Anti-Lea monoclonal antibody SPM 522 recognizes an extended Lea epitope.

Insights into the differential binding characteristics of anti-Lea and anti-LeaLex monoclonal antibodies (mAbs) provide information to develop LeaLex-based cancer immunotherapeutics while avoiding anti-Lea autoimmune reactions. We characterized the epitope recognized by anti-Lea mAb SPM 522. We synthesized the Lea 6-aminohexyl glycoside and report experimental evidence of a minor conformation in solution. The Lea and three other 6-aminohexyl glycosides were conjugated to BSA and titration experiments with SPM 522 show that: 1. SPM 522 binds to LeaLex better than to Lea; 2. the non-reducing Lea galactosyl residue is essential to binding. Competitive ELISA experiments using a panel of tri- to pentasaccharide fragments of LeaLex as well as Lea analogues indicate that: 1. the Lea ß-d-galactosyl α hydrophobic patch is crucial to binding; 2. the Lea fucosyl residue contributes to binding; 3. the Lexd-galactosyl residue also contributes to binding. These results indicate that anti-Lea mAb SPM 522 recognizes the Lea[1,3]-ß-d-Gal tetrasaccharide. We propose that a major recognition element is the extended hydrophobic surface defined by the Lea-ß-d-Gal residue extending to the α faces of the ß-d-GlcNAc and ß-d-Gal residues.

Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID-19) and the rationale for their utilization: A review.

SARS-CoV-2 has caused a pandemic which is putting strain on the health-care system and global economy. There is much pressure to develop both preventative and curative therapies for SARS-CoV-2 as there is no evidence to support therapies to improve outcomes in patients with SARS-CoV-2. Medications that inhibit certain steps of virus life cycle that are currently used to treat other illnesses such as Malaria, Ebola, HIV and Hepatitis C are being studied for use against SARS-CoV-2. To date, data is limited for medications that facilitate clinical improvement of COVID-19 infections.

An Infected Dog Bite With Neisseria canis: A Case Report and Review of the Literature.

Neisseria is a common bacteria that colonizes in humans. Of the 11 species, only two, N. meningitidis and N. gonorrhea, are pathogenic. Although sparse, there are case reports of other Neisseria species causing infections in humans. Neisseria canis, which is a part of normal flora in the mouths of dogs and cats, has been shown to have potential to be pathogenic in humans. The standard treatment for dog and cat bites is oral amoxicillin/clavulanic acid (Augmentin) or IV ampicillin/sulbactam (Unasyn). However, in cases where the patient has multiple antibiotic allergies, careful antibiotic selection must be made to ensure resolution of infection.

Knockout rates across the states as a way of predicting injury and knockout based on fighter sex, weight, or experience.

Combat sports, such as boxing and mixed martial arts [MMA], have the unique objective to finish a bout by way of knockout [KO] or technical knockout [TKO]. There are potentially both short- and long-term neurological injuries that can happen as a result of the repeated head trauma sustained in bouts, and thus it is imperative to identify the athletes that are at increased risk. Using an online database of professional boxing bouts [boxrec.com] over a 6-month period, KO/TKO rates were calculated across different states, weight classes, sex, and Fight Exposure Score [FES] categories. There was found to be a significant association between KO/TKO rates and weight class, sex, and FES category with heavyweights, males and FES 0 boxers having higher KO/TKO rates. KO/TKO rates were increased in winless boxers. KO/TKO rates across the states are documented in the study.

Patient Parameters Associated With a Positive Blood Culture Using NeuroShell: A Retrospective Chart Review.

Bacteremia is a common and life-threatening condition. It has an incidence of 140 to 160 per 100,000 person-years in the United States. Since bacteremia has many presentations, it can be challenging to diagnose. Subsequently there are very few guidelines on when to order a blood culture in an emergency setting. Neural networks are a means of machine learning and are presently being used in medicine to aid in decision making. With the use of machine learning, 22 variables that have been associated with infection and bacteremia were used to build a neural network to determine which variables associated with bacteremia are most associated with a positive blood culture.

Bilateral Cavernous Sinus Thrombosis in Presumed COVID-19 Infection.

Cavernous sinus thrombosis (CST) is a rare life-threatening condition where a blood clot develops within the cavernous sinus secondary to various etiologies, ranging from infection to aseptic causes (e.g., trauma or surgery). The dural sinuses and the cerebral veins have no valves, which allow retrograde blood flow according to pressure gradients. As a result, cavernous sinuses are vulnerable to septic thrombosis from infection at various sites including sphenoid and ethmoid sinuses. Less commonly, infections of the face, ears, nose, tonsils, soft palate, and teeth may lead to CST if treatment is delayed. Clinical findings of CST extending to the opposite cavernous sinus typically requires 24-48 hours after the initial presentation of orbital signs. However, we present a patient with facial and orbital cellulitis that was immediately treated with high-dose IV antibiotics within one hour of presentation and IV heparin six hours after admission and CST diagnosis. However, the patient developed a rapid progression of bilateral CST within six hours, unresponsive to treatment. Although facial cellulitis may lead to septic CST if untreated, the rapid progression of bilateral CST in the setting of acute hypoxic respiratory failure, renal failure, and coagulation abnormalities suggests a possible underlying infection and complications similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Bilateral Thalamic Stroke: A Case of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) or a Coincidence Due to Underlying Risk Factors?

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but potentially life-threatening side effect that has only been observed in adenovirus-based vaccines for coronavirus disease 2019 (COVID-19). VITT is an immune-mediated condition that generally presents within five to 10 days post-vaccination with thrombosis, thrombocytopenia, and coagulation abnormalities. A diagnosis of VITT is made clinically and through laboratory testing. Although VITT is an important differential to consider, it is believed that more emphasis should be placed on vaccination due to the safety and efficacy in overcoming COVID-19.

Micronutrients for potential therapeutic use against COVID-19; a review.

BACKGROUND: SARS CoV-2 has caused a pandemic that has challenged both clinicians and researchers in finding an effective treatment option. Currently there only exists a two series vaccine that has a high efficacy in preventing infection. There is no standard effective treatment against SARS CoV-2 however several nutraceuticals such as melatonin, zinc, selenium, vitamin C and vitamin D are being proposed as prevention and treatment options.

A Case of Digoxin Toxicity Due to Acute Renal Failure.

Since the publication of the Digitalis Investigation Group trial in 1997, digoxin use has declined significantly. Medications such as angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) and beta-blockers that have been demonstrated to have a decrease in morbidity and mortality are prescribed in favor of digoxin. Despite the reduction in digoxin use and improved therapeutic monitoring, digoxin toxicity remains a significant cause of morbidity and mortality. When digoxin toxicity is suspected, patients should be managed with supportive care, including discontinuation of the medication, and consideration for administration of digoxin-specific antibody fragment. We present a case of digoxin toxicity precipitated by acute renal failure, with a discussion on the pathophysiology and diagnosis of digoxin toxicity, along with the indications for administration of digoxin-specific antibody fragments. While digoxin toxicity is prescribed less commonly, physicians need to maintain a high index of suspicion and be comfortable with administering digoxin-specific antibody fragment in these scenarios.

Dercum's Disease: A Case Report of a Patient Having Both Type 1 and Type 2 Dercum's Disease.

Dercum's disease, or adiposis dolorosa, is a rare disorder which consists of multiple, painful lipomas within the subcutaneous tissue and has a distribution mainly in the abdomen and extremities. Dercum's disease can be defined as in combination with chronic painful adipose tissue. Although the etiology of Dercum's disease is not clear, it is thought to be a combination of a neurological and endocrine disorder. Treatment for this disease is centered at managing pain. Although there is no standard of care for managing pain, there are different pain management regimes that are promising.

Rare case of Marchiafava-Bignami disease due to thiamine deficiency and malnutrition.

Marchiafava-Bignami disease (MBD) is a rare, toxic demyelinating disorder of the central nervous system associated with chronic alcoholism and malnutrition. The clinical presentation is varied and non-specific, including symptoms of acute dementia, impaired consciousness, dysarthria, hemiparesis, pyramidal tract signs, seizure activity, ataxia and signs of interhemispheric disconnection. The differential diagnosis of MBD may include Wernicke's encephalopathy, multiple sclerosis, encephalitis, infectious or paraneoplastic leucoencephalopathy, infarction, Alzheimer's disease, multi-infarct dementia and frontotemporal lobar degeneration (Pick) disease. The diagnosis of MBD is dependent on MRI findings of hyperintensity of the corpus callosum on T2 and fluid-attenuated inversion recovery T2 sequences, with or without extracallosal lesions. The use of MRI in diagnosis has allowed for early initiation of treatment with parenteral thiamine, and improved the prognosis of MBD from frequently fatal to a mortality of less than 8%. Administration of thiamine within 14 days of symptom onset has demonstrated statistically better outcomes over delayed treatment. We present a case report of MBD diagnosed in a 72-year-old woman who presented with ataxia and slurred speech, in an effort to highlight the importance of obtaining MRI in patients presenting with behavioural disturbance and neurological findings, as well as discuss the relationship between thiamine supplementation and demyelinating diseases in the central nervous system.

Recurrent Herpes Zoster Ophthalmicus Preceded by Anabolic Steroids and High-Dose L-Arginine.

PURPOSE: To report a case of a 34-year-old male with recurrent herpes zoster ophthalmicus (HZO) preceded by a 6-week cycle of anabolic steroids and high-dose amino acid supplementation. Case Presentation. A 34-year-old man presented to our institution for left eye pain for one week associated with a vesicular rash in the V1 dermatome, respecting the midline. The patient had no significant past medical or past ocular history, including systemic immunosuppressive agents or HIV. However, prior to the onset of his symptoms the patient had completed a 6-week course of anabolic steroids including trenbolone, deca-durabolin, and testosterone as well as high-dose arginine supplementation averaging more than 40 grams a day. The best-corrected vision was 20/25 OS with slit-lamp examination remarkable for punctate staining and pseudodendrites at 6 o'clock, outside the visual axis. The patient was treated with oral acyclovir 800 mg five times a day for seven days along with prednisolone QID and moxifloxacin QID which was tapered over a month. Four months after resolution, the patient developed a recurrent HZO keratitis preceded by another cycle of anabolic steroids and amino acid supplementation. CONCLUSION: In vitro L-arginine supplementation has been associated with the proliferation and virulence of a variety of herpes viruses. Anabolic steroids have also been demonstrated by various studies to negatively affect cell-mediated immunity necessary to prevent viral infection. Thus, it is possible that anabolic steroids in conjunction with increased L-arginine intake may have precipitated a recurrent HZO in a previously healthy, immunocompetent individual.

Laparoscopic Vessel Endometriosis Resection Surgery: A Case Report and Review of Literature.

BACKGROUND: Endometriosis usually occurs in the pelvis and often involves the ovaries, the uterosacral and broad ligaments, and the pelvic peritoneum. In rare instances, it can occur in the vasculature of the pelvis. Patients with endometriosis present with abnormal pain, menstrual cycle disruption and infertility. Management of endometriosis is usually surgical with excision of the tissue via laparoscopic means. CASE: A 42-year-old Gravida 5, Para 2-0-3-2 patient with a 22 year history of endometriosis, who had had multiple laparoscopic endometriosis resections, total abdominal hysterectomy, and an exploratory laparotomy with bilateral salpingo-oophorectomy, presented with left pelvic pain when standing, dyspareunia, and a 3.7 cm cyst on ultrasound. The patient underwent laparoscopic vessel endometriosis resection and excision of endometriotic nodules from external iliac vessels. Final pathology report showed evidence of old endometriosis in all locations. On interval follow-up, the patient reported sustained relief from pain. CONCLUSION: Complete resection of endometriosis from large vessels can be successfully achieved laparoscopically by a well-experienced surgeon with delicate, proper techniques.

Recurrent herpes zoster ophthalmicus in a young, healthy individual taking high doses of l-Arginine.

PURPOSE: To report a case of a healthy, young male with recurrent herpes zoster ophthalmicus (HZO) and high-dose l-arginine supplementation. OBSERVATIONS: A 39-year-old man presented to another institution with a HZO involving the right eye. He was treated with oral acyclovir with complete resolution. Four months later the patient had a recurrent HZO episode and was started again on oral acyclovir. After resolution of the episode, the patient was continued on 1 g of oral acyclovir daily as a prophylactic measure. He then presented to our institution for a second opinion. The patient was otherwise healthy, with no past medical history involving systemic immunosuppressant agents or HIV. However, the patient was an active weight lifter taking high doses of amino acids. A diet recall was performed prior to both HZO episodes, which calculated an average intake of 46.5 g of l-arginine a day. Examination revealed 20/40 best-corrected acuity, anterior stromal haze in the visual axis, and inferior superficial punctate keratitis in the right eye. The patient was treated for dry eye disease with punctual plugs and artificial tears. The patient was instructed to decrease all supplemental arginine consumption while continuing with oral acyclovir prophylaxis for one year. CONCLUSIONS AND IMPORTANCE: l-arginine is associated with the replication and virulence of a variety of viruses in vitro, including herpes simplex and varicella zoster. Although arginine consumption increased prior to the initial and recurrent HZO infection, further investigation needs to be performed to deem if a true association exists.

Central Nervous System Infections.

Infections of the nervous system are potential life-threatening and are caused by pathogens such as bacteria, viruses, and fungi. Prompt recognition and treatment of a central nervous system (CNS) infection is crucial for patient survival, as these infections have a high morbidity and mortality. CNS infections include meningitis, encephalitis, and brain abscesses. This article seeks to detail the etiology, clinical course, diagnostic challenges, and treatment of CNS infections organized by infectious agent.

Laparoendoscopic Single-Site Surgery for Management of Heterotopic Pregnancy: A Case Report and Review of Literature.

BACKGROUND: Heterotopic pregnancy occurs when two pregnancies occur simultaneously in the uterus and an ectopic location. Treatment includes removal of the ectopic pregnancy with preservation of the intrauterine pregnancy. Treatment is done laparoscopically with either a Laparoendoscopic Single-Site Surgery (LESS) or a multiport laparoscopic surgery. CASE: We present a case of a first trimester heterotopic pregnancy in a 42-year-old gravida 5, para 0-1-3-1 female with previous history of left salpingectomy, who underwent laparoscopic right salpingectomy and lysis of adhesions (LOA) via Single-Incision Laparoscopic Surgery (SILS). CONCLUSION: Although LESS for benign OB/GYN cases is feasible, safe, and equally effective compared to the conventional laparoscopic techniques, studies have suggested no clinically relevant advantages in the frequency of perioperative complications between LESS and conventional methods. No data on the cost effectiveness of LESS versus conventional methods are available. LESS utilizes only one surgical incision which may lead to decreased pain and better cosmetic outcome when compared to multiport procedure. One significant undesirable aspect of LESS is the crowding of the surgical area as only one incision is made. Therefore, all instruments go through one port, which can lead to obstruction of the surgeon's vision and in some cases higher rate of procedure failure resulting in conversion to multiport procedure.

Lumacaftor/ivacaftor, a novel agent for the treatment of cystic fibrosis patients who are homozygous for the F580del CFTR mutation.

INTRODUCTION: Cystic Fibrosis (CF) is an autosomal recessive disease affecting up to 90,000 people worldwide. Approximately 73% of patients are homozygous for the F508del cystic fibrosis transmembrane conductance regulator [CFTR] mutation. Traditionally treatment has only included supportive care. Therefore, there is a need for safe and effective novel therapies targeting the underlying molecular defects seen with CF. Areas covered: In 2016, the Food and Drug Administration and the European Commission approved LUM/IVA (Orkambi), a CFTR modulator that includes both a CFTR corrector and potentiator, for CF patients homozygous for the F508del CFTR mutation. This article reviews the pharmacologic features, clinical efficacy, and safety of LUM/IVA and summarize the available pre-clinical and clinical data of LUM/IVA use. Expert commentary: LUM/IVA showed modest, but significant improvements from baseline in percent predicted FEV1 (ppFEV1) as well as a reduction in pulmonary exacerbations by 35% It was shown to be safe for short- and long-term use. Currently, LUM/IVA is the only oral agent in its class available and represents a milestone the development of therapies for the management of CF. Nonetheless, pharmacoeconomic data are necessary to justify its high cost before is use becomes standard of care.