Reply to correspondence ‘Topical ionic contra viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts’

We appreciate Dr Abdelmaksoud's thorough review of our manuscript (1) and would like to reply to the comments that were raised with this letter. First, it appears that the understanding is that the study describes the 'clinical response of common warts to a topical application of a fixed dose of 980 mg of the ICVT gel on the patients' lower back. It should be clarified that the main objective of this first-in-man study was evaluate the systemic exposure, safety and tolerability of ionic-contra-viral therapy (ICVT) (2).

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Angiolymphoid hyperplasia with eosinophilia: report of nine cases

Abstract

Background

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular proliferation characterized by dermal or subcutaneous red or brown papules or nodules, most commonly on the head and neck.

Objective

The aim of this study was to review the epidemiological and clinical characteristics of ALHE, focusing particularly on the histological and therapeutic features.

Methods

We performed a retrospective study of all cases of ALHE diagnosed in our dermatology and pathology departments between 2004 and 2015.

Results

Over 12 years, we collected nine cases of ALHE (0.75 case/year). There were four men and five women. The mean age was 43 years. Lesions presented as erythematous or violaceous papules or nodules in all cases, multiple in five cases, and localized on the head in eight cases or other sites in four cases. The diagnosis of ALHE was clinically suspected in only two cases. The histopathological findings showed an ill-circumscribed, intradermal slightly lobular proliferation of capillary-sized vessels around several central vessels. In all cases, the blood vessels were lined by large endothelial cells. An inflammatory infiltrate around the vessels was formed mainly of lymphocytes and eosinophils with isolated plasma cells and histiocytes. Surgery was the most common treatment in our series. Other local or general treatment has also been used with varying responses.

Conclusion

Angiolymphoid hyperplasia with eosinophilia is a rare epithelioid vascular tumor with a challenging clinical and histological diagnosis. Despite its benign nature, ALHE causes a therapeutic dilemma.

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ALK-positive primary cutaneous anaplastic large cell lymphoma: a case report and review of the literature

Abstract

Anaplastic large cell lymphoma (ALCL) limited to the skin is a distinct disease that is designated primary cutaneous ALCL (pcALCL). It has an indolent course with a significantly better prognosis compared to systemic ALCL (sALCL). Anaplastic lymphoma kinase (ALK) expression in lesions of cutaneous ALCL is classically considered to be a marker for skin involvement by sALCL. However, recent reports of patients with ALK-positive pcALCL challenge this concept and raise prognostic and therapeutic dilemmas. Herein, we report a case of ALK-positive pcALCL in a 45-year-old woman who was treated with local radiotherapy. We review previously reported cases in the literature to better characterize this rare variant. Overall, the rates of cutaneous recurrence, systemic dissemination, and disease-related mortality in ALK-positive pcALCL do not differ from those previously reported in pcALCL. ALK-positive pcALCL is diagnosed at younger age and has a better disease course in children compared to adults with lower incidences of skin recurrence and progression to systemic disease. We conclude that ALK-positivity in cutaneous ALCL does not necessarily imply systemic disease. ALK-positive pcALCL has an excellent prognosis and should be treated by excision and/or radiotherapy. However, patients must remain under close long-term follow-up as recurrence and progression to systemic disease may occur.

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Unusual location of a common dermatosis

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Q-switched Nd: YAG laser alone or with modified Jessner chemical peeling for treatment of mixed melasma in dark skin types: A comparative clinical, histopathological, and immunohistochemical study

Summary

Backgrounds

Treatment of mixed melasma remains challenging. Promising results have been achieved with low-fluence 1064-nm Q-switched Nd-YAG laser; however, multiple sessions are necessary with occurrence of complications especially in dark skin types. So, combination methods may be recommended.

Aims

To compare efficacy of Q-switched Nd-YAG laser alone or with modified Jessner's peel in mixed melasma in dark skin.

Patients/Methods

Nineteen patients with mixed melasma received 6 sessions of laser on left side of face and alternating laser and modified Jessner on right side. Evaluation was carried out clinically through modified melasma area and severity index at 1 month after last session. Using histopathological, immunohistochemical, and computerized morphometric analysis, objective evaluation of melanin particle surface area and MART-1-positive cells was performed for pre- and post-treated skin biopsies.

Results

There was significant clinical improvement on both sides of face (P < .001), without significant difference (P > .05). At the sixth laser session on left side of face, ill-defined mottled hypopigmentation was observed in 21.05% of patients. Histopathologically, melanin particle surface area and number of MART-1-positive cells (total, epidermal, and dermal) were significantly decreased after two treatment modalities (P < .001), without significant difference in their reduction percentage between both sides of face (P > .05).

Conclusion

Low-fluence Q-switched Nd-YAG laser alone and with modified Jessner's peel are equally effective regimens for mixed melasma clinically, histopathologically, and immunohistochemically. However, combined method is preferred, especially in dark skin, for obtaining better cosmetic result with fewer side effects of multiple laser sessions and decreasing cost rate of laser.

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Science as momentary truth

Publication date: Available online 19 October 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Leonardo Silva




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Side effects of intraoral devices for OSAS treatment

Publication date: Available online 14 October 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Andressa Otranto de Britto Teixeira, Ana Luiza Ladeia Andrade, Rhita Cristina da Cunha Almeida, Marco Antonio de Oliveira Almeida
IntroductionIntraoral devices have increasingly assumed a key role in the treatment of Obstructive Sleep Apnea Syndrome, but there are limitations to their indication and side effects that result from their continuous use, as well as the use of the Continuous Positive Airway Pressure (CPAP) device.ObjectivesTo evaluate the changes in dental positioning caused by the continuous use of mandibular advancement devices.MethodsA prospective longitudinal study with a sample of 15 patients, with evaluation of complete documentation after a mean time of 6.47 months, assessed changes in dental positioning due to the use of the Twin Block oral device for the treatment of patients with apnea. The following variables were evaluated: overjet, overbite, upper and lower intermolar distances, upper and lower intercanine distances, Little's irregularity index and the incisor mandibular plane angle (IMPA). An intraclass correlation test was performed and a correlation index>0.08 was accepted. After verifying the normal sample distribution (Shapiro-Wilks), a parametric test was used (t Test), with a significance level set at 5%.ResultsThere was a decrease in the values of overjet, overbite and Little's irregularity index, whereas there was an increase in the lower intercanine distance and IMPA values. All these variables are influenced, at different levels, by the forward inclination of the lower incisors, an action that can be expected due to the force applied by the device on the dentition. The other variables did not show statistically significant differences.ConclusionAfter a mean time of 6.47 months of use of the mandibular advancement device, there were statistically significant changes in the dental positioning, but they were not clinically relevant. However, it is relevant that this device is commonly in use over long periods of time, making the monitoring of these patients of the utmost importance for the duration of their therapy.



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Neutrophil–lymphocyte ratios in the prognostication of primary non-metastatic Nasopharyngeal Carcinoma

Publication date: Available online 19 October 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Kong Yew Liew, Abu Bakar Zulkiflee
IntroductionNasopharyngeal Carcinoma is a geographically and racially variable disease which has a high incidence in Malaysia. Based on current concepts in tumour related inflammation the inflammatory marker, Neutrophil–Lymphocyte Ratio was tested to find its relationship with prognosis in Nasopharyngeal Carcinoma.ObjectiveTo investigate the effect of the Neutrophil–Lymphocyte Ratio on prognosis in non-metastatic primary Nasopharyngeal Carcinoma patients and to further refine the cut off between high and low Neutrophil–Lymphocyte Ratio values.MethodsThe medical charts of patients with histologically confirmed Nasopharyngeal Carcinoma from 1st January 2005 until 31st December 2009 were reviewed retrospectively and the Neutrophil–Lymphocyte Ratio was calculated to see if there was any association between their higher values with higher failure rates.ResultsRecords of 98 patients (n=98) were retrieved and reviewed. Only Neutrophil–Lymphocyte Ratio (p=0.004) and TMN staging (p=0.002) were significantly different between recurrent and non-recurrent groups, with the Neutrophil–Lymphocyte Ratio being independent of TNM staging (p=0.007). Treatment failure was significantly higher in the high Neutrophil–Lymphocyte Ratio group (p=0.001). Disease Free Survival was also significantly higher in this group (p=0.000077).ConclusionHigh Neutrophil–Lymphocyte Ratio values are associated with higher rates of recurrence and worse Disease Free Survival in non-metastatic Nasopharyngeal Carcinoma patients undergoing primary curative treatment.



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Molecular control of regulatory T cell development and function

Yohko Kitagawa | Shimon Sakaguchi

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Insights into immune tolerance from AIRE deficiency

Irina Proekt | Corey N Miller | Michail S Lionakis | Mark S Anderson

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Simultaneous Reconstruction of Columella and Philtrum Using Prolabial Flap Combined with Abbe Flap in Secondary Bilateral Cleft Lip and Nasal Deformity

Open rhinoplasty and Abbe flap techniques are traditionally useful tools for the reconstruction of secondary bilateral cleft lip nasal (BCLN) deformity. We aimed to investigate the long-term outcomes of simultaneous columella and philtrum reconstruction using prolabial flap combined with Abbe flap in secondary BCLN deformity.From January 2009 to July 2014, 26 patients (17 males and 9 females; mean age 21 years) with secondary BCLN deformity were recruited. All patients had severe short columella and philtrum deficiency.

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Reconstruction after salvage laryngectomy

Publication date: December 2017
Source:Oral Oncology, Volume 75
Author(s): David H. Yeh, Axel Sahovaler, Kevin Fung
Both early and advanced stage laryngeal cancers are treated with organ-preserving strategies including radiation alone or concurrent chemoradiotherapy. While organ-preserving modalities have proven effective in eradicating cancer while also preserving laryngeal function, there remains a proportion of cases where residual or recurrent cancer prevails, or conversely, where radiotherapy renders a larynx dysfunctional. In these circumstances, salvage total laryngectomy is often the surgical treatment. The effects of radiotherapy to the neck, amplified by chemotherapy, can create an inhospitable surgical environment, making the salvage laryngectomy an operation fraught with the potential for major complications such as the dreaded pharyngocutaneous fistula.The introduction of vascularized tissue from outside the irradiated field decreases the risk of major wound complications. Free tissue transfer, with a variety of donor sites available, is commonly employed to reconstruct either a patch or a circumferential segment of the pharynx. When there is enough pharyngeal mucosa for primary closure, a vascularized onlay graft or a pharyngeal interposition graft can be used to reinforce the closure. This has been demonstrated to both reduce the severity of pharyngocutaneous fistula and decrease the risk of developing a pharyngocutaneous fistula compared to primary closure alone.Beyond mitigating the risk for perioperative complications, flap selection may have implications on the long-term outcomes after salvage total laryngectomy and these must be considered preoperatively. The purpose of this review is to examine the various options for reconstruction after salvage total laryngectomy and to examine some of their advantages and disadvantages in the short and long-term.



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Outcome by treatment modality in sinonasal undifferentiated carcinoma (SNUC): A case-series, systematic review and meta-analysis

Publication date: December 2017
Source:Oral Oncology, Volume 75
Author(s): Grégoire B. Morand, Nanina Anderegg, Domenic Vital, Kristian Ikenberg, Gerhard F. Huber, Michael B. Soyka, Matthias Egger, David Holzmann
ObjectiveSinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy first described by Frierson et al. in 1986. As the tumor is very rare, current treatment recommendations are based on institutional case reports. We thus felt the need to perform a comprehensive systematic review and meta-analysis to investigate how treatment modalities are associated with survival.DesignCase-series, systematic review and meta-analysisMethodsWe searched the OvidMedline, OvidEmbase, Web of Science, Biosis, Scopus and the Cochrane Library database libraries. We extracted aggregate and individual patient data for statistical analysis. To study the association between treatment modalities and survival, we used random-effects meta-regression for the aggregate- and cox mixed-effects models.Results379 citations were found; 29 case series could be included in the final analysis, including a total number of 390 single patients (34.6% female). Median age at diagnosis was 52 years. 80.9% of patients presented with a T4 tumor and 16.0% with nodal metastasis at diagnosis. In individual patient data (IPD) meta-analysis, single modality (surgery alone or radiation alone) treatment was associated with reduced survival compared to double modality (surgery & radiation or chemoradiation) treatment (adjusted Hazard Ratio [aHR] 2.97, 95% ConfidenceInterval [1.41–6.27]) and compared to triple modality (surgery & radiation & chemotherapy) treatment (aHR 2.80 95%-CI 1.29–6.05 for triple vs. single modality). Triple modality treatment was not superior to double modality treatment. (aHR 1.06, 95%-CI 0.59–1.92).ConclusionDouble and triple modality treatment are associated with improved survival over single modality but there is no evidence that triple modality is superior to double modality treatment.



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Interferon regulatory factor 6 variants affect nasolabial morphology in East Asian populations

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Daisuke Tomita, Tetsutaro Yamaguchi, Takatoshi Nakawaki, Yu Hikita, Mohamed Adel, Yong-Il Kim, Shugo Haga, Masahiro Takahashi, Akira Kawaguchi, Mutsumi Isa, Soo-Byung Park, Hajime Ishida, Koutaro Maki, Ryosuke Kimura
ObjectiveThe interferon regulatory factor 6 gene (IRF6) is one of the most conspicuous genes among a large number of candidate risk genes for non-syndromic cleft lip with or without cleft palate, which is considered to be a multifactorial defect. Variants of IRF6 are also suggested to affect normal craniofacial variations, especially in the area of the nose and the upper lip. In the present study, we used lateral cephalograms to establish the relationship between IRF6 and sagittal nasolabial morphology in healthy East Asian subjects.DesignGenomic DNA was extracted from 215 Japanese and 226 Korean individuals, and genotyped for five IRF6 single nucleotide polymorphisms (SNPs): rs17389541, rs642961, rs2013162, rs2235371, and rs7802. These SNPs were tested by multiple regression analyses for their association with craniofacial measurements obtained from lateral cephalometrics.ResultsWe detected a significant association between the derived variants, rs2013162 and rs2235371 and the distances between a facial bone plane indicated by distance from Nasion and Point A (NA plane) to soft tissue landmarks; the Subalare (NA-Sbal) and the Subnasale (NA-Sn) in the sagittal plane.ConclusionOur results indicate that IRF6 variants play an important role in the normal range of variation in nasolabial soft-tissue morphology.



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Interferon regulatory factor 6 variants affect nasolabial morphology in East Asian populations

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Daisuke Tomita, Tetsutaro Yamaguchi, Takatoshi Nakawaki, Yu Hikita, Mohamed Adel, Yong-Il Kim, Shugo Haga, Masahiro Takahashi, Akira Kawaguchi, Mutsumi Isa, Soo-Byung Park, Hajime Ishida, Koutaro Maki, Ryosuke Kimura
ObjectiveThe interferon regulatory factor 6 gene (IRF6) is one of the most conspicuous genes among a large number of candidate risk genes for non-syndromic cleft lip with or without cleft palate, which is considered to be a multifactorial defect. Variants of IRF6 are also suggested to affect normal craniofacial variations, especially in the area of the nose and the upper lip. In the present study, we used lateral cephalograms to establish the relationship between IRF6 and sagittal nasolabial morphology in healthy East Asian subjects.DesignGenomic DNA was extracted from 215 Japanese and 226 Korean individuals, and genotyped for five IRF6 single nucleotide polymorphisms (SNPs): rs17389541, rs642961, rs2013162, rs2235371, and rs7802. These SNPs were tested by multiple regression analyses for their association with craniofacial measurements obtained from lateral cephalometrics.ResultsWe detected a significant association between the derived variants, rs2013162 and rs2235371 and the distances between a facial bone plane indicated by distance from Nasion and Point A (NA plane) to soft tissue landmarks; the Subalare (NA-Sbal) and the Subnasale (NA-Sn) in the sagittal plane.ConclusionOur results indicate that IRF6 variants play an important role in the normal range of variation in nasolabial soft-tissue morphology.



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Historical Case of Cervical Penetrating Wound: From First Aid to Surgical Intervention

Objective. We report a case of cervical penetrating wound by posing the problem of its support and by analyzing the chain of survival of a patient to human sacrifice. Case Report. It was an 11-year-old boy admitted to the hosting service of cervical penetrating wound emergency occurring in a context of human sacrifice by weapon (knife). On admission, the conscious patient had a left cervical hematoma at the level of the cervical zone II and severe signs of acute anemia. The exploratory cervicotomy, carried out 12 hours after the trauma under transfusion, allowed us to highlight a section of the front edge of the sternocleidomastoid and previous jugular muscles under hyoid. We noted the presence of a linear wound of 1 cm at the level of the left internal jugular vein. The wound of the internal jugular vein has been repaired with the Prolene 4.O. The outcome was good, allowing the exit 10 days after cervicotomy. Conclusion. The causal circumstances of cervical penetrating wounds are diverse. Their importance or their severity depends on the causative circumstances dominated by aggression and attempts to autolysis. Human sacrifice, with use of the weapon, is an exceptional circumstance.

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Lingual Osseous Choristoma of the Tongue Base: Unusual Presentation of a Rare Entity

Osseous lesions of the tongue, also referred to as osseous choristomas, are benign growths of bony tissue. These lesions are not true neoplasms but rather represent growth of normal tissue at an abnormal location. Clinically, they appear as exophytic masses of the tongue, and they are treated by surgical excision. Lingual osseous choristomas are rare entities, with only 71 reported cases in the literature. We present the case of a lingual osseous choristoma of the tongue base in a 21-year-old female. Of the cases of lingual osseous choristoma reported in the literature, ours is only the fifth case to involve this location.

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A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately.

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