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Scientize Publishers - scientize - Publishers

Scientize Publishers

Introduction

Scientize is an open access, internationally peer-reviewed Publishers that are indulged in publishing original articles with an emphasis on the latest research findings. Scientize aspires to bring eminent original findings of research information across the globe into light and aims to build an efficient platform for the researchers/readers all over the world. Scientize publishes articles from around the world presenting results of major works like Case studies, Reviews from all the disciplines of emerging sciences. The motto of Scientize is to intellectualize the global society by providing them with the advancements in scientific research.

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Scientize Publishers is a comprehensive destination for the recent and the latest discoveries in the science, technology, medicine, and engineering. Scientize has been serving the scientific community relentlessly with its open access platform for publishing the research outcome to reach the global scientific fraternity. Scientize with its standard review process and prompt editorial policies is a credible source for publishing the advancements in science and technology to benefit the society at large. In order to promote an inclusive publication and access to information for all, we follow open access-author pay model.

In this journey of publishing, the publisher received several awards and accolades for dedicated service and strictly considering ethical practices. Scientize Publishers has become an obvious choice for the researchers and academicians to showcase their excellent contributions. The publisher provides authors and readers a complete platform to share their work with the global community.

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The primary focus is to publish original research work with high standard and novelty along with other types of articles including review articles, short communication, Editorial, case reports, Commentary, Perspectives etc. Authors are being requested to follow individual journal guidelines for further specifications.

With the primary goal of distributing scientific understanding pertaining to various recent subjects, the Scientize journals are helping the leading authors from all over the world to share and exchange their novel and path breaking ideas to the world. The journals are acting as successful outlets for numerous scholars including faculty members, researchers and students and other eminent members of the fellow community.

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A Challenging Case of Chemoresistance in Locally Advanced Breast Cancer

Alshamrani AM, Alothmani SK, Dahman MM, Howil AA, Alzahrani AJ (2020) A Challenging Case of Chemoresistance in Locally Advanced Breast Cancer. Annal Cas Rep Rev: ACRR-102.

Annals of Case Reports & Reviews

Case Report A Challenging Case of Chemoresistance in Locally Advanced Breast Cancer Abdullah Mohammed Alshamrani, Suhaib khalid Alothmani, Mohammed Mousa Dahman, Abdulaziz Abdullah Howil, Abdulrahman Jaman Alzahrani* General Surgery Department, Security Forces Hospital Program *Corresponding author: Abdulrahman Jaman Alzahrani, General Surgery Department, Security Forces Hospital Program, P.O. Box 3643, Riyadh 11481 Saudi Arabia. Email: a-alrahman@hotmail.com  Citation: Alshamrani AM, Alothmani SK, Dahman MM, Howil AA, Alzahrani AJ (2020) A Challenging Case of Chemoresistance in Locally Advanced Breast Cancer. Annal Cas Rep Rev: ACRR-102. Received Date: 06 March, 2020; Accepted Date: 11 March, 2020; Published Date: 17 March, 2020. Abstract Neoadjuvant chemotherapy is the standard of care in inoperable locally advanced breast cancer (LABC), as it helps in reducing tumor burden and facilitating surgical resection. We describe a 56-year-old post-menopausal woman who presented with a huge, right breast mass extending from the clavicle to the mid abdomen. A chest-abdomen-pelvis computed tomography showed the mass invading the pectoralis muscles and right axillary lymph node with no evidence of distant metastasis. A needle core biopsy revealed an infiltrating ductal carcinoma (Scarff-Bloom- Richardson grade 3). A multidisciplinary collaboration was undertaken, and the patient was started on docetaxel; however, after three cycles of docetaxel, she showed no improvement and was readmitted for palliative mastectomy with skin grafting. A post-operative histopathology examination of the excised tumor revealed an invasive micropapillary carcinoma. A multidisciplinary approach is the cornerstone for the treatment of LABC. In the case of chemoresistance, very few treatment options are available. Keywords: breast cancer, breast neoplasm, chemotherapy resistance, docetaxel. Introduction Breast cancer treatment depends on the stage of the disease and pathologic characteristics of the primary tumor, including tumor receptor status and grade. Patients are considered to have a localized disease if there is no clinical or radiological evidence of remote metastasis [1]. However, many patients with locally advanced breast cancer will relapse after tumor resection if they do not receive systemic therapy [2]. Several factors determine whether a patient with locally advanced breast cancer will relapse, including primary tumor size, number of axillary lymph nodes involved, and histological characteristics of the primary tumor [3]. The management of locally advanced breast cancer poses a lot of challenges to clinicians. Recently, it was reported that neoadjuvant chemotherapy is beneficial in locally advanced disease in that it can effectively eradicate subclinical disseminated tumoral lesions, thus improving the long term and disease-free rates in these patients [3]. Unfortunately, resistance to chemotherapy complicates treatment in locally advanced breast cancer. Chemoresistance to an anthracycline and/or a taxane is common in patients who receive one or both agents [4]. Some patients who receive a single, anti-neoplastic agent for an extended period may develop resistance to several other structurally unrelated compounds, further complicating treatment, as few treatment options are available for patients who develop chemoresistance to these drugs. After anthracycline- or taxane-based chemotherapy failure, capecitabine, gemcitabine, vinorelbine, or albumin-bound paclitaxel may be offered to these patients [4]. Despite salvage therapy with capecitabine as a single agent, or in combination with another chemotherapy agent, the response rates in these patients are still low and range from 20–30%, with a median duration of response of less than six months [5,6]. Additionally, salvage therapies do not always yield results that translate into improved long-term survival. We present the case of a patient with locally advanced breast cancer who failed to respond to three cycles of taxane-based chemotherapy and palliative mastectomy was performed as a result. Case Presentation This is the case of a 56-year-old, post-menopausal woman who, in October 2016, presented to the breast and endocrine clinic of our institution after noticing a breast mass the size of an olive, which increased with time. In August 2017, the patient’s family noticed the breast swelling had increased, and she started complaining of pain and a hot sensation over the right breast. Her medical and surgical histories were unremarkable. She reported a history of anorexia and weight loss and had a history of breastfeeding. She had no family history of breast cancer, oral contraceptive use, trauma, or exposure to radiation.  On physical examination, the patient was mildly cachectic and nervous and had stable vital signs. A local examination of the right breast showed a huge mass extending from the clavicle to the mid abdomen, which restricted the patient’s daily activities (Figure 1). The mass was tender and hard in consistency. Also, there was a palpable right axillary lymph node, which was firm and mobile. There was no discharge or clinical evidence of metastasis. Figure 1: Huge breast mass extending from the clavicle to the mid abdomen.  A mammography was performed, and it showed a huge isodense, fairly well-defined mass occupying most of the right breast, with enlargement of the breast. It measured approximately 20 cm in its largest dimension (Figure 2). The overlying skin was thickened, and no microcalcifications were observed. The axillary regions could not be included in the examination; however, some lymph nodes were noted. Figure 2: Huge, fairly well-defined, isodense mass occupying most of the right breast with enlargement of the breast. The mass measures approximately 20 cm in dimension and is associated with thickening of the overlying skin. No microcalcifications present.  An ultrasound examination of the right breast showed a fairly well-defined, large, complex, heterogeneous mass showing some vascularity. It measured approximately 16 cm in its largest dimension and occupied most of the right breast (Figure 3. Figure 3: Fairly well-defined, large, complex, heterogeneous mass showing some vascularity. The mass measures approximately 16 cm in dimension and occupies most of the right breast.  A chest-abdomen-pelvis computed tomography showed the mass invading the pectoralis muscles and right axillary lymph nodes (Figure 4). There was no evidence of distant metastasis. Figure 4: A chest-abdomen-pelvis computed tomography shows the mass invading the pectoralis muscles and right axillary lymph node. A core needle biopsy was performed, and a histopathology examination revealed infiltrating ductal carcinoma, with a Scarff-Bloom-Richardson grade of 3/3. There was no in situ component, lympho-vascular or perineural invasion, and no microcalcification. Furthermore, the tumor was estrogen-receptor-, progesterone-receptor-, and HER2-negative; the Ki-67 index was 60%.  A multidisciplinary collaboration was undertaken, and the patient was started on chemotherapy. After receiving three cycles of chemotherapy with docetaxel, the patient showed no improvement. After failure of chemotherapy, she was readmitted for a palliative mastectomy with skin grafting (Figure 5). A post-operative histopathology examination of the excised tumor revealed invasive micropapillary carcinoma of the right breast with necrosis. The tumor measured 27 cm in its largest dimension. Negative margins were achieved, and the lymph node ratio was 10/18. The patient did well, and her post-operative course was uneventful. A skin graft was obtained, and it had a viability of 90%. She was discharged on the sixth day post-operative and was followed up at the oncology, breast and endocrine clinics. Figure 5: Gross appearance of the right chest wall (A) and tumor (B) after breast resection. Skin grafting was performed after mastectomy (C). Discussion Locally advanced breast cancer predominantly represents primary breast cancer and includes stages of T3, T4, and TXN2, except for cases with distant metastases [1]. It is further classified into operable and inoperable types [1]. The characteristics of our patient were consistent with locally advanced breast cancer: her tumor measured approximately 20 cm in its largest dimension and directly extended to the chest wall. The rate of local recurrence in patients with locally advanced disease is typically high, with the risk of death increased in patients who do not respond to neoadjuvant chemotherapy [7]. The standard of care in operable, locally advanced breast cancer is radical surgery followed by post-operative chemotherapy and radiotherapy [8]. Neoadjuvant chemotherapy is an option in patients in whom breast conservation is a goal of therapy. In patients with inoperable, locally advanced breast cancer complicated with skin edema, ulceration, and extension to the chest wall, the best approach is to decrease infiltration prior to surgery [3]. Surgery as a first line of treatment is ineffective in preventing early local recurrence and distant metastases [2]. Thus, the treatment options in patients with inoperable locally advanced breast cancer include systematic chemotherapy and local radiotherapy [3]. Evidence shows that locally advanced breast cancer is usually complicated by the presence of distant micro-metastases, which could subsequently develop into new metastases if only simple regional treatment options are offered [2]. Therefore, treatment for locally advanced breast cancer is usually centered on pre-operative neoadjuvant chemotherapy to control the disease locally and convert the inoperable LABC into a resectable one. This approach has been shown to effectively prevent distance metastases and improve patient survival [2]. Although clinicians have a better understanding of the treatment options for breast cancer due to improvements in their knowledge of the interconnectedness of signaling pathways and biological behaviors, the treatment of locally advanced disease remains challenging. Breast cancer treatment requires the joint efforts of a multidisciplinary team, as the alternatives for treatment are constantly expanding. It is essential to develop a plan based on knowledge of the benefits and potential acute and late toxic effects of each of the therapy regimens. In our case, a multidisciplinary collaboration was undertaken, and the patient was started on docetaxel therapy. However, three cycles of chemotherapy with docetaxel did not result in the improvement of her condition. The patient was symptomatic, and an impending ulceration of the skin overlying the tumor prompted the medical team to offer palliative mastectomy with skin grafting. The mechanism underlying chemoresistance in our patient was not investigated. Resistance to therapy is caused, in part, by a process called genetic amplification, which allows cancer cells to increase their immortality and invasion properties, thereby rendering the disease uncontrollable and causing a high mortality [9]. In an experimental study that investigated the mechanisms underlying acquired resistance to taxanes in MCF-7 breast cancer cell lines, investigators determined that acquired resistance was specific to the chemotherapeutic agent selected and was not due to processes that led to multidrug resistance [10]. Furthermore, they demonstrated that paclitaxel-resistant tumor cells had a low accumulation of paclitaxel and had a very high expression of drug efflux proteins [10]. In conclusion a multidisciplinary approach is the cornerstone for the treatment of locally advanced breast cancer. Neoadjuvant chemotherapy is the standard of care in patients with inoperable locally advanced disease. However, in the case of chemoresistance, few treatment options are available and surgical resection may be considered. References 1.       Garg PK, Prakash G (2015) Current definition of locally advanced breast cancer. Curr Oncol22: e409-e410.2.       Zhou X, Li Y (2016) Local Recurrence after Breast-Conserving Surgery and Mastectomy Following Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer-a Meta-Analysis. Breast Care 11: 345-351.3.       Wang M, Hou L, Chen M, Zhou Y, Liang Y, et al. (2017) Neoadjuvant Chemotherapy Creates Surgery Opportunities For Inoperable Locally Advanced Breast Cancer. Sci Rep 7: 44673. 4.       Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, et al. (2005) Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 23: 7794-7803.5.       Polyzos A, Kalbakis K, Kentepozidis N, Giassas S, Kalykaki A, et al. (2011) Salvage treatment in metastatic breast cancer with weekly paclitaxel and bevacizumab. Cancer Chemother Pharmacol 68: 217-223.6.       Roché H, Vahdat LT (2011) Treatment of metastatic breast cancer: second line and beyond. Ann Oncol 22: 1000-1010.7.       Spanheimer PM, Carr JC, Thomas A, Sugg SL, Scott-Conner CE, et al. (2013) The Response to Neoadjuvant Chemotherapy Predicts Clinical Outcome and Increases Breast Conservation in Advanced Breast Cancer. American journal of surgery 206: 2-7.8.       National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology – Breast Cancer, v.2. [Internet]. 2007 [cited 2019 Jun 24]. 9.       Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B (2017) The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv Pharm Bull 7: 339-348.10.   Wang H, Vo T, Hajar A, Li S, Chen X, et al. (2014) Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells. BMC Cancer 14: 37.  

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April 2020

Impact Factor 0.560

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An Uncommon Presentation of Breast Adenomyoepithelioma: A Case Report

Alshamrani AM, Alzarea AA, Alshalwah MZ, Alrabee EA, A D Saud (2020) An Uncommon Presentation of Breast Adenomyoepithelioma: A Case Report. Annal Cas Rep Rev: ACRR-103.

Annals of Case Reports & Reviews

Case Report An Uncommon Presentation of Breast Adenomyoepithelioma: A Case Report Abdullah Mohammed Alshamrani*, Abdullah Ahmed Alzarea, Muruf Zaid Alshalwah, Eman Ali Alrabee, Alrasheedi Saud D General Surgery Department, Security Forces Hospital Program, Riyadh, Saudi Arabia *Corresponding author: Abdullah Mohammed Alshamrani, General Surgery Department, Security Forces Hospital ProgramP.O. Box 3643, Riyadh 11481 Saudi Arabia. Tel: 0096655 326 6990; Email: alshamraniabdullah92@gmail.com  Citation: Alshamrani AM, Alzarea AA, Alshalwah MZ, Alrabee EA, A D Saud (2020) An Uncommon Presentation of Breast Adenomyoepithelioma: A Case Report. Annal Cas Rep Rev: ACRR-103.  Received Date06 March, 2020; Accepted Date: 11 March, 2020; Published Date: 17 March, 2020. Abstract Background: A breast adenomyoepithelioma is an uncommon tumor characterized by the presence of epithelial and myoepithelial cells. Case Report: We describe a 47-year-old woman who presented with a right breast mass of four-year duration. An examination of the breasts revealed two masses in the right inner quadrant of the right breast measuring 1 x 1 cm and 2 x 2 cm in dimension. A mammogram favored a lesion highly suspicious of malignancy, suggesting further examination. An ultrasound examination confirmed the mammography and a biopsy was subsequently performed. A biopsy revealed findings suggestive of duct adenoma. The tumor was excised, and the specimen was sent for histopathological examination. The histopathological findings were consistent with adenomyoepithelioma. The patient was discharged one day after surgery and did not present any complaints. Conclusion: Although most adenomyoepitheliomas have a benign course, it is essential for clinicians to identify these tumors, as the radiologic and cytologic characteristics can mimic malignant lesions. A definitive diagnosis can be made after a histopathologic examination, and tumor excision may be helpful in preventing recurrence or malignant change. Keywords: Adenomyoepithelioma, breast, myoepithelial cells, neoplasm Introduction Breast adenomyoepitheliomas are rare tumors characterized by a biphasic neoplastic proliferation of luminal and myoepithelial cells around small epithelial lined spaces [1]. These tumors have been described to have several histologic patterns, including the tubular, lobulated, or spindle subtypes [2]. The spindle subtype is primarily composed of spindled myoepithelial cells with visible epithelial lined spaces that may be challenging to identify in some sections. Consequently, this subtype may be erroneously mistaken for a leiomyoma [2]. The tubular growth pattern is composed of small, round tubules lined by luminal epithelial cells. Although this subtype has a histologic pattern similar to that in tubular adenomas, it is characterized by more prominent and hyperplastic myoepithelial cells. The lobular subtype comprises clear, eosinophilic, or plasmacytoid myoepithelial cells proliferating around epithelial-lined spaces [2].  Many adenomyoepitheliomas are benign and the standard treatment is tumor resection with negative margins [3]. However, there have been cases of local recurrence or isolated metastasis to the lymph nodes, and some cases of malignant transformation have been reported [4]. Given that these tumors are rare, few reports have described the clinical presentation and histologic findings in patients with breast adenomyoepitheliomas [3,5]. We report a case of an uncommon presentation of breast adenomyoepithelioma in a middle-aged woman.  Case Report A 47-year-old woman presented with a complaint of a right breast mass of four-year duration. Her history was remarkable for hypertension and dyslipidemia. She also reported experiencing trauma to the right breast after an object fell on it, which caused bruising to the breast; however, she ignored it.  One year later, the patient noticed a right breast mass, which was painless and did not change in size. However, she did not seek medical advice. Two years later, she was offered a mammography during a breast awareness campaign and was subsequently transferred to our hospital for further evaluation of the breast mass.  The patient had no history of nipple discharge, skin changes, or masses in other parts of the body. Her menstrual cycle was regular, and she was nulliparous. No family history of breast cancer was reported. An examination of the breasts revealed two masses in the right inner quadrant of the right breast measuring 1 x 1 cm and 2 x 2 cm in dimension. The masses had irregular borders and were fixed. There was no nipple discharge or retraction. There were also no skin changes or palpable axillary lymph nodes. The left breast was normal with no palpable axillary lymph node. A mammogram showed a round, dense lesion measuring 3.5 x 3.8 cm in the right breast and another measuring about 1 cm in dimension (Figure 1).              

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April 2020

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Life-Threatening Methemoglobinemia Caused by Topical Anesthetic Given Prior to Transesophageal Echocardiography

Egbuche O, Nwagbara K, Hanna B, Abe T, Onwuanyi A (2020) Life-Threatening Methemoglobinemia Caused by Topical Anesthetic Given Prior to Transesophageal Echocardiography. Annal Cas Rep Rev: ACRR-104.

Annals of Case Reports & Reviews

Case Report Life-Threatening Methemoglobinemia Caused by Topical Anesthetic Given Prior to Transesophageal Echocardiography Obiora Egbuche1 MD, MPH; Kenechukwu Nwagbara2* MD, MPH; Bishoy Hanna1 MD; Temidayo Abe1 MD; Anekwe Onwuanyi1,3 MD 1Morehouse School of Medicine, Department of Cardiovascular Disease, Atlanta, GA.2Mercy Hospital Joplin, Missouri, USA.3Grady Health System, Atlanta, GA. *Corresponding author: Kenechukwu Nwagbara MD, MPH, Department of Hospital Medicine, Mercy Hospital 100 Mercy Way Joplin, MO. Tel: 682-970-5475; Email: kcnwagbara@gmail.com  Citation: Egbuche O, Nwagbara K, Hanna B, Abe T, Onwuanyi A (2020) Life-Threatening Methemoglobinemia Caused by Topical Anesthetic Given Prior to Transesophageal Echocardiography. Annal Cas Rep Rev: ACRR-104. Received Date: 15 March, 2020; Accepted Date: 19 March, 2020; Published Date: 26 March, 2020 Abstract Topical benzocaine spray is a local anesthetic agent that is commonly used during transesophageal echocardiography (TEE). This agent is believed to be safe because it has very low systemic absorption. We report a case of life-threatening methemoglobinemia following very minimal dose of benzocaine spray. Introduction / Background Methemoglobinemia is a rare but potentially life-threatening medical condition that may occur after use of high doses of topical anaesthetics for endoscopic procedures. We present a case of profound, life-threatening methemoglobinemia following minimal dose of topical benzocaine spray for transesophageal echocardiography (TEE) in a patient with normal hemoglobin levels. Clinicians who use benzocaine during a TEE need to be aware that this potential complication can occur even with use of very minimal doses, be able to recognize early symptoms, and promptly initiate management.  Case Report A 66-year-old male with a medical history of schizophrenia presented after a gun-shot injury to the chest. He developed respiratory failure due to massive hemopneumothorax requiring a chest tube and short-term mechanical ventilation. Following clinical improvement, he was extubated to a nasal cannula. However, his clinical course was complicated by encephalopathy, staphylococcal bacteremia and persistent fever requiring a TEE to exclude infective endocarditis. The patient received 0.5 second of benzocaine spray prior to procedure and was noted to be cyanotic shortly after the procedure. Oxygen saturation persistently remained around 70% despite escalation of respiratory support to a bilevel positive airway pressure. An immediate arterial blood gas revealed a methemoglobin level of 69.5%. The pH, partial pressure of oxygen, and carbon dioxide were 7.47, 194 mmHg and 34 mmHg respectively. The patient responded favorably to treatment with 2 doses of intravenous methylene blue and repeat methemoglobin level was 0.2%. Discussion Methemoglobinemia is a rare disease. It is a hemoglobinopathy that can be either inherited or acquired [1-3]. The acquired methemoglobinemia is due to exposure to an oxidizing chemical or drug resulting in conversion of ferrous hemoglobin to ferric hemoglobin. Methemoglobinemia usually occurs when the oxidizing mechanisms surpasses the endogenous reducing mechanisms that primarily include the enzymatic activity of cytochrome b5 reductase and nicotinamide adenine dinucleotide (NADH) methemoglobin reductase [1-3]. The ferric hemoglobin binds tightly to oxygen and does not release oxygen to the tissues. Oxygen deprivation at tissue level may lead to cyanosis and even death [1-3].  Clinically, acquired methemoglobinemia is usually characterized by cyanosis, low oxygen saturation on pulse oximetric readings, chocolate-brown arterial blood, and a normal or high partial pressure of oxygen on an arterial blood gas sample. Symptoms can range from lethargy, stupor, deteriorating consciousness to dysrhythmias [4], and cardiopulmonary collapse [5]. The occurrence of neurologic abnormalities and death is proportional to the degree of methemoglobinemia [5]. The diagnosis of methemoglobinemia is confirmed by direct measurement of methemoglobin levels on arterial blood sampling. Treatment is effective when initiated promptly and includes oxygen therapy, discontinuation of causative medications, and intravenous administration of the antidote methylene blue, a thiazine dye that acts as an electron donor activating the nicotinamide adenine dinucleotide phosphate methemoglobin reductase pathway [5]. In the hospital setting, patients who develop cyanosis which fail to respond to supplemental oxygen following exposure to topical anesthetics should be suspected to have methemoglobinemia. Various medications have been implicated as potential causes of methemoglobinemia. Some of these medications include antibiotics (trimethoprim, sulphonamides, dapsone), local anesthetics (lidocaine, benzocaine), nitrites and nitrate derivatives [6]. The local anesthetics are usually employed in various endoscopic procedures. Transesophageal echocardiography is a commonly performed cardiac procedure with a low incidence of complications in the United States [6]. Local anesthetic agents are used during TEE to anesthetize the oropharynx before esophageal intubation. A typical 1-second spray provides 150 to 200mg of the medication. Investigations in healthy volunteers indicate that a 2-second spray marginally affects systemic methemoglobin levels (0.8%-0.9%) [7]. Several risk factors may predispose a patient to develop methemoglobinemia on exposure to benzocaine. These include excessive dose, elderly age, enzyme deficiencies, hypoxia, malnutrition, mucosal erosion/damage and sepsis [4]. Our patient received 0.5 second spray of benzocaine and developed life-threatening methemoglobinemia. He had poor pulmonary reserve and may have aspirated the benzocaine spray since he was unable to protect his airway due to encephalopathy. Rapid absorption of benzocaine spray through the respiratory epithelium may have contributed to development of profound methemoglobinemia. Conclusion Profound life-threatening methemoglobinemia may occur with minimal doses of benzocaine spray and may be more common in encephalopathic patients with poor pulmonary reserve. Early recognition and prompt treatment may be life-saving and obviate the need for intubation and mechanical ventilation. References 1.       Ashurst J, Wasson M (2011) Methemoglobinemia: a systematic review of the pathophysiology, detection, and treatment. Delaware medical journal. 83: 203-208.2.       Moore TJ, Walsh CS, Cohen MR (2004) Reported adverse event cases of methemoglobinemia associated with benzocaine products. Archives of internal medicine. 164: 1192-1196.3.       Greer FR, Shannon M (2005) Infant methemoglobinemia: the role of dietary nitrate in food and water. Pediatrics. 116:784-786.4.       Filipiak-Strzecka D, Kasprzak JD, Wiszniewska M, Walusiak-Skorupa J, Lipiec P (2015) The influence of lidocaine topical anesthesia during transesophageal echocardiography on blood methemoglobin level and risk of methemoglobinemia. The international journal of cardiovascular imaging. 31(4):727-731.5.       Kane GC, Hoehn SM, Behrenbeck TR, Mulvagh SL (2007) Benzocaine-induced methemoglobinemia based on the Mayo Clinic experience from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors. Archives of internal medicine. 167: 1977-1982.6.       BheemReddy S, Messineo F, Roychoudhury D (2006) Methemoglobinemia following transesophageal echocardiography: a case report and review. Echocardiography (Mount Kisco, NY). 23: 319-321. 7.       Guertler AT, Pearce WA (1994) A prospective evaluation of benzocaine-associated methemoglobinemia in human beings. Annals of emergency medicine. 24: 626-630.

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April 2020

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About A Lockdown: Are the Novel Etiological Therapies for the SARS-CoV-2 Effective?

Nataly EC and Augusto FAR (2020) About A Lockdown: Are the Novel Etiological Therapies for the SARS-CoV-2 Effective? Annal Cas Rep Rev: ACRR-106.

Annals of Case Reports & Reviews

Mini Review  About A Lockdown: Are the Novel Etiological Therapies for the SARS-CoV-2 Effective? Echevarria-Castro, Nataly and Fernandez-Aristi, Augusto R* School of Medicine, Research and Innovation Centre of the Faculty of Health Sciences., Universidad Peruana de Ciencias Aplicadas, Lima, Peru *Corresponding author: Augusto R. Fernandez-Aristi, School of Medicine, Research and Innovation Centre of the Faculty of Health Sciences., Universidad Peruana de Ciencias Aplicadas, Lima, Peru. Email: pcmerfer@gmail.com   Citation: Nataly EC and Augusto FAR (2020) About A Lockdown: Are the Novel Etiological Therapies for the SARS-CoV-2 Effective? Annal Cas Rep Rev: ACRR-106. Received Date: 26 March, 2020; Accepted Date: 30 March, 2020; Published Date: 06 April, 2020 Abstract Even though the humankind is familiar to disease outbreaks and pandemics, one of the few that has negatively impacted not only public health, but economy, finances among other vital government sectors is the COVID-19 caused by the SARS-CoV-2. These Viral family are common pathogens that can cause a variety of clinical entities, from respiratory symptoms to gastrointestinal ones ranging from mild to death threating cases. Many countries worldwide had already reported numerous index and imported cases and the death toll continues to trend up most dramatically in European and Asian countries. For this reason, one of the main strategies to control and contain the widespread dissemination of the virus are social isolation and even lockdown. In spite this measure, the number of cases continues to trend up with the lethality rate and the burden of the disease slowly increasing. Even though this disease presents a challenge, not only in diagnosis, but in specific etiological treatment, many researchers are developing many SARS-CoV-2 specific drugs and agents to decrease the alarming numbers of mortality and death toll. Given those treatments are novel, most of them have increasingly growing information regarding effectiveness and safety. In this article, we will try to compilate all the current novel therapies that are currently being developed for this on-growing pandemic.  Background The first few cases of this novel Coronavirus appeared in early December 2019, in the city of Wuhan, China. This first poll of patients was composed by 44 new cases of an unknown entity pneumonia, among which some had a common history of contact with wild animal’s trade in the Huanan Seafood Wholesale market. [1]. In January of this year, a working group organized by doctors, epidemiologists and other scientists discovered the causal agent, called 2019-nCoV [2]. As the days passed, the increase in new cases within the city and the appearance of cases outside of China began to attract the attention of the entire scientific community. Prevention measures began to be applied throughout the country, such as social isolation and the application of quarantine laws. Despite Chinese efforts, at the end of January, the first patient with a positive result of the 2019-nCoV virus was found in France. Few days later, new cases began to appear in various countries in Europe (Germany, Italy, Spain) [3,4] and America [5]. Following the trend that occurred in China, the virus spread geographically until on March 11, 2020, the WHO declared the COVID 19’s pandemic (new name of the previously called virus 2019 - nCoV). At the time of writing this article, 417 966 cases have been confirmed worldwide, with a total of 18 615 deaths, with Italy, Spain and the United States being the new sources of infection [6]. Various studies have been carried out throughout these months and a lot of useful information has been discovered. It is known that Covid19 can affect patients of all ages, both sexes. It is compatible with cough, fever (> 37.5 C), myalgia, fatigue, rhinorrhea, nausea or vomiting, diarrhea or even respiratory distress that can lead to acute respiratory distress syndrome and to death [7,8]. Several studies have been realized to predict which of these patients going to present serious complications. It has been shown that advanced age (> 70 years), have comorbidities as hypertension, coronary heart disease or diabetes, high fever (> 39 C), initial tachypnea or dyspnea, accomplish qSOFA criteria (FR> 22, sensory disturbance, MAP <100), a high CURB65 score, leukocytosis or leukopenia, lymphocytosis or lymphopenia, thrombocytosis or thrombopenea, elevated LDH, ferritin or procalcitonin [9,10] predisposes to severe disease. The treatment of these severe manifestations is merely symptomatic and is based on support measures pending the immune response of the guest [11,12]. For the medical community, this situation is an emerging problem due to the few specific tools that are available for the Covid 19. For this reason, the main scope of this article is to give a focused review of the pathophysiology of the SARS-CoV-2 and novel therapies being developed and used to treat this viral entity.    Virology and pathogenesis Coronavirus are a widespread subfamily of enveloped, RNA single stranded positive viruses that can infect either humans or animals [13] being the most important reservoirs bats (Rhinolophus affinis) and Civets (Civettictis civetta) [14]. Inside this viral subfamily, four genera Alpha, Beta, Gamma and Delta exists; but the only ones that could potentially cause diseases in humans are the first two [15]. The Beta Coronavirus genera is the most feared one since it has strains, such as SARS-CoV, MERS-CoV and the new SARS-CoV-2; that can cause severe respiratory insufficiency and other clinical traits such as hepatic insufficiency and neurologic disturbances [16]. Upon complete genomic sequencing, the resemblance between the SARS-CoV-2 and its other genera counterparts are a least 95% [17] with its main differences in the mutation and adaptability rate, being the SARS-CoV-2 less dramatic [18] than the MERS-CoV and SARS-CoV. The genome of the SARS-CoV-2 encodes 2 polyproteins (ppa1a and pp1b), 16 non-structural proteins (NSP) translated from one of the first open reading frames (ORF 1a/1b) and 4 structural proteins that elicits attachment, transmembrane transport and interferes with host immune response [15]. The first of these structural proteins is the Spike (S) Glycoprotein which elicits the entry to the Type II pneumocyte through the ACE2 receptor. After the interaction of the receptor with the S1 subunit, the envelope of the virus fuses with the host cell through the S2 subunit [18,19]; thus, releasing the RNA to the cytoplasm and promoting the formation of a double membrane vesicle called the Replication-Transcription Complex (RCT) [20]. From this start-point, more RNA is synthetized for further encoding of accessory and other structural proteins [15,19]. The cytoplasmatic RNA concentration spike activates the sensors RIG-I and MDA 5, that starts innate immune response [21]. These sensors ends-up in the phosphorylation of IRF-3 and starts the Interferon-I (IFN-I) transcription [15,21]. Another innate immune response is the cytoplasmic increase of catalyse 2,5-oligoadenylate (2’-5’OA) that serves as a second messenger for the activation of RNAse L which serve as cleavage for viral st-RNA [22, 23]. At this point, the Matrix (M) protein of the SARS-CoV-2 directly induces the suppression of the IFN-I transcription along with the highly sensitive to ds-RNA ORF4a which transcripts nsp-1 that cleaves host’s mRNA. [18,21] Other mechanism of immune suppression is the activation of ORF4b which encodes NS2a that serves as phosphodiesterase for the 2’-5’ OA; completely shutting down the host cell immune response [23]. Finally, once the host cell is completely infected, the SARS-CoV-2 starts a cytokine storm by the upregulation of IL-1-β driven by the ORF3a and Envelope (E) structural protein [18,23]; overall causing cell death and cytopathy through pyroptosis, necrosis and apoptosis. The membrane ruptures further sheds more viral particles, thus promoting the interaction and infection of other host cells. Vaccines: Are we there yet? Multiple advances are being developed to find an efficient and safe vaccine to generate immunity in the host. Most of the advances are based on the target surface - exposed spike (S protein) glycoprotein as the greatest generator of cellular and humoral immune response [24,25]. Various strategies have been carried out, such as using the entire S protein or only cell-anchored protein regions (S1 subunit RBD region) and expressing it in virus-like particles, DNA or viral vectors to generate immunogenicity [26,27]. This technique intends to obtain antibodies that inhibit viral-cellular binding and viral uncoating. One of the actions is to use the C-terminal region of the RBD in porcine Delta Coronavirus [28]. It is planned to use viral vectors (Adenovirus, rabies virus) to achieve immunity against MERS CoV, due to the immunogenic similarity of SARV-CoV-2 and MERS CoV [29]. Despite the genetic similarity between the SARV-CoV and the SARV-CoV-2, when comparing the protein S of both viruses, it was discovered that in the immunogenic region of the first (S1 subunit) it had multiple variable residues [30], so it could be that if a SAR-CoV vaccine is injected in the host, a humoral response against SARV-CoV-2 will not develop. Other viral particles that are planned to generate an immune response are viral epitopes that interact with cytotoxic T lymphocytes [31]. By March 20, 2 phase 1 vaccines [32] are available by the WHO. The first one was done in Beijing, China using a Non-Replicating Viral Vector (adenovirus). Said vaccine is planned to be inoculated in healthy young people between 18 and 60 years old, currently in the participant recruitment phase. The first results of phase 1 are expected to come out in approximately 6 months [33]. The second, carried out by the National Institute of Allergy and Infectious Diseases in the United States, plans to use an mRNA that encodes protein S in its entirety. There are 45 young healthy subjects who will receive the vaccine for the first time on day 1 and for the second time on day 29 and follow them for 12 months to see safety, reactogenicity and immunogenicity. Currently the study has already started, and the first results will be released in June [34]. Additionally, 42 vaccines are in preclinical stage. Hydroxychloroquine: A multi-use drug? Hydroxychloroquine is a drug mainly used to treat malaria and various rheumatic diseases. Has multiple mechanism of action, the principal is to increase the liposomal pH in the antigen presenting cells (ACP), causing a decrease in the TLR signalling of the dendritic cells, decreasing the presentation of antigens to the T cells with anti-inflammatory effects [35]. It also interferes with the union of various viruses with the cell, altering the synthesis of sialic acid in the binding ligands, inhibiting virus-cell union [36]. It is part of the WHO essential drugs list, is used worldwide due to the efficacy, safety and economic accessibility that has [37]. In vitro effectiveness has been seen in the treatment of various infectious diseases such as HVB, HVA, polio, influenza virus A and B, and finally SARS-CoV-1, where it shows to inhibit viral replication in lung cells [38, 39]. On February 2020, a research letter published an in vitro experiment evaluating the efficacy of hydroxychloroquine in Vero E6 cells infected with SARS-CoV-2, demonstrating the decrease of viral replication at an effective concentration of 6.90 UM [40]. These in vitro studies began to be replicated in various cities in Asia and Europe, demonstrating the efficacy and safety against Covid19 at doses of approximately 200 mg-500mg twice a day for 10 days [41,42]. Various clinical trials are currently underway to see if such effectiveness and safety can also be demonstrated in vitro. These studies, still in the recruitment phase of participants, will use varying doses between 0.1g BID and 1g every 2 days [43]. Despite all good pre-clinical evidence, the WHO and CDC have not established specific recommendations for the use of hydroxychloroquine due to lack of evidence in randomized clinical studies in real patients. Remdesevir: A faithful copy-cat? In the 2016, after the Ebola Virus outbreak, a monophosphoromidate pro-drug called GS-5734 was developed by Gilead Sciences for the treatment of this disease [44]. At that time, the compound was used in multiple murine and non-human primate models [45,46] and showed good distribution to peripheral blood mononuclear cells, turning to its active form after 2 hours of infusion with an acceptable intracellular half-life of 14 hrs [47]. It also showed relatively low half-maximum effective concentrations (EC50) in tissue cultures [47]. Afterwards, one of the first clinical experiences with the drug was a compassionate-use treatment of a British nurse suffering of Meningoencephalitis caused by Ebola Virus that resulted in the resolution of the entity along with any complications [48]. This drug, renamed as Remdesevir (RDV), also exhibited antiviral activity against Marburg Virus [46], Members of the Paramyxoviridae family and Pneumoviridae [49]; demonstrating the broad-spectrum antiviral activity. Regarding the use of RDV in the SARS-CoV-2 outbreak, reports in primary human airway epithelial cell cultures showed inhibition of the virus along with less lung cytopathy [47]. The mechanism proposed for these effects is that the triphosphate form of this nucleotide analogue functions as a competitive inhibitor of the divergent RNA-dependent RNA polymerase composed of nsp7, nsp8 and nsp12 [50]. This causes arrested RNA synthesis with a delayed chain termination due to the exchange of normal viral ATP to a stop signalling in i+3 and i+4 positions [50]. Also, probable viral resistance to RDV was tested with a model of a Beta coronavirus called Murine Hepatitis virus (MHV) and showed that two amino acid substitutions (F467L and V553L) elicited an increase in intracellular EC50 [51] due to the exonuclease effect of nsp14 that these mutations promoted [52]. In spite this trait, the viral fitness of the mutant strains is decreased and are mostly outcompeted by Wild-Type strains of the MHV model [46, 50] and probably confers a protective motif for the RDV against future resistance. Using this knowledge, RDV was used in rhesus macaque models to test the efficacy of prophylactic and therapeutic models [53] and elicited promising results such as preventing clinical disease, inhibited replication in tissues and improved pulmonary function [53]. This preliminary data was used for the treatment of a patient with COVID-19 in Washington, DC that resulted in improved clinical condition without any adverse effect [54]. In this matter, two phase 3 RCT are being performed in China to evaluate the efficacy and safety of parenteral RDV in regimens that resulted with positive outcomes in Ebola virus diseases treatment [55]. We as a community must wait for the results of these promising RCT’s and decide if the RDV would be beneficial as treatment. Lopinavir/Ritonavir: Similarities between HIV and SARS-CoV-2? In mid-2003, in south China, the first severe and transmissible epidemic appeared, SARS epidemic [56]. Due to the need to find an efficient therapy, in 2004 a study was carried out with Lopinavir, a type 1 aspartate protease inhibitor and Ritonavir, a cytochrome p450 inhibitor, two world-known drugs whose combination is used to fight the Immunodeficiency Virus human type 1 (HIV-1) disease. It demonstrated a decrease in the SARS-CoV viral load and a lower adverse clinical outcome [57]. However, due to methodological flaws, it could not be verified if this result could happen in the general population. Additionally, various case reports mentions the use of lopinavir/ritonavir has a positive outcome with MERS-CoV [58], but cause lack of human clinical trials, this cannot be demonstrated. Considering these antecedents, a recently published study was made using lopinavir/ritonavir to treat the new SARS-CoV-2 epidemic to demonstrate its efficacy and safety [59]. The result of the study showed that the use of Lopinavir / Ritonavir was not found to be associated with a decrease in viral load or clinical improvement or mortality in a population with severe manifestations, however, it found that in clinically stable patients, the time to clinical improvement improved despite the adverse effects (nausea, vomiting, diarrhea, abdominal discomfort, leukopenia, lymphopenia) [59]. More evidence is needed to recommend the use of this medicine against COVID infection19. Interferon: A helpful coadjutant? As explained before in this article, IFN is one of the first innate immune response elicited by the cell host to prevent further cell infection. The main mechanism of action is to modulate various expression of immune genes that leads to activation, growth and differentiation of NK cells and T cells among others [60]. Physicians have plenty expertise using this molecule as a broad-spectrum antiviral agent, especially in Hepatitis B and C treatment [61]. Regarding the use in the Beta Coronavirus subgenera, in previous years of the outbreaks of SARS-CoV and MERS, various non-human primate models showed that coadjutant treatment with Ribavirin [62] and LPV/r [63] did not developed respiratory insufficiency along with no lung histopathologic abnormalities [62,63]. In addition to this serum, urine and BAL viral loads were lower in the treated group with these drugs [62,63]. In Spite these promising results, specimens in the LPV/r study died unexpectedly and developed subtle weight loss over the course of the treatment [63]. With these data, in 2014 Omrani, et al performed a retrospective case-control study comparing 20 patients being treated with Ribavirin + IFN alfa-2a and 24 patients without it [64]. The results were positive for 14-day survival benefit compared to the control group along with significant decrease in neutrophil levels [64]. One of the main adverse effects in the treatment group was decreased of a mean of 4.32 gr/dL in haemoglobin levels [64]. Regarding the use of IFN in SARS-CoV-2, some guidelines [65] use alpha interferon atomization as an inhaled drug along with LPV/r as weak recommendation with low levels of evidence. In order to reduce the gap knowledge and given that the MERS and SARS-CoV-2 share a close resemblance, the MIRACLE trial is being performed in China in order to evaluate the efficacy and safety of this combination [66] with the primary outcome of 90-day mortality along with various secondary outcomes such as ICU mortality, In-hospital Mortality, Vasopressor-free days among other variables [66]. By the time of this article, the trail is still enrolling patients and the main data result is still not available. Conclusions Even though the novel strain of Beta Coronavirus continues to increase the number of new cases and mortality rate with dramatic death toll data, especially in Italy, many drugs with uses on other diseases are currently being tested for this new strain such as LPV/r and Hydroxychloroquine. Even drugs developed at first for other viral entities such as IFN and RDV are showing promising data on human and non-human models for the treatment of this novel strain. In addition to this, vaccines using structural viral proteins such as S protein are being developed given that it exerts immunogenicity. To wrap up, in spite the high virulence and mortality rates that we are experiencing with this pandemic, all these treatments shed a light at the end of the tunnel to solve this challenge nature has given to us. The only thing we must do is continue with proper patient care and wait for the data of the many RCT´s being performed with these agents.  References 1.       Lu H, Stratton C, Tan Y. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. Journal of Medical Virology. 2020; 92:401–4022.       Hui D, Azar E, Madani T, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China. International Journal of Infectious Diseases. 91 Jan 2020 264–2663.       Li Q, Guan X, Wu Peng, Wang X, Zhou L, et. Al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. New England Journal of Medicine. Jan 29 2020 1-94.       Spiterri G, Fielding J, Diercke M, Campese C, Enouf V, Gaymard A, et al. First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020. Euro Surveill. 2020 Mar 5; 25(9): 2000178.5.       Giovanetti M, Benvenuto D, Angeletti S, Ciccozzi M, the first two cases of 2019‐nCoV in Italy: Where they come from? J Med Virol. 2020 May;92(5):518-5216.       Holshue M, DeBolt C, Lindquist S, Lofy K, Wiesman J, Bruce H, First Case of 2019 Novel Coronavirus in the United States. New England Journal of Medicine, Mar 2020 5;382(10):929-936.7.       Kinross P, Suetens C, Gomes Dias J, Alexakis L, Wijermans A, Colzani E, et al. Rapidly increasing cumulative incidence of coronavirus disease (COVID-19) in the European Union/European Economic Area and the United Kingdom, 1 January to 15 March 2020. Euro Surveill. 2020 Mar 198.       John Hopkins Coronavirus Resource Center [internet]. Johns Hopkins University, Baltimore, MD, USA. Jan 22 2002 Cited [Mar 19 2002]. Available: https://coronavirus.jhu.edu/map.html9.       Guan WJ, Zheng-yi N, Hu Y, Liang W, Ou C, He J. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Feb 2810.   Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Feb 19.11.   Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.12.   Wu C, Chen X, Cai Y, Xai J, Zhou X, Xu S, et. al. Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 1313.   Khan, S; Siddique, R; Shereen, MA; Ali, A; et al. The emergence of a novel coronavirus (SARS-CoV-2), their biology and therapeutic options. J. Clin. Microbiol. 2020; pii: JCM.00187-20. doi: 10.1128/JCM.00187-20.14.   Zhou, P; Yang, XL; Wang, XG; Hu, B; et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-3.15.   Guo, YR; Cao, QD; Hong, ZS; Tan, YY; et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Mil Med Res. 2020 Mar 13;7(1):11.16.   Adhikari, S; Meng, S; Wu, Y; Mao, Y; et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infect Dis Poverty. 2020 Mar 17;9(1):29.17.   Sah, R; Rodriguez-Morales, A; Jha, R; Chu, D; et al. Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Isolated in Nepal. Microbiol Resour Announc. 2020 Mar 12;9(11).18.   Sin-Yee, F; Kit-San, Y; Zi-Wei, Y; Chi-Ping, C; et al. A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. Emerg Microbes Infect. 2020 Mar 14;9(1):558-570.19.   Walls, A; Park, YJ; Tortorici, A; Wall, A. Structure, Function, and Antigenicity of the SARSCoV-2 Spike Glycoprotein. Cell. 2020; pii: S0092-8674(20)30262-2.20.   Sawicki, SG; Sawicki, DL. Coronavirus transcription: a perspective. Curr Top Microbiol Immunol. 2005; 287:31-55.21.   Wong LY, Lui PY, Jin DY. A molecular arms race between host innate antiviral response and emerging human coronaviruses. Virol Sin. 2016; 31:12–23.22.   Drappier M, Michiels T. Inhibition of the OAS/RNase L pathway by viruses. Curr Opin Virol. 2015; 15:19–26.23.   Thornbrough JM, Jha BK, Yount B, et al. Middle East respiratory syndrome coronavirus NS4b protein inhibits host RNase L activation. mBio. 2016;7: e0025824.   Dhama K, Sharun K, Tiwari R, Dadar M, Malik Y, Singh

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April 2020

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Rare Case of Yersinia Enterocolitica Causing Infection of a Temporal Venolymphatic Malformation

Cantwell P, Zaman R, Rawlins J (2020) Rare Case of Yersinia Enterocolitica Causing Infection of a Temporal Venolymphatic Malformation. Annal Cas Rep Rev: ACRR-108.

Annals of Case Reports & Reviews

Case Report                Rare Case of Yersinia Enterocolitica Causing Infection of a Temporal Venolymphatic Malformation  Phillip Cantwell*, Raj Zaman, Jeremy Rawlins Department of Plastic Surgery, Royal Perth Hospital, Australia *Corresponding author: Phillip Cantwell, Department of Plastic Surgery, Royal Perth Hospital, Australia.                         Email: pcc998@uowmail.edu.au  Citation: Cantwell P, Zaman R, Rawlins J (2020) Rare Case of Yersinia Enterocolitica Causing Infection of a Temporal Venolymphatic Malformation.  Annal Cas Rep Rev: ACRR-108. Received Date: 01 April, 2020; Accepted Date: 07 April, 2020; Published Date: 13 April, 2020  Abstract Described is the case of a 29-year-old male with Y. enterocolitica subclinical colitis causing an infected venolymphatic malformation, presenting as a large septic left temporal swelling. The patient was given IV antibiotics and over the course of a week the swelling significantly decreased in size and the patient’s diarrhoea subsided; thus, the decision was made to not operate.  Most extraintestinal case reports of Y. enterocolitica occur in immunosuppressed patients. Our case demonstrates a situation where even a young and healthy individual can develop seeding sepsis outside of the intestinal tract. Clinical record A 29-year-old male with no past medical history presented to the emergency department with a 2-day history of left temporal swelling, fever and intermittent diarrhoea for several weeks in the lead-up. Upon examination, the patient had a temperature of 38.4°C, a heart rate of 120 BPM, a non-tender abdomen, and a large swelling in his left temporal region. Blood was taken, which demonstrated an elevated white cell count of 12.5x109/L and a C-reactive protein of 160mg/L. Blood cultures taken at that time later grew Yersinia enterocolitica. As the patient was stable, an MRI was performed to characterise the swelling in his left temporal region (Figure 1), which showed an infected venolymphatic malformation.   Figure 1: MRI images of the patient on admission (a) coronal view; (b) axial view. The patient was given IV antibiotics; initially cephazolin, which was changed to cefepime on the advice of the Infectious Diseases team when blood culture results were made available. During the course of a week, the swelling significantly decreased in size and the patient’s diarrhoea subsided; thus, the decision was made to not operate. The patient was discharged home on a 3-week course of oral antibiotics (ciprofloxacin) with clinic follow up. At the one-month review, the left temporal swelling was no longer noticeable, and repeat MRI showed a significant decrease in swelling (Figure 2).Figure 2: MRI images of the patient one month after discharge from hospital (a) coronal view; (b) axial view Discussion This case demonstrates an extraintestinal manifestation of Yersinia enterocolitica. The diagnosis was confirmed with a positive blood culture in conjunction with MRI findings of the infected left temporal venolymphatic malformation. Upon introduction of the appropriate antibiotics (cefepime), both fever and swelling were reduced, supporting the diagnosis. The infected site did not undergo fine needle aspiration or drainage given the confidence in diagnosis and risk to the patient associated with both of these procedures. Yersinia enterocolitica is a gram-negative bacterial species in the family enterobacteriaceae, most commonly causing gastrointestinal infections, such as enteritis and pseudoappendicular syndrome [1]. Most cases of Y. enterocolitica self-resolve without requiring antibiotics [2], with transmission occurring zoonotically or via the consumption of contaminated foods (i.e., via contaminated food, water, or milk) [2,3]. Although rare, there have been case reports of person-to-person transmission [3]. After ingestion, Y. enterocolitica has a predilection for the terminal ileum, where the bacteria are able to penetrate M cells within Peyer’s patches [3]. This typically leads to the presentation of fever, diarrhoea, and abdominal pain approximately one week after exposure [3]. Iron is considered to be an essential growth factor for bacteria; therefore, patients with iron overload are at higher risk of Y. Enterocolitica extraintestinal disease [3]. The majority of Y. enterocolitica infections occur sporadically with the sources unknown, however large outbreaks have previously been reported [3]. Most infections are self-limiting and do not require antibiotics, with therapy indicated for patients with septicaemia, focal extraintestinal infection, or who are immunocompromised [3]. The mortality rates of patients with Y. Enterocolitica septicaemia is 7.5% [4]. Extraintestinal manifestations of Y. enterocolitica are uncommon [1], however case reports involving infection of aneurysms, the respiratory system, and the skeletal system have been reported [1,2]. No known cases of Y. enterocolitica causing infected vascular malformations have been identified in the literature. We present a case of Y. enterocolitica subclinical colitis causing an infected venolymphatic malformation and presenting as a large septic left temporal swelling. Most extraintestinal case reports of Y. enterocolitica occur in immunosuppressed patients [2]. Our case demonstrates a situation where even a young and healthy individual can develop seeding sepsis outside of the intestinal tract. Thus, heightened clinical investigation and historical examination are recommended to contribute to the knowledge base and the advancement of best practice. Lessons: Yersinia enterocolitica is a gram-negative bacterial species in the family enterobacteriaceae, most commonly causing gastrointestinal infections, such as enteritis and pseudoappendicular syndrome. Most extraintestinal manifestations of Yersinia enterocolitica occur in immunosuppressed patients. The majority of Yersinia  enterocolitica infections occur sporadically with the sources unknown, however large outbreaks have previously been reported. With appropriate response, antibiotic therapy may be a valid alternative for treatment in patients with infectious collections where drainage may put patients at high morbidity risk. References 1.       Hagensee M (1994) Mycotic aortic aneurysm due to Yersinia enterocolitica. Clinical Infectious Diseases 19: 801-802.2.       Mofredj A, Guerin JM, Leibinger F, Masmoudi R (2003) Spontaneous Pleural Empyema due to Yersinia enterocolitica. Southern Medical Journal 96: 525-527.3.       Watanabe K, Watanabe N, Jin M, Matsuhashi T, Koizumi S, et al. (2014) Mesenteric lymph node abscess sue to Yersinia enterocolitica: case report and review of the literature. Clinical Journal of Gastroenterology 7: 41-47. 4.       Gayraud M, Scavizzi M, Mollaret H, Guillevin L, Hornstein M (1993) Antibiotic treatment of Yersinia enterocolitica septicaemia: a retrospective review of 43 cases. Clinical Infectious Diseases 17: 405-419.

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April 2020

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Experience of Using Silicone Gel Sheet (Lady Care3) for Laparoscopic Surgical Wounds: An Investigation into Safety and Efficacy

Kakinuma T, Kakinuma K, Matsuda Y, Sato I, Yanagida K (2020) Experience of Using Silicone Gel Sheet (Lady Care3) for Laparoscopic Surgical Wounds: An Investigation into Safety and Efficacy. Annal Cas Rep Rev: ACRR-109.

Annals of Case Reports & Reviews

Research Article Experience of Using Silicone Gel Sheet (Lady Care3) for Laparoscopic Surgical Wounds: An Investigation into Safety and Efficacy Toshiyuki Kakinuma*, Kaoru Kakinuma, Yoshio Matsuda, Ikuo Sato, Kaoru Yanagida, Michitaka Ohwada Department of Obstetrics and Gynecology, International University of Health and Welfare Hospital, Japan.  *Corresponding author: Toshiyuki Kakinuma, Department of Obstetrics and Gynecology, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara, Tochigi 329-2763, Japan. Tel: +81-287-39-3060; Fax No.: +81-287-39-3001; Email: tokakinuma@gmail.com  Citation: Kakinuma T, Kakinuma K, Matsuda Y, Sato I, Yanagida K (2020) Experience of Using Silicone Gel Sheet (Lady Care3) for Laparoscopic Surgical Wounds: An Investigation into Safety and Efficacy. Annal Cas Rep Rev: ACRR-109. Received Date: 03 April, 2020; Accepted Date: 09 April, 2020; Published Date: 17 April, 2020 Abstract Background and Objective: While there has been an increase in the number of laparoscopic surgery in Japan, few studies have reported about scars from wounds by laparoscopic surgery. Silicone gel sheets are widely used as part of multidisciplinary treatment for hypertrophic scars and keloids, and their usefulness has been reported. The present study examined the efficacy and safety of a silicone gel sheet (Lady Care3) for laparoscopic surgical wounds.Subjects and methods: Subjects were 15 cases who underwent laparoscopic surgery during the period from March 2017 to March 2018. Silicone gel sheets (Lady Care3) were applied to the wounds (umbilicus, lower abdomen) for one week to six months postoperatively. The JSW Scar Scale was used in evaluating the wounds. The wounds were evaluated visually and through interviews before the application of silicone gel sheets, at three months following surgery, and six months following surgery. Results: The JSW Scar Scale scores for the umbilicus surgical wound were 7.4±2.4 before application, 2.7±1.6 at three months following surgery, and 0.9±0.7 at six months following surgery. Those for the lower abdomen surgical wounds were 4.7±2.3, 0.8±1.1, and 0.3±0.5, respectively. Three cases reported pruritus; however, all were mild, and it was tolerable to continue to use silicone gel sheets in those cases. Conclusion: Significant decreases were observed in the JSW Scar Scale scores from an early postoperative stage, and no serious adverse events were observed. Therefore, the present study suggested that the silicone gel sheet (Lady Care3) is safe and efficacious. Keywords: Hypertrophic scar, keloid, silicone gel sheet, laparoscopic surgery Introduction When the skin suffers damage due to trauma or surgery, the wound healing mechanism, which includes processes such as inflammatory cell infiltration, angiogenesis, and regeneration of the extracellular matrix, is triggered. Hypertrophic scarring and keloids are types of fibroproliferative disease that present as redness caused by the overproduction of collagen fibers by fibroblasts during the wound healing process. These conditions are accompanied by itching and pain, as well as severe psychological stress placed on the patient by the cosmetic problems these conditions cause. Thus, their prevention is an important consideration. Silicone gel sheeting has come into widespread use as part of multidisciplinary treatment of hypertrophic scars and keloids, and studies have reported that they are effective in the prevention of these conditions after Cesarean section.  The number of laparoscopic surgeries performed in Japan in increasing annually, but few studies have investigated the issue of surgical wound scarring. Here, we report on the effectiveness and safety of silicone gel sheeting (Lady Care 3) when used on laparoscopic surgical wounds. Subjects and Methods  This study was conducted after receiving the approval of this hospital’s Institutional Review Board ethical review number (13-B-384). The subjects were 15 patients who underwent laparoscopic surgery between March 2017 and March 2018. Laparoscopic surgery was performed by inserting a 5 mm trocar (ENDOPATH® Trocar System, Johnson & Johnson, Tokyo) for closed trocar entry into the umbilicus using the 4-port parallel method (Figure. 1).  Figure 1: Trocar insertion sites. After the laparoscopic surgery was completed the trocar was removed and a 12 mm trocar (for two layers of rectus abdominis muscle layer subcutaneous tissue) and a 5 mm trocar (for the subcutaneous tissue only) to suture the surgical wound (round body needles, 2-0 absorbable suture [VICRYL® Johnson & Johnson, Tokyo]). The epidermis was closed using dermatological adhesive tape (DERMABOND® Advanced, Johnson & Johnson, Tokyo). During a period between one week and six months after surgery, silicone gel sheeting (Lady Care 3, Gyne Mom Co., Ltd., Saitama; Fig. 2) was affixed to the surgical wounds (umbilicus, lower abdomen) of 15 patients in the Silicone group.   Figure 2: Lady Care 3 (Gyne Mom Co., Ltd.) Surgical wound assessment was done in both groups at three time points (post-1W, post-3M, post-6M) using the JSW Scar Scale (Table 1). The scores were converted to numerals for the purpose of comparison. Statistical analyses were performed using the student’s t-test and the chi-squared test. Statistical significance was set at P<0.05. Table 1: JSW Scar Scale 2011 (Classification and Evaluation of Keloids and Hypertrophic Scars). Results Mean age was 45.7±13.1 years, Body mass index (BMI) was 23.0±4.1. The breakdown of laparoscopic surgery included 6 laparoscopic total hysterectomy, 1 laparoscopic myomectomy, 4 laparoscopic appendectomy, and 4 laparoscopic ovarian tumor resection. JSW Scar Scale scores for the umbilicus surgical wound were 7.4±2.4 (pre-affixation: post-1W), 2.7±1.6 (post-3M), and 0.9±0.7 (post-6M). JSW Scar Scale scores for the lower abdomen surgical wounds were 4.7±2.3, 0.8±1.1, and 0.3±0.5 respectively (Fig. 3).  The JSW Scar Scale scores for the post-3M time point (both umbilicus and lower abdomen wounds) were significantly lower than at pre-affixation (post-1W).  Although no serious adverse events occurred in the Silicone group, three patients experienced itchiness (Fig. 3).   Figure 3: Variations in JSW Scar Scale scores. Discussion Hypertrophic scarring and keloids are frequently observed in daily medical practice. Hypertrophic scarring in particular commonly occurs at surgical wound sites, and as a result they are a problem likely to be faced by all surgical specialists. In addition to associated itching and pain, patients often suffer a great deal of psychological stress due to cosmetic problems associated with such scarring, and therefore it is often advisable to have “scar-less healing” as a goal.  When the skin is damaged as a result of trauma or surgery, the wound healing mechanism, which includes processes such as inflammatory cell infiltration, angiogenesis, and regeneration of the extracellular matrix, is triggered. Normally, the redness that occurs at the wound site gradually disappears, and then is replaced by a white-colored mature scar. In cases of hypertrophic scarring and keloids, some instigating factor during the course of the wound healing process causes wound healing to be delayed and the wound to be maintained over a longer than normal period of time. Possible instigating factors include foreign objects, infections, mechanical irritation, genetic factors, wound-delaying factors, cytokines, and hormones [1-5]. However, the specific causes remain unknown.  Several treatments are available for hypertrophic scarring and keloids, including pharmacotherapy, compression therapy, surgery, cryotherapy, radiotherapy, and laser therapy, and in many cases multiple therapies are utilized. However, these conditions are often difficult to treat and manage, and thus effort must be made to prevent their occurrence.  Since silicone gel sheet therapy was first reported as a novel treatment of post-burn scarring in children by Perkins et al. in 1982 [6], it has come into clinical use in the treatment of hypertrophic scarring and keloids. Although its mechanism of action remains unknown, much discussion of this has taken place over the years. Quinn reported that the speed at which water vapor moved at the sites where silicone gel sheeting had been affixed was relatively slower than at the sites of scarring [7]. Katz and Davey et al. reported that acts as an alternate stratum corneum, which they assumed reduced the loss of water vapor and reduced collagen proliferation and capillary activity [8-9]. Suetake et al. compared the stratum corneum functioning at sites where silicone gel sheeting was affixed and sites where plastic film (vinylidene chloride) was affixed, and they reported that the fact that the film sites contained more moisture in the stratum corneum suggests that the silicone gel sheeting ensures a level of moisturization that is conducive to improvement in symptoms [10]. On the other hand, in addition to the moisturizing effect, it is also conceivable that direct external force applied to the scar site by the silicone gel sheeting may have a protective effect, or that the protective effect may arise from the excessive traction placed on the surrounding tissue and this external stimulation also may explain the protective effect of silicone gel sheeting.10) In addition, many types of plastic film utilize organic solvents as adhesives and as a result when they are used on hypertrophic scars or keloids problems such as peeling away of the stratum corneum and contact dermatitis may occur. However, silicone gel sheeting is less likely to cause these problems, and thus it is conceivable that silicone gel may allow the epidermis to rest. Physical protection from direct external irritation from clothing and preventing the patient from scratching the scar site may also alleviate symptoms.  Currently, none of the various theories that have been presented as explanations for the mechanism of action of silicone gel sheeting on hypertrophic scars and keloids have been completely verified and none have been shown to have specificity with regard to these conditions. However, according to a number of reports, the moisturizing effect that protects the epidermis from dryness, the physical protection of the surface of the skin they provide, the physical protective effect they have that allows the tissues underneath to rest, and the mechanical effect of placing traction on the surrounding tissues which allows the scar site to rest are all conceivable explanations as they all are related to protection of the scar site and to allowing the site to rest.  Data have suggested that silicone gel sheets, which are a therapeutic material that is widely used as part of the multidisciplinary treatment of hypertrophic scarring and keloids, are effective in the prevention of postoperative development of hypertrophic scarring and keloids [11] In their study of prevention of the development of fibrous hypertrophic scarring and keloids, Gold et al. reported Chan et al. reported that in the silicone gel usage group itching, pain, scar height, redness, and hardness all showed that there was a significant protective effect on the scar tissue [12]. In the present study of the efficacy of silicone gel sheeting on laparoscopic surgical wounds, we also found that at post-3M the JSW Scar Scale scores in the Silicone group were significantly lower, indicating that the wounds had improved faster than in the Control group.  The Lady Care 3 that we utilized in the present study is a soft skin adhesive silicone gel sheet for medical use whose main components have been registered with the Drug Master File (DMF) of the US Food and Drug Administration (FDA), as is the case with the entire Lady Care series product line. It was developed for use after laparoscopic surgery and is elliptical in shape and measures 30 mm in diameter. The previous products in the Lady Care series have already been used in the prevention of the formation of hypertrophic scarring after Cesarean section. As is the case with the other products in the Lady Care series, Lady Care 3 is pliable and can be affixed in a way that allows it to be formed to the shape of the body where it is being used, which in turn allows it to directly adhere to the affected site. As it is durable, it can be removed prior to bathing and replaced, which means that it is reusable. Normally, a single sheet can be used for 1-2 months. Problems associated with its use include the fact that during seasons when people experience increased sweating, such as the summer, the adhesiveness of the silicone gel sheeting can be reduced or lost, and itching has been reported by many patients. In the present study we found that itching occurred during use of the Lady Care 3 sheets in three patients (20%). All cases were mild and continued use of the product was possible. However, we believe it is necessary to devise a thinner silicone gel sheet that allows sweat to be wiped off more frequently. Currently, a thinner version of the Lady Care 3 sheet that has stronger adhesiveness is under development, and thus we hope to study this new product in the future with larger numbers of study subjects and over a longer observation period.  Conclusion The fact that the JSW Scar Scale score in the Silicone group was significantly lower sooner after surgery than the Control group, and the fact that there were no serious adverse events associated with the use of the silicone gel sheet, suggest that the silicone gel sheeting (Lady Care 3) is both safe and effective.  There is no conflict of interest in this study. Reference 1.       Ogawa R, Okai K, Tokumura F, Mori K, Ohmori Y, et al. (2012) The relationship between skin stretching/contraction and pathologic scarring: the important role of mechanical forces in keloid generation. Wound Repair Regen 20:149-57.2.       Moles A, Hamel O, Perret C, Bord E, Roger Robert R, et al. (2014) Symptomatic vertebral hemangiomas during pregnancy. J Neurosurg Spine 20: 585-591.3.       Quong WL, Kozai Y, Ogawa R (2017) A Case of Keloids Complicated by Castleman's Disease: Interleukin-6 as a Keloid Risk Factor. Plast Reconstr Surg Glob Open 5: e1336.4.       Nakashima M, Chung S, Takahashi A, Kamatani N, Kawaguchi T, et al. (2010) A genome-wide association study identifies four susceptibility loci for keloid in the Japanese population. Nat Genet 42: 768-771.5.       Ogawa R, Watanabe A, Than Naing B, Sasaki M, Atsushi Fujita A, et al. (2014) Associations between keloid severity and single-nucleotide polymorphisms: importance of rs8032158 as a biomarker of keloid severity. J Invest Dermatol 134: 2041-2043.6.       Perkins K, Davey RB, Wallis KA (1983) Silicone gel: a new treatment for burn scars and contractures. Burns Incl Therm Inj 9: 201-204.7.       Quinn KJ (1987) Silicone gel in scar treatment. Burns Incl Therm Inj 13: 33-40.8.       Katz BE (1995) Silicone gel sheeting in scar therapy. Cutis 56: 65-67.9.       Davey RB, Wallis KA, Bowering K (1991) Adhesive contact media--an update on graft fixation and burn scar management. Burns 17: 313-319.10.   Suetak T, Sasai S, Zhen YX, Tagami H (2000) Effects of silicone gel sheet on the stratum corneum hydration. Br J Plast Surg 53: 503-507.11.   Gold MH, Foster TD, Adair MA, Burlison K, Lewis T (2001) Prevention of hypertrophic scars and keloids by the prophylactic use of topical silicone gel sheets following a surgical procedure in an office setting. Dermatol Surg 27:641-644. 12.   Chan KY, Lau CL, Adeeb SM, Somasundaram S, Nasir-Zahari M (2005) A randomized, placebo-controlled, double-blind, prospective clinical trial of silicone gel in prevention of hypertrophic scar development in median sternotomy wound. Plast Reconstr Surg 116: 1013-1020.

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April 2020

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