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A 66-year-old immunocompetent man with preceding travel through the Northeastern United States developed Guillain-Barré syndrome. A broad search for infections revealed intraerythrocytic parasites on blood smear and positive polymerase chain reaction for Babesia microti; elevated IgM/IgG serologies for Ehrlichia chaffeensis; elevated IgM/IgG serologies and qualitative polymerase chain reaction for Epstein-Barr virus; and fecal culture growth of Arcobacter butzleri. In this report, we discuss the known or suspected association of these infectious agents with Guillain-Barré syndrome. This case also highlights the importance, in the setting of endemic exposure, of screening for multiple coinfections that can be transmitted by the same arthropod vector.

Dental caries is caused by biofilm-forming acidogenic bacteria, especially Streptococcus mutans, and is still one of the most prevalent human bacterial diseases. The potential use of cannabidiol (CBD) in anti-bacterial therapies has recently emerged. Here we have studied the anti-bacterial and anti-biofilm activity of CBD against S. mutans. We measured minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC). The bacterial growth and changes in pH values were measured in a kinetic study. The biofilm biomass was assessed by Crystal Violet staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) metabolic assay. Spinning Disk Confocal Microscopy (SDCM) was used to assess biofilm structure, bacterial viability and extracellular polysaccharide (EPS) production. CBD inhibited S. mutans planktonic growth and biofilm formation in a dose-dependent manner, with similar MIC and MBIC values (5 µg/mL). CBD prevented the bacteria-mediated reduction in pH values that correlated with bacterial growth inhibition. SDCM showed a decrease of 50-fold in live bacteria and EPS production. CBD significantly reduced the viability of preformed biofilms at 7.5 µg/mL with an 80 ± 3.1% reduction of metabolic activity. At concentrations above 20 µg/mL, there was almost no bacterial recovery in the CBD-treated preformed biofilms even 48 h after drug withdrawal. Notably, precoating of the culture plate surfaces with CBD prior to incubation with bacteria inhibited biofilm development. Additionally, CBD was found to induce membrane hyperpolarization in S. mutans. Thus, CBD affects multiple processes in S. mutans including its cariogenic properties. In conclusion, we show that CBD has a strong inhibitory effect against cariogenic bacteria, suggesting that it is a potential drug adjuvant for reducing oral pathogenic bacterial load as well as protecting against dental caries.

Streptococcus halichoeri is a relatively newly identified species of pyogenic streptococci that causes zoonotic infection in humans. S. halichoeri was first described in 2004 as indigenous to seals, and only 8 reports of human S. halichoeri infection have been published. S. halichoeri grows as small, white, nonhemolytic colonies and may be strongly catalase-positive on routine blood agar media, which can lead to isolates being misidentified as coagulase-negative staphylococci. S. halichoeri tests positive for Lancefield group B antigen, like S. agalactiae, but can be identified with matrix-assisted laser desorption/ionization time of flight mass spectrometry or partial 16S rRNA sequencing. We describe 3 cases of S. halichoeri bone and joint infections in patients in the United States with underlying health conditions. In addition, we examine the microbiologic characteristics of S. halichoeri and discuss the importance of fully identifying this organism that might otherwise be disregarded as a skin commensal.

Objective We report a case of pituitary apoplexy (PA) with negative radiographic findings for PA and cerebrospinal fluid (CSF) analysis consistent with neutrophilic meningitis. PA is a rare endocrinopathy requiring prompt diagnosis and treatment. Presentation with acute neutrophilic meningitis is uncommon. Methods The diagnostic modalities included pituitary function tests (adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, prolactin), brain computed tomography and magnetic resonance imaging (MRI), and CSF analysis. Results A 67-year-old man presented with worsening headache, nausea, and retching. He was somnolent with an overall normal neurologic examination other than a peripheral vision defect in the left eye. MRI showed a pituitary mass bulging into the suprasellar cistern with optic chiasm elevation, consistent with pituitary macroadenoma. Laboratory evaluation revealed decreased levels of adrenocorticotropic hormone, random cortisol, thyroid-stimulating hormone, thyroxine, luteinizing hormone, and testosterone. He had worsening encephalopathy with left eye ptosis and decreased vision, prompting a repeat computed tomography and MRI, showing no interval change in the pituitary adenoma or evidence of bleeding. CSF analysis revealed a leukocyte count of 1106/mm3 (89% neutrophils), a total protein level of 138 mg/dL, red blood cell count of 2040/mm3 without xanthochromia, and glucose level of 130 mg/dL. The CSF culture result was negative. Transsphenoidal resection revealed a necrotic pituitary adenoma with apoplexy. Conclusions Including PA in the differential diagnosis of acute headache is important, particularly in patients with visual disturbances. PA can present with sterile meningitis, mimicking acute bacterial meningitis. While neuroimaging can help detect PA, the diagnosis of PA remains largely clinical.

Objectives Simulation is a commonly used modality to teach paediatric procedural skills, however, it is resource intensive. Which paediatric skills are best taught using simulation is not known. This study aims to examine what skills to simulate, allowing for the best use of resources in ever expanding curricula. Method We administered a questionnaire to community and hospitalist general paediatricians in Canada asking them to rate the importance of maintaining competency in each paediatric procedural skill and the frequency with which they perform the skill in their practice. Results Skills that were rated as highly important and also high frequency were: bag-mask ventilation (BMV), lumbar puncture, neonatal cardiopulmonary resuscitation (CPR), specimen procurement for infectious diseases, immunization, and ear curettage. Skills that were rated as highly important but low frequency were: paediatric CPR, intraosseous needle insertion, neonatal intubation, defibrillation, gathering specimens for evidence of child maltreatment, paediatric intubation, cervical spine immobilization, and oral/nasogastric tube placement. Conclusion Paediatric procedural skills are rated variably in terms of importance and frequency of use in general paediatric practice. Eight skills of high importance are infrequently performed and should be targeted for teaching via simulation.

A 70-year-old woman presented with aphasia caused by acute infarction in the left middle cerebral artery. Cardiac investigation revealed progressively increasing mobile mass in the left atrial appendage over 2 months (from 9 to 15 mm). Decision was made to proceed with mass resection, and pathological evaluation confirmed Masson tumor. (Level of Difficulty: Advanced.), Graphical abstract

A 53-year-old female patient presented for evaluation of a murmur. The examination revealed a 2/6 systolic ejection murmur in the left upper sternal border. Transthoracic echocardiography with color Doppler showed increased blood flow around the apex of the right ventricle. Further imaging revealed the right coronary artery emerging from the pulmonary artery. (Level of Difficulty: Beginner.), Graphical abstract, A 53-year-old woman presented for evaluation of a murmur. The examination revealed a 2/6 systolic ejection murmur in the left upper sternal border…

It has been confirmed that bacterial biofilm covering dental implants is the main microbial source causing preimplant infectious and inflammatory diseases. The purpose of this study was to evaluate the antibacterial/antibiofilm effect of chlorhexidine, incorporated into a sustained-release varnish of chlorhexidine (SRV-CHX) coating, on dental abutments.Three kinds of dental abutments were used: a high-performance semi-crystalline engineering thermoplastic polyetheretherketone (PEAK) healing abutment, a titanium healing abutment, and a titanium permanent abutment. These abutments were coated with SRV-CHX or SRV-placebo and exposed daily to fresh cultures ofSRV-CHX-coated abutments 2 and 3 were able to inhibitCoating of dental abutments with SRV-CHX demonstrated long-term effective inhibition of

Metastasis to the gastrointestinal tract is rare. We performed a retrospective analysis to identify patients with metastatic disease to the gastrointestinal tract using two databases containing pathology results from all endoscopic procedures conducted by nearly 200 gastroenterologists in a community setting over a 14-year period. Forty-nine patients were diagnosed with metastasis to the gastrointestinal tract by endoscopy during the study period. Most were women (71%). The most common metastases to the gastrointestinal tract identified by endoscopy were breast cancers (n = 18), followed by melanomas (n = 12), ovarian cancers (n = 7), kidney cancers (n = 5), prostate cancers (n = 2), lung cancer (n = 1), and pancreatic cancer (n = 1). Three patients had unknown primary sites. Among women, the three leading known primary tumor sites were breast, ovary, and melanoma. Among men, the three leading primary tumor sites were melanoma, kidney, and prostate. The stomach was the most common portion of the gastrointestinal tract involved by metastases. Most affected women and were most frequently encountered in the stomach.

Objective The objective of this study was to identify nephrology topics of lowest perceived competency and importance for general paediatricians. Methods Surveys were distributed to general paediatricians, paediatric residents, paediatric residency program directors, and paediatric nephrologists. Perceived importance and competence were rated on a 5-point Likert scale. Means and 95% confidence intervals were calculated. Results Mean perceived competency from general paediatricians across all nephrology domains was 3.0, 95%CI (2.9 to 3.1) and mean importance was 3.2, 95%CI (3.1 to 3.3). Domains scoring below the means for competence and importance, respectively were kidney stones (2.5, 95%CI [2.2 to 2.7]) and 2.6, 95%CI [2.3 to 2.8]), acute kidney injury (2.5, 95%CI [2.2 to 2.8] and 2.4, 95%CI [2.1 to 2.8]), chronic kidney disease (1.9, 95%CI [1.7 to 2.2] and 2.1, 95%CI [1.8 to 2.4]), tubular disorders (1.8, 95%CI [1.6 to 2.0] and 2.0, 95%CI [1.8 to 2.3]), and kidney transplant (1.6, 95%CI [1.4 to 1.8] and 1.7, 95%CI [1.4 to 1.9]). Residents, program directors, and paediatric nephrologists agreed that stones, chronic kidney disease, tubular disorders, and transplant were of lower importance. However, acute kidney injury was the domain with the largest discrepancy in perceived importance between residents (4.4, 95%CI [4.2 to 4.6]), nephrologists (4.2, 95%CI [3.8 to 4.6]), and program directors (4.2, 95%CI [3.7 to 4.7]) compared to general paediatricians ([2.4, 95%CI [2.1 to 2.8]; P Conclusion Paediatricians did not believe acute kidney injury was important to their practice, despite expert opinion and evidence of long-term consequences. Educational interventions must address deficits in crucial domains of renal health in paediatrics.

BackgroundThe COVID-19 pandemic has a worldwide impact on all health services, including childhood immunizations. In Canada, there is limited data to quantify and characterize this issue.MethodsWe conducted a descriptive, cross-sectional study by distributing online surveys to physicians across Ontario. The survey included three sections: provider characteristics, impact of COVID-19 on professional practice, and impact of COVID-19 on routine childhood immunization services. Multivariable logistic regression identified factors associated with modification of immunization services.ResultsA total of 475 respondents answered the survey from May 27thto July 3rd2020, including 189 family physicians and 286 pediatricians. The median proportion of in-person visits reported by physicians before the pandemic was 99% and dropped to 18% during the first wave of the pandemic in Ontario. In total, 175 (44.6%) of the 392 respondents who usually provide vaccination to children acknowledged a negative impact caused by the pandemic on their immunization services, ranging from temporary closure of their practice (n=18; 4.6%) to postponement of vaccines in certain age groups (n=103; 26.3%). Pediatricians were more likely to experience a negative impact on their immunization services compared to family physicians (adjusted odds ratio [aOR]=2.64, 95% CI: 1.48-4.68), as well as early career physicians compared to their more senior colleagues (aOR=2.69, 95% CI: 1.30-5.56), whereas physicians from suburban settings were less impacted than physicians from urban settings (aOR=0.62, 95% CI: 0.39-0.99). The most frequently identified barriers to immunizations during the pandemic were parental concerns around COVID-19 (n=305; 77.8%), lack of personal protective equipment (PPE; n=123; 31.3%) and healthcare workers’ concerns of contracting COVID-19 (n=105; 26.8%).ConclusionsCOVID-19 has caused substantial modifications to pediatric immunization services across Ontario. Strategies to mitigate barriers to immunizations during the pandemic need to be implemented in order to avoid immunity gaps that could lead to an increase in vaccine preventable diseases.HIGHLIGHTSWe have conducted a descriptive, cross-sectional study by distributing online surveys to pediatricians and family physicians across Ontario to assess the impact of the COVID-19 pandemic on their immunization practices.The COVID-19 pandemic has caused a substantial decrease in in-person visits and a related disruption to routine childhood immunization services during the first wave of the pandemic.The main barriers to immunizations during the pandemic included parents’ and healthcare providers’ concerns of contracting COVID-19, and lack of appropriate personal protective equipment (PPE).Solutions to maintain childhood immunizations during the pandemic included assistance in providing PPE to clinical practices, dedicated centers for vaccination, and parental education.

Antibiotic resistance is a serious public health problem throughout the world. Overcoming methicillin and multidrug-resistant Staphylococcus aureus (MRSA/MDRSA) infections has become a challenge and there is an urgent need for new therapeutic approaches. We have previously demonstrated that the endocannabinoid Anandamide (AEA) can sensitize MRSA to antibiotics. Here we have studied the mechanism of action using a MDRSA clinical isolate that are sensitized by AEA to methicillin and norfloxacin. We found that AEA treatment halts the growth of both antibiotic-sensitive and antibiotic-resistant S. aureus. The AEA-treated bacteria become elongated and the membranes become ruffled with many protrusions. AEA treatment also leads to an increase in the percentage of bacteria having a complete septum, suggesting that the cell division is halted at this stage. The latter is supported by cell cycle analysis that shows an accumulation of bacteria in the G2/M phase after AEA treatment. We further observed that AEA causes a dose-dependent membrane depolarization that is partly relieved upon time. Nile red staining of the bacterial membranes indicates that AEA alters the membrane structures. Importantly, 4′-6-diamidino-2-phenylindole (DAPI) accumulation assay and ethidium bromide efflux (EtBr) assay unveiled that AEA leads to a dose-dependent drug accumulation by inhibiting drug efflux. In conclusion, our study demonstrates that AEA interferes with cell division, alters the membrane properties of MDRSA, and leads to increased intracellular drug retention, which can contribute to the sensitization of MDRSA to antibiotics.

In his manuscript we summarize the role played by the variety of pro inflammatory agents generated by neutrofiles and by macrophages and how these cells may act in synergy to injure human and tissues in various inflammatory and in post inflammatory conditions. Screening the vast published literature, we found that most of papers published on inflammation, tend to stress only the role played by a very few pro inflammatory agents as key agents in inflammation. This is unreasonable to try to understand how leukocytes kill microbial cells and injure mammalian cells in various medical conditions. This is since the PMNs and macrophages produce numerous inflammatory agents.

A middle age man with a history of diabetes mellitus type 2, hypertension, migraine and eosinophilic granulomatosis with polyangiitis (EGPA) with polyneuropathy in remission presented with paresthesia and motor weakness soon after receiving the Pfizer-BioNTech COVID-19 messanger RNA (mRNA) vaccine. The patient had polyneuropathy 10 years ago secondary to EGPA, which had resolved. EGPA was diagnosed on the basis of typical symptoms and positive sural nerve biopsy. Five days after receiving the first dose of COVID-19 vaccine, he developed heaviness and reduced dexterity of both the upper extremities, which progressed to patchy and asymmetric motor weakness of all four extremities. Given the lack of clear alternative explanation after a thorough work up, recrudescence of underlying asymptomatic polyneuropathy due to a possible reaction to COVID-19 mRNA vaccine was considered although a temporal association with vaccine dose does not prove causality. He was treated with corticosteroids with slow improvement of his symptoms.

Background: We report a young woman who presented with acute psychosis and autonomic dysfunction who was diagnosed with Anti-N-Methyl-D-Aspartate Receptor Encephalitis (anti-NMDARE). Her life-threatening autonomic instability was controlled only after the placement of a permanent cardiac pacemaker. Case Presentation: A 29-year-old woman presented with abnormal movements and depersonalization. Vital signs showed BP 132/94 mmHg, HR 110 beats/min, RR 26 cycles/min, temperature of 101 F and spO2 of 80 % on RA. She was emergently intubated. Laboratory evaluation showed elevated CRP 6.98 mg/dL and CK 3329 U/L. Brain MRI revealed an abnormality in the right amygdala and hippocampus. Infectious workup was negative; however, a high titer of CSF NMDAR antibody was present. CT abdomen and pelvis revealed a 1.1 cm cyst within the left ovary. With a diagnosis of anti-NMDARE, she was treated with plasmapheresis, methylprednisolone, and immunoglobulin G therapy and underwent bilateral salpingo-oophorectomy with pathology confirming a teratoma. Despite these treatments, she continued to display autonomic dysfunction. Telemetry showed tachycardia-bradycardia with asystole that remained refractory to treatment and required placement of a permanent pacemaker (PPM). She showed clinical improvement after PPM and treatment ( Figure ). Conclusion: This is a rare case of severe bradyarrhythmia in anti NMDARE that necessitated placement of a permanent cardiac pacemaker. Neural-mapping studies show that the amygdala and hippocampus strongly modulate autonomic control. Disruption of cortical circuitry related to autonomic tone likely lead to arrhythmias in our case. Class I indications for pacemakers in the ICU include asystole, symptomatic bradycardia with hypotension and/or unresponsive to atropine. Early recognition, cardiorespiratory support, multistep pharmacological care and sometimes early electrophysiological support in anti-NMDARE are paramount.

Background The COVID-19 pandemic has a worldwide impact on all health services, including childhood immunizations. In Canada, there is limited data to quantify and characterize this issue. Methods We conducted a descriptive, cross-sectional study by distributing online surveys to physicians across Ontario. The survey included three sections: provider characteristics, impact of COVID-19 on professional practice, and impact of COVID-19 on routine childhood immunization services. Multivariable logistic regression identified factors associated with modification of immunization services. Results A total of 475 respondents answered the survey from May 27th to July 3rd 2020, including 189 family physicians and 286 pediatricians. The median proportion of in-person visits reported by physicians before the pandemic was 99% and dropped to 18% during the first wave of the pandemic in Ontario. In total, 175 (44.6%) of the 392 respondents who usually provide vaccination to children acknowledged a negative impact caused by the pandemic on their immunization services, ranging from temporary closure of their practice (n = 18; 4.6%) to postponement of vaccines in certain age groups (n = 103; 26.3%). Pediatricians were more likely to experience a negative impact on their immunization services compared to family physicians (adjusted odds ratio [aOR] = 2.64, 95% CI: 1.48–4.68), as well as early career physicians compared to their more senior colleagues (aOR = 2.69, 95% CI: 1.30–5.56), whereas physicians from suburban settings were less impacted than physicians from urban settings (aOR = 0.62, 95% CI: 0.39–0.99). Some of the proposed solutions to decreased immunization services included assistance in accessing personal protective equipment, dedicated centers or practices for vaccination, universal centralized electronic immunization records and education campaigns for parents. Conclusions COVID-19 has caused substantial modifications to pediatric immunization services across Ontario. Strategies to mitigate barriers to immunizations during the pandemic need to be implemented in order to avoid immunity gaps that could lead to an eventual increase in vaccine preventable diseases.

Background Due to the slow progression of many chronic liver diseases, including hepatitis C, it is not practical or safe to monitor disease progression by serial liver biopsies. Noninvasive laboratory scoring systems based on routine laboratory tests are appealing surrogate markers of liver fibrosis for the staging and monitoring of chronic liver diseases such as hepatitis C. Methods We explored the accuracy of three scoring systems: the fibrosis-4 score (FIB-4), the aspartate aminotransferase to platelet ratio index (APRI score), and the aspartate aminotransferase to alanine aminotransferase ratio (AAR) in 496 patients with chronic hepatitis C virus (HCV) infection who had undergone percutaneous liver biopsy at a viral hepatitis clinic in Shreveport, Louisiana. Results For FIB-4, the area under the receiver operating characteristic curve (AUROC) for hepatic fibrosis stages ≥ 1, ≥ 2, ≥ 3, and 4 (cirrhosis) ranged from 0.74 (95% CI, 0.678 - 0.802) to 0.802 (95% CI, 0.751 - 0.854). At a cutoff value of 1.45, FIB-4 was 82% sensitive for advanced fibrosis or cirrhosis (stage 3 or 4) but was only 58% specific for these findings. Increasing the FIB-4 cutoff value to 3.25 reduced the sensitivity for detecting advanced fibrosis or cirrhosis to 39%, but this higher cutoff was 92% specific for these findings. Corresponding AUROCs for the APRI and AAR scores were inferior to FIB-4. Conclusion The FIB-4 index outperformed APRI and AAR in our HCV infected population in predicting severe fibrosis or cirrhosis.

Candidiasis is a fungal infection caused by Candida species that have formed a biofilm on epithelial linings of the body. The most frequently affected areas include the vagina, oral cavity and the intestine. In severe cases, the fungi penetrate the epithelium and cause systemic infections. One approach to combat candidiasis is to prevent the adhesion of the fungal hyphae to the epithelium. Here we demonstrate that the endocannabinoid anandamide (AEA) and the endocannabinoid-like N-arachidonoyl serine (AraS) strongly prevent the adherence of C. albicans hyphae to cervical epithelial cells, while the endocannabinoid 2-arachidonoylglycerol (2-AG) has only a minor inhibitory effect. In addition, we observed that both AEA and AraS prevent the yeast-hypha transition and perturb hyphal growth. Real-time PCR analysis showed that AEA represses the expression of the HWP1 and ALS3 adhesins involved in Candida adhesion to epithelial cells and the HGC1, RAS1, EFG1 and ZAP1 regulators of hyphal morphogenesis and cell adherence. On the other hand, AEA increased the expression of NRG1, a transcriptional repressor of filamentous growth. Altogether, our data show that AEA and AraS have potential anti-fungal activities by inhibiting hyphal growth and preventing hyphal adherence to epithelial cells.

The autoimmune disorder rheumatoid arthritis (RA) is a relapsing and chronic inflammatory disease that affects the synovial cells, cartilage, bone, and muscle. It is characterised by the accumulation of huge numbers of polymorphonuclear neutrophils (PMNs) and macrophages in the synovia. Auto-antibodies are deposited in the joint via the activity of highly cationic histones released from neutrophil extracellular traps (NETs) in a phenomenon termed NETosis. The cationic histones function as opsonic agents that bind to negatively charged domains in autoantibodies and complement compounds via strong electrostatic forces, facilitating their deposition and endocytosis by synovial cells. However, eventually the main cause of tissue damage is the plethora of toxic pro-inflammatory substances released by activated neutrophils recruited by cytokines. Tissue damage in RA can also be accompanied by infections which, upon bacteriolysis, release cell-wall components that are toxic to tissues. Some amelioration of the damaged cells and tissues in RA may be achieved by the use of highly anionic heparins, which can neutralize cationic histone activity, provided that these polyanions are co-administrated with anti-inflammatory drugs such as steroids, colchicine, or methotrexate, low molecular weight antioxidants, proteinase inhibitors, and phospholipase A2 inhibitors.

Objective: To describe the outcomes with use of a combination of tocilizumab and methylprednisolone administered around the time of endotracheal intubation in patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. Data Sources: Retrospective chart review. Study Selection/Data Extraction: Twenty-one consecutive patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. Initial ventilator parameters were positive end-expiratory pressure 14 cm H2o and target plateau pressure 29 cm H2o to maximize lung recruitment. Methylprednisolone (125 mg every 6hr for 24 hr with tapering to 60 mg every 12 hr) was administered shortly after patients were intubated (median 11 hr after intubation). Data Synthesis: No patient in the cohort died while hospitalized (mortality, 0%; 95% CI, 0%–18%) and 18 patients have been discharged from the acute care setting. Twenty of 21 patients (95%) have been liberated from mechanical ventilation after a median duration of 8 days (range, 4–30 d). Following 48 hours of methylprednisolone, the A-a o2 gradient decreased from 455 ± 103 to 228 ± 109 mm Hg (difference 227 ± 108 mm Hg; p < 0.01). Conclusions: Our positive experience with tocilizumab in combination with methylprednisolone started early after endotracheal intubation may be one avenue for reducing the morbidity and mortality seen with severe coronavirus disease 2019 and merits further exploration in clinical studies.

Background: Pituitary apoplexy (PA) is a rare endocrinopathy that requires prompt diagnosis and treatment. Presentation with acute neutrophilic meningitis is uncommon. Clinical Case: A 67-year-old man presented to our hospital with a 2-week history of worsening bilateral frontal headache, nausea, and dry heaving. On admission, the patient was somnolent with a score of 13 on the GCS assessment (E2, V5, M6). The neurological exam was overall normal with normal ocular motion and intact cranial nerves, except for a left eye peripheral vision defect. Plain head CT revealed a well-circumscribed ovoid pituitary mass with suprasellar enlargement, consistent with a pituitary macroadenoma. Sellar MRI showed a pituitary mass, roughly 20 x 19 x 24 mm, bulging into the suprasellar cistern with optic chiasm elevation. Analysis of pituitary function revealed low ACTH concentration of 2.8 pg/mL (n = 7.2 - 63.3 pg/mL), a low random cortisol level of 1.7 ug/dL (n = 2.9 - 19.4 ug/dL), a low TSH of < 0.1 uIU/mL (n = 0.35 - 4.9 uIU/mL), a low free T4 level of 0.72 ng/dL (n = 0.77 - 1.48 ng/dL), a low LH of 0.8 IU/L (n = 1.7 - 8.6 IU/L) with a very low total testosterone level of < 3 ng/dL (n = 300 - 720 ng/dL) and normal prolactin, IGF-1 and GH levels. On hospital day 2, the patient had worsening encephalopathy with left eye ptosis and decreased vision. Repeat CT and MRI showed no interval change in the pituitary adenoma or evidence of bleeding. An immediate lumbar puncture was performed and CSF analysis revealed an increased leukocyte count of (1106/mm3) with 89% neutrophilic granulocytes, and increased total protein level of 138 mg/dL (n = 15 - 40 mg/dL), red blood cell count of 2040 without xanthochromia and glucose of 130 mg/dL (n = 40 - 70 mg/dL). Based on the laboratory results and new symptoms, empirical antibiotic (vancomycin, ceftriaxone, and ampicillin) therapy was started for suspected bacterial meningitis before the confirmation of the CSF culture study. CSF culture did not grow any organisms. Given the sudden visual impairment and neurological deterioration, the patient underwent transsphenoidal resection of the tumor with free nasal mucosal graft reconstruction. Histological examination revealed a necrotic pituitary adenoma with apoplexy and no evidence of hemorrhage. Postoperatively, his neurological exam greatly improved. His left pupil was reactive to light and the third palsy was improving. Conclusion: This case reinforces the importance of including PA in the differential diagnosis of acute headache, particularly in patients presenting with visual disturbances. Patients with PA often present with sterile meningitis due to increased debris and blood in the subarachnoid space which closely mimics acute bacterial meningitis. While MRI remains a sensitive imaging modality for the detection of PA, the latter remains a clinical diagnosis. Timely diagnosis with high clinical suspicion and treatment is essential.

Extraosseous Ewing’s sarcoma is a rare and aggressive malignant tumor with a poor prognosis. The pancreas is an extremely uncommon primary site, with only 27 cases that have been published worldwide. We report a 26-year-old female who presented with 5 days of left upper quadrant pain, nausea, and vomiting. On examination, she was anicteric and had epigastric and left upper quadrant tenderness without guarding, rebound tenderness, or a palpable mass. She had slightly elevated serum aminotransferase and lipase levels. Abdominal computerized tomography revealed a multilobulated tumor arising from the body and tail of the pancreas. A biopsy confirmed a small round cell tumor, and immunohistochemistry was positive for CD99 in approximately 70% of the tumor cells. A fluorescence in situ hybridization (FISH) assay showed a 22q12 rearrangement. She was diagnosed with extraosseous Ewing sarcoma of the pancreas and underwent multiagent neoadjuvant chemotherapy followed by surgical resection, but subsequent imaging revealed evidence of systemic disease progression. She chose to go on hospice care and died a few weeks later.

Aim. To assess the effect of treating chronic hepatitis C virus (HCV) infection with direct acting antiviral drugs (DAAs) on glycemic control in patients with concomitant diabetes mellitus (DM). Methods. We performed a retrospective case-control study in a viral hepatitis ambulatory clinic in Shreveport, Louisiana, during the period 11/01/2014 to 12/31/2017. All the clinic patient ages 18 years and above with treatment-naïve/biopsy-proven chronic hepatitis C and DM (hemoglobin A1C level≥6.5%) who were eligible for treatment were included in the study. Of 118 such patients, 59 were treated with oral DAAs for 8-12 weeks with the goal of achieving a sustained virologic response (SVR). A control group of 59 patients did not receive treatment for their hepatitis C and was followed in the clinic. Patients in the control group did not receive treatment either due to insurance issues or refusal of hepatitis C treatment. Results. Fifty-five of the 59 patients treated with DAAs (93%) achieved a SVR. Six months after treatment completion, their mean±SEM HbA1C level had decreased by 1.1±0.03% (P<0.0001). Four of the 59 patients treated with DAAs did not achieve a SVR. Their mean HbA1C 6 months after treatment completion had increased by 0.8±0.2%. Furthermore, there was no improvement in HbA1C levels over time in the untreated group (mean HbA1C increase, 0.2±0.05%; P<0.0001 vs. the treatment group, which had a mean HbA1C decrease of 0.9±0.2%). Conclusion. This controlled study demonstrated that treatment of chronic hepatitis C with DAAs results in statistically significant and meaningful reductions in hemoglobin A1C levels in patients with coexisting diabetic mellitus if a SVR is achieved.

Endocannabinoid/endocannabinoid-like (EC/EC-like) are natural endogenous compounds which have been found to affect MRSA pathogenicity. Our previous studies showed that EC/EC-like was able to impair staphylococcal biofilm formation and maintenance as well as to alter biofilm-associated virulence factors. In the present study, we investigated the combinatory effect of the selected EC/EC-like with a natural antimicrobial agent, poly-L-lysine, on cariogenic bacteria Streptococcus mutans growth and biofilm formation. Among four tested EC/EC-like, only two, anandamide (AEA) and oleoylethanolamide (OEA), exhibited synergistic combinatory effect with poly-L-lysine against S. mutans. We attribute this distinct effect to differences in the fatty acid chain structure of the selected EC/EC-like compounds. Moreover, AEA exerted a specific antibiofilm mode of action against S. mutans by effecting total inhibition of biofilm formation while still allowing bacteria viability. Finally, we postulate that the presence of EC/EC-like and poly-L-lysine could enhance the permeability and efficacy of each other via hydrophobic and electrostatic interactions with the S. mutans membrane. In conclusion, we assume that a combination of endogenous natural compounds such as EC/EC-like and poly-L-lysine may benefit oral hygiene by preventing dental plaque.

Purpose The authors investigated the impact of the use of an efficient multiple-choice question (MCQ) test-enhanced learning (TEL) intervention for continuing professional development (CPD) on knowledge retention as well as self-reported learning behaviors. Method The authors conducted a randomized controlled trial comparing knowledge retention among learners who registered for an annual CPD conference at the University of Toronto in April 2016. Participants were randomized to receive an online preworkshop stand-alone MCQ test (no feedback) and a postworkshop MCQ test (with feedback) after a 14-day delay. Controls received no pre-/posttesting. The primary outcome measure was performance on a clinical vignette-based retention and application test delivered to all participants four weeks post conference. Secondary outcomes included self-reported changes in learning behavior, satisfaction, and efficiency of TEL. Results Three hundred eight physicians from across Canada registered for the four-day conference; 186 physicians consented to participate in the study and were randomized to receive TEL or to the control group in 1 of 15 workshops, with 126 providing complete data. A random-effects meta-analysis demonstrated a pooled effect size indicating moderate effect of TEL (Hedges g of 0.46; 95% CI: 0.26-0.67). The majority of respondents (65%) reported improved CPD learning resulting from pretesting. Conclusions Testing for learning can be leveraged to efficiently and effectively improve outcomes for CPD. Testing remains an underused education intervention in CPD, and the use of formative assessment to enhance professional development should be a key target for research.

Ecthyma gangrenosum is a rare and highly lethal cutaneous infection classically associated with Pseudomonas aeruginosa bacteremia. We report a 58-year-old man with multiple myeloma receiving chemotherapy who presented with 2 days of painless left periorbital swelling that rapidly progressed to a blackish eschar. His absolute neutrophil count was 0.10/mm(3); platelet count, 14,000/mm(3); and hemoglobin, 6 g/dL. Computed tomography showed diffuse left periorbital cellulitis. Blood cultures grew pan-sensitive Pseudomonas aeruginosa, and the patient died from sepsis and multiorgan failure.

Background: Diabetic myonecrosis is a rare complication of long-standing, poorly controlled diabetes mellitus, and is more common in patients with microvascular complications. The diagnosis is frequently missed due to symptoms mimicking other conditions associated with diabetes mellitus. Clinical Case: A 31-year-old woman with a past medical history of long-standing type I diabetes mellitus, end-stage renal disease, diabetic retinopathy, and cataracts presented to our hospital with a chief complaint of right thigh pain and swelling for a week. She did not have any other relevant symptoms and denied a history of trauma. On admission, physical examination revealed right thigh edema, induration, tenderness on palpation, more pronounced in the medial aspect of the thigh, and decreased range of motion of the right hip. Laboratory analysis showed leukocytosis of 13.29 k/uL (normal = 4.23 - 9.71 k/uL) with neutrophilic predominance of 91.4 %, elevated inflammatory markers (ESR > 130 mm/h (normal = 0 - 30 mm/h), CRP 33.84 mg/dL (normal Conclusion: This case reinforces the importance of including diabetic myonecrosis in the differential diagnosis of acute to subacute nontraumatic muscular pain in diabetic patients, particularly in patients with poor glycemic control and known complications. While muscle biopsy can be performed for histological confirmation, the typical imaging findings and clinical presentation can lead to the diagnosis, making further invasive testing unnecessary. In most described cases, the course of this condition is self-limiting.

A 29-year-old woman with known sickle cell disease (SCD) and iatrogenic iron overload presented to the emergency department with a recurrent pain crisis and fever. Blood cultures obtained at a recent prior admission for the same complaints grew M avium. Bone marrow biopsy revealed non-caseating granulomas, but stains for mycobacteria and fungi were negative. Disseminated non-tuberculous mycobacterial infections (NTMIs) occur almost exclusively in immunosuppressed patients. SCD is not considered a risk factor for the development of disseminated NTMIs, making diagnosis challenging in this population. However, a number of case reports describing disseminated NTMIs in patients with SCD have been published. This case adds to the current literature, suggesting SCD with iatrogenic iron overload is a possible risk factor for disseminated NTMIs. Potential mechanisms for this increased risk include 1) functional asplenia, 2) iatrogenic iron overload, 3) chronic indwelling central venous catheters, and 4) hydroxyurea use. Further investigation is required to describe the strength and mechanism of the relationship between SCD and disseminated NTMIs.

Barrett's esophagus (BE) is associated with an increased incidence of adenocarcinoma. The dysplasia in BE that precedes cancer is usually endoscopically flat. Unlike in the colon, polypoid dysplastic lesions superimposed on BE are uncommon. Furthermore, villous tumors of the esophagus are rare, and few cases have been reported in the literature. We report an 85-year-old man who was found to have a circumferential villiform-appearing esophageal tumor with mucus secretions with recurrent bronchopulmonary aspiration. A diffuse villiform tumor of the entire esophagus with mucin production is rare and, to our knowledge, has not been previously described in the literature.

The arterial partial pressure of oxygen in the arterial blood reveals limited information about pulmonary oxygen transfer. In 989 hospitalized patients undergoing arterial blood gas testing, we compared conventional indices of oxygen transfer: (1) P(A-a) O2 (A-a); (2) PaO2/PAO2 (a/A); and (3) the P/F ratio Nine hundred twenty-five of the patients were receiving supplemental oxygen therapy (FIO2 .24-1.00) and 65 were breathing room air. In patients receiving supplemental O2, the a/A ratio closely correlated with the P/F ratio (r = .98 to .99); the A-a O2 difference did not correlate as closely with the a/A ratio (r = -.77 to -.85) or with the P/F ratio (r = -.72 to -.80). In those breathing room air (FIO2 .21), the a/A ratio was closely and inversely correlated with the A-a difference (r= -.97 to -.98); correlations between the a/A and P/F ratios (r=.88 to .89) and between the P/F ratio and A-a O2 difference (r = -.78 to -.79) were less robust. We conclude that the a/A ratio is the preferred oxygen transfer parameter over the wide range of FIO2 levels encountered clinically.

Background:Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) are two major contributors to dental caries. They have a symbiotic relationship, allowing them to create an enhanced biofilm. Our goal was to examine whether two natural polyphenols (Padma hepaten (PH) and a polyphenol extraction from green tea (PPFGT)) could inhibit the caries-inducing properties of S. mutans and C. albicans. Methods: Co-species biofilms of S. mutans and C. albicans were grown in the presence of PH and PPFGT. Biofilm formation was tested spectrophotometrically. Exopolysaccharides (EPS) secretion was quantified using confocal scanning laser microscopy. Biofilm development was also tested on orthodontic surfaces (Essix) to assess biofilm inhibition ability on such an orthodontic appliance. Results: PPFGT and PH dose-dependently inhibited biofilm formation without affecting the planktonic growth. We found a significant reduction in biofilm total biomass using 0.625 mg/mL PPFGT and 0.16 mg/mL PH. A concentration of 0.31 mg/mL PPFGT and 0.16 mg/mL PH inhibited the total cell growth by 54% and EPS secretion by 81%. A reduction in biofilm formation and EPS secretion was also observed on orthodontic PVC surfaces. Conclusions: The polyphenolic extractions PPFGT and PH have an inhibitory effect on S. mutans and C. albicans biofilm formation and EPS secretion.

Balamuthia mandrillarisis a rare cause of granulomatous meningoencephalitis associated with high mortality. We report a 69-year-old Caucasian female who presented with a 3-day history of worsening confusion and difficulty with speech. On admission, she was disoriented and had expressive dysphasia. Motor examination revealed a right arm pronator drift. Cerebellar examination showed slowing of finger-nose testing on the left. She was HIV-negative, but the absolute CD4 count was low. Neuroimaging showed three cavitary, peripherally enhancing brain lesions, involving the right frontal lobe, the left basal ganglia, and the left cerebellar hemisphere. She underwent right frontal craniotomy with removal of tan, creamy, partially liquefied necrotic material from the brain, consistent with granulomatous amoebic encephalitis on tissue staining. Immunohistochemical studies and PCR tests confirmed infection withBalamuthia mandrillaris. She was started on pentamidine, sulfadiazine, azithromycin, fluconazole, flucytosine, and miltefosine. The postoperative course was complicated by an ischemic stroke, and she died a few weeks later.