin in rats

Publication date: Available online 15 December 2018

Source: Allergology International

Author(s): Tomoharu Yokooji, Takahiro Fukushima, Koh Hamura, Naoki Ninomiya, Ryo Ohashi, Takanori Taogoshi, Hiroaki Matsuo

Abstract
Background

Aspirin enhances food allergy symptoms by increasing absorption of ingested allergens. The objective of this study is to elucidate the role of aspirin in facilitating intestinal absorption of the wheat allergen, gliadin, in rats.

Methods

Plasma concentrations of gliadin were determined after oral administration by gavage or administration into a closed intestinal loop in rats. We used an in situ intestinal re-circulating perfusion experiment to examine the effect of pepsin on aspirin-facilitated gliadin absorption. Fluorescein isothiocyanate (FITC)-labeled dextran-40 (FD-40) was used as a marker of non-specific absorption. The molecular size of gliadin and its allergenicity in plasma were examined using immunoblot analysis and intradermal reaction tests with Evans blue dye (EBD) extravasation, respectively.

Results

Aspirin increased plasma concentrations of gliadin after oral administration but had no effect in the closed intestinal loop study. An in situ intestinal re-circulating perfusion study showed that FITC-labeled gliadin was absorbed similarly to FD-40. Aspirin increased absorption of both intact and pepsin-digested gliadin, with a more significant effect on absorption of pepsin-treated gliadin. Immunoblotting showed that most gliadin was absorbed in intact form. When the gliadin fraction was extracted from rat plasma after gavage and injected intradermally into gliadin-sensitized rats, EBD extravasation was observed at injection sites in a gliadin dose-dependent manner.

Conclusions

Aspirin increased the absorption of intact and pepsin-digested gliadin via the paracellular pathway, maintaining their allergenicity. Moreover, the effect of aspirin on gliadin absorption was enhanced by modification and digestion of gliadin in the stomach.



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Iatrogenic meningoencephalocele after traumatic perforation of the cribriform plate during nasal intubation of a preterm infant

Publication date: Available online 15 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): M. Renaud, L. Fath, M. Cheptou, L. Dillenseger, S. Riehm, A. Venkatasamy, C. Debry, I. Djennaoui

Abstract

Traumatic iatrogenic meningoencephaloceles infants are rare and there is no consensus on management in the literature. This article presents a case of a meningoencephalocele diagnosed 15 months after a traumatic perforation of the cribriform plate due to a difficult intubation of a preterm infant that was treated by an endoscopic endonasal surgery. A close collaboration between pediatricians and ENT surgeons appears essential for early diagnosis and management. Endoscopic endonasal approach for meningoencephalocele management has several advantages and is a safe procedure when performed by an experienced surgeon.



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Bruce Neil Procter Benjamin AO OBE MBBS (Syd) FRACS FACS (Hon) 1931–2018

Publication date: Available online 14 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Nancy M. Bauman



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Home Environment and Diseases in Early Life are Associated with Allergic Rhinitis

Publication date: Available online 14 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Xue Kang, Hailuo Tu, Tengfei Tian, Zhiqun Huang, Liping Luo, Li Shen, Jing Ye

Abstract
Objective

Risk factors in relation to allergic rhinitis (AR) remain unclear despite considerable interest. This study aimed to analysis the relationship between home environment and diseases in early life and AR.

Methods

In a case-control survey, 242 AR patients and 258 healthy persons responded to questionnaires designed to capture pre-pregnancy/pregnancy diseases, maternal medication usage, diseases in early life of participants, family allergic history and home environmental factors. Forty risk factors potentially connected with AR were investigated and analyzed with chi-square test and logistic regression.

Results

There was no correlation between mother's disorders such as periodontitis, chronic rhinitis, diabetes etc. and AR (p>0.05). A logistic regression analysis showed that neonatal jaundice (p<0.001), respiratory system infection (p<0.001), diarrhea (p<0.01), eczema (p<0.01) in the early life and home environmental factors such as house decoration (p<0.01), mold environment (p<0.001), keeping flowers and plants (p<0.001), passive smoking (p<0.01) were associated with AR.

Conclusion;Diseases in early life and home environment are closely associated with AR.



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TP53 inactivation and expression of methylation-associated proteins in gastric adenocarcinoma with enteroblastic differentiation

Abstract

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare variant of aggressive adenocarcinoma. We demonstrated previously that GAED is genetically characterized by frequent TP53 mutation. In this study, we aimed to further clarify the mechanism of inactivation of TP53 in GAED in the light of promoter methylation of TP53, and expression of methylation-associated proteins such as Ten-eleven translocation (TET) 1 and 5-hydroxymethylcytosine (5-hmc) in addition to ATM mutations. We analyzed 51 cases of GAED. The ATM mutation was detected in only one case. Promoter methylation of TP53 was detected in 18% and frequency of loss of heterozygosity (LOH) at TP53 locus was 37.2%. Reduced TET1 expression was found in 29 cases (56.9%) and was significantly associated with advanced stage (p = 0.01), lymph node metastasis (p = 0.04), and macroscopic type (p = 0.01). Reduced 5-hmc expression was found in 28 cases (54.9%) and was significantly associated with advanced stage (p = 0.01), gender (p = 0.01), tumor location (p = 0.03), tumor size (p = 0.01), and lymph node metastasis (p = 0.01). Among 9 cases with TP53 promoter methylation, reduced expression of TET1 was observed in 6 cases, and reduced expression of 5-hmc was observed in 5 cases. Reduced expression of both TET1 and 5-hmc was significantly associated with adverse clinical outcomes. In summary, promoter methylation of TP53 is partly involved in loss of p53 expression. Aberrant methylation by reduced TET1 and 5-hmc may be involved in the development of aggressive GAED.



https://ift.tt/2LkHzTP

Updated Sniffin’ Sticks normative data based on an extended sample of 9139 subjects

Abstract

Purpose

To provide up-to-date and detailed normative data based on a large-scale sample, increasing diagnostic validity by reference to narrow age groups as previous normative values were based upon smaller sample sizes—especially in the group of older subjects.

Method

Data were obtained from 9139 healthy subjects (4928 females aged 5–96 years and 4211 males aged 5–91 years). The standard "Sniffin' Sticks" test was applied, comprising threshold (T), discrimination (D) and identification (I) subtests, and yielding a TDI sum score.

Results

Hyposmia was established at a TDI score of less than 30.75. Age-related changes were found in each domain, most pronounced for thresholds. Individuals aged 20–30 years performed best, whereas children below the age of 10 and adults above the age of 71 scored only half as well. Sex-related differences were in favor of women.

Conclusions

Data provide guidance for assessing individual olfactory performance in relation to specific age groups. Significant gender and age effects were observed, with a most pronounced increase of olfactory test scores between age 5 through 20 years and a dramatic decrease at the age of 60 through 71 years.



https://ift.tt/2BpEKg2

Regulation of TIM-3 expression in a human T cell line by tumor-conditioned media and cyclic AMP-dependent signaling

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Su Jin Yun, Bokyoung Lee, Kuniharu Komori, Mi Jin Lee, Byoung Gill Lee, Kyongmin Kim, Sun Park

Abstract

T cell immunoglobulin and mucin domain-3 (TIM-3) expression increases in exhausted T cells, which inhibits T cell function. TIM-3 expression is supposedly up-regulated in tumor-bearing individuals via chronic antigenic stimulation of T cells. Considering the immunosuppressive nature of the tumor microenvironment, we investigated whether tumor-secreted molecules might enhance TIM-3 expression in Jurkat T cells. We observed that TIM-3 expression was increased by the activation of prostaglandin (PG) E2 and cyclic AMP (cAMP) signaling pathways. Adenylate cyclase activation led to protein kinase A (PKA)-dependent upregulation of the TIM-3 minimal promoter region and of upstream conserved non-coding sequences. TIM-3 expression in Jurkat T cells was increased by the exposure to breast tumor cell-conditioned media partially through the interaction between PGE2 and its receptor, EP4. Our results propose that tumor-secreted molecules such as PGE2, which activates PKA and EPAC, may regulate TIM-3 expression in T cells.



https://ift.tt/2UNpjXC

Chlamydia trachomatis ct143 stimulates secretion of proinflammatory cytokines via activating the p38/MAPK signal pathway in THP-1 cells

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Lina Jia, Feng Sun, Jie Wang, Ding Gong, Lina Yang

Abstract

Chlamydia trachomatis (Ct) infections can cause bacterial sexually-transmitted and preventable blindness. The Ct infections induced excessive cytokines generation which attributed to pathologic changes in host cells. However, the precise mechanisms of Ct-induced cytokines production are still unclear.CT143 protein was identified as a novel Ct specific protein with high immunogenicity. In the present study. The CT143 fusion protein was recombined and purified. The mice immune serum was prepared by immunizing BALB/c mice with the purified fusion protein. The specificity of the antibody was confirmed using Immunoblotting. Indirect immunoflurescence assay (IFA) and Immunoblotting assays were performed to detect the temporal and spatial characteristics of CT143 in Ct infected cells. ELISA was performed to analyze the secretion of proinflammatory cytokines IL-1β, IL-8 and TNF-α by human macrophages under the stimulation of CT143 protein. Finally, the involvement of p38 signaling in CT143-induced cytokine secretion was validated. CT143 protein was located in the inclusion body and represented an Elementary body (EB)-related protein, which may be encoded by the mid- and late-stage expressing genes. CT143 protein could stimulate the secretion of inflammatory cytokines in macrophages which differentiated from THP-1 This induction may be mediated by the activation of p38 signaling. In summary, CT143 protein is involved in inflammatory processes during Ct infection.



https://ift.tt/2BoNSkG

IgE blockade in autoimmunity: Omalizumab induced remission of bullous pemphigoid

Publication date: Available online 14 December 2018

Source: Clinical Immunology

Author(s): Talia James, Sam Salman, Brittany Stevenson, Christine Bundell, Gavin Kelly, David Nolan, Mina John

Abstract

Bullous pemphigoid (BP) is a blistering dermopathy and a prototypic antibody-mediated autoimmune disease. Detection of IgG autoantibodies against hemidesmosomal proteins BP180 and/or BP230 are diagnostic and levels can correlate with disease activity. Therapies include corticosteroids and oral immunosuppressants, while intravenous immunoglobulin and rituximab are reserved for treatment resistant cases. Here we describe a patient with severe BP which was refractory to standard first line therapy, intravenous immunoglobulin and rituximab induced depletion of peripheral B cells. Use of the monoclonal anti-IgE antibody omalizumab resulted in rapid resolution of blistering despite ongoing high levels of anti-skin IgG antibodies. To our knowledge this is the first case of BP responsive to omalizumab after failure of rituximab to be reported. This case adds to emerging data on omalizumab as a novel BP treatment as well as providing new evidence of an independent role for autoreactive IgE-mediated inflammation in the formation of BP skin lesions.



https://ift.tt/2UQ7tDF

Taxonomy and phylogeny of Cutibacterium (formerly Propionibacterium) acnes in inflammatory skin diseases

Publication date: Available online 15 December 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): S. Corvec, M.-A. Dagnelie, A. Khammari, B. Dréno

Summary

Since its discovery, Propionibacterium acnes has undergone various name changes, and has been known since 2016, as Cutibacterium acnes. Herein we set out the history and rational of these taxonomic changes together with a description of a new genus, Cutibacterium, which includes five species within the cutaneous ecosystem. Modern microbiological techniques allow finer distinction between species and subspecies while also enabling the identification of separate subtypes within the population of Cutibacterium acnes. Phylogeny and molecular typing techniques thus provide a better understanding of the subtypes involved in certain inflammatory skin diseases, including acne, folliculitis and progressive macular hypomelanosis.

Résumé

Depuis sa découverte, Propionibacterium acnes a subi différents changements de noms. Désormais appelé Cutibacterium acnes depuis 2016, nous présentons l'histoire et les bases de ces changements taxonomiques avec la description, au sein d'un nouveau genre Cutibacterium, de cinq espèces de l'écosystème cutané. En effet, les techniques microbiologiques modernes ont permis de mieux distinguer les espèces et sous-espèces mais elles ont aussi permis de séparer des sous-types au sein de la population de Cutibacterium acnes. La phylogénie et les techniques de typage moléculaire permettent ainsi une meilleure compréhension des sous-types impliqués dans certaines pathologies inflammatoires cutanées, notamment l'acné, les folliculites ou l'hypomélanose maculeuse progressive.



https://ift.tt/2LmNw2Y

Histoire du psoriasis

Publication date: Available online 14 December 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): B. Halioua



https://ift.tt/2Ces1y1

Mast Cell Granules: Modulating adaptive immune response remotely

Publication date: Available online 14 December 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Rohit Jain, Shweta Tikoo, Wolfgang Weninger



https://ift.tt/2CelF1T

Refining the tumor-node-metastasis staging system for individualized treatment of differentiated thyroid carcinoma

Publication date: February 2019

Source: Oral Oncology, Volume 89

Author(s): Young Nam Kim, Mijin Kim, Hyeon Seon Ahn, Kyunga Kim, So Young Park, Hye In Kim, Min Ji Jeon, Won Gu Kim, Sun Wook Kim, Won Bae Kim, Jae Hoon Chung, Young Kee Shong, Tae Yong Kim, Tae Hyuk Kim

Abstract
Background

Patients with differentiated thyroid carcinoma (DTC) are staged according to the single age cut point in addition to anatomic extent. A novel staging system is needed to properly show the character and prognosis of DTC by considering age as a continuous variable. We aimed to refine stage and prognostic groups of the eighth edition tumor-node-metastasis (TNM-8) staging system for DTC and to suggest a possible revision.

Methods

We conducted a retrospective data abstraction study of patients with newly diagnosed DTC who were treated at one of two tertiary referral centres in Seoul, Korea between 1994 and 2005. We used recursive partitioning analysis to derive a new staging classification (TNM-RPA) and compared its prediction of cancer-specific survival with that of TNM-8.

Results

The cohort comprised 6342 patients with DTC who were followed up for a median of 11.4 years. Higher TNM-RPA groups were associated with increased risk of death (10-year cancer-specific survival for stages IA, IB, IIA, IIB, III, and IV: 99.6%, 98.1%, 93.0%, 92.4%, 75.1%, and 56.6%, respectively; P < 0.001). The C-index values were 0.869 (95% CI, 0.833–0.905) for the TNM-RPA and 0.819 (0.789–0.850) for TNM-8. The proportions of variance explained for the ability of the TNM-RPA and TNM-8 stages to predict cancer-specific survival were 7.1% and 5.7%, respectively.

Conclusion

This study presents a RPA-based TNM stage groupings that incorporate multiple age cutoffs and essential anatomic information, which can be conveniently used to facilitate the individual prediction of long-term cancer-specific survival in patients with DTC.



https://ift.tt/2QUjV5Y

Impact of high‐ versus low‐risk genotype on sinonasal radiographic disease in cystic fibrosis

Objective

Understanding of how specific mutations impact the cystic fibrosis transmembrane conductance regulator (CFTR) protein has given rise to the classification of CF patients into low‐risk and high‐risk genotypes. Few prior studies have investigated differences in sinonasal disease between low‐risk and high‐risk CF genotypes. This multi‐institutional review aimed to evaluate radiographic sinus disease severity based on genotype.

Methods

A review was conducted on adult patients with CF evaluated between 2005 to 2017 at three academic institutions. Data including age, gender, CFTR mutation, and presence of a maxillofacial/sinus computed tomography scan was collected. A modified Lund‐Mackay score (MLMS) was assigned to each scan, and the presence of sinus aplasia or hypoplasia was determined. Patients were further grouped depending on genotype into low‐ or high‐risk for comparison.

Results

A total of 126 patients were included with 99 patients in the high‐risk and 21 in the low‐risk groups. The high‐risk group had significantly higher MLMS than the low‐risk group (mean 13.88 vs. 8.06, P < 0.0001, 95% CI −8.196 to −3.462) The rate of frontal (P < 0.01), maxillary (P = 0.04), and sphenoid (P < 0.001) hypoplasia/aplasia was significantly higher in high‐risk patients compared to low‐risk.

Conclusion

This is one of the largest studies to date evaluating the impact of CF genotype on paranasal sinus development and disease. Genotype appears to impact sinonasal disease severity and also potentially paranasal sinus cavity development to a degree, although the exact mechanism is unknown.

Level of Evidence

4. Laryngoscope, 2018



https://ift.tt/2QWbtmJ

FDG‐PET/CT for diagnosis and follow‐up of necrotizing (malignant) external otitis

Objective

Imaging is important for the diagnosis and follow‐up of necrotizing external otitis (NEO). The best imaging modality is controversy. To suggest 2‐deoxy‐2‐[fluorine‐18] fluoro‐D‐glucose‐positron emission tomography/computed tomography (18F‐FDG‐PET/CT) as an alternative to technetium‐99m and gallium‐67 scans for diagnosis and assessment of response to treatment for patients with NEO.

Study Design

Case series.

Methods

Tertiary referral center. From 2013 through 2017, 12 patients were diagnosed with NEO based on clinical features and positive FDG uptake within the temporal bone on PET/CT. Mean age was 74 ± 11.5; 83% of the patients were male; and 83% had diabetes.

Results

PET/CT scans were reviewed independently by two nuclear medicine specialists. Imaging located osteomyelitis in external ear canal, mastoid, temporomandibular joint, and nasopharyngeal region (100%, 50%, 16%, 8%, respectively).

Mean follow‐up was 16 months. Eight patients (67%) underwent a second PET/CT scan after active otitis resolved and after at least 6 weeks of antibiotic treatment. The scan demonstrated no or substantially reduced FDG uptake and treatment was stopped. The patients had no NEO symptoms at the end of follow‐up. One patient had significant uptake, and antibiotic treatment was continued until a third scan demonstrated no FDG uptake. Two patients died before the second PET/CT, and two were lost to follow‐up.

Conclusion

18F‐FDG‐PET/CT is a reliable imaging modality for diagnosis, disease localization, and decision making regarding treatment cessation. 18F‐FDG‐PET/CT should be considered as the imaging modality of choice for initial diagnosis and follow‐up in NEO patients. Larger, controlled studies are warranted.

Level of Evidence

4. Laryngoscope, 2018



https://ift.tt/2QSADTq

Significance of intraparotid node metastasis in predicting local control in primary parotid cancer

Objective

To analyze the metastasis rate in intraglandular lymph nodes (IGLNs) with a focus on discussing the significance of IGLN metastasis in local control (LC) of parotid gland cancer (PGC).

Methods

A total of 337 patients were enrolled. Information including age; sex; and pathologic variables such as tumor (T) stage, IGLN metastasis, and follow‐up findings was extracted and analyzed.

Results

IGLN metastasis was noted in 111 (32.9%) patients. Tumor stage, pathologic nodal stage, perineural invasion, resection status, and lymphovascular invasion were significantly related to IGLN metastasis. Local recurrence was noted in 67 (19.9%) patients. IGLN metastasis was an independent predictor of LC. The 10‐year LC rate was 94% for patients without IGLN metastasis, 56% for patients with metastasis in no more than two IGLNs, and 22% for patients with metastasis in more than two IGLNs. This difference was significant (P < 0.001).

Conclusion

The IGLN metastasis rate is relatively high in PGC patients and is significantly associated with disease grade and T stage. IGLN metastasis is associated with poorer local LC, and patients with more than two metastatic nodes have the worst prognosis.

Level of Evidence

4. Laryngoscope, 2018



https://ift.tt/2SN7giz

In Response to combination of panendoscopy and positron emission tomography/computed tomography increases detection of unknown primary head and neck carcinoma



https://ift.tt/2QSAP56

In reference to combination of panendoscopy and positron emission tomography/computed tomography increases detection of unknown primary head and neck carcinoma



https://ift.tt/2SQHQAr

The Role of Free Tissue Transfer in the Management of Chronic Frontal Sinus Osteomyelitis

Objectives/Hypothesis

Chronic frontal sinus infection is managed with a combination of medical and surgical interventions. Frontal bone osteomyelitis due to recurrent infection following trauma or prior open surgery may require more significant debridement. Free tissue transfer may allow for extensive debridement with replacement of tissue, and definitive eradication of osteomyelitis.

Study Design

Retrospective chart review.

Methods

Patients undergoing free flap obliteration of the frontal sinus for frontal bone osteomyelitis at a single institution were included in the study. Clinical, radiologic, and surgical data were collected. Surgeries before and after free flap obliteration were compared by Wilcoxon signed rank test.

Results

Fifteen patients were identified; however, one patient had less than 6 months of follow‐up and was excluded from analysis. Of the remaining 14 patients, mean follow‐up duration was 26 months (range, 6–120 months). Mean number of surgeries prior to free flap was 3.7 (range, 1–8 surgeries). Free flap obliteration resolved chronic frontal sinusitis in all patients. Two patients experienced postoperative infection, and the overall complication rate was 29%. Eight patients underwent cranioplasty (six immediate, two delayed) without complication. All patients received planned courses of postoperative antibiotics. A statistically significant decrease in the number of surgeries after free flap obliteration was observed P ≤ .01).

Conclusions

Extensive debridement followed by free tissue transfer and antibiotics offers a definitive treatment for complicated, recurrent frontal osteomyelitis. Simultaneous cranioplasty provides immediate protective and aesthetic benefit without complication. Consideration should be given for free tissue transfer and cranioplasty earlier in the algorithm for treatment of refractory frontal sinus osteomyelitis.

Level of Evidence

4 Laryngoscope, 2018



https://ift.tt/2SV0EPp

Vitamin D Supplements Don’t Reduce Cancer Incidence

12/13/2018

In the largest-ever randomized trial testing vitamin D for cancer prevention, the supplement did not lower the risk of developing cancer. The Vitamin D and Omega-3 Trial (VITAL) includes a nationally representative sample of nearly 26,000 participants.

Indian Journal of Nephrology (Indian J Nephrol)

ORIGINAL ARTICLES 

Epidemiology and outcomes of acute kidney injury in critically ill: Experience from a tertiary care center Highly accessed articlep. 413
PS Priyamvada, R Jayasurya, Vijay Shankar, S Parameswaran
DOI:10.4103/ijn.IJN_191_17  
There is only limited information on the epidemiology and outcomes of acute kidney injury (AKI) in critically ill patients from low- and middle-income countries. This study aims to identify the etiology, short-term outcomes, and determinants of mortality in patients with AKI admitted to multiple medical and surgical Intensive Care Units (ICU's) in a tertiary care center. The study also aims to compare the clinical characteristics and outcomes of community-acquired AKI (CAAKI) and hospital-acquired AKI (HAAKI). A prospective, observational study was done from June 2013 to October 2015. All patients over 18 years with AKI admitted in various medical and surgical ICU's seeking nephrology referral were included. AKI was defined according to KDIGO criteria. The follow-up period was 30 days. A total of 236 patients were recruited from five medical and nine surgical ICU's. Majority (73.3%) were males. About 53.38% patients had CAAKI, whereas 46.61% had HAAKI. The predominant etiologies for AKI were sepsis (22.4%), trauma due to road traffic accidents (21.18%), acute abdomen (perforation, acute pancreatitis, bowel gangrene, intestinal obstruction and cholangitis) (18.64%), and cardiac diseases (10.59%). Sepsis and acute abdomen were the most common causes of CAAKI, whereas trauma and cardiac causes were the predominant causes of HAAKI (P < 0.05). Patients with HAAKI were younger, admitted in surgical units, had lower SOFA scores, lower serum creatinine, lesser need for dialysis, longer hospital stay, and earlier stages of AKI compared to patients with CAAKI (P < 0.05). The 30-day mortality was 52.54%. The mortality was not different between CAAKI and HAAKI (56.3% vs. 48.18%; relative risk = 0.86: 95% confidence interval 0.67–1.1). The mortality was similar across different stages of AKI.
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Skin microcirculatory changes in relation to arteriovenous fistula maturationp. 421
Siew Cheng Chai, Wan Azman Wan Sulaiman, Arman Zaharil Mat Saad, Aida Hanum Rasool, Amran Ahmed Shokri
DOI:10.4103/ijn.IJN_402_17  
Maturation of arteriovenous fistula (AVF) involves complex vascular remodeling. In this study, we evaluated the changes of skin microvascular perfusion over the extremity with AVF maturation using the laser Doppler fluximetry (LDF). A total of 45 patients with chronic kidney disease, Stages IV–V, were included; they had undergone AVF creation from July 2014 to June 2016 at our institute. The measurement of skin microvascular perfusion was accomplished proximal and distal to the fistula anastomosis site: pre- and post-operative day 1, week 2, week 6, and week 12. Thirty-two patients with mean age of 55.6 had achieved AVF maturation. There were 40.6% radial-based and 59.4% brachial-based AVF. There was a 32.8% reduction of mean skin perfusion distal to the fistula by day 1 compared to the baseline perfusion; however, perfusion increased 47% by week 2 compared to day 1 and no dramatic change was subsequently noted. There was an increase of mean skin perfusion, proximal to fistula anastomosis, over 12 weeks with 35.8% at day 1 from the baseline. However, the changes of the mean skin perfusion were not statistically significant. There was no significant relation of skin perfusion changes with the type of fistula, diabetes mellitus, hypertension, and hyperlipidemia. LDF successfully detected the subclinical change of skin microvascular perfusion in relation to AVF creation. Reduction of skin perfusion distal to the fistula suggests that in patients with existing perfusion inadequacy of extremities, they may experience ischemic symptoms as early as day 1 postoperation, and require close monitoring for distal limb ischemic-related complications.
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Urinary neutrophil gelatinase-associated lipocalin and urinary soluble CXCL16 as biomarkers of activity in pediatric lupus nephritisp. 427
MA El-Gamasy, W El-Naghy
DOI:10.4103/ijn.IJN_265_17  
One of the challenges of treating patients with lupus nephritis (LN) is to assess disease activity. The aim of this study was to measure the urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary soluble chemokine (C-X-C motif) ligand 16 (CXCL16) levels in children and adolescents with systemic lupus erythematosus (SLE) and investigate whether they are elevated in active LN. This study was conducted on 80 patients diagnosed as SLE by the Systemic Lupus International Collaborating Clinics criteria and 60 apparently healthy individuals as controls. Global and renal disease activities were evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal SLEDAI, respectively. uNGAL and urinary CXCL16 were measured for all participants by ELISA. Renal biopsy was done for all cases at initial diagnosis and was graded using ISN/RPS classification. uNGAL and CXCL16 were higher in patients than in the controls (8.9 ± 3.56 ng/dl and 1067 ± 367 ug/L vs. 2.26 ± 1.95 ng/dl and 471 ± 106 ug/L, respectively). uNGAL had higher sensitivity and specificity than urinary CXCL16 as predictor of LN (95% and 90% vs. 85% and 80%, respectively). There was significant positive correlations between uNGAL levels, 24-h urinary proteins (r = 0.732, P = 0.001), and SLEDAI (r = 0.359, P = 0.001). There was also significant positive correlations between urinary CXCL16 levels, 24-h urinary proteins (r = 0.47, P = 0.001), and SLEDAI (r = 0.17, P = 0.001). uNGAL and CXCL16 were reliable indicators of the activity of LN.
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Optimization of treatment modality in elderly end-stage renal disease population: Peritoneal dialysis versus transplantp. 433
A Kaul, MR Behera, R Kishore, B Karthikeyan, DS Bhadauria, P Mishra, N Prasad, A Gupta, RK Sharma
DOI:10.4103/ijn.IJN_305_17  
Despite kidney transplantation (KT) being considered as the best treatment modality for end-stage renal disease (ESRD), patient and graft survival in the elderly population is poorer than younger individuals. Many authors argue that prolonged life expectancy outweighs the risk of remaining on dialysis, but few studies had compared the treatment modalities, especially with peritoneal dialysis (PD). A retrospective study was conducted at a tertiary care institute to compare outcome of elderly ESRD patients, who received KT with those continued on PD; and to evaluate the predictors of patient survival. Patient survival at 1 year was (76.2% vs. 91.1%); 5 years (53.7% vs. 21.8%); and 10 years (35.6% vs. 0.00%) among KT and PD population, respectively. Infection was the most common cause of death among KT group (35 [41.2%] vs. 34 [28.2%]) while cardiovascular mortality in PD group (55 [46.2%] vs. 7 [8.2%]). Technique survival at 1, 5, and 10 years in PD group was 92.8%, 58.5%, and 0%, respectively. Similarly, graft survival at 1, 5, and 10 years in KT group was 98.7%, 90.2%, and 90.2%, respectively. Multivariate analysis showed body mass index (BMI) (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82–0.93, p < 0.001), and albumin (HR 0.55, 95% CI 0.37–0.80, p = 0.002) were significant predictors of survival. In the 1st year, patient survival was better in PD than KT, but after adjustment for BMI and albumin, both short-term and long-term survival in elderly KT group was better than that of PD. Hence, elderly ESRD patients should not be barred from KT just because of age.
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Role of blood oxygen level-dependent MRI in differentiation of acute renal allograft dysfunctionp. 441
Hira Lal, Ezaz Mohamed, Neelam Soni, Priyank Yadav, Manoj Jain, Dharmendra Bhadauria, Anupma Kaul, Narayan Prasad, Amit Gupta, RK Sharma
DOI:10.4103/ijn.IJN_43_18  
Early graft dysfunction after renal transplantation manifests as acute rejection (AR) or acute tubular necrosis (ATN). Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging is a noninvasive method of assessing tissue oxygenation, which may be useful for predicting acute allograft dysfunction. This was a prospective study involving 40 patients scheduled for renal transplantation from August 2012 to August 2014. In addition, 15 healthy donors were also enrolled in this study. All recipients underwent BOLD MR imaging (MRI) and R2* mapping 10–20 days after transplant, and additionally within 48 h of biopsy if there was any evidence of graft dysfunction. The healthy donors underwent BOLD MRI 1–2 days before surgery. The biopsies were grouped into AR, ATN, and no evidence of AR or ATN. The mean medullary R2*, cortical R2*, corticomedullary gradient, and medullary: cortical R2* ratio were compared between groups using one-way analysis of variance. Spearman's correlation and multinomial linear regression were applied to determine the influence factors of R2* value. Overall, nine patients had graft dysfunction. Six were reported as AR, two as ATN, and one as no evidence of ATN or rejection. The mean medullary and cortical R2* were significantly higher in ATN group compared with AR and normal group, whereas the mean medullary and cortical R2* of AR group were significantly lower than normal group. The corticomedullary gradient of AR group was significantly lower compared with ATN and normal group. Medullary R2*:cortical R2* ratio was significantly lower in AR group compared with normal group. No significant difference was noted between the 15 donors and patients with normal graft function. R2* values on BOLD MRI are significantly decreased in AR allografts and increased in an early stage of ATN allografts, suggesting that BOLD MRI can become a valuable tool for discriminating between AR and ATN.
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Prevalence and clinical correlates of white coat effect in patients with chronic kidney disease and the role of automated blood pressure device in its assessmentp. 448
Srinivas Shenoy, Shankar Prasad Nagaraju, Nileshwar R Rau, Ravindra A Prabhu, Uday Venkat Mateti, Dharshan Rangaswamy, Indu R Rao, Karan Saraf
DOI:10.4103/ijn.IJN_418_17  
Context: Hypertension in chronic kidney disease (CKD) is an important modifiable cardiovascular risk factor. Patients with CKD can have clinically significant white coat effect (WCE), making routine clinic blood pressure (BP) measurements an unreliable indicator of actual BP control. Automated BP monitoring is useful in identifying WCE. The utility of automated BP monitoring has seldom been part of clinical practice in developing countries. Aim: The goal of this study was to estimate the prevalence and determinants of WCE in adult patients with CKD in an outpatient setting using an automated BP device. Materials and Method: In this prospective observational study, patients with CKD attending the nephrology clinic over a period of 6 months (January 2016 to July 2016), who were suspected to have WCE by the treating physician, were assigned to measurement of BP by both the standardized manual BP recording by a single nephrologist and with automated machine as per a defined protocol. Clinical, demographic characters that would influence outcomes were also studied. Results: Among 118 patients with CKD with suspected WCE, 57.6% showed WCE. The mean systolic and diastolic BPs were significantly lower with automated machine when compared with manual BP recordings in patients with WCE (p = 0.04). WCE was seen in all stages of CKD. Occurrence of WCE in CKD was not dependent on factors such as old age, sex, diabetes mellitus, or smoking status in our study. Conclusion:WCE is a highly prevalent and underdiagnosed entity in patients with CKD. Automated machine is a useful and time-saving tool in detection of WCE in patients with CKD attending the outpatient clinic and guide management.
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Acute pyelonephritis: A single-center experiencep. 454
L Umesha, SM Shivaprasad, EN Rajiv, MM Satish Kumar, V Leelavathy, CG Sreedhara, MR Niranjan
DOI:10.4103/ijn.IJN_219_16  
Acute pyelonephritis (APN), although a common clinical entity, still not much is known about the clinical profile in the Indian scenario. We prospectively collected clinical, biochemical, and radiological data of patients hospitalized with a diagnosis of APN from March 2014 to June 2016. A total of 296 cases were included in the study. Mean age was 53.85 ± 9.78 years. Male to females ratio was 1.93:1. Among the risk factors recognized for complicated pyelonephritis (PN), diabetes mellitus (DM) (54.4%) was the most common factor followed by renal calculi (14.4%), benign prostatic hyperplasia (6.7%), immunocompromised state (3.3%), stricture urethra and meatal stenosis (3.3%), and neurogenic bladder (2%). Urinary culture was negative in 153 (51.7%) and positive in 143 patient (48.3%). Most common organism isolated was Escherichia coli (29.7%), followed by Klebsiella pneumoniae (5.4%), pseudomonas (5.4%), Enterococcus (4.4%), and Proteus in 10 (3.4%). Serum creatinine of more than 1.5 mg/dl at admission was seen in 96.3% patients; 40% of them had underlying chronic kidney disease with DM being the most common. Multiorgan dysfunction either at admission or during the course in hospital stay was seen in 31.8% patients. Twelve (2%) had emphysematous PN. Six patients had Class II, 4 had Class III, 1 with Class I, and another with Class IV. A total of 18 deaths were noted (6.1%). Hemoglobin <10 g/dl, serum creatinine at admission >1.5 mg/dl, HbA1c% >10%, and immunosuppression had statistically significant association with the development of multiorgan dysfunction on univariate analysis, but on multivariate analysis, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance. Even with attributable risk of mortality, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance on multivariate analysis. HbA1c% adds to the predictive parameters to recognize at-risk patients to intensify the treatment and avoid complications.
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Hepatitis C virus-associated membranoproliferative glomerulonephritis treated with directly acting antiviral therapyp. 462
S Nayak, A Kataria, MK Sharma, A Rastogi, E Gupta, A Singh, SC Tiwari
DOI:10.4103/ijn.IJN_235_17  
Hepatitis C virus (HCV) infection has been shown to affect kidneys with various histopathological pattern on the kidney biopsy. These commonly include a membranoproliferative glomerulonephritis (MPGN) pattern with mixed cryoglobulinemia (CG), thrombotic microangiopathy, membranous nephropathy, and vasculitis affecting medium and small vessels of the kidneys causing polyarteritis nodosa. It has been rarely associated with MPGN without detectable CG. We present one such patient who presented to us with HCV-associated MPGN without detectable CG, who recovered completely with directly acting antiviral therapy without any immunosuppression.
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Systemic lupus erythematosus with linear IgA bullous dermatosis and renal vascular lesions: An extremely rare associationp. 465
R Malipatel, V Gnanapriya, A Manocha, YK Inchara
DOI:10.4103/ijn.IJN_200_17  
We report a rare case of systemic lupus erythematosus presenting initially with cutaneous manifestations of linear IgA bullous dermatosis. Later the patient developed renal abnormalities due to thrombotic microangiopathy and lupus nephritis with inflammatory necrotizing vasculitis. Paucity of immune deposits was observed on Immunofluorescence. This association of SLE with these cutaneous and renal lesions is rarely reported in the literature.
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Xanthogranulomatous pyelonephritis: Intrahepatic and intrathoracic extensionp. 468
U Anandh, N Birajdar, R Kumar, S Babu
DOI:10.4103/ijn.IJN_213_17  
A 32-year-old female presented to us with worsening cough and expectoration, low-grade fever, and malaise for 3 months. She gave a history of pregnancy loss secondary to urinary tract infection (UTI) a year back. At that time, she was told to have an obstructive right renal calculus. She also had a history of recurrent UTI in the past 1 year. She had no other comorbidities. Her clinical evaluation revealed an enlarged right kidney and reduced air entry in the right hemithorax. Radiological investigations revealed a large right kidney invading into the inferior surface of the right lobe of the liver and the right pleural space. A clinical diagnosis of xanthogranulomatous pyelonephritis was made, and she was advised nephrectomy. Intraoperatively, the right kidney was found to invade both the right lobe of the liver and the right pleural cavity through a right diaphragmatic defect. Histopathology of the kidney revealed the presence of foamy histiocytes suggestive of xanthogranulomatous pyelonephritis. Invasive xanthogranulomatous pyelonephritis is known, however, invasion into the extra-abdominal structures has not been reported in the literature. Our case is a rare manifestation of a rare clinical entity – xanthogranulomatous pyelonephritis.
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Crystalline nephropathy in renal transplant: A series of 4 casesp. 472
K Mnif, S Yaich, M Mars, K Kammoun, F Fendri, K Charfeddine, F Jarraya, T Boudawara, J Hachicha
DOI:10.4103/ijn.IJN_76_17  
Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. The most common forms of crystalline nephropathies (CNs) are nephrocalcinosis and oxalate nephropathy. The causes of early allograft dysfunction are changing constantly, and recently calcium oxalate (CaOx) crystal deposition has been added to this list. CaOx deposition in renal allograft is important and probably under-recognized cause of delayed graft function that requires adequate awareness with early intervention to improve the allograft outcome. Here, we describe four cases of irreversible renal graft injury due to CNs.
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Allopurinol-induced drug reactions with eosinophilia and systemic symptoms syndrome with interstitial nephritisp. 477
T Aatif, J Fatihi, H El Annaz, O Qamouss
DOI:10.4103/ijn.IJN_166_17  
Allopurinol-induced drug reactions with eosinophilia and systemic symptoms (DRESS) is a severe illness related to hypersensitivity syndrome characterized by fever, skin rash, lymph node enlargement, hematological abnormalities, especially eosinophilia and atypical lymphocytosis, and single or multiple organ involvement. The syndrome is difficult to diagnose in view of its clinical heterogeneity and long latency period within 8 weeks after start treatment. We report a case of DRESS syndrome in a 64-year-old man, induced by allopurinol treatment for asymptomatic hyperuricemia, started 8 weeks earlier but stopped only 3 days after because of the onset of rash. The diagnosis was retained due to combining of interstitial nephritis with the clinical findings of fever, skin rash, cervical lymphadenopathy, eosinophilia, and reactivation of human herpesviruses specifically HHV-6. The glucocorticoids were started to relieve hypersensitivity. Five days later, the patient became afebrile, and the rash improved significantly. However, interstitial nephritis with renal function impairment progressed to severe azotemia, and even anuria requiring hemodialysis. Allopurinol-induced DRESS syndrome is associated with significant mortality, and care must, therefore, be exercised when given this drug.
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Autosomal dominant polycystic kidney disease: Presence of hypomorphic alleles in PKD1 Genep. 482
S Pandita, D Khullar, R Saxena, IC Verma
DOI:10.4103/ijn.IJN_236_17  
Autosomal dominant polycystic kidney disease is characterized by multiple cysts in both kidneys manifesting in adult life. In general, the disorder is caused by a pathogenic variant in one allele of PKD1 or PKD2 genes, while the other allele is normal. Pathogenic variants in both the alleles are rare and have variable phenotypes, from lethal or perinatal presentation to a mild form in later adulthood, depending on the type of variant. Here, we describe a proband with two variants (p.Thr1773Ile and p.Ala1871Thr in trans) in PKD1 gene, who presented with disease at age 24 years. Both the parents and one brother had a variant in one allele, the other being wild type only and had normal ultrasound findings. Segregation studies suggest that both the variants may act as "hypomorphic" or "incompletely penetrant" alleles and acting together resulted in haploinsufficiency of protein PC1 in renal cells, leading to cystogenesis in the proband. The consequences of the presence of two hypomorphic variants have been poorly documented in literature. We reviewed the few published cases having two hypomorphic variants and the data conform to the conclusions that we reached by study of the family described. It is emphasized that to resolve the significance of suspected hypomorphic variants, segregation studies in the parents and siblings are essential.
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An unusual association of renal cell carcinoma and renal malakoplakia with focal segmental glomerulosclerosis in an elderly patientp. 485
M Vijayan, P Koshy, R Parthasarathy, M Mathew, G Abraham
DOI:10.4103/ijn.IJN_289_17  
The association of malignancy and glomerulonephritis may be missed, especially in elderly patients. Here, we report a case of eosinophilic variant of renal cell carcinoma and renal parenchymal malakoplakia discovered on renal biopsy in a patient with steroid-dependent nephrotic syndrome. The presence of malakoplakia in our biopsy was probably due to systemic steroid therapy for glomerulonephritis, presence of concomitant asymptomatic urinary tract infection, and/or history of diabetes mellitus. The patient had remission of proteinuria following laparoscopic removal of the tumor, indicating probable remission of glomerulonephritis.
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Kidney transplantation from a hepatitis C virus-positive donor to a hepatitis C virus-negative recipient Highly accessed articlep. 488
M Kamalkiran, V Ravikiran, C Shashidhar, K. V. R Prasad, V Yeldandi
DOI:10.4103/ijn.IJN_267_17  
Kidney transplantation from a hepatitis C virus (HCV)-positive donor to an HCV-negative recipient till recently has been a contraindication. In view of the excellent sustained virological response (SVR) rates with directly acting antiviral agents, HCV-positive donors are being considered for the HCV-negative recipients in a few centers. We report the successful transplantation of an HCV-negative recipient transplanted with an HCV-positive donor kidney. Donor was treated with sofosbuvir and ribavirin for 12 weeks. At 10th and 16th weeks of starting treatment, her HCV-RNA PCR was negative. Three weeks later, transplantation was performed with basiliximab induction and triple immunosuppression with tacrolimus, mycophenolate, and prednisolone. The recipient was administered sofosbuvir and ribavirin for 12 weeks. He attained good graft function with a stable creatinine. His serial alanine transaminases were normal on 3rd, 6th, and 12th months, respectively. Six months posttransplant his anti-HCV antibody, and HCV-RNA PCR were negative.
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LETTERS TO EDITORTop

Cystinuria in a 13-Month-Old girl with absence of mutations in the SLC3A1 and SLC7A9 genesp. 490
MD Al-Mendalawi
DOI:10.4103/ijn.IJN_46_18  
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Improving crossmatch techniques and graft outcomesp. 491
L Vincent
DOI:10.4103/ijn.IJN_362_17  
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Estimated glomerular filtration rate using creatinine-based chronic kidney disease epidemiology collaboration equationp. 492
AA Rani, V Viswanathan
DOI:10.4103/ijn.IJN_439_17  
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