Clinical Rheumatology

Correction to: Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in Behçet's disease: which and when to use? The authors wish to acknowledge that whilst this study and that published in Hammad et al [1] explore different areas – blood cell ratios and serum endocan, respectively – the reader may identify some similarities between the papers owing to the same patient cohort being analysed in both studies.

Correction to: Mortality in patients with systemic lupus erythematosus in Colombia: a case series The presentation of data on the Table 3 of the published version of the above mentioned article was incorrect. The heading "Bacterial infections" should be presented under the heading "Infections". The original article has been corrected.

Correction to: Piriformis pyomyositis, a cause of piriformis syndrome—a systematic search and review The First name of the co-author of the article mentioned above was incomplete. The author's complete name should have been "Md Abu Bakar Siddiq" instead of "Abu Bakar Siddiq". The original article has been corrected.

Letter to Editor: Serum interleukin-37 level and interleukin-37 gene polymorphism in patients with Behçet disease

Correction to: PANLAR consensus statement on biosimilars The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".

Reversible alopecia areata: a little known side effect of leflunomide Abstract Leflunomide is a disease-modifying anti-rheumatic drug (DMARD) used in the management of rheumatoid arthritis (RA) and psoriatic arthritis. Commonly reported adverse effects include diarrhea, nausea, hepatotoxicity, hypertension, and transient global hair loss; however, additional side effects may be associated with the medication not reported in the monograph. We describe a rare case of reversible alopecia areata (AA) associated with the use of leflunomide and provide a literature review of three published similar cases. We use the Naranjo adverse drug reaction score to show the AA in our case is a "probable" side effect of leflunomide. Currently, AA is not listed as an adverse effect in the leflunomide product monograph. However, it would appear that based on our case and the three other reported cases, the likelihood of AA being an adverse effect of leflunomide is at least possible to probable.

Prevalence of frailty and its associated factors in patients with rheumatoid arthritis: a cross-sectional analysis Abstract Objectives The aims of the present research were to assess the prevalence of frailty and its potential associated factors in a cohort of adult patients with rheumatoid arthritis (RA). Methods Consecutive RA patients and healthy controls were assessed according to the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI), and classified as frail, pre-frail, or non-frail. Chi-square, analysis of variance (ANOVA), and multinomial logistic regression analyses were used to test the prognostic value of frailty for the outcomes of interest. Results Two hundred and ten consecutive RA patients (65.7% female, mean age 60.4 years) and 100 healthy controls (63% female, mean age 59.1 years) were included. According to SHARE-FI criteria, 35 RA patients (16.6%) were categorized as frail, 68 (32.4%) as pre-frail, and 107 (51%) as non-frail, while 8 control subjects were categorized as frail, (8%), 17 as pre-frail (17%), and 75 as non-frail (75%) (chi-squared 12.8; P = 0.0016). The results from logistic regression analysis revealed that age (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.07–1.17; P < 0.0001), comorbidities (OR = 1.51, 95% CI = 1.01–2.27; P = 0.0446), and high disease activity (OR = 1.10, 95% CI = 1.04–1.16; P = 0.0006) were independently associated with frailty in RA. Conclusions Frailty or pre-frailty are common in RA. The SHARE-FI may be a useful tool for the screening of frailty in RA and may summarize the results of a comprehensive RA assessment providing a marker of deficits accumulation.

Detection of Familial Mediterranean Fever attacks by using a connected activity tracker and assessment of impact of attacks to daily physical activities: a pilot study Abstract Objective The objective of this study was to assess the impact of Familial Mediterranean Fever (FMF) attacks on daily physical activity and detect FMF attacks using a connected activity tracker. Methods Patients with FMF according to the Tel-Hashomer criteria were included in this prospective observational study. Attack-related data were collected weekly via phone call to avoid memory bias. Median steps in attack and attack-free days were calculated and compared using the Wilcoxon rank test. Sensitivity and specificity threshold for capturing attacks was set to two thirds of median steps per day in the whole observation period. Results Twelve patients participated in the study. The median age of patients was 26 (18–32) years, and 7 (58.3%) of them were male. Patients with attacks (n = 10) walked a median of 6990 (4552–11,531) steps per day in attack-free days, whereas this number decreased to a median of 1841 (590–4783) steps in attack days (p = 0.005). The activity tracker captured 42 of 45 attack days and 312 of 361 attack-free days. The cutoff value had 93% sensitivity and 86% specificity for capturing attacks. Conclusions FMF attacks significantly impair the physical activity of patients. Activity tracking may be a reasonable method to document FMF attacks. This might prevent errors due to memory bias and help accurately identify and treat patients with FMF.

Elevated circulating T cell subsets and cytokines expression in patients with rheumatoid arthritis Abstract Objective This study aimed to assess the role of different subsets of circulating follicular helper T cells (Tfh), central memory (TCM), effector memory (TEM), Naïve T, chemokines, and cytokines in the pathogenesis of rheumatoid arthritis (RA). Methods Blood samples from RA patients (n = 44) and healthy controls (n = 37) were analyzed. The frequencies of circulating Tfh, TCM, TEM, and Naïve T cell subsets were enumerated, and the expression of co-stimulatory molecules, such as inducible co-stimulator (ICOS) and programmed death-1 (PD1), on these cells was evaluated by flow cytometry. The disease state in RA patients was assessed using the DAS28. Concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were measured. Cytokines and chemokines, such as IL-1β, TNF-α, IL-4, IL-6, IL-9, IL-17A, MCP-1, IL-10, IL-12p70, and IL-21, were measured by a cytometric beads array assay. Results The percentages of circulating PD1+ICOS+ Tfh, PD1+ICOS+ TEM, and PD1+ICOS+ TCM of PBMCs from RA patients were higher than those in healthy controls. Furthermore, expression of circulating PD1+ICOS+ Tfh, PD1+ICOS+ TEM, and PD1+ICOS+ TCM showed a positive correlation with DAS28. In addition, increased levels of IL-1β, IL-6, and MCP-1 were detected in the patients with RA compared to healthy controls. Conclusions Elevated circulating T cell subsets and cytokines expression profile were observed in RA patients. IL-6, MCP-1, and IL-1β were significantly increased in RA, and PD1+ICOS+ TEM, PD1+ICOS+ TCM, and PD1+ICOS+ Tfh cell subsets were positively correlated with disease activity DAS28. Therefore, PD1+ICOS+ TEM, PD1+ICOS+ TCM, and PD1+ICOS+ Tfh cells might serve an important role in the progression of RA.

MEFV gene mutations in children with Henoch–Schönlein purpura and their correlations—do mutations matter? Abstract Objective To explore the frequency of MEFV gene mutations in children with Henoch–Schönlein purpura who had no prior familial Mediterranean fever diagnosis and to evaluate the association of MEFV mutations with the clinical and laboratory features of Henoch–Schönlein purpura. Methods Data of 1120 patients diagnosed with Henoch–Schönlein purpura were reviewed retrospectively. The spectrum and degree of organ involvement and acute phase reactant levels were documented for each patient. Blood for MEFV gene mutation analysis was obtained either at the time of the Henoch–Schönlein purpura diagnosis or during follow-up visits. Pathological specimens of patients who underwent biopsy (renal/skin) were evaluated with special consideration for immunofluorescent examinations. Results Two hundred and thirty-eight (21.3%) patients were found to have one of the MEFV mutations in which exon 10 mutations were the most common (16.7%). Abdominal pain, joint involvement, scrotal involvement, and relapse were more frequent, and acute-phase reactant levels were significantly high in patients with MEFV mutations. More severe characteristics were observed in the presence of homozygous exon 10 mutations. There was no significant association between exon 2 variants and clinical course of Henoch–Schönlein purpura. Patients carrying MEFV mutations did not have significantly higher levels of IgA deposits in the biopsy materials. Conclusion Henoch–Schönlein purpura in patients with homozygous exon 10 MEFV mutations seems to be more severe than that in patients carrying other mutations. In patients with exon 10 MEFV mutations, Henoch–Schönlein purpura might be considered as an associated presentation of familial Mediterranean fever rather than a separate clinical entity. Key points • p.M694V mutation is more common in Henoch–Schönlein purpura than in the general population. • p.E148Q variants have no impact on clinical symptoms and laboratory findings in Henoch–Schönlein purpura patients. • The majority of Henoch–Schönlein purpura patients with familial Mediterranean fever have no IgA deposits. • Henoch–Schönlein purpura in familial Mediterranean fever patients may be considered as an integral clinical feature of familial Mediterranean fever.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Cancer Research and Clinical Oncology

Stuttering as the first sign of CAR-T-cell-related encephalopathy syndrome (CRES)

Combined loss of TFF3 and PTEN is associated with lethal outcome and overall survival in men with prostate cancer Abstract Background Trefoil Factor 3 (TFF3) has been implicated in Prostate Cancer (PCa) progression. However, its prognostic value and association with other biomarkers have not been fully explored. We assessed the combined value of TFF3 and PTEN in two cohorts: one is managed surgically for localized PCa and the second is managed non-surgically by androgen deprivation therapy for advanced disease. Design 228 radical prostatectomies (RP) and 318 transurethral resection of prostate (TURP) samples were assessed by immunohistochemistry (IHC) for TFF3 and by IHC and fluorescent in situ hybridization (FISH) for PTEN. Results of biomarkers expression were correlated with various pathological and clinical outcome parameters including biochemical recurrence (BCR) in the RP cohort and cancer-specific mortality (PCSM) and overall survival (OS) in the TURP cohort. Results TFF3 expression was detected in 131/226 (57.9%) RP samples and 148/318 (46.5%) of TURP cases. In general, TFF3 positivity was less frequently observed with advanced Gleason Groups. TFF3 expression was also assessed in relation to PTEN expression. Only 15–16% of TFF3-expressed cases were present in association with complete loss of PTEN expression in the TURP and localized cohorts, respectively. Loss of TFF3 expression was not related to BCR after RP, but was prognostic in the non-surgical cohort and associated with decrease OS and PCSM (HR 2.31, CI: 1.67–3.18, p < 0.0001) and (HR 3.99, CI: 2.43–6.56; p < 0.0001), respectively. Adjusting for Gleason score, combined loss of TFF3/PTEN was most associated with OS (HR 2.33, CI: 1.49–3.62; p < 0.0001) and PCSM (HR = 3.44, CI: 1.75–6.78, p < 0.0001). Conclusion The study documents for the first time significant association for combined status of TFF3 expression and PTEN loss in OS and PCSM in patients not managed by surgical intervention. Prospective assessment of PTEN and TFF3 may provide further insight into molecularly subtyping PCa and aid in stratifying patients at risk for lethal disease.

Patient-reported outcomes and health-related quality of life for cetuximab versus bevacizumab in metastatic colorectal cancer: a prospective cohort study Abstract Purpose Uncertainty exists regarding Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) of patients with metastatic colorectal cancer (mCRC) treated with cetuximab or bevacizumab. We conducted a prospective cohort study comparing PROs and HRQoL from both therapies. Methods We assessed PROs and HRQoL from patients treated with cetuximab or bevacizumab using QLQ-C30 and QLQ-CR29 questionnaires at three sequential time points, including baseline. Global Health Status (GHS), functional and symptom scales, and Overall Treatment Utility (derived from clinical and patient-reported outcomes) were compared for the two treatment strategies. Results Between January 2017 and April 2018, 44 patients were allocated to cetuximab (n = 19) or bevacizumab (n = 25). Except for RAS mutation status, patient baseline characteristics were generally well balanced across treatment groups. A higher proportion of patients experienced a deterioration in GHS (≥ 10%) in cetuximab arm − 53.8% (95% CI 25.1–80.8%) at 6 weeks and 66.7% (95% CI 29.9–92.5%) at 12 weeks—comparing to bevacizumab cohort: 18.2% (95% CI 5.2–40.3%) at 6 weeks and 12.5% (95% CI:1.6–38.3%) at 12 weeks. Treatment utility rates at 6 and 12 weeks were, respectively, 88.6% and 69.8% for bevacizumab, compared to 49% and 19.1% for cetuximab (p = 0.004), a difference confirmed in subset analyses. Conclusions In patients with mCRC, cetuximab-containing regimens led to a progressive negative impact on PROs and global HRQoL, when compared to baseline and bevacizumab. Future research is needed to confirm these results. Our findings demonstrate the value of PROs when assessing comparative effectiveness of different treatment regimens.

HALFMOON TomoTherapy (Helical ALtered Fractionation for iMplant partial OmissiON): implant-sparing post-mastectomy radiotherapy reshaping the clinical target volume in the reconstructed breast Abstract Purpose To report the dosimetric feasibility of the radiation technique HALFMOON (Helical ALtered Fractionation for iMplant partial OmissiON) for post-mastectomy radiation therapy (PMRT) in intermediate–high-risk breast cancer patients with implant-based immediate breast reconstruction, where the clinical target volume (CTV) does not include the whole implant (implant-sparing approach). Methods In the HALFMOON technique, the CTV consisted of skin, subcutaneous tissues, and pectoralis major muscle, excluding the implant, chest wall muscles, and rib plane. The HALFMOON plans were compared with conventionally contoured CTV plans, in which the whole implant, chest wall muscles, and ribs plane were included in the CTV, in a ratio 1:3. All patients underwent hypofractionated treatment of 40.05 Gy/15 fractions, using helical Tomotherapy®. Results Eighteen patients undergoing HALFMOON technique were compared to 54 subjects treated with conventionally contoured CTV plans. No difference was found in the planning target volume coverage between the two groups. Conversely, a statistically relevant dose reduction in HALFMOON patients was observed for ipsilateral lung (D15%, p < 0.0001; D20%, p < 0.0001; D35%, p = 0.003), contralateral lung (D20%, p = 0.048), contralateral breast (D15%, p = 0.031; D20%, p = 0.047), and stomach (Dmean, p = 0.011). Regarding the implant, V90% and D50% decreased by 46% and 8%, respectively, in the HALFMOON plans (p < 0.0001). Conclusion The HALFMOON approach is technically feasible and resulted in high-dose conformity of the target with a significant reduction of radiation dose delivered to implant and other organs. A clinical study is needed to assess the impact on reconstruction cosmetic outcome and local control.

Modulation of phospho-proteins by interferon-alpha and valproic acid in acute myeloid leukemia Abstract Purpose Valproic acid (VPA) is suggested to be therapeutically beneficial in combination with interferon-alpha (IFNα) in various cancers. Therefore, we examined IFNα and VPA alone and in combinations in selected AML models, examining immune regulators and intracellular signaling mechanisms involved in phospho-proteomics. Methods The anti-leukemic effects of IFNα and VPA were examined in vitro and in vivo. We mapped the in vitro phosphoprotein modulation by IFNα-2b and human IFNα-Le in MOLM-13 cells by IMAC/2D DIGE/MS analysis and phospho-flow cytometry, and in primary healthy and AML patient-derived PBMCs by CyTOF. In vivo, IFNα-Le and VPA efficacy were investigated in the immunodeficient NOD/Scid IL2γ−/− MOLM-13Luc+ mouse model and the syngeneic immunocompetent BNML rat model. Results IFNα-2b and IFNα-Le differed in the modulation of phospho-proteins involved in protein folding, cell stress, cell death and p-STAT6 Y641, whereas VPA and IFNα-Le shared signaling pathways involving phosphorylation of Akt (T308), ERK1/2 (T202/T204), p38 (T180/Y182), and p53 (S15). Both IFNα compounds induced apoptosis synergistically with VPA in vitro. However, in vivo, VPA monotherapy increased survival, but no benefit was observed by IFNα-Le treatment. CyTOF analysis of primary human PBMCs indicated that lack of immune-cell activation could be a reason for the absence of response to IFNα in the animal models investigated. Conclusions IFNα-2b and IFNα-Le showed potent and synergistic anti-leukemic effects with VPA in vitro but not in leukemic mouse and rat models in vivo. The absence of IFNα immune activation in lymphocyte subsets may potentially explain the limited in vivo anti-leukemic effect of IFNα-monotherapy in AML.

Assessment of tumor-associated immune cells in laryngeal squamous cell carcinoma Abstract Purpose This study investigated the characteristics of tumor-associated immune cells (TAICs) in laryngeal squamous cell carcinoma (LSCC) and their correlation with clinicopathological variables. Methods The immune cell infiltrates of 71 specimens of stages I–IV LSCC were examined. The density of TAICs expressing CD3, CD4, CD8, CD68, and CD163 was assessed using immunohistochemical staining and image analysis in peritumoral and intratumoral regions. Results Higher densities of CD3+ and CD8+ cell and lower densities of CD68+ and CD163+ cell infiltrations were found in early tumor stages than in late tumor stages. A higher percentage of patients with strong CD3+ and CD8+ immune cell infiltration and weak CD68+ cell infiltration in both tumor regions presented with T1 stage tumors compared with T4 stage tumors. Further, strong CD68+ cells infiltration in both regions was observed in a greater number of patients who had a relapse, while a weak CD3+ cells infiltration in both regions was found in a greater number of patients with nodal lymphatic metastasis. The univariate analysis showed that a high density of peritumoral CD3+ and CD8+ immune cells in both regions was significantly associated with a favorable overall survival (OS) (P = 0.004; P = 0.006; P = 0.042). In contrast, a high density of intratumoral CD68+ cells and peritumoral CD163+ cells was significantly associated with poor OS durations (P = 0.026; P = 0.030). The multivariate analysis demonstrated that a high density of peritumoral CD163+ cells correlated with poor OS after adjusting for tumor stage, recurrence, and nodal lymphatic metastasis (P = 0.034). This study found different patterns of TAIC infiltration in LSCC. The density and location of TAICs infiltration correlated with the clinicopathological characteristics of LSCC. Conclusion A combined analysis of the density of TAICs and their location may help predict patient survival and response to checkpoint inhibitors.

Safety and efficacy of 125 I brachytherapy for bilateral lung recurrences from hepatocellular carcinoma after resection or ablation Abstract Purpose To evaluate the safety and efficacy of 125I brachytherapy to treat bilateral lung recurrences from hepatocellular carcinoma (HCC) after resection or ablation. Materials and methods We retrospectively recruited 95 patients with bilateral lung recurrences from hepatocellular carcinoma (HCC) after resection or ablation who had received 3–6-month sorafenib with or without stereotactic body radiotherapy (SBRT), from October 2011 to January 2015; patients were then randomly divided into two groups, 44 patients received computed tomography (CT)-guided 125I brachytherapy (group A), and 51 patients were treated with supportive and symptomatic treatments (group B). Results The median survival time was 19 months (range of 3–36 months). The local response rate (LRR) at 3, 6, 12, 18, 24, 30 and 36 months in group A was 81.8%, 65.9%, 59.1%, 45.0%, 38.6%, 22.7%, 11.4%, respectively, and 64.7%, 47.1%, 33.3%, 25.4%, 15.7%, 11.7%, 7.8%, respectively, in group B (P < 0.05). The mean progression-free survival time (PFST) and overall survival (OS) of group A were significantly longer than those of group B. Alpha fetoprotein (AFP) and tumor size were independent factors that affected the PFST and OS, normal AFP levels and less than 1-cm tumor diameter had better PFST and OS (P < 0.05). No massive bleeding or serious complications occurred. Conclusion CT-guided 125I brachytherapy is safe and effective for the treatment of bilateral lung recurrences from HCC after resection or ablation.

Information needs, communication and usage of social media by cancer patients and their relatives Abstract Purpose The aim of this study was to evaluate cancer patients' need for information, their communication and usage of social media. Methods We developed a standardized questionnaire comprising sections on information needs, communication behavior and usage of social media with respect to cancer and combined this with a validated instrument on eHealth literacy for patients. This questionnaire was provided online and with the help of bloggers and leaders of social media groups, distributed in their networks. Results The Internet was the most important information source (n = 308; 77.4%). Yet, most of the participants wanted to get information from their doctor (n = 342; 85.9%). With respect to trust in a source of information, oncologists were named most often (n = 285; 71.6%). On the one hand, many participants got in contact with others, especially peers, via social media (n = 319; 80.3%) with a growing bond to their family members on the other hand (n = 324; 81.6%). The cancer diagnosis was an impulse for starting with active participation in social media for some participants (n = 196; 49.2%). Conclusions With social media gaining importance as source of information for patients, improving the quality of information in these networks is an important task in health care systems.

Neutrophil extracellular traps enhance procoagulant activity in patients with oral squamous cell carcinoma Abstract Background Hypercoagulability is a major cancer-associated complication linked to poor patient prognosis. The production of neutrophil extracellular traps (NETs) is increasingly found to be linked with the development and metastasis of cancer, as well as with thrombi formation in cancer patients. We hypothesized that the neutrophil NET release may be triggered by specific cytokines in oral squamous cell carcinoma (OSCC) patients, thereby predisposing them to a hypercoagulable state. Moreover, we have evaluated the interaction between NETs and endothelial cells (ECs). Methods NET procoagulant activity was assessed based on fibrin and purified coagulation complex production assays, as well as by measuring coagulation time (CT). We further used confocal microscopy to quantify the exposure of phosphatidylserine (PS), fibrin strands, and cell FVa/Xa binding. Results OSCC patients with stage III/IV exhibited elevated plasma NET levels compared to stage I/II or CTR (all P < 0.05). Neutrophils from OSCC patients are predisposed to amplified NET release compared to those from CTR. Furthermore, depleting IL-8, IL-6, and TNF-α led to a reduction in NET release in the plasma. OSCC NETs increased thrombin and fibrin generation and decreased CT significantly (P < 0.05). When NETs were isolated and used to treat ECs, these cells exhibited disrupted morphology by retracting from their cell–cell junctions and convert to a procoagulant phenotype. These effects could be attenuated by approximately 70% using DNase I. Conclusions Our findings are consistent with a model wherein OSCC drives a systemic inflammatory state, which, in turn, drives neutrophils to prime and release NETs, which drive the development of a hypercoagulable state. Intervening in this process may be a viable means of disrupting these undesirable coagulation dynamics in stage III/IV OSCC patients.

Accuracy of Raman spectroscopy in discrimination of nasopharyngeal carcinoma from normal samples: a systematic review and meta-analysis Abstract Objectives The aim of this review was to systematically evaluate the diagnostic accuracy of Raman spectroscopy (RS) in the identification of nasopharyngeal carcinomas from normal nasopharyngeal tissue. Methods We searched six databases (PubMed, Embase, Cochrane Library, Web of Science, Scopus and CNKI) up to September 2018 for all published studies that assessed the diagnostic accuracy of RS in the detection of nasopharyngeal carcinomas. Non-qualifying studies were screened out in accordance with the specified exclusion criteria and relevant information about the diagnostic performance of RS extracted. A random effects model was adopted to calculate the pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic threshold and diagnostic odds ratio (DOR). Additionally, we conducted a summary receiver-operating characteristic (SROC) curve analysis and threshold analysis, reporting area under the curve (AUC) to evaluate the overall performance of RS. Results Three studies examined RS analysis in vivo, the pooled sensitivity and specificity of RS of which were 0.90 and 0.91, respectively, with an AUC of 0.9617. Eighteen studies assessed ex vivo samples, for which RS exhibited particularly high accuracy for the analysis of blood plasma. Conclusions RS was demonstrated to be a reliable technique for the detection of nasopharyngeal carcinoma with high accuracy, but additional studies are required to improve its performance and expand its application in ex vivo detection.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Computational Neuroscience

Slow-gamma frequencies are optimally guarded against effects of neurodegenerative diseases and traumatic brain injuries Abstract We introduce a computational model for the cellular level effects of firing rate filtering due to the major forms of neuronal injury, including demyelination and axonal swellings. Based upon experimental and computational observations, we posit simple phenomenological input/output rules describing spike train distortions and demonstrate that slow-gamma frequencies in the 38–41 Hz range emerge as the most robust to injury. Our signal-processing model allows us to derive firing rate filters at the cellular level for impaired neural activity with minimal assumptions. Specifically, we model eight experimentally observed spike train transformations by discrete-time filters, including those associated with increasing refractoriness and intermittent blockage. Continuous counterparts for the filters are also obtained by approximating neuronal firing rates from spike trains convolved with causal and Gaussian kernels. The proposed signal processing framework, which is robust to model parameter calibration, is an abstraction of the major cellular-level pathologies associated with neurodegenerative diseases and traumatic brain injuries that affect spike train propagation and impair neuronal network functionality. Our filters are well aligned with the spectrum of dynamic memory fields including working memory, visual consciousness, and other higher cognitive functions that operate in a frequency band that is - at a single cell level - optimally guarded against common types of pathological effects. In contrast, higher-frequency neural encoding, such as is observed with short-term memory, are susceptible to neurodegeneration and injury.

Spatiotemporal discrimination in attractor networks with short-term synaptic plasticity Abstract We demonstrate that a randomly connected attractor network with dynamic synapses can discriminate between similar sequences containing multiple stimuli suggesting such networks provide a general basis for neural computations in the brain. The network contains units representing assemblies of pools of neurons, with preferentially strong recurrent excitatory connections rendering each unit bi-stable. Weak interactions between units leads to a multiplicity of attractor states, within which information can persist beyond stimulus offset. When a new stimulus arrives, the prior state of the network impacts the encoding of the incoming information, with short-term synaptic depression ensuring an itinerancy between sets of active units. We assess the ability of such a network to encode the identity of sequences of stimuli, so as to provide a template for sequence recall, or decisions based on accumulation of evidence. Across a range of parameters, such networks produce the primacy (better final encoding of the earliest stimuli) and recency (better final encoding of the latest stimuli) observed in human recall data and can retain the information needed to make a binary choice based on total number of presentations of a specific stimulus. Similarities and differences in the final states of the network produced by different sequences lead to predictions of specific errors that could arise when an animal or human subject generalizes from training data, when the training data comprises a subset of the entire stimulus repertoire. We suggest that such networks can provide the general purpose computational engines needed for us to solve many cognitive tasks.

Neural network model of an amphibian ventilatory central pattern generator Abstract The neuronal multiunit model presented here is a formal model of the central pattern generator (CPG) of the amphibian ventilatory neural network, inspired by experimental data from Pelophylax ridibundus. The kernel of the CPG consists of three pacemakers and two follower neurons (buccal and lung respectively). This kernel is connected to a chain of excitatory and inhibitory neurons organized in loops. Simulations are performed with Izhikevich-type neurons. When driven by the buccal follower, the excitatory neurons transmit and reorganize the follower activity pattern along the chain, and when driven by the lung follower, the excitatory and inhibitory neurons of the chain fire in synchrony. The additive effects of synaptic inputs from the pacemakers on the buccal follower account for (1) the low frequency buccal rhythm, (2) the intra-burst high frequency oscillations, and (3) the episodic lung activity. Chemosensitivity to acidosis is implemented by an increase in the firing frequency of one of the pacemakers. This frequency increase leads to both a decrease in the buccal burst frequency and an increase in the lung episode frequency. The rhythmogenic properties of the model are robust against synaptic noise and pacemaker jitter. To validate the rhythm and pattern genesis of this formal CPG, neurograms were built from simulated motoneuron activity, and compared with experimental neurograms. The basic principles of our model account for several experimental observations, and we suggest that these principles may be generic for amphibian ventilation.

Short term memory properties of sensory neural architectures Abstract A functional role of the cerebral cortex is to form and hold representations of the sensory world for behavioral purposes. This is achieved by a sheet of neurons, organized in modules called cortical columns, that receives inputs in a peculiar manner, with only a few neurons driven by sensory inputs through thalamic projections, and a vast majority of neurons receiving mainly cortical inputs. How should cortical modules be organized, with respect to sensory inputs, in order for the cortex to efficiently hold sensory representations in memory? To address this question we investigate the memory performance of trees of recurrent networks (TRN) that are composed of recurrent networks, modeling cortical columns, connected with each others through a tree-shaped feed-forward backbone of connections, with sensory stimuli injected at the root of the tree. On these sensory architectures two types of short-term memory (STM) mechanisms can be implemented, STM via transient dynamics on the feed-forward tree, and STM via reverberating activity on the recurrent connectivity inside modules. We derive equations describing the dynamics of such networks, which allow us to thoroughly explore the space of possible architectures and quantify their memory performance. By varying the divergence ratio of the tree, we show that serial architectures, where sensory inputs are successively processed in different modules, are better suited to implement STM via transient dynamics, while parallel architectures, where sensory inputs are simultaneously processed by all modules, are better suited to implement STM via reverberating dynamics.

A computational model of large conductance voltage and calcium activated potassium channels: implications for calcium dynamics and electrophysiology in detrusor smooth muscle cells Abstract The large conductance voltage and calcium activated potassium (BK) channels play a crucial role in regulating the excitability of detrusor smooth muscle, which lines the wall of the urinary bladder. These channels have been widely characterized in terms of their molecular structure, pharmacology and electrophysiology. They control the repolarising and hyperpolarising phases of the action potential, thereby regulating the firing frequency and contraction profiles of the smooth muscle. Several groups have reported varied profiles of BK currents and I-V curves under similar experimental conditions. However, no single computational model has been able to reconcile these apparent discrepancies. In view of the channels' physiological importance, it is imperative to understand their mechanistic underpinnings so that a realistic model can be created. This paper presents a computational model of the BK channel, based on the Hodgkin-Huxley formalism, constructed by utilising three activation processes — membrane potential, calcium inflow from voltage-gated calcium channels on the membrane and calcium released from the ryanodine receptors present on the sarcoplasmic reticulum. In our model, we attribute the discrepant profiles to the underlying cytosolic calcium received by the channel during its activation. The model enables us to make heuristic predictions regarding the nature of the sub-membrane calcium dynamics underlying the BK channel's activation. We have employed the model to reproduce various physiological characteristics of the channel and found the simulated responses to be in accordance with the experimental findings. Additionally, we have used the model to investigate the role of this channel in electrophysiological signals, such as the action potential and spontaneous transient hyperpolarisations. Furthermore, the clinical effects of BK channel openers, mallotoxin and NS19504, were simulated for the detrusor smooth muscle cells. Our findings support the proposed application of these drugs for amelioration of the condition of overactive bladder. We thus propose a physiologically realistic BK channel model which can be integrated with other biophysical mechanisms such as ion channels, pumps and exchangers to further elucidate its micro-domain interaction with the intracellular calcium environment.

From receptive profiles to a metric model of V1 Abstract In this work we show how to construct connectivity kernels induced by the receptive profiles of simple cells of the primary visual cortex (V1). These kernels are directly defined by the shape of such profiles: this provides a metric model for the functional architecture of V1, whose global geometry is determined by the reciprocal interactions between local elements. Our construction adapts to any bank of filters chosen to represent a set of receptive profiles, since it does not require any structure on the parameterization of the family. The connectivity kernel that we define carries a geometrical structure consistent with the well-known properties of long-range horizontal connections in V1, and it is compatible with the perceptual rules synthesized by the concept of association field. These characteristics are still present when the kernel is constructed from a bank of filters arising from an unsupervised learning algorithm.

A coarse-graining framework for spiking neuronal networks: from strongly-coupled conductance-based integrate-and-fire neurons to augmented systems of ODEs Abstract Homogeneously structured, fluctuation-driven networks of spiking neurons can exhibit a wide variety of dynamical behaviors, ranging from homogeneity to synchrony. We extend our partitioned-ensemble average (PEA) formalism proposed in Zhang et al. (Journal of Computational Neuroscience, 37(1), 81–104, 2014a) to systematically coarse grain the heterogeneous dynamics of strongly coupled, conductance-based integrate-and-fire neuronal networks. The population dynamics models derived here successfully capture the so-called multiple-firing events (MFEs), which emerge naturally in fluctuation-driven networks of strongly coupled neurons. Although these MFEs likely play a crucial role in the generation of the neuronal avalanches observed in vitro and in vivo, the mechanisms underlying these MFEs cannot easily be understood using standard population dynamic models. Using our PEA formalism, we systematically generate a sequence of model reductions, going from Master equations, to Fokker-Planck equations, and finally, to an augmented system of ordinary differential equations. Furthermore, we show that these reductions can faithfully describe the heterogeneous dynamic regimes underlying the generation of MFEs in strongly coupled conductance-based integrate-and-fire neuronal networks.

Membrane potential resonance in non-oscillatory neurons interacts with synaptic connectivity to produce network oscillations Abstract Several neuron types have been shown to exhibit (subthreshold) membrane potential resonance (MPR), defined as the occurrence of a peak in their voltage amplitude response to oscillatory input currents at a preferred (resonant) frequency. MPR has been investigated both experimentally and theoretically. However, whether MPR is simply an epiphenomenon or it plays a functional role for the generation of neuronal network oscillations and how the latent time scales present in individual, non-oscillatory cells affect the properties of the oscillatory networks in which they are embedded are open questions. We address these issues by investigating a minimal network model consisting of (i) a non-oscillatory linear resonator (band-pass filter) with 2D dynamics, (ii) a passive cell (low-pass filter) with 1D linear dynamics, and (iii) nonlinear graded synaptic connections (excitatory or inhibitory) with instantaneous dynamics. We demonstrate that (i) the network oscillations crucially depend on the presence of MPR in the resonator, (ii) they are amplified by the network connectivity, (iii) they develop relaxation oscillations for high enough levels of mutual inhibition/excitation, and (iv) the network frequency monotonically depends on the resonators resonant frequency. We explain these phenomena using a reduced adapted version of the classical phase-plane analysis that helps uncovering the type of effective network nonlinearities that contribute to the generation of network oscillations. We extend our results to networks having cells with 2D dynamics. Our results have direct implications for network models of firing rate type and other biological oscillatory networks (e.g, biochemical, genetic).

Slowdown of BCM plasticity with many synapses Abstract During neural development sensory stimulation induces long-term changes in the receptive field of the neurons that encode the stimuli. The Bienenstock-Cooper-Munro (BCM) model was introduced to model and analyze this process computationally, and it remains one of the major models of unsupervised plasticity to this day. Here we show that for some stimulus types, the convergence of the synaptic weights under the BCM rule slows down exponentially as the number of synapses per neuron increases. We present a mathematical analysis of the slowdown that shows also how the slowdown can be avoided.

Outgrowing seizures in Childhood Absence Epilepsy: time delays and bistability Abstract We formulate a conductance-based model for a 3-neuron motif associated with Childhood Absence Epilepsy (CAE). The motif consists of neurons from the thalamic relay (TC) and reticular nuclei (RT) and the cortex (CT). We focus on a genetic defect common to the mouse homolog of CAE which is associated with loss of GABAA receptors on the TC neuron, and the fact that myelination of axons as children age can increase the conduction velocity between neurons. We show the combination of low GABAA mediated inhibition of TC neurons and the long corticothalamic loop delay gives rise to a variety of complex dynamics in the motif, including bistability. This bistability disappears as the corticothalamic conduction delay shortens even though GABAA activity remains impaired. Thus the combination of deficient GABAA activity and changing axonal myelination in the corticothalamic loop may be sufficient to account for the clinical course of CAE.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

BLDE University Journal of Health Sciences, a publication of BLDE University, is a peer-reviewed online journal with Semiannual print on demand compilation of issues published. The journal’s full text is available online at http://www.bldeujournalhs.in. The journal allows free access (Open Access) to its contents and permits authors to self-archive final accepted version of the articles on any OAI-compliant institutional / subject-based repository.

Digital health in India – As envisaged by the National Health Policy (2017) Suptendra Nath Sarbadhikari BLDE University Journal of Health Sciences 2019 4(1):1-6

An exploratory study to assess the prevalence and risk factors of malnutrition among under-five children residing in selected rural areas of district Sirmaur, Himachal Pradesh Priyanka Devi, Simarjeet Kaur BLDE University Journal of Health Sciences 2019 4(1):7-10 INTRODUCTION: Nutrition is one of the most essential things of life, and it becomes an integral part for the growth and development of body and maintenance of health. In rural areas of India, there is widespread undernutrition. AIM: This study aims to assess the prevalence and to explore the most probable risk factors influencing malnutrition among under-five children. SETTING AND DESIGN: A quantitative nonexperimental exploratory study design was conducted in selected rural areas of district Sirmaur, Himachal Pradesh, India. SUBJECTS AND METHODS: A total of 200 children and their mothers were selected by purposive sampling technique. Anthropometric assessment and semi-structured interview schedule was used as tool for data collection. RESULTS: The prevalence of stunting was 40% and wasting was 19.5%. Maternal factors, birth characteristics, breastfeeding practices, environmental factors, and dietary practices affect malnutrition among under-five children. CONCLUSION: The recapitalization of the study suggests that there was high prevalence of malnutrition, and various risk factors are responsible for malnutrition among under-five children.

Biochemical alterations in plasma total bile acid, creatinine, sodium, potassium, chloride, and bicarbonate in rabbits overdosed with ibuprofen and supplemented with guava leaf (Psidium guajava) extracts Mathew Folaranmi Olaniyan, Precious Oluwamosope Okunola BLDE University Journal of Health Sciences 2019 4(1):11-16 STUDY BACKGROUND: Ibuprofen is an analgesic and a nonsteroidal anti-inflammatory drug while Psidium guajava leaf has antioxidative, antimicrobial, anti-inflammatory, and analgesic activities. AIM AND OBJECTIVE: The aim of the study is to evaluate plasma total bile acids (TBAs), creatinine, and electrolytes in rabbits overdosed with ibuprofen and supplemented with guava leaf (P. guajava) extracts. JUSTIFICATION: There exists a little information on the change in the plasma levels of TBA and electrolytes in ibuprofen toxicity supplemented with guava leaf extract. MATERIALS AND METHODS: Fifteen rabbits (weight – 0.8–1.4 kg; age – 1.5 ± 0.4 years, n = 5/group) were grouped into control (a); rabbits administered 1600 mg/KgBW of ibuprofen (B1) before being fed with 400 mg/KgBW of guava leaf aqueous extract (B2) and rabbits administered 1600 mg/KgBW of ibuprofen administration (C1) before being fed with 400 mg/KgBW of guava leaf methanolic extract (C2). Plasma creatinine, sodium, potassium, chloride, and bicarbonate levels were determined using COBAS C111 chemistry autoanalyzer while TBA was determined by spectrophotometry. RESULTS: The results showed a significant increase in the plasma level of TBA, potassium, and creatinine in the rabbits following the administration of 1600 mg/KgBW of ibuprofen (P < 0.05) and a significant decrease in the plasma TBA, potassium, and creatinine in the same rabbits when they were given 400 mg/KgBW of guava leaf extract following ibuprofen overdose (P < 0.05). CONCLUSION: There was a significant increase in the plasma values of TBA, creatinine, and potassium following the administration of ibuprofen possibly due to ibuprofen toxicity which was significantly reduced upon the administration of 400 mg/KgBW of guava leaf extract.

Studies on the trends of transfusion-transmissible infections in a district-level hospital in West Bengal, India G Mukherjee, S Ghosh, A Mukherjee, T Mondal, S Mondal BLDE University Journal of Health Sciences 2019 4(1):17-19 BACKGROUND: Therapeutic use of blood is the most sophisticated part of treatments in medical sciences. Transfusion of blood saves patients' lives as well as it has also the risk of infective disease, if it is contaminated. AIMS AND OBJECTIVES: The current study focuses on the status of TTI amongst the voluntary Blood donors over a period of time. MATERIALS AND METHODS: In this study, HIV, HCV, HBsAg and Syphilis (by RPR) screening test report for the year 2011 to 2017 of a district Hospital Blood Bank in West Bengal has been presented. Tests were done by ELISA and Syphilis by Rapid Plasma Reagin test. RESULTS: No significant changes in the incidence of above noted cases have been observed and no Malaria positive case was detected. CONCLUSION: This indicates a good awareness amongst the people regarding these diseases having immense public health importance.

Flipped classrooms in medical education: Tool to encourage self-directed and active learning Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava BLDE University Journal of Health Sciences 2019 4(1):20-21 The goal of medical education is to produce a competent graduate, who possesses all the skills to meet the needs of the society. Nevertheless, it is not new that most of the students are deficient in critical thinking and complex reasoning, which are must for a successful doctor. Out of the many approaches which have been tried upon, one among them is a flipped classroom, which is a hybrid approach (combination of classroom teaching and self-directed online learning outside the classroom). The advantage of the method is that it enhances the time available for active learning. Moreover, the method has its own limitations and they should be considered before planning such sessions. In conclusion, flipped classroom is a wonderful tool to integrate e-learning with the traditional learning and simultaneously help the medical students to become a self-directed learner.

To pee and to poo: Cross-organ principles and mechanisms in renal and gastrointestinal physiology Hwee-Ming Cheng, See-Ziau Hoe BLDE University Journal of Health Sciences 2019 4(1):22-27 Cross-organ principles can be recognized and taught as an expression of the shared functional symmetry and common design in physiology. This integrated concept will help students to appreciate the unifying mechanisms that maintain the homeostatic balance in the body. In this article, the cross-organ similarities in gastrointestinal and renal physiology are extracted to aid learning and teaching. Some fun conversations between the Kiddo Urinary (U) and the Gastro Intestinal (I) are included to promote enjoyment in physiology.

Retrocerebellar arachnoid cyst of the posterior fossa presenting with headache Reddy Ravikanth BLDE University Journal of Health Sciences 2019 4(1):28-29 Arachnoid cysts are benign, fluid-filled, cyst-liked malformations related to the arachnoid mater. Arachnoid cysts involving the posterior fossa are less common and exert local mass effect resulting in the symptoms and signs of cerebellar and brainstem dysfunction. Here, we present a case of a 14-year-old female with a retrocerebellar arachnoid cyst.

Chondrosarcoma at the sinonasal region Santosh Kumar Swain, Smrutipragnya Samal, Mahesh Chandra Sahu BLDE University Journal of Health Sciences 2019 4(1):30-33 Chondrosarcoma is a rare and potentially lethal neoplasm and even rarer in the head-and-neck area. It is a very uncommon clinical condition at the sinonasal tract. The determination of this neoplasm depends on the histopathological consideration indicating harmful chondroid tissue multiplication. The prognostic elements for chondrosarcomas are grading of tumor and histological picture of tumor edges. The primary treatment of this tumor is radical surgery with wide safe margin. The other adjuvant treatments such as radiation and/or chemotherapy remain uncertain. The biopsy confirmed the diagnosis of myxoid chondrosarcoma. Here, we present a rare case of chondrosarcoma of a 48-year-old man presented with mass at the nasofacial region.

Hyponatremia correction causing extrapontine myelinolysis Binoy Damodar Thavara, Harsha Padikkal Veettil BLDE University Journal of Health Sciences 2019 4(1):34-38 Rapid correction of hyponatremia will result in extrapontine myelinolysis (EPM). We report a case of 25-year-old male patient who presented with traumatic brain injury (TBI) causing left temporal extradural hematoma (EDH). EDH was managed conservatively. The patient had addiction to alcohol, tobacco smoking, paan (containing betel nuts), and some other addictive substances, details of which were not available. The patient's Glasgow Coma Scale (GCS) and serum sodium were normal at admission. On the 7th and 8th days, serum sodium was 107 and 101 milliequivalent/liter (meq/l), respectively, but GCS was normal. Slow infusion of 3% sodium chloride 100 ml was given on the 7th day and 200 ml on the 8th day. However, serum sodium was raised to 128 meq/l on the 10th day. On the 11th day, GCS was deteriorated and the patient developed quadriparesis. Magnetic resonance imaging (MRI) scan showed bilateral symmetrical basal ganglia T2-weighted hyperintensities suggestive of EPM. In severe hyponatremic patient, it is the rapid rise of serum sodium level which causes EPM. Rapid rise of serum sodium can occur even if hyponatremia was corrected with gradual addition of sodium. Consumption of alcohol and addictive substances contributed along with hyponatremia correction, to the development of EPM. Early detection of hyponatremia is the paramount factor in TBI to prevent the debilitating disease of EPM. MRI plays a crucial role in definite diagnosis of EPM.

Complicated Plasmodium vivax infection with malarial hepatopathy and splenic abscess Priya Bansal, Ankit Gupta, Ravi Meena BLDE University Journal of Health Sciences 2019 4(1):39-41 Malaria is a serious health burden in the tropical countries. Jaundice is a known manifestation of complicated falciparum malaria but is unusual with Plasmodium vivax infection. Only a few cases of vivax malarial hepatopathy have been reported till date. Here, we present a rare case of vivax malaria hepatopathy with secondary splenic abscess. No such case of dual complications of vivax malaria in the same patient has been reported till date to the best of our knowledge.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Oral and Maxillofacial Surgery, Medicine, and Pathology

Intraparotid lymph node toxoplasmosis diagnosis by fine needle aspiration cytology Publication date: Available online 31 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Hélder Domiciano Dantas Martins, Beatriz Araújo Suassuna Vaz, Larissa Suellen da Silva Lins, Brenna Louise Cavalcanti Gondim, Lucio Roberto Cançado Castellano, Paulo Rogério Ferreti Bonan Abstract Toxoplasmosis is a relatively common disease caused by the Toxoplasma gondii parasite. Its clinical manifestations are dependent on the immune status of the patient, and the correct diagnosis is established based on a combination of direct parasite visualization and serological assays for the detection of host antibodies acting against the parasite. This study presents a case of intraparotid lymph node toxoplasmosis diagnosed by fine needle aspiration cytology presenting bradyzoite- and tachyzoite-compatible structures associated with serology assays. After diagnosis, treatment comprised a triple antimicrobial scheme and follow-up for six months, and the patient reached total regression. Thus, it is concluded that FNAC associated to serology assays comprise adequate tools for toxoplasmosis diagnoses.

Orthognathic treatment in Greig cephalopolysyndactyly syndrome: A case report Publication date: Available online 28 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Tayfun Cıvak, Goksu Trakyali, Altan Varol Abstract Typical Greig cephalopolysyndactyly syndrome (GCPS) is characterized by preaxial polydactyly or mixed pre- and postaxial polydactyly, true widely spaced eyes, macrocephaly. Individuals with mild GCPS may have subtle craniofacial findings. The diagnosis of GCPS is based on clinical findings and family history. GLI3 is the only gene known to be associated with GCPS. It has an autosomal dominant inheritance. The literature fails in documentations of any treatment protocol for defective jaw relationship in these patients. Therefore, we report on a patient with GCPS presenting polysyndactyly, frontal bossing, high forehead, skeletal Class III deformity due to maxillary retrognathism and mandibular prognathism, treated with orthognathic surgery by means of double jaw surgery and orthodontic treatment with fixed appliances.

Benign fibro-osseous lesion and odontoma of the mandible: A report of a rare, hybrid lesion and review of literature Publication date: Available online 24 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Rekha Reddy, Rohan Jagtap, Deeba Kashtwari, Christopher C. Hambrook, Danielle L. Freburg-Hoffmeister, Mohammed N. Islam, Donald M. Cohen, Archana Shenoy, Indraneel Bhattacharyya Abstract This report documents a case of a 12-year-old male with a combined benign fibro-osseous lesion (BFOL) and odontoma. Radiographic imaging revealed an extensive, well-defined, multilocular, radiolucent lesion with small radiopaque entities in the left mandible. Microscopic examination revealed a central BFOL with associated odontomas. To the best of the authors' knowledge, this is the third report of a combined BFOL and odontoma and an extensive review of the English language literature on combined BFOL and odontoma cases is included. This case is important because it demonstrates the importance of diagnosing bone lesions with an accompanying radiograph. The initial biopsy was signed out as a BFOL with a comment that there was tooth-like material as well and a possibility that it represented an odontoma. The patient was operated on in our teaching hospital and the lesion completely excised with a diagnosis of dentigerous cyst. The hard tissue was grossed only as it appeared tooth-like. Seeing the final diagnosis, we requested decalcification of the hard tissue. Based on clinical, radiographic and histologic findings, the final diagnosis of BFOL and odontoma was made. Another reason for reporting this case is that the paucity of published cases of these combined lesions makes treatment decisions a challenge. Further future reporting of BFOL arising in association with odontomas with long-term follow-up information is paramount to better understand these entities vis-à-vis their nature and behavior.

End-to-end anastomosis of transected parotid duct in an emergency department: Clinical benefits from immediate repair and overview of treatment options Publication date: Available online 24 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Ioannis Papadiochos, Paschalis Strantzias, Georgios Mitsopoulos, Kalliopi Melaki Abstract Parotid duct injuries (PDIs) are not considered common complications of facial trauma. However, their associated morbidity may be increased by the formation of parotid sieloceles and fistulae. This article reports the case of a 31-year-old male patient who was presented to the emergency department of Evangelismos General Hospital of Athens, due to a sharp penetrating injury on left side of his face. Since transection of PD was clinically diagnosed, an end-to-end anastomosis was immediately carried out under local anesthesia. Within the early postoperative period, various angiocatheters of progressively increased diameters were used for stenting the repaired PD. After 10 months of follow-up, there were no clinical and ultrasonographic signs of sialocele or fistula formation. This case report aimed first to underscore the benefits of immediate surgical management in case of PDIs and second, to describe the postoperative management for maintenance of both PD patency and parotid gland function. PDIs in the context of emergency facial trauma are advisable to be timely recognized and treated immediately, by securing the saliva outflow to the oral cavity and maintaining a wide enough ductal lumen.

A case of a huge mandibular tumor composed of ameloblastoma and high-grade sarcoma Publication date: Available online 23 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Yusei Fujita, Hiromi Tamura, Shusuke Okunaga, Masakazu Hamada, Ken Wakabayashi, Hiroka Ando, Shiro Adachi, Tetsuro Sumi Abstract Ameloblastoma is a benign odontogenic tumor of the jaw. Sarcoma is a rare neoplasm that accounts for only about 1% of all tumors. Here, we report a quite rare case of simultaneous occurrence of an ameloblastoma and a high-grade sarcoma in the mandible of a 65-year-old man. He was referred to our hospital because of his difficulties in eating and drinking due to a remarkable swelling of the right mandible. He had first noticed the swelling about six years before and consulted a clinic one year before, but he had refused any examination or treatment. He underwent an incisional biopsy, and it revealed a high-grade spindle cell sarcoma with massive necrosis. Therefore, we suggested surgery, but he had never hoped any operation. His poor nutritional status gradually further declined, and he died due to massive hemorrhage from the tumor. In the autopsy, the histological findings revealed that the tumor was predominantly composed of high-grade spindle cell sarcoma and contained a small amount of epithelial component which was a granular cell variant of ameloblastoma. Metastatic tumors were seen in the bilateral lungs and the liver. They contained only the sarcomatous element.

Evaluation of therapeutic effects of teriparatide in a rat model of zoledronic acid-induced bisphosphonate-related osteonecrosis Publication date: Available online 23 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): H. Ikeda, D. Yoshiga, S. Kokabu, W. Ariyoshi, H. Tsurushima, O. Sakaguchi, J. Tanaka, J. Kaneko, M. Habu, M. Sasaguri, E. Jimi, T. Nishihara, I. Yoshioka, K. Tominaga Abstract Osteonecrosis of the jaw is a complication in patients using bisphosphonate agents. In this study, we aimed to investigate the effects and mechanism of teriparatide (TPTD) in a rat model of bisphosphonate-related osteonecrosis (BRON). Osteonecrosis was induced by administration of zoledronic acid (ZOL). Four weeks after ZOL injection, the rats underwent a surgery in which drilling holes were made. These holes were filled with freeze-dried Aggregatibacter actinomycetemcomitans. After the four-weeks period, TPTD or saline (n = 9) was intermittently administered for four weeks. Later, rats were euthanized, and the mandible and femur bones were examined the amount of necrosis and bone regeneration. Serum receptor activator of NF-κB ligand (RANKL), osteocalcin (OC), and C-terminal crosslinking telopeptide of type I collagen (CTX) were also examined. TPTD administration reduced necrotic bone area of the mandibles and femurs in the BRON rat model and induced new bone formation. In addition, TPTD injection increased the number of osteoclasts. The suggested underlying mechanism is the induction of protein levels of RANKL by TPTD. Furthermore, the serum levels of bone metabolism biomarkers (OC and CTX) were upregulated in the TPTD injection group. In conclusion, ZOL has negative effects on osteoclasts. TPTD was found to be effective in eliminating the negative effects of ZOL. TPTD had positive effects in preventing bone resorption and promoting osteogenesis. In addition, TPTD improved osteoclastogenesis, which in turn led to the improvement of BRON.

A case of large developing odontoma, so-called ameloblastic fibro-odontoma, of the mandible Publication date: Available online 8 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Hideki Watanabe, Hitoshi Osano, Hisao Igarashi, Akihiro Dohi, Yoshiyuki Mori Abstract Large developing odontoma is a rare odontogenic tumor showing proliferation of both odontogenic epithelium and ectomesenchyme, with enamel and dentin formation. A case of large developing odontoma affecting the lower molar region to the mandibular ramus of a 14-year-old girl is reported. Panoramic and computed tomography images showed a clearly demarcated, multilocular radiolucency extending from the left lower molar region to the mandibular ramus, containing a tooth-like radiopacity. With the patient under general anesthesia, the mass was removed. The histopathological diagnosis was developing odontoma. There was no sign of recurrence at 1 year after tumor removal.

Calcium pyrophosphate dihydrate crystal deposition of the temporomandibular joint: A case report and review of the literature Publication date: Available online 8 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Isao Miyamoto, Atsushi Kasamatsu, Kazuya Hiroshima, Nao Ishida, Shin Takeuchi, Toshikazu Takahara, Sho Ishida, Shusaku Yoshimura, Takao Baba, Yasuhiro Saito, Manabu Iyoda, Hideki Tanzawa Abstract Calcium pyrophosphate dihydrate crystal deposition disease (CPPDd) induces arthritis in the surrounding joints with symptoms, such as pain, swelling, and restricted joint movement. CPPDd occurs primarily in the major joints; however, the main manifestation of this disease in the temporomandibular joint (TMJ) is relatively rare. We describe a case of CPPDd in the TMJ of a 54-year-old Japanese woman who was referred to our hospital with the complaints of unpainful swelling in the right TMJ region and restricted mouth opening. Computed tomography (CT) and magnetic resonance imaging (MRI) showed 46 × 42-mm and 27 × 18-mm calcified masses in the right TMJ region. The masses were both outside and inside the mandibular condyle, both of which extended to the skull base. Since we suspected a tumor in the TMJ, the lesion was partially excised for biopsy with the patient under general anesthesia. The microscopic examination showed deposits of calcium pyrophosphate dihydrate crystals, which resulted in a histopathologic diagnosis of CPPDd. According to the suggestion of the neurosurgeon, we removed as much as possible of only the CPPDd tissue on the outside of the mandibular condyle via the preauricular approach to avoid damaging the cranial nerves. The patient was satisfied with the postoperative facial symmetry without limited mouth opening. The postoperative follow-up was uneventful.

Amelioration of limited mouth opening after treatment of primary biliary cholangitis: A case report Publication date: Available online 8 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Takeshi Kaneuji, Daigo Yoshiga, Wataru Ariyoshi, Ikuo Nakamichi, Hironori Tanimoto, Junpei Tanaka, Ikuya Miyamoto, Manabu Habu, Sho Mitsugi, Tatsuji Nishihara, Tetsu Takahashi, Kazuhiro Tominaga, Izumi Yoshioka Abstract Primary biliary cholangitis is a slow-progressing autoimmune disease of the liver characterized by the presence of portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Herein, we report a case of temporomandibular joint disorder that concurred with primary biliary cholangitis. A 54-year-old woman presented to us with severe pain on the left side of the temporomandibular joint and difficulty in mouth opening. We used pharmacotherapy, occlusal sprint, and arthrocentesis for the treatment; however, there was no improvement. Magnetic resonance imaging revealed malposition of the articular disk on the left side of the joint and joint effusion. Thus, we performed arthroscopic surgery under general anesthesia. Postoperatively, she developed impaired liver function and itchiness of the skin. A liver biopsy was performed by a hepatologist, and a diagnosis of primary biliary cholangitis was made, as suspected. The temporomandibular joint pain and trismus persisted postoperatively; however, these symptoms improved after primary biliary cholangitis therapy. Thus, we suggest a relationship between temporomandibular joint disorder and primary biliary cholangitis from this disease trajectory and suspect that interleukin-17 may play an important role in the pathogenesis of temporomandibular joint disorder.

Severe stomatitis caused by misuse of methotrexate in an elderly patient with chronic rheumatoid arthritis Publication date: Available online 4 May 2019 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Kohta Yamada, Kei Tomihara, Manabu Yamazaki, Makoto Noguchi Abstract Methotrexate (MTX) is an antifolate that has been used as a chemotherapeutic agent for the treatment of neoplasm, such as leukemia and osteosarcoma. Moreover, MTX is also commonly used for treatment of chronic rheumatoid arthritis (RA). Here, we report a case of severe stomatitis in a patient with RA, which was caused by misuse of MTX. An 83-year-old female patient visited our department with the chief complaint of oral mucosal pain, accompanied by extreme fatigue. Severe stomatitis lesions were observed throughout her oral mucosa. Moreover, blood examination revealed pancytopenia. The patient reported a history of RA, and had been prescribed MTX since 2004. Although 6 mg MTX should be used twice per week, the patient mistakenly used MTX every day following her last consultation, for a period of 1 month. These findings led to a diagnosis of severe stomatitis, pancytopenia, and sepsis, all induced by misuse of MTX. Ultimately, she was treated with blood transfusion, antibiotics, and intravenous hyper alimentation, as well as administration of granulocyte colony-stimulating factor. MTX for the treatment of RA should be carefully managed to limit the risk of its misuse, especially in elderly patients, because of the severity and potential lethality of symptoms.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com