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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.

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

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.

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…

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.

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.

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.

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.

Background It is widely believed that plasma electrolyte levels are normally distributed. Statistical tests and calculations using plasma electrolyte data are often reported based on this assumption of normality. Examples include t tests, analysis of variance, correlations and confidence intervals. The purpose of our study was to determine whether plasma sodium (Na+), potassium (K+), chloride (Cl−) and bicarbonate ( HCO 3 − ) distributions are indeed normally distributed. Methods We analyzed plasma electrolyte data from 237 consecutive adults (137 women and 100 men) who had normal results on a standard basic metabolic panel which included plasma electrolyte measurements. The skewness of each distribution (as a measure of its asymmetry) was compared to the zero skewness of a normal (Gaussian) distribution. Results The plasma Na+ distribution was skewed slightly to the right, but the skew was not significantly different from zero skew. The plasma Cl− distribution was skewed slightly to the left, but again the skew was not significantly different from zero skew. On the contrary, both the plasma K+ and HCO 3 − distributions were significantly skewed to the right (P HCO 3 − distributions were bimodal. Conclusions In adults with a normal basic metabolic panel, plasma potassium and bicarbonate levels are not normally distributed and may be bimodal. Thus, statistical methods to evaluate these 2 plasma electrolytes should be nonparametric tests and not parametric ones that require a normal distribution.

Contribution on "My Story of International Arbitration" at the Shenzhen Court of International Arbitration, marking the 40th anniversary of the Shenzhen Special Economic Zone.

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.

Criticism of the quality of investor-State dispute settlement (ISDS) decision-making often focuses on inconsistency (comparing ISDS decisions), and less frequently, incorrectness (evaluating individual ISDS decisions on a standalone basis). This article situates incorrect ISDS decision-making within the broader context of public international law and develops potential policy responses, guided by three considerations. First, criticism of ISDS decision-making has been significant. Second, criticism of particular ISDS decisions, even when widespread and intense, does not necessarily establish their incorrectness. Finally, development of policy options should be informed by a broad understanding of ‘incorrectness’, to include instances of questionable legal analysis that cast doubt on the reliability of ISDS legal conclusions and outcomes; that approach can support not only the avoidance of incorrect ISDS decision-making in a strict sense, but also, more expansively, the achievement of correct ISDS decision-making, consisting of two core elements: correct identification and precise application of applicable law.

Remarks prepared for panel discussion on US-China Relations: Challenges and Opportunities, organized by the Hong Kong International Arbitration Centre as part of the 2020 ADR in Asia Conference.

Many newly-created international commercial courts are supporting integrated commercial dispute resolution services, which blur lines between litigation, arbitration, and mediation services. Such “one-stop” commercial dispute resolution services will affect international arbitration generally and investment arbitration specifically. This chapter examines the likely impact of integrated international dispute resolution services on the investment arbitration regime in three respects: institutionalization, transparency, and enforcement. The chapter reaches the following conclusions. Regarding institutionalization, integrated dispute resolution services likely will contribute to the building momentum for greater institutionalization within the investment arbitration regime. Regarding transparency, integrated dispute resolution services likely will give rise to additional transparency gains within the regime by placing even greater attention on the need for coherent development of law, which requires public access to decision-making. Regarding enforcement, integrated dispute resolution services likely will narrow the existing enforceability gap between arbitral awards, on the one hand, and court judgments and mediated settlement agreements, on the other. A narrower enforceability gap would reduce the significance of one of the key advantages of international arbitration: an unmatched global enforcement regime. The diminished significance of that advantage likely would place additional pressure on the investment arbitration regime to address key vulnerabilities, notably recurrent perceptions of incoherent jurisprudence and arbitrator conflicts of interest.

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.

Objective Despite agreement that preadult onset of depression is associated with greater illness severity, and that children can meet the diagnostic criteria for major depressive disorder (MDD), few studies have examined the presentation of MDD among young children. This is the first nationwide study of MDD among preadolescent children in Canada. Methods Pediatrician members (2500) of a Canadian pediatric surveillance network were surveyed monthly over 3 years to report new cases of MDD among 5- to 12-year-olds. Survey response and questionnaire completion rates were 80% and 85%, respectively. Symptom presentation and duration, impairment, medical and psychiatric history, and management were reported. Results Twenty-nine new cases of MDD were identified by pediatricians. Of these, 23 (79%) experienced symptoms for >6 months before presentation with global functional impairment. Parental depression or anxiety, commonly maternal, was present in 21 cases (72%). Twenty-two children (76%) reported suicidal ideation; 6 (21%) had attempted suicide. Twenty-three children (79%) were treated with medication. Thirteen children (45%) were treated with 2 or more medications. Conclusions Children with MDD frequently had a parental history of mood disorders, experienced long-standing symptom presence, high symptom burden and functional impairment prior to presentation; and commonly treatment with polypharmacy.

Objective To determine the relationship between estimated cardiorespiratory fitness (CRF) and femoral neck (FN) bone mineral density (BMD) in men. Patients and Methods This cross-sectional study included 2569 men aged 50 to 90 years (mean, 63.5 years) who had at least 1 health examination at a preventive medicine clinic between January 27, 1998, and February 24, 2015. Maximal treadmill tests were conducted using the Balke protocol and were used to estimate CRF. We stratified patients into low, moderate, and high CRF categories. The FN BMD was measured by dual-energy x-ray absorptiometry. Odds ratios (ORs) for T-scores of −2.5 or less (osteoporosis) and −1.0 or less (low BMD) were calculated for categorical CRF and were adjusted for weight, age, and days per week of resistance activity. Results The sample prevalence of osteoporosis in the FN was 4.1% and of low BMD was 49.4%. There was a significant inverse association between higher CRF category and osteoporosis measured at the FN (moderate vs low: OR=0.34; 95% CI, 0.16-0.74; high vs low: OR=0.19; 95% CI, 0.09-0.42) and low BMD (moderate vs low: OR=0.64; 95% CI, 0.43-0.96; high vs low: OR=0.43; 95% CI, 0.29-0.65). Conclusion In men, CRF is directly associated with BMD. These results suggest that moderate-to-high CRF levels attained through regular physical activity may attenuate age-related decline in BMD. Further studies are needed to determine whether this translates to a lower risk of osteoporotic fracture in more fit men.

Background: Immune checkpoint inhibitors have changed the therapeutic milieu for patients with metastatic melanoma. However, their use may promote autoimmunity in virtually any organ in the body due to the blockade of intrinsic immune down regulators such as cytotoxic T-lymphocyte antigen- 4 (CTLA-4), programmed cell death 1 (PD1) or its ligand (PDL1). Immune mediated adverse neurological events are rare with these agents, however, and are seen in < 1% of treated patients. We report a patient with immune checkpoint inhibitor associated autoimmune encephalitis, with complete clinical recovery after treatment.Case Report: A 49-year-old female with metastatic melanoma currently on nivolumab therapy but recently on ipilimumab/nivolumab combined therapy presented with a new headache. She also reported associated confusion, loss of balance, personality changes and language difficulty. Magnetic resonance imaging of the brain did not reveal any evidence of metastasis, infarct, meningitis, or encephalitis. Lumbar puncture revealed an elevated protein level and pleocytosis, with a normal glucose level. She was started on empiric glucocorticoid therapy with a presumptive diagnosis of immune checkpoint inhibitor associated autoimmune encephalitis. She improved considerably by day 3 of treatment with complete resolution of neurological symptoms by day 5.Conclusion: Immune checkpoint inhibitors are increasingly important in cancer immunotherapy as they can cause sustained remissions in patients with metastatic melanoma and other malignancies. Because these drugs block immune-regulatory targets, they can lead to enhanced activation of immune system resulting in immune-related adverse events. Autoimmune encephalitis is a rare immune-related adverse event associated with immune checkpoint inhibitors. The incidence of autoimmune encephalitis is higher with combination or sequential CTLA-4 (ipilimumab) and PD1(nivolumab) inhibitor therapy than with monotherapy. With more widespread use of immunotherapy, it is important for clinicians to be aware of this rare and reversible cause of encephalitis. Early recognition and prompt initiation of immunosuppressive therapy with glucocorticoids is essential to enhance neurological recovery.

Drug-associated thrombocytopenia is often unrecognized. We report a 76-year-old female with lymphoma who presented with easy bruising and oral bleeding. She had undergone screening for hepatitis B virus (HBV) prior to starting rituximab and was found to have hepatitis B core serum antibody (IgG anti-HBc). She was therefore treated with prophylactic entecavir 0.5 mg daily to prevent reactivation of HBV. Her initial platelet count was 136,000/mm3. Five days after starting entecavir, she presented with bruising and oral bleeding and was found to have a platelet count of 7,000/mm3. A coagulation profile and the rest of the blood parameters (RBC and WBC counts) were normal. Entecavir was stopped, and she was given 3 units of apheresed platelets followed by intravenous immunoglobulin (1 g/kg) for 5 consecutive days. Her platelet counts improved and normalized in one week. She was diagnosed with entecavir-induced thrombocytopenia based on the temporal relationship and after carefully excluding alternate causes of thrombocytopenia. This case highlights the importance of recognizing drug-induced thrombocytopenia (DITP) as a reversible cause of thrombocytopenia.

IntroductionCow’s milk is a dietary staple for children in North America. Though clinical guidelines suggest children transition from whole (3.25% fat) milk to reduced (1% or 2%) fat milk at age 2 years, recent epidemiological evidence supports a link between whole milk consumption and lower adiposity in children. The purpose of this trial is to determine which milk fat recommendation minimises excess adiposity and optimises child nutrition and growth.Methods and analysisCow’s Milk Fat Obesity pRevention Trial will be a pragmatic, superiority, parallel group randomised controlled trial involving children receiving routine healthcare aged 2 to 4–5 years who are participating in the TARGet Kids! practice-based research network in Toronto, Canada. Children (n=534) will be randomised to receive one of two interventions: (1) a recommendation to consume whole milk or (2) a recommendation to consume reduced (1%) fat milk. The primary outcome is adiposity measured by body mass index z-score and waist circumference z-score; secondary outcomes will be cognitive development (using the Ages and Stages Questionnaire), vitamin D stores, cardiometabolic health (glucose, high-sensitivity C-reactive protein, non-high density lipoprotein (non-HDL), low density lipoprotein (LDL), triglyceride, HDL and total cholesterol, insulin and diastolic and systolic blood pressure), sugary beverage and total energy intake (measured by 24 hours dietary recall) and cost effectiveness. Outcomes will be measured 24 months postrandomisation and compared using analysis of covariance (ANCOVA), adjusting for baseline measures.Ethics and disseminationEthics approval has been obtained from Unity Health Toronto and The Hospital for Sick Children. Results will be presented locally, nationally and internationally and published in a peer-reviewed journal. The findings may be helpful to nutrition guidelines for children in effort to reduce childhood obesity using a simple, inexpensive and scalable cow’s milk fat intervention.Trial registration numberNCT03914807; pre-results.

A core theme of China’s Belt and Road Initiative (“BRI”) is connectivity, which extends to BRI-related dispute resolution. But BRI-related advances in dispute resolution connectivity will be occurring in an international trade environment that is becoming increasingly fractured; the extent to which a fractured trade environment might impede BRI-related opportunities for dispute resolution connectivity merits close consideration. A range of initiatives in Asia lower the risk of states “detaching” themselves from China. Particularly with respect to dispute resolution, China has participated in the conclusion of a Regional Comprehensive Economic Partnership agreement, the launch of the China International Commercial Court (“CICC”) and the International Commercial Dispute Prevention and Settlement Organization, as well as the development of a number of instruments that improve the enforceability of dispute resolution outcomes in a range of settings, including a few dozen bilateral treaties on judicial assistance as well as a set of multilateral instruments covering mediated settlement agreements (the Singapore Convention on Mediation), choice of court agreements (the Hague Choice of Court Convention), and court judgments (the Hague Judgments Convention). But a low risk of separation from China does not entail a low risk of criticism of China. Malaysia’s recent suspension, and subsequent resumption, of a few major BRI projects provides one clear example. In the particular context of dispute resolution, many responses to the launch of the CICC by China’s Supreme People’s Court have been critical or, at a minimum, skeptical. Rather than leading to separation, criticism instead can be a form of engagement. International engagement with the BRI and the Asian Infrastructure Investment Bank has been strong notwithstanding significant criticism of both initiatives. An increasingly fractured trade environment likely will not impede China’s advancement of dispute resolution connectivity, particularly given the active rulemaking and institution building occurring on China’s side of the divide.

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.

As UNCITRAL Working Group III discussions on investment arbitration reform continue, geography remains a relevant factor when analyzing investment treaty practice, although not along traditional North-South lines. Over the past several years, three distinct models of investment treaty practice have emerged, which can be identified by geographic region: (i) a European model (as reflected in recent European Union practice), (ii) a ‘regional South’ model (as reflected in recent practice by Brazil, India, and the Southern African Development Community), and (iii) a Pacific Rim model (as reflected in the CPTPP as well as recent treaty practice by the ASEAN States, the Pacific Alliance States, China and Korea). Of the three models, the Pacific Rim approach most closely resembles the extraordinarily active investment treaty practice that occurred in the 1990s and 2000s. The Pacific Rim model can be seen as retaining three fundamental elements from that earlier treaty practice: (i) the ability of disputing parties to select decision-makers, (ii) the imposition of treaty obligations on States but not investors, and (iii) the inclusion of a core set of substantive obligations. Recent treaty practice by ASEAN, the Pacific Alliance, China and Korea, together with the entry into force of the CPTPP, illustrate the resilience of the Pacific Rim model. This Pacific Rim consensus on investment treaty practice could be further confirmed by the conclusion and entry into force of an RCEP investment chapter that follows the Pacific Rim approach. The availability of investment chapters following the Pacific Rim model in two mega-regional FTAs (CPTPP and RCEP) would create significant opportunities for institutionalization in the Pacific Rim region, in particular through the potential development of a CPTPP appellate mechanism and an RCEP appellate mechanism. In addition, China's recent UNCITRAL submission illustrates how the Pacific Rim model can be preserved while considering, at the same time, significant levels of institutionalization within the investment arbitration regime. The compatibility of the Pacific Rim model with ambitious investment arbitration reform, together with the widespread acceptance of the model, confirm the importance of the Pacific Rim consensus for the future of the investment arbitration regime.

Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections.

Remarks at Evolution of Investment Policymaking in RTAs and IIAs conference organized by the Inter-American Development Bank and the International Centre for Trade and Sustainable Development, held in Geneva, Switzerland in June 2018.

Primary cardiac sarcoma has poor prognosis, but it occurs rarely with an autopsy incidence of 0.001% to 0.003%. The surgical resection of the tumor can relieve symptoms and extend survival. A 59-year-old male presented with mild dyspnea. His TEE and cardiac MRI revealed a large multi-lobar mass.

Aspergillus endocarditis is frequently associated with immunocompromised states and has a high rate of mortality. A 62-year-old man with type 2 diabetes mellitus, CAD, sarcoidosis on chronic steroids presented with an acute right lower extremity pain. Angiogram revealed a complete right iliac

Intravascular papillary endothelial hyperplasia, also known as Masson tumor, is a rare vascular growth that usually manifests on the skin. It is extremely rare for it to be located in left atrial appendage (LAA). LAA is a common site for thrombi due to its complex anatomic, histologic and functional

Aim C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are often ordered together in patients with suspected infection or inflammation. However, the test results can disagree in as many as 33% of patients. Our aim was to further examine CRP/ESR disagreements and their stability on repeat testing. Methods We analyzed simultaneously ordered CRP and ESR results in 70 adult patients who had been tested on three separate occasions a median of 4 weeks apart. Results Initial CRP/ESR disagreements occurred in 14 of the 70 patients (20%; 95% CI, 12–31). Only four of these 14 patients had stable CRP/ESR disagreements throughout the study (two with lupus nephritis and one with osteomyelitis had persistent high ESR/normal CRP disagreements and one with rheumatoid arthritis had a persistent high CRP/normal ESR disagreement). The other 10 patients with initial CRP/ESR disagreements later exhibited CRP/ESR agreements. Of the 56 patients with initial CRP/ESR agreements, only 10 developed a CRP/ESR disagreement (or disagreements) on subsequent testing. Conclusion CRP/ESR disagreements are common in clinical practice. Three mechanisms were identified to explain CRP/ESR disagreements: (i) slight fluctuations in the CRP and ESR around the upper limits of normal for these tests; (ii) development of an intercurrent illness; and (iii) different time courses of CRP and ESR elevations, in which the CRP rose and fell faster than the ESR.

Clinical manifestations of cancer can be categorized as resulting from direct tissue injury from the primary tumor, distant metastatic spread, or aberrant biological activity, also known as a paraneoplastic syndrome. Soft tissue sarcomas are a rare group of malignant tumors of mesenchymal origin which typically present with direct tissue injury, exerting their harmful potential by compression and mass effect. We describe a rare case of an occult retroperitoneal soft tissue sarcoma presenting with marantic endocarditis. To date, there is a paucity of available medical literature relating sarcoma to marantic endocarditis.

Fourteen editors-in-chiefs have steered G astroenterology to success since its inception in 1943. Five (Alvarez, Ivy, Aaron, Grossman, and Donaldson) are no longer with us. Their personalities and editorships, along with those of Marvin Sleisenger, are presented by their admirers. Fordtran, Ockner, Goyal, LaRusso, Podolsky, Brenner, Rustgi, and Omary describe their own backgrounds, experiences, and personal reflections on serving as editor-in-chief of G astroenterology.

This chapter summarizes the evolution of the corporate social impact field, from corporate philanthropy and volunteerism to the rise of Corporate Social Responsibility (CSR) and to today’s Era of Innovation. Tracking this evolution, it presents examples ranging from Patagonia to Unilever’s Dove brand. In each case, a company of a different size and industry seeks to apply the power of its assets in new ways to proactively and intentionally deliver positive business and social impact.

The fragmented international investment law regime—which is composed of thousands of treaties—is harmonizing in two fundamental respects. First, in the near future, five agreements could govern a very substantial share of global investment: a U.S.-China bilateral investment treaty (“BIT”), an EU-China BIT, and three “mega-regional” free trade agreements (“FTAs”): the Transatlantic Trade and Investment Partnership (“TTIP”), the Trans-Pacific Partnership (“TPP”), and the Regional Comprehensive Economic Partnership (“RCEP”).

Investment obligations and investor-State arbitration provisions normally have been negotiated under BITs; in recent years, however, and with increasing frequency, such provisions have been negotiated in the larger context of FTAs. For investment provisions, the movement from BITs to FTAs recently has taken an additional, significant step: the negotiation of such provisions in the even larger context of mega-regional FTAs. This shift in context—from BITs to FTAs, and now from FTAs to mega-regional FTAs—will significantly affect the content and operation of investment provisions. Indeed, investment arbitration under mega-regional FTAs likely will be distinctive in several important respects. This chapter addresses five distinctive characteristics of investment arbitration under mega-regional FTAs. With the conclusion of the TPP, and likely conclusion of an RCEP agreement, those five characteristics ultimately could be seen, more generally, as characteristics of 21st century investment arbitration.

Serious, life-threatening conditions may result from too much gastric acid secretion by parietal cells, too little secretion of gastric acid and intrinsic factor by parietal cells, or loss of secreted gastric hydrochloric acid from the body. Understanding the physiology and pathophysiology of gastric secretion and its regulation can improve patient care and clinical outcomes. Gastric secretion remains highly relevant to practicing clinicians.