Prehospital Ground Transport Rapid Sequence Intubation for Trauma and Traumatic Brain Injury Outcomes

No abstract available

http://bit.ly/2DoRsfI

Cytomorphological spectrum of scalp lesions in the population of a developing country: A retrospective study

BACKGROUND

Scalp lesions are frequently encountered in clinical practice. Fine‐needle aspiration cytology (FNAC) can characterize most of these lesions; however, there is little published work on cytology of scalp lesions.

METHODS

Records of all the patients subjected to FNAC from January 2011 to August 2016 were retrieved from the archives of the Cytopathology section of our Institute. Out of the 71 852 cases reviewed, 896 patients, who presented with palpable scalp lesions, were included in the study. Aspirates were obtained with a 23‐gauge needle attached to a 10 mL disposable plastic syringe. May–Grünwald–Giemsa stained and Pap stained slides were prepared. Special stains and immunocytochemical analysis were done when necessary.

RESULTS

Out of the 896 cases of aspirates from scalp lesions, 155 (17.2%) aspirates were found to be inadequate for diagnosis. One hundred and fifty‐seven (21%) out of 741 adequate aspirates showed features of inflammatory or reactive pathology comprising of abscesses (57), cystic lesions (24), tubercular lesions (16), and reactive lymphadenopathy (66). Four hundred and fifteen (56%) aspirates revealed a tumor‐like etiology comprising of epidermal cyst (395), sebaceous cyst (4), dermoid cyst (1), calcinosis (7), vascular malformation (7), hematoma (5), and juvenile xanthogranulomatous lesion (1). Tumorous lesions formed 22.3% of the aspirates. Of these, 7 cases (4.2%) were of metastases to the scalp.

CONCLUSION

In a developing country, FNAC is a useful and cost‐effective investigation for the diagnosis of a wide spectrum of scalp lesions. It allows rapid diagnosis and permits timely intervention thereby preventing complications due to delay in diagnosis.

http://bit.ly/2Sx1ztA

Image quantification technology of the heterochromatin and euchromatin region for differential diagnosis in the lobular endocervical glandular hyperplasia

Background

Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci et al. in 1999 and is believed to be a precancerous lesion of minimal deviation adenocarcinoma and gastric‐type adenocarcinoma in the uterine cervix. LEGH lesions do not always exhibit apparent cellular and structural atypia, so are difficult to distinguish from normal endocervical cells (EC cells) with cytological examination. Therefore, we often struggle to make a definite diagnosis of LEGH.

Methods

We used microscopy images of cytological specimens that were diagnosed as EC cells and LEGH cells. Signal intensity in whole nuclear area and in heterochromatin and euchromatin regions, euchromatin area ratio, and nuclear morphological features were quantified in each cell nucleus of the cases. Statistical analyses were conducted to determine statistical significance. Finally, we performed linear support vector machine (LSVM) modeling as a discriminant analysis using the quantified features.

Results

Signal intensity in whole nuclear area, and heterochromatin and euchromatin regions of EC cell nuclei were higher than that of the LEGH cell nuclei. Morphologically, EC cell nuclei were larger than LEGH cell nuclei, and nuclei of LEGH cells had irregular nuclear respectively membrane structure and an elongated shape. The LSVM accuracy of 10‐fold cross validation and leave‐one‐case‐out cross‐validation (LOCOCV) using all measured features were 84.7% to 89.3% and 78.6% to 86.0%, respectively.

Conclusions

The LVSM analysis using features extracted from signal intensity and morphological analysis was useful for discrimination of EC cells vs LEGH cells. We therefore believe that this image analysis method could be used for early detection of LEGH.

http://bit.ly/2DGPI1t

Cytological features of uterine tumors resembling ovarian sex‐cord tumors in liquid‐based cervical cytology: a potential pitfall. Report of a unique and rare case

Uterine tumors resembling ovarian sex‐cord tumors (UTROSCTs) are rare uterine neoplasms of uncertain etiology that resemble the sex cord tumors of the ovary and display a combined sex cord, epithelial, and smooth muscle immunophenotype. Most tumors are associated with a benign clinical course. We report the first cytological description of uterine UTROSCTs in liquid‐based cervical cytology (LBC). A menopausal woman was discovered to have a uterine intraluminal polypoid mass protruding through the vagina. A Pap test was performed, and the LBC preparation showed isolated tumor cells with scant cytoplasm and slightly irregular, ovoid nuclei with fine chromatin and small nucleoli. Final histological evaluation identified a UTROSCT. This diagnostic possibility, albeit rare, should be included in the differential diagnosis when isolated malignant‐appearing adenocarcinomatous cells are seen in women in the above scenario. As these features are not specific, they may result in misinterpretation with tumors that are more common and aggressive.

http://bit.ly/2Svwqqr

Efficacy and Safety of Safflower Yellow in Early Diabetic Nephropathy: A Meta-Analysis

Background. Diabetic nephropathy (DN) is a major cause of end-stage renal disease. In order to palliate renal function impairment and reduce kidney related mortality, it is crucial to treating DN patients at the early stage. This study aims to assess the efficacy and safety of conventional therapy combined with safflower yellow versus conventional therapy alone in early DN patients. Methods. A meta-analysis of randomized controlled trials that compared safflower yellow plus conventional therapy with conventional therapy alone in early DN patients was conducted. Papers were searched using the electronic databases and reference lists. Two reviewers working independently extracted relevant data and carried out risk-of-bias assessments. Statistical analysis was undertaken in Review Manager 5.3. Results. Fourteen trials (1,072 patients) were included in the meta-analysis. Conventional therapy combined with safflower yellow was associated with a higher effective rate (RD, 0.24; 95% CI, 0.17 to 0.30) and a greater decline in urinary albumin excretion rates (SMD, -1.34; 95% CI, -1.77 to -0.92), fasting blood glucose (MD, -0.57; 95% CI, -0.98 to -0.16), serum creatinine (MD, -12.36; 95% CI, -14.66 to -10.06), and blood urea nitrogen (SMD, -0.93; 95% CI, -1.13 to -0.73) in the subgroup with a follow-up time > 15 days. The incidence of adverse events did not differ significantly between these two regimens (RD, -0.01; 95% CI, -0.03 to 0.01). Findings were similar in the subgroup with a follow-up time

http://bit.ly/2tlamzz

“Gentlemen, you can never learn too much anatomy”

http://bit.ly/2TOY26c

Higher urate in LRRK2 mutation carriers resistant to Parkinson's disease

Abstract

Objective

LRRK2 mutations, the most common genetic cause of Parkinson's disease (PD) display incomplete penetrance, indicating the importance of other genetic and environmental influences on disease pathogenesis in LRRK2 mutation carriers. The present study investigates whether urate, an antioxidant, Nrf2 activator, and inverse risk factor for idiopathic PD, is one such candidate biomarker of PD risk modulation in pathogenic LRRK2 mutation carriers.

Methods

Banked plasma samples or urate levels were obtained for three cohorts of age‐ and sex‐matched subjects with and without a known LRRK2 mutation in PD and unaffected controls to conduct a pilot study of 192 subjects from the LRRK2 Cohort Consortium (LCC) and two validation studies of 380 additional subjects from the LCC and of 922 subjects from the Parkinson Progression Marker Initiative. Urate levels were compared by multiple regression between subjects with and without a PD diagnosis conditional on LRRK2 status, controlling for age and sex.

Results

Non‐manifesting LRRK2 mutation carriers had significantly higher levels of urate than those who developed PD in each of the three independent cohorts. A meta‐analysis demonstrated an adjusted mean difference of 0.62 mg/dL (p<0.001), with similar results for separate assessments of women (p<0.02) and men (p<0.001). A 2 mg/dL increment in urate concentration decreased the odds of having PD by more than 50% (OR = 0.48; p = 0.004).

Interpretation

These findings identify and substantiate urate as a biomarker of resistance to PD among LRRK2 mutation carriers.

This article is protected by copyright. All rights reserved.

http://bit.ly/2STi6XS

Serum neurofilaments increase at PML onset in natalizumab‐treated MS patients

ABSTRACT

This study analyzed serum neurofilament light chains (NfL) in 2 European cohorts of 312 MS patients to investigate whether NfL are biomarkers of PML during natalizumab treatment. The cohort comprised 25 PML, 136 natalizumab‐treated, and 151 untreated MS patients. Patients subsequently developing PML had similar NfL to other natalizumab‐treated MS patients. At PML onset, NfL were 10‐fold higher than in the pre‐PML condition and in natalizumab‐treated or untreated MS patients, and NfL continued to increase until onset of immune reconstitution inflammatory syndrome. The results suggest that in natalizumab‐treated patients NfL may represent an early and accessible marker of PML.

This article is protected by copyright. All rights reserved.

http://bit.ly/2N9wh64

Serum folate receptor α (sFR) in ovarian cancer diagnosis and surveillance

Collectively, our data demonstrate that sFR could improve diagnostic accuracy. Additionally, the monitoring of sFR and CA125 (and potentially other markers) could conceivably improve cancer surveillance, affecting prognosis. We have initiated a prospective clinical trial studying sFR induction in the initial diagnosis and surveillance of OVCA as a means to abrogate potential limitations of this biomarker.

Abstract

Novelty and Impact Statement: Our findings suggest that soluble folate receptor (sFR) could be used in both the initial diagnosis and surveillance of patients with ovarian cancer. Our cohort constitutes one of the largest comparison groups for sFR analyzed so far. We have defined the background level of sFR using healthy volunteers. This is also the first study to prospectively follow patients in the surveillance setting to concurrently identify differential changes in tumor markers CA‐125 and sFR.

http://bit.ly/2tmbpiY

Repeated Treatment with 90Y-Microspheres in Intrahepatic Cholangiocarcinoma Relapsed After the First Radioembolization

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


http://bit.ly/2TPa27I

A case‐control‐family study of idiopathic rapid eye movement sleep behavior disorder

Abstract

Background

To determine the familial aggregation of idiopathic rapid eye movement sleep behavior disorder (iRBD), neurodegenerative diseases, and related biomarkers.

Methods

A total of 404 and 387 first‐degree relatives of 102 patients with iRBD and 89 controls were recruited, respectively. Among them, 204 and 208 relatives of patients and controls underwent face‐to‐face clinical assessment, while 97 and 75 relatives underwent further video‐polysomnographic assessment, respectively.

Results

Compared with relatives of controls, relatives of patients demonstrated higher levels of RBD features including chin tonic electromyography activity (mean: 1.5&pm;7.5 vs. 0.3&pm;1.0, p=0.04) and behavioral events (n [weighted %]: 12 [11.3] vs. 2 [1.9], adjusted hazard ratio [aHR]=7.69, 95% confidence interval [CI]=1.54‐33.33, p=0.009) during rapid eye movement sleep, probable diagnosis (n [%]: 57 [14.9] vs. 20 [4.9], aHR=3.45, 95% CI=1.96‐6.25, p <0.001), and definite diagnosis (n [weighted %]: 10 [8.4] vs. 2 [1.4], aHR=5.56, 95% CI=1.16‐25.00, p=0.03). They also had higher risks of Parkinson's disease (3.1% vs 0.5%, aHR=5.88, 95% CI=1.37‐25.00, p=0.02), dementia (6.9% vs. 2.6%, aHR=2.44, 95% CI=1.15‐5.26, p=0.02), constipation (8.3% vs. 2.4%, adjusted odds ratio=4.21, 95% CI=1.34‐13.17, p=0.01), and motor dysfunction (MDS‐UPDRS part III motor score, mean: 1.9&pm;3.2 vs. 0.9&pm;2.3, p=0.002). The unaffected relatives of patients demonstrated a higher likelihood ratio of prodromal Parkinson's disease (median [interquartile range]: 0.27 [1.19] vs. 0.22 [0.51], p=0.03).

Interpretation

iRBD is familial aggregated from isolated features to full‐blown sleep disorder. Relatives of patients carry a higher risk of alpha‐synucleinopathy in terms of neurodegenerative diseases and prodromal markers, suggesting a familial aggregation and staging pathology of alpha‐synucleinopathy.

This article is protected by copyright. All rights reserved.

http://bit.ly/2GnlKUl

Blood pressure variability and hemorrhagic transformation in patients with successful recanalization after endovascular recanalization therapy: a retrospective observational study

Abstract

Objective

Although BP variability has been regarded as a risk factor for hemorrhagic transformation (HTF) after intravenous thrombolysis, its effect on HTF after endovascular recanalization therapy (ERT) remains to be elucidated. We aimed to study the relationship between BP variability and symptomatic intracerebral hemorrhage (sICH) after successful recanalization with ERT.

Methods

A total of 211 patients with acute ischemic stroke and successful recanalization (Thrombolysis in Cerebral Infarction 2b or 3) after ERT were included between January 2013 and May 2017. The BP data following ERT was obtained over the first 24 hours using parameters including mean, maximum, minimum, difference between maximum and minimum, standard deviation, coefficient of variation, successive variations, and time rate (TR) of BP variation for systolic BP (SBP) and diastolic BP (DBP). sICH was defined as parenchymal hemorrhage type 2 with neurological deterioration of 4 points of more on the National Institute of Health Stroke Scale.

Results

Among the included patients, 20 (9.5%) developed sICH after successful ERT. The parameters linked with BP fluctuation over time were significantly related to sICH. After adjusting for confounders, the TR of SBP (per 0.1 mmHg/min increase) variation was independently associated with sICH (odds ratio, 1.71; 95% confidence interval, 1.013–2.886).

Interpretation

Time‐related BP variability in the first 24 hours following successful ERT was more correlated with sICH than other absolute BP level. This suggests that maintaining a stable BP may be an important factor in preventing sICH after successful ERT.

This article is protected by copyright. All rights reserved.

http://bit.ly/2IcI04Y

Medical Trichology : Trigeminal trophic syndrome simulating pityriasis amiantacea,Nerve sheath myxoma of scalp,Woolly hair nevus type 2,Trichodynia silenced effectively with propranolol,Serum interleukin-15 is a marker of alopecia areata severity,Tubular hair casts in trichoscopy of hair and scalp disorders,Research on the balance of thiol-disulfide in blood serum in women with telogen effluvium,Light microscopic morphology of hair from scalp, eyebrow, axilla, and pubic regions

COMMENTARY
	Autistic-undisciplined thinking in the practice of medical trichology	p. 1
	Ralph Michel Trueb, Hudson Dutra, Maria Fernanda Reis Gavazzoni Dias DOI:10.4103/ijt.ijt_79_18   Medical trichology is the branch of dermatology that deals with the scientific study of the hair and scalp in health and disease. As any discipline, the practice of medical trichology is not immune to malpractice, either deliberately or carelessly. In his publication "Autistic Undisciplined Thinking in Medicine and How to Overcome It," Swiss psychiatrist Eugen Bleuler describes yet another form of malpractice in medicine reflecting autistic-undisciplined thinking. Autism is not limited to psychopathology, but inherent to the thinking of man throughout history in his drive for knowledge, with thousands of theories lacking any basis in reality. Bleuler recognized the drive character of autistic thinking and how it leads to conclusions that are unshakable because they are determined by, and fulfill, emotional needs, rather than rational argumentation. Even with correct questions, the complexity and incalculability of some problems are often so great that it cannot do justice to realistic thinking and the boundaries between inadequately substantiated hypothesis and autistic sham explanation disappear. Statistics, careful research design, and the attempt to impose stringent methods on our thinking are to be commended. The habituation of the public to useless medicine, to misconceptions, is not hygiene, but negligent endangerment. It has created an industry that largely lives on the autistic thinking of patients and doctors and because it is prosperous, makes propaganda among lay people as well as among doctors that necessarily leads to abuses. This article aims at exposing the most prevalent among abuses in trichological practice due to autistic-undisciplined thinking, specifically: iron supplementation, antiandrogenic treatment, and individualized cell-based therapy in female androgenetic alopecia, treatment of folliculitis decalvans with retinoids, and the value of nutritional therapies.
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ORIGINAL ARTICLES
	Light microscopic morphology of indigenous Ghanaian African hair from scalp, eyebrow, axilla, and pubic regions	p. 8
	Yusra Kalmoni, Frederick Kwaku Addai, Saviour Kweku Adjenti, Kevin Kofi Adutwum-Ofosu, John Ahenkorah, Bismarck Afedo Hottor, Richard Michael Blay DOI:10.4103/ijt.ijt_70_18   Context: Relatively scanty literature on autochthonic African Negroid hair morphology provokes research interest for anthropological, forensic, and cosmetic purposes. Aims: This study aimed to contribute basic morphological information on Ghanaian African hairs. Settings and Design: The study was done in selected second-cycle schools in Accra, Ghana, using convenient sampling. Subjects and Methods: Hairs were obtained by pluck method, from 30 males and 30 females aged 15–20 years. Ghanaian African autochthony was established if individuals had two generations of indigenous Ghanaian parentage. Scalp, eyebrow, axilla, and pubic hairs were image captured using a digital light microscope eyepiece connected to a computer. Diameters of hair strands were measured; types of the medulla and the form and shape of the hair roots were studied. Statistical Analysis Used: ANOVA test (SPSS Version 17.0) was used to compare the means of quantitative hair features among the sexes and the four regions of the body studied. Results: Pubic hair shaft was thickest (respective male and female diameters were 100.21 μm, 88.40 μm) and eyebrow hair was thinnest (53.97 and 46.69-μm diameters in males and females, respectively). Axillary and scalp hairs were the closest in diameters with 76.21 and 72.02 μm, respectively, in males and 73.07 and 71.15 μm, respectively, in females. Continuous type medulla was predominant in all hairs, with a trend of percentage occurrence in descending order from the pubic, axilla, eyebrow, and scalp in both sexes. Conclusions: Bodily regional differences in diameter of hair shaft and medullary presence were affirmed.
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	Tubular hair casts in trichoscopy of hair and scalp disorders	p. 14
	Mahesh Mathur, Prakash Acharya, Alina Karki, Jyoti Shah, Nisha Kc DOI:10.4103/ijt.ijt_77_18   Introduction: Hair casts have been reported in a variety of hair and scalp disorders. Trichoscopy allows a quick and noninvasive method for the evaluation of hair and scalp disorders in high magnification. However, the study of hair casts seen in trichoscopy is lacking. Objective: The main objective is to study the occurrence and patterns of tubular hair cast (THC) in different hair and scalp disorders. Patients and Methods: The patients with hair and scalp disorders presenting at the dermatology department of our hospital were evaluated using trichoscopy. Cases of primary parakeratotic disorders and behavioral disorders were excluded. After a detailed history and evaluation of the hair and scalp, histopathology, light microscopic examination, potassium hydroxide examination, and fungal culture were done when necessary. Results: THC was seen in total 21 cases of seven different hair and scalp disorders. Of these, the majority of cases were of discoid lupus erythematosus (DLE) (5/21) and maximum frequency of THCs within a disorder was seen in cases of pemphigus foliaceus (PF) (50%). Proximal casts occurred in 90.47% of cases. Single cast involving two shafts was seen in a case of PF, and two casts within a single shaft were seen in two cases of DLE and one case of alopecia areata. Conclusions: THCs in trichoscopy can be seen in various hair and scalp disorders and their study may help during the diagnosis of those disorders when combined with other trichoscopic features.
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	Research on the balance of thiol-disulfide in blood serum in women with telogen effluvium	p. 20
	Ayşe Akbas, Fadime Kılınç, Sertaç Sener, Akta Akınş, Cemile Bıçer, Orhan Şen DOI:10.4103/ijt.ijt_78_17   Backgrounds: Telogen effluvium (TE) is the most common reason for hair loss in humans. Although the exact etiopathogenesis of TE has not been revealed clearly and completely, multifactorial etiologies are to be blamed. In recent years, since oxidative stress (OS) has been shown to play an important role in the etiopathogenesis of so many diseases, the effects of OS on several skin diseases are researched and analyzed. Thiols are antioxidant components that include sulfur group, and the balance of thiol-disulfide has an important role in the formation and prevention of OS. This balance is destroyed in many diseases and its effect on TE is not clearly understood yet. Objectives: In this study, we aimed to search the thiol–disulfide balance that could reveal OS in patients with TE. Materials and Methods: Fifty-two patients with TE and control group of 46 persons were included in the study. Native thiol, disulfide, and total thiol levels were evaluated by a new, automatic spectrophotometric method. Disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol rates were calculated. Results: There was no statistical difference between TE patients and control group in terms of native thiol, disulfide, and total thiol levels. Thiol–disulfide balance was fixed and not affected in TE patients.
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	Serum interleukin-15 is a marker of alopecia areata severity	p. 26
	Adel Ali Ebrahim, Rehab Mohammed Salem, Asmaa Adel El Fallah, Esraa Taha Younis DOI:10.4103/ijt.ijt_80_18   Background: Interleukin-15 (IL-15) is a cytokine that is involved in many inflammatory and autoimmune diseases. Although alopecia areata (AA) is an autoimmune disease, serum levels of IL-15 have not been studied well in AA patients. Aim of the Work: We aims at evaluating the serum levels of IL-15 in active AA. Subject and Methods:This case-control study included 40 AA patients and 40 apparently healthy matched controls. Written informed consents were obtained from all the participants. The scalp was examined to assess sites, number, and size of alopecia patches, and the severity of AA lesions was assessed using the Severity of Alopecia Tool score (SALT score) which determine the percentage of hair loss in the scalp. The body was carefully examined to detect any alopecia patches in any hairy area. Nail examination was carried out to detect any nail involvement. Serum IL-15 levels were measured using an ELISA kits. Results: Serum levels of IL-15 in patients were significantly higher than those in the control group (P < 0.001). Serum levels in alopecia totalis were significantly higher than those with one or two patches, and serum levels in patients with both scalp and body involvement were significantly elevated than the levels of patients with either scalp or body involvement. There was a statistically significant positive correlation between SALT score and serum levels of IL-15 (P < 0.001). Conclusion: Serum IL-15 may be a marker of AA severity.
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CASE REPORTS
	Trigeminal trophic syndrome simulating pityriasis amiantacea	p. 31
	Luisa Groba Bandeira, Maria Cláudia Alves Luce, Bruno De Castro E Souza, Priscila Kakizaki, Neusa Yuriko Sakai Valente DOI:10.4103/ijt.ijt_16_18   We report a case of trigeminal trophic syndrome (TTS) on the scalp of a 69-year-old woman. Initially, the diagnosis of pityriasis amiantacea was considered. The review of pathological antecedents and knowledge of TTS were fundamental for the diagnosis of this illness. We performed a brief review on TTS and differential diagnoses.
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	Nerve sheath myxoma of scalp: A rare site of presentation	p. 34
	Shakti Kumar Yadav, Sompal Singh, Namrata Sarin, Roshina Naeem, Sonam Kumar Pruthi DOI:10.4103/ijt.ijt_45_18   Nerve sheath myxoma, a superficial myxoid tumor, was first described in 1969 by Harkin and Reed. Tumor has cytological and histological resemblance with neurothekeoma, another cutaneous myxoid lesion. Nerve sheath myxoma affects individuals of all age groups and equal predilection for both genders with most favored sites being the fingers and knee. Here, we present a case report of nerve sheath myxoma of the scalp, diagnosed and confirmed with histopathology and immunohistochemistry.
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	Woolly hair nevus type 2: Rare entity	p. 38
	Farhana Tahseen Taj, Shraddha Kologi DOI:10.4103/ijt.ijt_28_18   Woolly hair nevus is a rare non hereditary disorder of scalp characterized by curling and kinking of hair. It can present in childhood or adolescent age. Dermoscopy is a useful noninvasive technique to help in the diagnosis of wolly hair nevus. We report a case of woolly hair nevus associated with linear epidermal nevus.
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LETTER TO EDITOR
	Trichodynia silenced effectively with propranolol	p. 41
	Piotr Brzezinski, Vijay Zawar, Anca Chiriac DOI:10.4103/ijt.ijt_8_19
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Induction of HT-29 Colon Cancer Cells Apoptosis by Pyrogallol with Growth Inhibiting Efficacy Against Drug-Resistant Helicobacter pylori

Background: Colon cancer is the most aggressive form of cancers, that causes 0.5 million deaths per year around the globe. Targeting colon cancer by conventional therapeutic options elicits toxicity. Traditional medicines take a lead to alleviate the existing clinical challenges.

Objective: To investigate antibacterial activity against Helicobacter Pylori and in vitro anti-colon cancer activity by Acacia nilotica extract (ACE) and its active constituent pyrogallol.

Methods: Pyrogallol isolated from A. nilotica by column chromatography and HPLC and structure was elucidated by spectral analysis. Antibacterial activity was done by flow cytometry. Cytotoxicity was measured by MTT assay. Apoptotic morphology and nuclear fragmentation were assessed with AO/ethidium bromide and DAPI staining. DNA fragmentation was done by electrophoresis. Western blot used to analyze the molecular mechanism of apoptosis. Cell cycle arrest was determined using flow cytometry of propidium iodide stained cells. Cell migration was determined by wound healing assay.

Results: ACE (20 µg/ml) and pyrogallol (10 µg/ml) treatment reduced the survival of H.pylori at 61% and 62%, respectively. MTT results show that HT-29 cells are more sensitive to pyrogallol with an IC50 value of 35μg/ml compared to ACE. Pyrogallol treated HT-29 cells reached dead state i.e. late apoptotic state with severe nuclear fragmentation. Pyrogallol elicits dose dependent DNA fragmentation in HT-29 cells. Pyrogallol induced apoptosis by simultaneous down-regulation of Bcl-2 and up-regulation of BAX and cytochrome c. Pyrogallol arrested HT-29 cells in S and G2/M phase of cell cycle. Further pyrogallol exhibited marked antimetastatic potential by inhibiting the migration of HT-29 cells dose dependently.

Conclusion: Both ACE and pyrogallol repressed the growth of H.pylori and as significant anti-colon cancer agent.

http://bit.ly/2DBcKHl

Network-based Drug Discovery, Anti-cancer Molecular Targets and Therapeutic use of Phytochemicals

http://bit.ly/2SBA3ex

A Review on Camptothecin Analogs with Promising Cytotoxic Profile

Camptothecin (CPT), obtained from Camptotheca acuminata (Nyssaceae), is a quinoline type of alkaloid. Apart from various traditional uses, it is mainly used as a potential cytotoxic agent acting against a variety of cancer cell lines. Though searches have been continued for last six decades, still it is a demanding task to design potent and cytotoxic CPTs. Different CPT analogs are synthesized to enhance the cytotoxic potential as well as to increase the pharmacokinetic properties of these analogs. Some of these analogs were proven to be clinically effective in different cancer cell lines. In this article, different CPT analogs have been highlighted extensively to get a detail insight about the structure-property relationships as well as different quantitative structure-activity relationships (QSARs) modeling of these analogs are also discussed. This study may be beneficial for designing newer CPT analogs in future.

http://bit.ly/2SudU1o

Repositioning of Difluorinated Propanediones as Inhibitors of Histone Methyltransferases and their Biological Evaluation in Human Leukemic Cell Lines

Background: At present, 'pharmaco-epigenomics' constitutes the hope in cancer treatment owing to epigenetic deregulation- a reversible process and playing a role in malignancy.

Objective: Chemotherapy has many limitations like host-tissue toxicity, drug resistance. Hence, it is imperative to unearth targets to better treat cancer. Here, we intend to repurpose a set of our previously synthesized difluorinated Propanediones (PR) as Histone lysine Methyltransferase inhibitors (HMTi).

Methods: The cell lines of leukemic origin viz. histiocytic lymphoma (U937) and acute T-cell leukemia (JURKAT) were treated with PR-1 to 7 after docking studies with active pocket of HMT. The cell cycle analysis, in vitro methylation and cell proliferation assays were carried out to delineate their physiological role.

Results: A small molecule PR-4, at 1 and 10µM, has shown to alter the methylation of histone H3 and H4 in both cell lines. Also, treatment shows an increase in G2/M population and a subsequent decrease in the G0/G1 population in U937. In JURKAT, an increase in both G2/M and S phase population was observed. The sub-G1 population showed a steady rise with increase in dose and prolonged time intervals in U937 and JURKAT cell lines. In SRB assay, the PR showed a cell growth of 42.6 and 53.4% comparable to adriamycin; 44.5 and 53.2% in U937 and JURKAT, respectively. The study suggests that PR-4 could emerge as a potential HMT inhibitor.

Conclusion: The molecule PR-4 could be a lead in developing more histone lysine methyltransferases inhibitors with potential to be pro-apoptotic agents.

http://bit.ly/2DAfIM8

Biochemical and Pharmacological Applications of Essential Oils in Human Health Especially in Cancer Prevention

Background: Essential oils (EOs) are aromatic, volatile and concentrated hydrophobic liquids extracted from plant material. EOs are also called as ethereal oils, volatile oils or aetherolea. EOs also play a crucial role in plant defence and signalling processes. They are mostly used in perfumes, cosmetics, soaps and other products for flavouring food, drinks, adding scents to incense and household cleaning products. EOs have a long medicinal history.

Methods: Reported research literature and online contents related to the use of EOs for their biochemical pharmacological applications in cancer prevention therapy were reviewed. The most relevant and updated citations were included in this review.

Results: This review elaborates the various types of EOs, their biochemical characteristics, and pharmacology. Medicinal benefits of essential oil products range from various skin treatments to different types of therapies for cancer and are dependent entirely on historical backgrounds of use of EOs for these properties. EOs have antimicrobial, anticancer, antioxidant, antiparasitical, insecticidal, anti-inflammatory, viricidal, fungicidal, wound healing, antihypertensive, analgesic properties and other medicinal properties. The efficiency of EOs in medical treatments and treatment of cancers are these days a subject of interest in most countries.

Conclusion: This review elaborated the potentials of EOs in regulating cancer cell growth and have explored the probable EOs that can be used in drug development.

http://bit.ly/2SvfxMp

Meet Our Editorial Board Member

http://bit.ly/2DFPd87

Association of Phytol with Toxic and Cytotoxic Activities in an Antitumoral Perspective: A Meta-Analysis and Systemic Review

Background: Phytol have various pharmacological activities such as antimicrobial, cytotoxic, antitumoral, antimutagenic, anti-atherogenic, antidiabetic, lipid-lowering, antispasmodic, antiepileptic, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant and immunoadjuvant. Several studies point to an association of phytol with implications for apoptosis and necrosis at cellular levels in cancer, yet no clear conclusions were drawn.

Method: To clarify this, we conducted a meta-analysis of non-clinical studies of phytol and its associations with toxicity and cytotoxicity emphasizing the mechanisms of apoptosis and necrosis induction and its importance in tumor therapy. Relevant studies were systematically searched in PubMed and Web of Science. The association between phytol and cyto-/toxicity was assessed by odds ratio (ORs) and 95% confidence intervals (CI). Twentythree studies were finally included in the meta-analysis. A significant association between phytol and toxicity (OR: 1.47; 95% CI = 0.86–2.48) was found among in vivo studies and cytotoxicity (OR: 1.81; 95% CI = 1.12– 2.65, p

Conclusion: This study confirms that the association between phytol and cyto-/toxicity depends on the dose/concentration used in the given experimental conditions. Thus, there are still great prospects for new research aimed at the use of phytol and its metabolite as anticancer agents.

http://bit.ly/2SyNhby

Fisetin Attenuates AKT Associated Growth Promoting Events in AflatoxinB1 Induced Hepatocellular Carcinoma

Background: Recently, we have reported that Fisetin, a natural flavonol, is able to regress Aflatoxin- B1 (AFB1) induced hepatocellular carcinoma (HCC) by suppressing reactive oxygen species (ROS) led proinflammatory factors in rats. In the current study, we aimed to delineate whether Fisetin does so by modulating the cell growth promoting signaling cascade in HCC. The reciprocal interplay of 3-phosphoinositol kinase (PI3K) vs phosphatase and tensin homologue deleted on chromosome 10 (PTEN) displays Akt, a protein kinase B, to get phosphorylated at Thr308 by a 3-phosphoinositol dependent kinase 1 (PDK1). This commits cells of neoplastic niche to undergo rapid proliferation by p-Aktthr308 dependent phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9 position.

Method: In this study, the effect of in vivo treatment of 20 mg/kg b.w. Fisetin on relative profile of all these factors were studied in the liver from the HCC rats induced by two doses of 1mg/kg b.w. AFB1 i.p.

Result: As compared to the untreated HCC liver, liver from Fisetin treated HCC group rats showed a significant decline in the activity and level of p-Aktthr308 which was consistent with a similar decline in PDK1 level. Concordantly, the level of p-GSK3βSer 9 was also found to be declined significantly in those Fisetin-treated HCC livers.

Conclusion: A concomitant decline in immunohistochemically detected number of the proliferating cell nuclear antigen (PCNA), a cell proliferation marker, in the HCC liver, further confirmed anti-cell proliferative role of Fisetin during HCC growth in vivo. These findings suggest that Fisetin is able to suppress Akt dependent cell growth signaling mechanisms in HCC mainly by down regulating PDK1 dependent Akt phosphorylation.

http://bit.ly/2DCrhlW

An Overview of Natural Plant Products in the Treatment of Hepatocellular Carcinoma

Background: Liver cancer is the fifth most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Among the liver cancers, hepatocellular carcinoma has been reported to be responsible for 85-90% of primary liver cancer and it is the second most common cause of cancer mortality with 700,000 deaths documented annually. The major risk factors of HCC include chronic infections with the hepatitis B (HBV) or hepatitis C (HCV) virus, chronic liver diseases, alcoholism as well as dietary carcinogens, such as aflatoxins. Highest incidence rates are estimated to occur in Asia and Africa.

Objective: The effectiveness of current man-made agents in treating chronic liver disease is not satisfactory and they have uninvited side effects. Herbal medicines are extensively used all over the world; however, there is still a vast gap in their acceptance by the scientific community. Plants are rich in secondary metabolites and phytochemicals obtained from both, dietary and non-dietary sources. Natural plant products are potent therapeutic as well as chemopreventive agents for numerous chronic diseases like cardiovascular, metabolic, neurodegenerative and neoplastic diseases.

Results: Dietary phytochemicals such as curcumin, resveratrol, quercetin, silibinin, N-trans-feruloyl octopamine, lycopene, emodin, caffeine, urolithin A and Phloretin have been found to be useful for the treatment of HCC and other diseases. According to recent reports 60% of the anticancer medication in current use has been obtained from natural sources.

Conclusion: Thus, derivatives from plants have played an essential role in cancer prevention due to their pleiotropic abilities to scavenge free radicals, inhibit cell growth and induce apoptosis.

http://bit.ly/2Sx9l6A

Pre-clinical Validation of Mito-targeted Nano-engineered Flavonoids Isolated From Selaginella bryopteris (Sanjeevani) As A Novel Cancer Prevention Strategy

Background: Novel bioactive plant secondary metabolites, including flavonoids, offer a spectrum of chemo-protective responses against a range of human tumor models. However, the clinical translation of these promising anti-cancer agents has been hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration.

Objective: To circumvent the challenges associated with herbal drug development and for effective integration into clinical setting, nano-engineering is one of the emerging pragmatic strategies which has promise to deliver therapeutic concentrations of bio-actives upon oral administration.

Method: We assessed the nano-encapsulated flavonoid-rich fraction isolated from a traditional Indian herb Selaginella bryopteris (Sanjeevani) (NP.SB). Both in vitro and in vivo studies were performed to evidence the epigenetic protection mechanisms of NP.SB through a mitochondrial-targeted pre-clinical validation strategy.

Results: The mito-protective activity of NP.SB revealed a dose-dependent effect when tested in GC-1 spg (mouse spermatogonial epithelial) and B/CMBA.Ov (mouse ovarian epithelial) following exposure to Nsuccinimidyl N-methylcarbamate, a potential human carcinogen. Smaller size, rapid internalization, faster mobility and site specific delivery conferred significant cancer protection in cultured cells. Notably, this encapsulated flavonoid supplementation; prevented emergence of neoplastic daughter clones from senescent mother phenotypes in pro-oxidant treated GC-1 spg and B/CMBA.Ov cells by selective abrogation of mitochondrial oxidative stress-induced aberrant epigenetic modifications. In vivo studies using a diethylnitrosamine and 2- acetylaminofluorene mouse model demonstrated that NP.SB has a significant inhibitory effect on tumor growth which clearly substantiated our in vitro findings.

Conclusion: Anti-carcinogenic property in conjunction with low toxicity of NP.SB, underscores the translational significance of dietary flavonoids as cancer-protective agents for preferential application in clinical settings.

http://bit.ly/2SwKuzW

The Cellular Uptake and Apoptotic Efficiency of Colchicine is Correlated with Downregulation of MMP-9 mRNA Expression in SW480 Colon Cancer Cells

Background: Colchicine, a tricyclic alkaloid, is commonly used in treatment due to its antiinflammatory and anti-fibrotic effects. Besides its toxicity at high doses, colchicine is reported for its potential anticancer effects at lower concentrations. The present study aimed to evaluate the anticancer effects of colchicine in SW480 cells.

Methods: The effect of colchicine on cell proliferation was determined by MTT assay. The cellular colchicine uptake was measured by HPLC analysis. The apoptotic effects was evaluated by annexin v binding assay and MMP-9 mRNA expression was determined by RT-PCR experiments.

Results: Colchicine showed significant cytotoxicity at 10 ng/ml and higher concentrations and caused a cell cycle arrest of SW480 cells at G2/M phase. The results of HPLC analysis showed that colchicine uptake was increased in correlation with treated concentrations. Colchicine concentrations have increased the amount of apoptotic cell population. The elisa and western blot measurements showed that colchicine led to nuclear translocation of NF-κB proteins and increased caspase levels. The real time PCR experiments showed that colchicine has inhibitory effect on MMP-9 mRNA expression in a concentration dependent manner.

Conclusion: These results illustrated that low dose colchicine efficiently induced cell death and apoptosis of SW480 cells and the inhibition of MMP-9 mRNA levels was significantly correlated with the amount of cellular colchicine uptake, suggesting that colchicine has a potential value in the treatment of human colorectal cancer.

http://bit.ly/2DGHbvt

Retraction: Festuccia, C., Gravina, G. L., Angelucci, A., Millimaggi, D., Muzi, P., Vicentini, C. and Bologna, M. (2005), Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro. Int. J. Cancer, 115: 630–640. http://bit.ly/2DByr9Z.

The above article, published online on 7 February 2005, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor‐in‐Chief, Prof. Peter Lichter, the Union for International Cancer Control and John Wiley & Sons, Ltd. The retraction has been agreed due to reuse of several figure panels in the paper. Due to the time elapsed since the publication of the article, the original data for these figures are no longer available for re‐analysis. The authors are therefore not able to confirm the accuracy of the reported results or provide updated figures to replace the duplicated panels.

Reference

International Journal of Cancer

Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro

Volume 115, Issue 4, 1 July 2005, Pages: 630–640, Claudio Festuccia, Giovanni Luca Gravina, Adriano Angelucci, Danilo Millimaggi, Paola Muzi, Carlo Vicentini and Mauro Bologna

Version of Record online : 7 FEB 2005, DOI: https://doi.org/10.1002/ijc.2091710.1002/ijc.20917

http://bit.ly/2Svr6mE

SUcceSS, SUrgery for Spinal Stenosis: protocol of a randomised, placebo-controlled trial

Introduction

Central lumbar spinal stenosis (LSS) is a common cause of pain, reduced function and quality of life in older adults. Current management of LSS includes surgery to decompress the spinal canal and alleviate symptoms. However, evidence supporting surgical decompression derives from unblinded randomised trials with high cross-over rates or cohort studies showing modest benefits. This protocol describes the design of the SUrgery for Spinal Stenosis (SUcceSS) trial —the first randomised placebo-controlled trial of decompressive surgery for symptomatic LSS.

Methods and analysis

SUcceSS will be a prospectively registered, randomised placebo-controlled trial of decompressive spinal surgery. 160 eligible participants (80 participants/group) with symptomatic LSS will be randomised to either surgical spinal decompression or placebo surgical intervention. The placebo surgical intervention is identical to surgical decompression in all other ways with the exception of the removal of any bone or ligament. All participants and assessors will be blinded to treatment allocation. Outcomes will be assessed at baseline and at 3, 6, 12 and 24 months. The coprimary outcomes will be function measured with the Oswestry Disability Index and the proportion of participants who have meaningfully improved their walking capacity at 3 months postrandomisation. Secondary outcomes include back pain intensity, lower limb pain intensity, disability, quality of life, anxiety and depression, neurogenic claudication score, perceived recovery, treatment satisfaction, adverse events, reoperation rate and rehospitalisation rate. Those who decline to be randomised will be invited to participate in a parallel observational cohort. Data analysis will be blinded and by intention to treat. A trial-based cost-effectiveness analysis will determine the potential incremental cost per quality-adjusted life year gained.

Ethics and dissemination

Ethics approval has been granted by the NSW Health (reference:17/247/POWH/601) and the Monash University (reference: 12371) Human Research Ethics Committees. Dissemination of results will be via journal articles and presentations at national and international conferences.

Trial registration number

ACTRN12617000884303; Pre-results.

http://bit.ly/2BAeksx

Identifying priorities for cancer caregiver interventions: protocol for a three-round modified Delphi study

Introduction

Cancer is often considered a chronic disease, and most people with cancer have a caregiver, often a family member or friend who provides a significant amount of care during the illness trajectory. Caregivers are frequently in need of support, and a range of interventions have been trialled to improve outcomes. Consensus for optimal ways to support caregivers is not known. The aim of this protocol paper is to describe procedures for a modified Delphi study to explore expert consensus about important factors when developing caregiver interventions.

Methods and analysis

Online modified Delphi methodology will be used to establish consensus for important caregiver intervention factors incorporating the Patient problem, Intervention, Comparison and Outcome framework. Round 1 will comprise a free-text questionnaire and invite the panel to contribute factors they deem important in the development and evaluation of caregiver interventions. Round 2 is designed to determine preliminary consensus of the importance of factors generated in round 1. The panel will be asked to rate each factor using a 4-point Likert-type scale. The option for panellists to state reasoning for their rating will be provided. Descriptive statistics (median scores and IQR) will be calculated to determine each item's relative importance. Levels of consensus will be assessed based on a predefined consensus rating matrix. In round 3, factors will be recirculated including aggregate group responses (statistics and comment summaries) and panellists' own round 2 scores. Panellists will be invited to reconsider their judgements and resubmit ratings using the same rating system as in round 2. This will result in priority lists based on the panel's total rating scores.

Ethics and dissemination

Ethics for this study has been gained from the Deakin University Human Ethics Advisory Group. It is anticipated that the results will be published in peer-reviewed journals and presented in a variety of forums.

http://bit.ly/2BAefVL

Comparison of the contributions of female and male authors to medical research in 2000 and 2015: a cross-sectional study

Objectives

The proportion of women engaged in clinical research has increased over time. However, it is unclear if women and men contribute to the same extent during the conduct of research and, if so, if they are equally rewarded by a strategic first or last author position. We aim to describe the prevalence of women authors of original articles published 15 years apart and to compare the research contributions and author positions according to gender.

Design

Repeated cross-sectional study.

Setting

Published original articles.

Participants

1910 authors of 223 original articles published in the Annals of Internal Medicine in 2000 and 2015.

Primary and secondary outcomes measures

Self-reported contributions to 10 aspects of the article (primary) and author position on the byline.

Results

The proportion of women authors increased from 32% (n=243) to 41% (n=469) between 2000 and 2015 (p<0.0001). In 2000, women authors were less frequently involved than men in the conception and design (134 (55%) vs 323 (61%); p=0.0256), critical revision (171 (70%) vs 426 (81%); p=0.0009), final approval (196 (81%) vs 453 (86%); p=0.0381) and obtaining of funding (39 (16%) vs 114 (22%); p=0.0245). Women were more frequently involved than men in administration and logistics (85 (35%) vs 137 (26%); p=0.0188) and data collection (121 (50%) vs 242 (46%); p=0.0532), but they were similarly involved in the analysis and interpretation of data, drafting of the manuscript, provision of materials/patients and statistical expertise. Women were less often last authors than men (22 (9%) vs 82 (16%); p=0.0102). These gender differences persisted in 2015.

Conclusions

The representation of women among authors of medical articles increased notably between 2000 and 2015, but still remained below 50%. Women's roles differed from those of men with no change over time.

http://bit.ly/2TNEcbF

Fitz-Hugh-Curtis syndrome

http://bit.ly/2tmhfR9

Nitrous oxide myelopathy with functional vitamin B 12 deficiency

Recreational use of nitrous oxide as a 'legal high' is increasing in the UK. Physicians should be 'street wise' to this increasing prevalence and aware of the potential neurological complications which may result from misuse. We describe a 17-year-old male patient who presented to neurology with a severe myelopathy following prolonged recreational use of nitrous oxide. MRI demonstrated characteristic changes affecting the dorsal columns and blood tests demonstrated a 'functional' B₁₂ deficiency. Clinical and radiological improvement was noted following initiation of vitamin B₁₂ replacement.

http://bit.ly/2tlcrvm

Bilateral osteonecrosis of the hip in panhypopituitarism

Osteonecrosis, also known as avascular necrosis, is a condition that causes significant morbidity and loss of function. It is a common complication seen with supraphysiological steroid use. Early diagnosis is critical as it impacts prognosis. We report a 20-year-old man who developed bilateral osteonecrosis of the hip following 6 years of low-dose steroid replacement therapy for panhypopituitarism secondary to a transsphenoidal resection of a growth hormone-secreting pituitary macroadenoma. The patient presented with several weeks of right-sided hip pain and significant loss of function. X-ray and MRI showed bilateral osteonecrosis of the hips with the right side more severely affected than the left. He was initiated on analgesics and bisphosphonates and underwent right hip total arthroplasty followed 1 year later by left hip arthroplasty. Postsurgery, the patient is mobilising well and his pituitary hormones are well balanced. He continues on low-dose glucocorticoid replacement which will continue lifelong.

http://bit.ly/2GHalhg

Diffuse plane xanthoma developing in association with prior monoclonal gammopathy

http://bit.ly/2tlVxgn

Biceps tendon rupture associated with ciprofloxacin use for spontaneous bacterial peritonitis prophylaxis

http://bit.ly/2GHb95M

Unusual presentation of acute pancreatitis following high tibial osteotomy

We report a case of a 55-year-old man taxi driver admitted electively for high tibial osteotomy for relief of bilateral medial compartment osteoarthritis. He was obese and an ex-smoker but medical history was otherwise unremarkable. Day 1 postoperatively the patient started to suffer vomiting episodes and the abdomen was distended. C Reactive protein and white cell count were both elevated but other bloods were normal. CT abdomen and pelvis was performed which showed acute interstitial pancreatitis. Glasgow score was calculated as 2. He was treated aggressively with analgesia, intravenous fluid and intravenous antibiotics. He has made a good recovery following these conservative measures. To our knowledge, this is the first case in the literature reporting pancreatitis as a complication of high tibial osteotomy. This case highlights the importance of close monitoring for abdominal complications even in the setting of elective orthopaedic surgery where it is a rare phenomenon.

http://bit.ly/2GHb5my

Concealed diagnosis of duodenal perforation in a patient with emphysematous pyelonephritis: the dilemma of air in the right perirenal space

http://bit.ly/2to6m1s

Spontaneous cholecystocutaneous fistula: empirically treated for a missed diagnosis, managed by laparoscopy

A 70-year-old woman was referred to our hospital from primary health centre with complaints of pain in the abdomen, swelling and discharging sinus in the right hypochondrium since 2 years. She had received anti-tubercular treatment for 18 months as the wedge biopsy of the sinus tract suggested granulomatous lesion. As the symptoms did not subside she was referred to our hospital. Her blood investigation reports at our hospital were normal. Ultrasound of the abdomen suggested cholelithiasis with normal common bile duct. CT fistulogram findings were diagnostic of cholecystocutaneous fistula (CCCF). She underwent laparoscopic cholecystectomy and excision of the sinus tract. Postoperative recovery was uneventful. Indiscriminate usage of anti-tubercular drugs should be discouraged and possibility of CCCF should be considered in patients presenting with discharging sinus in the anterior abdominal wall. CT fistulogram is helpful in making diagnosis of CCCF. Cholecystectomy with excision of the sinus tract is the treatment of choice.

http://bit.ly/2GEhcYQ

Laparoscopic management of epidermoid cyst in an unusual location

The pararectal space or presacral space is a potential site for various cysts and tumours because it consists of many types of embryonic tissues. Although epidermoid cyst is a well-known entity, encountering a pararectal epidermoid cyst is relatively rare. The incidence of cystic tumours in the pararectal space has been reported to be 1 in 40 000 to 63 000 patients. Most of the tumours are asymptomatic and are incidentally discovered during routine imaging studies. Herein, we report a case of pararectal epidermoid cyst in a 51-year-old woman which was managed laparoscopically in a gastroenterology institute in South India.

http://bit.ly/2tmhdbZ

Dopamine agonist-responsive Cushings disease

A 47-year-old Caucasian man was referred to our clinic with a severe clinical and biochemical phenotype of endogenous hypercortisolism for further evaluation and treatment. In addition to confirming adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, we found left temporal hemianopsia, massively increased prolactin, increased growth hormone/insulin-like growth factor 1 values, hypogonadotropic hypogonadism and central hypothyroidism. As the cause of these abnormalities we revealed an invasive macroadenoma of the pituitary secreting ACTH, prolactin and growth hormone, resulting not only in a clinically predominant picture of Cushing's syndrome but also causing hypogonadotropic hypogonadism and central hypothyroidism. The patient responded surprisingly well to dopamine agonist treatment leading not only to normalisation of prolactin levels but also to clinical and biochemical remission of Cushing's syndrome. Tumour size decreased successively in follow-up MRI scans. Despite lacking immunohistochemical analysis of tumour tissue, we assume plurihormonal secretion of ACTH, prolactin and growth hormone from pituitary macroadenoma, which fortunately responded well to dopamine agonist treatment.

http://bit.ly/2GEh6jW

Spontaneous simultaneous bilateral patellar tendon rupture

Bilateral patellar tendon rupture is an extremely rare occurrence, especially in otherwise healthy individuals without systemic disease. The authors report the case of a man who presented with simultaneous, spontaneous bilateral rupture of his patellar tendons. He had a history of unilateral patellar tendinopathy but no other predisposing risk factors such as steroid or fluoroquinolone use. He underwent surgical repair and following intensive rehabilitation, he returned to baseline physical activity 6 months post injury.

http://bit.ly/2tlct6s

Atypical anaplastic astrocytoma with unique molecular features and diffuse leptomeningeal spread in a child with long-term survival

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%–12% of paediatric central nervous system tumours¹ and have poor prognosis, with 2-year survival less than 30%² and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Next generation cancer gene panel sequencing revealed an usual pattern of 12 amplifications and four mutations not previously described.

http://bit.ly/2GH9D3A

Allergic bronchopulmonary aspergillosis presumably unmasked by PD-1 inhibition

Programmed cell death-1 (PD-1) inhibitors stimulate immune recognition of tumour cells in cancer patients, but have significant autoimmune side effects including pneumonitis. We report the case of a patient with asthma and mild eosinophilia who developed unusual pulmonary side effect of bronchiectasis, severe eosinophilia (absolute eosinophil count: 3200 c/mm³) and elevated IgE levels (7050 IU/mL; normal: <164 IU/mL) 4 months into therapy with the PD-1 inhibitor pembrolizumab. Aspergillus fumigatus IgG was elevated at 15.60 U/mL (normal: <12.01 U/mL). He responded to therapy with corticosteroids and voriconazole and was able to resume pembrolizumab thereafter with good clinical response.

http://bit.ly/2tj3Auj

Morvans syndrome treated successfully with rituximab and lacosamide

We describe a woman with both central and peripheral nervous system symptoms consistent with Morvan's syndrome who was successfully treated with immunosuppression including rituximab and the new antiepileptic drug lacosamide against peripheral nerve hyperexcitability. Despite being over 8 months in hospital and 4 months in an intensive care unit she recovered fully. It is also the first case where cerebrospinal fluid neurofilament-light (NfL) levels were followed during the disease course. The clinical course resembled that of anti-NMDA receptor encephalitis, where patients often recover surprisingly well despite severe symptoms and an extensive time in intensive care. A possible explanation is the comparatively low levels of NfL, indicating disease processes that are not characterised by extensive neuroaxonal degeneration.

http://bit.ly/2GH9zkm

Spontaneous pneumomediastinum and subcutaneous emphysema in a child with unknown aetiology

Spontaneous subcutaneous emphysema and pneumomediastinum in children without any predisposing factors is a rare entity. We present a case of an adolescent boy with spontaneous pneumomediastinum. He is a 14-year-old boy brought to the hospital with an odd feeling in the neck and chest. Initial chest X-ray revealed subcutaneous emphysema and pneumomediastinum. He was further evaluated with CT thorax and abdomen with contrast which revealed extensive pneumomediastinum with associated surgical emphysema in the chest wall and neck. Expert opinions from the cardiothoracic and respiratory teams were obtained. The child was discharged with safety netting and description of red flag signs. Repeat chest X-ray in 2 weeks showed complete resolution of the pneumomediastinum and subcutaneous emphysema. We will briefly discuss about the diagnosis and treatment of spontaneous pneumomediastinum and subcutaneous emphysema.

http://bit.ly/2tkjLau

Visceral leishmaniasis with haemophagocytic lymphohistiocytosis

A 27-year-old man presented with high-grade intermittent fever for 4 months, generalised fatigue for 2 months, intermittent gum bleeds for 1 month and loss of weight of 15 kg. He appeared cachectic with generalised wasting, had pallor and features of reticuloendothelial system proliferation. His liver span was 17 cm. He had massive splenomegaly. His cardiovascular, respiratory and neurological examination were normal. He was diagnosed to have visceral leishmaniasis (VL) based on bone marrow (BM) examination that showed Leishmania donovani (LD) bodies and was treated with liposomal amphotericin (LA). During the course of therapy, he developed bleeding from various mucosal and venepuncture sites. His further evaluation, which included a repeat BM aspirate, showed haemophagocytes. Final diagnosis made was VL with secondary haemophagocytic lymphohistiocytosis. He was continued on LA with intravenous hydrocortisone. He developed refractory distributive shock with multiorgan dysfunction and succumbed to his illness.

http://bit.ly/2GH9vB8

Ergometrine-induced atrial fibrillation at caesarean section

A 36-year-old woman with a history of one previous caesarean section presented to the birthing suite of a regional hospital with spontaneous rupture of membranes at 39+2/40 weeks. Syntocinon was administered to initiate uterine contractions in the absence of labour, as the patient desired vaginal birth. A caesarean section was subsequently indicated and ergometrine was administered for uterine atony. The patient immediately developed atrial fibrillation (AF). AF is the most common sustained arrhythmia in the general population, but is rare in the obstetric population. AF occurring in an intrapartum setting following the administration of syntocinon and ergometrine, is not documented in the literature. We suggest the initiation of paroxysmal AF was precipitated by an abrupt alteration in autonomic tone caused by administration of syntocinon followed by ergometrine.

http://bit.ly/2ti39Aq

Texture and sensory characterization of functional yogurt supplemented with flaxseed during cold storage

Flaxseed was used as a functional ingredient in yogurt formulation. In this study, we found that the addition of 2.63% flaxseed into yogurt samples lead to produce functional food with satisfactory texture, sensory characteristics that sustained these properties until 17.17 days after cold storage

Abstract

In this study, flaxseed was used as a functional ingredient in yogurt formulations. The goal of this study was to produce prebiotic yogurt supplemented with flaxseed and investigation of its texture and sensory properties. Yogurt samples containing 0%–4% flaxseed was produced and stored at refrigerator (4–5°C) for 28 days. Textural properties were determined by texture analysis, and sensory characteristics were assessed by 26 trained panelists. Addition of flaxseed to yogurt samples increased the hardness, gumminess, chewiness, cohesiveness, and springiness values in produced yogurt samples. However, adhesiveness level was reduced in a sample enriched with flaxseed. By increasing flaxseed concentration, the color of samples was significantly different than the control sample; L* value was diminished and a* and b* value increased. Sensory scores including taste and mouthfeel, appearance, and overall acceptance showed reduction trend in samples containing a high level of flaxseed. In general, results showed that the addition of 2.63% flaxseed into yogurt samples lead to produce functional food with satisfactory texture, sensory characteristics that sustained these properties until 17.17 days after cold storage.

http://bit.ly/2I8UcU3

A Comprehensive Meta-Analysis of Association between EGFR Mutation Status and Brain Metastases in NSCLC

Abstract

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have different clinicopathological characteristics compared with EGFR wild type NSCLC. A growing number of studies focused on the relevance between EGFR mutation status and brain metastases (BM) in NSCLC, but it remains controversial. Therefore, this study performed a comprehensive meta-analysis to untangle this issue. Several electronic databases including Pubmed, Embase, Web of science and Cochrane database were thoroughly searched. The odds ratio (OR) with 95% confidence interval (95%CI) was pooled to evaluate the relevance. Meta-regression analysis and subgroup analysis were conducted according to the heterogeneity. A total of 26 studies were identified finally in this meta-analysis. The overall OR was 1.58 (95%CI: 1.36–1.84), which indicated that EGFR mutation had a positive association with BM of NSCLC. The subgroup analysis resulted from eleven studies with lung adenocarcinoma revealed a higher possibility of BM in NSCLC with EGFR mutation compared with EGFR wild (p < 0.05). There was no significant difference in the risk of BM between NSCLC EGFR exon 19 mutation and exon 21 point mutation (p = 0.23). This meta-analysis suggests that EGFR mutation can be a risk factor for BM in NSCLC.

http://bit.ly/2GpVjNO

FMO1 gene expression independently predicts favorable recurrence-free survival of classical papillary thyroid cancer

Future Oncology, Ahead of Print.


http://bit.ly/2DEKpzA

Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA

Future Oncology, Ahead of Print.


http://bit.ly/2SAhKGv

Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer

The androgen receptor (AR) has potential clinical relevance in metastatic breast cancer (mBC) since it might be a treatment target and has been associated with endocrine resistance. A minimal‐invasive way to determine AR expression on metastatic tumor cells is by characterization of circulating tumor cells (CTCs). Here, we assessed AR mRNA expression in CTCs (CTC‐AR) and in matched primary tumor samples from mBC patients representing different breast cancer subtypes. In addition, we explored CTC‐AR‐status in relation to outcome on endocrine therapy. AR, and 92 AR or estrogen receptor (ER) related genes, were measured in CellSearch‐enriched CTCs from 124 mBC patients and in 52 matched FFPE primary tissues using quantitative reverse‐transcriptase PCR. AR in CTCs was considered positive if the expression was 1 standard deviation higher than the expression measured in 11 healthy blood donors. A total of 31% of the mBC patients had AR‐positive (AR+) CTCs. 58% of the matched CTC and primary tissues samples were discordant with respect to AR status, observing both switches from AR+ to AR‐negative (AR‐) and vice versa. There was no statistically significant difference in progression‐free survival for patients treated with ER‐targeting drugs and CTC‐AR‐status (13 AR+ / 37 AR‐ cases, p=0.28). Thus, AR can be determined in RNA isolated from CTCs, with in our set 31% AR‐positive samples. Given the discordance between AR status in CTC samples and corresponding primary tumors, determination of AR expression in CTCs might be a promising tool to select mBC patients for AR inhibiting agents.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Svn2my

Trans-scrotal ultrasonography evaluation of the cross-bred Ongole bulls

Abstract

Very limited information is available on the trans-scrotal ultrasonography of cross-bred Ongole bulls with scrotal swelling in India. The present study was carried out on the bulls presented to the hospital with the history of scrotal swelling. Haematology revealed increased leucocyte count, neutrophilia and mild reduction in haemoglobin levels. Microscopic evaluation of the semen revealed abnormal morphology and the presence of the dead spermatozoa. Trans-scrotal ultrasonography helps in the differential diagnosis of scrotal disorders and to identify the appropriate aetiology for developement of the condition. On ultrasonography, all the bulls showed abnormal scrotal morphology. Among these, one had the presence of normal echogenicity testes which are surrounded by the anechoic fluid which will cover by a hyper echoic scrotal skin. The second one showed the anechoic fluid was mixed with the hyper echoic fibrinous threads and degenerative changes in one testis. Third bull showed the diffused hyper echoic threads scattered within the anechoic fluid and different echogenicity of the two testes. In conclusion, trans-scrotal ultrasonography is helpful in the differential diagnosis of the scrotal swells in large animals.

http://bit.ly/2SSCNDm

Editorial

http://bit.ly/2N3XruV

Adenosine deaminase behavior in experimental infection by Brucella ovis and its participation in the modulation of the inflammatory response

Abstract

The objective of this study was to evaluate the activity of adenosine deaminase (ADA) and its participation in the modulation of the inflammatory responses of mice experimentally infected with B. ovis. We used 48 animals, divided in two groups: group A (control) and group B (infected). We evaluated ADA activity and C-reactive protein (CRP) concentrations at four time points (days 7, 15, 30, and 60) post-infection (PI). There was a reduction in ADA activity in the acute phase (day 15 PI), followed by elevation when the infection became chronic (days 30 and 60 PI). Serum C-reactive protein levels were higher in infected animals than in the control group at all time points post-infection (P < 0.05). ADA regulates levels of extracellular adenosine, an anti-inflammatory molecule, suggesting that the enzyme had different behaviors depending on the stage of infection, i.e., ADA had anti-inflammatory action in the acute phase, but with the chronicity of the disease, the ADA had pro-inflammatory action. Therefore, we conclude that ADA participates in the pathogenesis of experimental ovine brucellosis.

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