Renal proximal tubule injury is induced by agents/conditions known to cause endoplasmic reticulum (ER) stress, including cyclosporine A (CsA), an immunosuppressant drug with nephrotoxic effects. However, the underlying mechanism by which ER stress contributes to proximal tubule cell injury is not well understood. In this study, we report lipid accumulation, sterol regulatory element-binding protein-2 (SREBP-2) expression, and ER stress in proximal tubules of kidneys from mice treated with the classic ER stressor tunicamycin (Tm) or in human renal biopsy specimens showing CsA-induced nephrotoxicity. Colocalization of ER stress markers [78-kDa glucose regulated protein (GRP78), CHOP] with SREBP-2 expression and lipid accumulation was prominent within the proximal tubule cells exposed to Tm or CsA. Prolonged ER stress resulted in increased apoptotic cell death of lipid-enriched proximal tubule cells with colocalization of GRP78, SREBP-2, and Ca(2+)-independent phospholipase A(2) (iPLA(2)β), an SREBP-2 inducible gene with proapoptotic characteristics. In cultured HK-2 human proximal tubule cells, CsA- and Tm-induced ER stress caused lipid accumulation and SREBP-2 activation. Furthermore, overexpression of SREBP-2 or activation of endogenous SREBP-2 in HK-2 cells stimulated apoptosis. Inhibition of SREBP-2 activation with the site-1-serine protease inhibitor AEBSF prevented ER stress-induced lipid accumulation and apoptosis. Overexpression of the ER-resident chaperone GRP78 attenuated ER stress and inhibited CsA-induced SREBP-2 expression and lipid accumulation. In summary, our findings suggest that ER stress-induced SREBP-2 activation contributes to renal proximal tubule cell injury by dysregulating lipid homeostasis.

Background Point-of-Care Ultrasound (PoCUS) is an ultrasound examination performed by the clinician to answer a focused question or guide an invasive procedure. Despite gaining popularity and evidence supporting the use of PoCUS, core Internal Medicine (IM) residency programs in Canada have yet to implement a comprehensive PoCUS curriculum. The objective of this study was to create a formal PoCUS curriculum. Methods We conducted a systematic needs assessment with a survey that assessed IM attending and resident comfort, training, and application of PoCUS. We also performed a literature review of selected PoCUS-guided procedures and diagnostics to assess the evidence. A working group analyzed the collected data and designed a graduated 3-year curriculum. Results The needs assessment demonstrated that PoCUS education was both necessary and in high demand. The PoCUS-guided procedures and diagnostics that were identified by the survey to be necessary for IM training were then evaluated by a literature review. Based on the evidence, a progressive 3-year curriculum was created. The working group decided on the method and timing of curriculum delivery. Conclusion McMaster University is the first IM residency program to introduce a graduated 3-year curriculum complete with competency assessment and quality assurance. Résumé Contexte L'échographie ponctuelle est un examen d'échographie effectué par le clinicien pour répondre à une question ciblée ou guider une procédure invasive. Malgré l'obtention de la popularité et des preuves appuyant l'utilisation de la messagerie instantanée, les programmes de résidence au Canada pour la médecine interne de base (GI) n'ont pas encore mis en œuvre un programme exhaustif. L'objectif de cette étude était de créer un programme d'études officiel. Méthodes Nous avons effectué une évaluation systématique des besoins avec un sondage qui évaluait la présence de GI et le confort des résidents, la formation et l'application de ces programmes. Nous avons également effectué un examen de la documentation de certaines procédures et diagnostics guidés pour évaluer la preuve. Un groupe de travail a analysé les données collectées et conçu un programme gradué de trois ans. Résultats L'évaluation des besoins a démontré que l'éducation était à la fois nécessaire et trèsdemandée. Les procédures et les diagnostics qui ont été identifiés par le sondage comme étant nécessaires à la formation en GI ont ensuite été évalués par un examen de la documentation. Sur la base des données probantes, un programme d'études progressive de trois ans a été créé. Le groupe de travail a décidé de la méthode et ducalendrier de l'exécution des programmes. Conclusion L'Université McMaster est le premier programme de résidence en GI à présenter un programme gradué de trois ans complété par l'évaluation des compétences et l'assurance de la qualité.  

An intramyocardial dissecting hematoma is a rare mechanical complication after an acute myocardial infarction that carries a high mortality rate. Because intramyocardial dissecting hematomas are associated with multiple cardiac complications, cardiac imaging is an integral component to guiding therapy. We present a case of an intramyocardial dissecting hematoma treated conservatively. Here we explore the role of surgery in patients with intramyocardial dissecting hematomas as well as issues of optimal medical management including the decision to anticoagulate. In conclusion, this report offers a unique commentary on a rare case of an intramyocardial dissecting hematoma.RésuméUn hématome disséquant intramyocardique est une rare complication mécanique après un infarctus aigu du myocarde qui comporte un taux élevé de mortalité. Parce que les hématomes dissection intramyocardique associés à de multiples complications cardiaques, l’imagerie cardiaque est une composante intégrale de guider le traitement. Nous présentons un cas d’hématome disséquant intramyocardique traités conservativement. Ici, nous examinons le rôle de la chirurgie chez les patients souffrant d’hématomes dissection intramyocardique ainsi que des questions de gestion médicale optimale y compris la décision d’anticoagulate. En conclusion, ce rapport offre un unique commentaire sur un cas rare d’un hématome disséquant intramyocardique.A dissecting intramyocardial hematoma is a rare mechanical complication after an acute myocardial infarction (AMI) that carries a high mortality rate. The pathophysiology of a dissecting intramyocardial hematoma involves hemorrhagic dissection through an area of necrotic tissue between the spiral myocardial fibres of the ventricle.1 Although most intramyocardial dissections occur in the left ventricle, the dissection plane can progress to lower pressure areas and involve the right ventricle as myocardial fibres are shared.1 Intramyocardial dissections are most commonly seen as a complication of an acute AMI, but have also been described following blunt chest trauma, and rarely, from cardiac echinococcus infections.2 Because intramyocardial hematomas are associated with multiple cardiac complications such as ventricular rupture, biventricular dysfunction, and thrombus formation, cardiac imaging is an integral component to guiding therapy. We present a case of intramyocardial dissection treated with conservative management.CaseA 58-year-old male presented to the emergency department with a one-day history of shortness of breath occurring at rest. Further history revealed progressive dyspnea with exertion over the prior two months and intermittent chest tightness. He denied symptoms of typical angina. His medical history was significant for hypertension, hypercholesterolemia, and peripheral vascular disease with remote aorto-bifemoral bypass surgery. He had a 20-pack year history of smoking. His only medication on presentation was low-dose aspirin.On examination, his vital signs were as follows: temperature of 36.6°C, heart rate of 98 BPM, blood pressure of 131/105 mmHg, respiratory rate of 20, and an oxygen saturation of 99% on room air. His precordial examination was normal and there was no evidence of volume overload. Initial laboratory investigations showed a mildly elevated high-sensitivity troponin I which peaked at 39 ng/L. Chest radiography showed mild vascular redistribution but no evidence of overt heart failure. ECG showed sinus rhythm with poor R-wave progression but no ST-segment deviation or Q-waves to suggest a prior MI. The patient was subsequently admitted to hospital for further work-up of his shortness of breath.A transthoracic echocardiogram was performed which showed a dissecting intramyocardial hematoma from the mid segment of the left ventricular septum extending to the apex of the left ventricle (Figure 1 and Supplemental Videos 1 and2). The hematoma occupied approximately 50% of the left ventricular cavity, and the estimated left ventricular ejection fraction was 25–30%. The hematoma did not appear to receive any flow from the cavity of the left ventricle itself. There was no left ventricular thrombus identified. All other segments of the ventricle were either hypokinetic or akinetic and thinned. Surgical options were explored, but it was determined that the patient would be at excessive risk for morbidity and mortality with surgical resection of the hematoma due to the extent of left ventricular involvement. The patient was started on medical treatment for congestive heart failure. Due to the concern for myocardial rupture, no anticoagulation or anti-platelet therapies were given. Cardiac catheterization was not performed as there was no good option for revascularization.Six days later, cardiac magnetic resonance imaging (MRI) was performed to reassess the hematoma. The MRI identified a well-defined heterogeneity within the left ventricular mid to apical cavity extending into the apex, raising concern for an intramural dissecting hemorrhage of the myocardium or intracavitary thrombus (Supplemental Video 3). There was also late enhancement of the left ventricular septal and apical segments extending into the right ventricle, indicating an extensive left anterior descending artery territory AMI (Figure 2). Although it was unclear whether the thrombus was contained within the myocardium, anticoagulation was not pursued because of the concern that it would impair healing of, or potentially worsen, the hematoma. A repeat echocardiogram was performed two months after initial presentation, which showed an ejection fraction of 20–25%, a new large apical thrombus, and complete thrombosis of the intramyocardial dissection (Figure 3 and Video4). This was confirmed by cardiac MRI (Figure 4). The patient was subsequently started on warfarin therapy.Figure 1: Two-dimensional echocardiogram from four-chamber view showing the somewhat mobile intramyocardial dissecting hematoma occupying the distal one third of the LV cavity (arrow).Figure 2: Post-gadolinium enhanced cardiac MRI showing an extensive antero- septal and apical transmural MI (yellow arrow) extending into the apical part of the RV and the non-enhancing intramyocardial dissecting hematoma (red arrow). Figure 3: Two-dimensional echocardiogram from four-chamber view at follow-up showing a large wall-adherent apical thrombus (arrow).Figure 4: Post-gadolinium enhanced cardiac MRI confirming structure seen on echocardiogram was a showing a large, non-enhancing and wall-adherent apical thombus (arrow).DiscussionThis case describes a left ventricular dissecting intramyocardial hematoma which was likely the result of a late presenting AMI. Although coronary angiography was not performed to identify the culprit lesion, based on non-invasive imaging we suspect that the myocardial dissection originated in the left ventricle following an extensive antero-septal AMI.1,3 While the mild troponin elevation and lack of overt ischemic signs on electrocardiogram challenge this assertion, the severe regional hypokinesis and signs of ventricular thinning and remodelling on echocardiogram and MRI suggested infarcted tissue, likely in the LAD territory.There is limited data available on the appropriate management of dissecting intramyocardial hematomas following AMI. This is mainly due to their relative infrequency, with the literature limited to case reports and case series. Acute surgical options include application of pericardial patches or other prosthetic material (such as gore-tex or teflon felt), accompanied by excision of necrotic tissue, and coronary artery bypass grafting.1A case review in 1993 examined survival rates in 16 patients with intramyocardial hematomas treated either surgically or medically. This case review observed that only 10% of patients treated conservatively survived past 30 days in contrast to all patients treated surgically.1 While this may suggest that surgical management offers a better prognosis, the finding may have also been due to patients undergoing surgery being at lower risk (due to anatomic factors related to the hematoma or patient comorbidities) compared to those treated conservatively. Conversely, Vargas-Barron et al., examined 15 patients with intramyocardial dissections with a 12-month follow-up period, with 9 patients presenting with an apical free-wall dissection and 6 patients with dissections extending into the septum and/ or right ventricle.4 In the first group, all patients were treated conservatively with all patients surviving to follow up at one year, although 4 patients had worsening heart failure.4 In the second group, 80% of those treated surgically died, compared to 50% who underwent coronary angioplasty and 100% of those conservatively managed.4 This study suggests that conservative management may be a reasonable option in patients with less complicated hematomas, while those with more complicated features are at a high mortality risk irrespective of the course of treatment. While our patient likely fit into the latter group with a more extensive dissection, the primary reason for surgical exclusion was the extent of the hematoma without well-perfused residual tissue to surgically remodel the ventricle.Patients who are conservatively managed for an intramyocardial hematoma are at high risk for further major adverse events and require close follow-up. Concomitant heart failure secondary to MI can lead to left ventricular dysfunction and significant comorbidities, and treatment with proven heart failure medications is essential. Patients with a reduced ejection fraction are also at increased risk of apical thrombus formation.In patients with a myocardial dissection, the decision to anticoagulate must carefully balance the increased risk of stroke and possibility of dissection extension, a potentially devastating consequence. Studies investigating ventricular remodelling after an AMI suggest substantial remodelling, infarct thinning, and reduction of infarct extent typically occur within the first month of healing.5 Thus, deferring any anticoagulation for at least4 weeks may be prudent to allow for healing of the hematoma, as long as no clear indications (e.g., left ventricular thrombus) arise.In our patient, a follow-up echocardiogram performed after two months revealed a large apical thrombus, and anticoagulation was initiated at that point in time.Little is known about the long-term survival of conservatively treated dissecting intramyocardial hematomas. In a study of 8 patients with intramyocardial dissecting hematomas treated with medical management, six were alive at a mean follow up of 12 months.4 One case report has identified a case of a medically treated intramyocardial dissection with event free follow up extending to 40 months.6 Cases of prolonged survival seem to be related to a decrease in size or complete resolution of the hematoma, as was seen in our patient, underscoring the need for serial cardiac imaging both to determine prognosis and to guide therapeutic decisions.7 With improvement or resolution of the hematoma, the primary risks of morbidity and mortality will likely be related to heart failure as well as arrhythmias from scarring; long-term prognosis will depend on optimal heart failure management (e.g., evidence based heart failure medications and evaluating for implantable cardioverter defibrillator [ICD] and cardiac resynchronization therapy [CRT] placement). Finally, in appropriate patients, cardiac transplantation may be considered as a treatment option.References1. Pliam M, Sternlieb J. Intramyocardial dissecting hematoma: An unusual form of subacute cardiac rupture. J Cardiac Surg 1993;8(6):628–37.2. Sari I, Davutoglu V, Kucukdurmaz Z. Intramyocardial dissection after subacute anterior wall myocardial infarction: An unusual form ofmyocardial rupture with subsequent spontaneous healing. Echocardiography2007;25(2):228–30.3. Tighe D, Paul J, Maniet A, et al. Survival in infarct related intramyocardial dissection: Importance of early echocardiography and prompt surgery. Echocardiography 1997;14(4):403–8.4. Vargas-Barrón J, Roldán F, Romero-Cárdenas Á, et al. Dissecting intramyocardial hematoma: Clinical presentation, pathophysiology, outcomes and delineation by echocardiography. Echocardiography 2009;26(3):254–61.5. Hillenbrand H, Sandstede J, Störk S, et al. Remodeling of the infarct territory in the time course of infarct healing in humans. Magnetic Reson Mat Phys Biol Med 2011;24(5):277–84.6. Drozdz J, Kasprzak J, Krzeminska-Pakula M. Spontaneous closure (thrombosis) of the intramyocardial dissection: 40-month follow-up. J Am Soc Echocardio 2002;15(9):1023–24.7. Vargas-Barrón J, Romero-Cárdenas A, Roldán F, et al. Long-term follow-up of intramyocardial dissecting hematomas complicating acute myocardial infarction. J Am Soc Echocardio 2005;18(12):1422.e1–1422.e6.

Vanishing bile duct syndrome (VBDS) is a rare acquired disorder associated with progressive destruction and disappearance of intrahepatic bile ducts which eventually leads to cholestasis. VBDS has been linked to a variety of etiologies, including autoimmune disorders, infectious diseases, primary neoplasms, genetic abnormalities, and many classes of medications, including antibiotics, nonsteroidal anti-inflamatories (NSAIDs), anticonvulsants, antipsychotics and others. We present the case of VBDS associated with anabolic androgenic steroid (AAS) exposure in an otherwise healthy 29-year-old male. Resume Le syndrome de disparition des canaux biliaires (SDCB) est une affection acquise rare caractérisée par la destruction progressive et la disparition des canaux biliaires intrahépatiques entrainant une cholestase. Le SDCB a été associé à diverses étiologies, dont des affections auto-immunes, des maladies infectieuses, des néoplasmes primaires, des anomalies génétiques et de nombreuses classes de médicaments, incluant des antibiotiques, des anti-inflammatoires non stéroïdiens, des anticonvulsivants, des antipsychotiques et autres. Nous présentons un cas de SDCB associé à la prise d’un stéroïde androgénique anabolisant chez un homme de 29 ans par ailleurs en bonne santé.  

Post-thrombotic syndrome (PTS) describes residual leg swelling, pain, and venous insufficiency that persists after acute deep vein thrombosis (DVT). PTS occurs in 40 to 60% of patients and contributes significantly to patient morbidity and healthcare costs. Despite standard therapy including anticoagulation, early ambulation, and compression stockings. PTS is more common in iliofemoral DVT. Despite conflicting evidence, there has been increasing use of endovascular therapies such as thrombolysis, thrombectomy, and venous stenting to reduce the incidence of PTS. May-Thurner Syndrome (MTS) is a significant risk factor for the development of iliofemoral DVT and PTS because of the compression of the left common iliac vein by the overlying right common iliac artery. The main objective is to review the evidence for endovascular management of iliofemoral DVT using MTS as an illustration of a patient population that may benefit from this therapy. Currently, endovascular therapies are not the recommended routine management of nongangrenous iliofemoral DVT. But can be considered in exceptional cases, such as MTS or other compressive syndromes, for obtaining venous patency and potentially prevent severe PTS.ResumeLe syndrome postphlébitique (SPP) correspond à un œdème résiduel des jambes, à de la douleur et à une insuffisance veineuse qui persiste après une thrombose veineuse profonde (TVP) aiguë. Il survient chez de 40 à 60 % des patients et contribue grandement à la morbidité du patient et aux coûts en soins de santé, malgré les traitements classiques comprenant l’anticoagulothérapie, l’ambulation précoce et les bas de contention. Le SPP est plus fréquent dans les cas de TVP iliofémorales. Malgré des données probantes contradictoires, on utilise de plus en plus les traitements endovasculaires comme la thrombolyse, la thrombectomie et la mise en place d’endoprothèses veineuses pour réduire la fréquence du SPP. Le syndrome de May-Thurner (SMT) est un facteur de risque important de l’apparition d’une TVP iliofémorale et du SPP en raison de la compression de la veine iliaque commune gauche par l’artère iliaque commune droite contre le plan vertébral. Le principal objectif consiste à examiner les données probantes relatives à la prise en charge endovasculaire de la TVP iliofémorale en utilisant le SMT pour illustrer une population de patients qui pourrait bénéficier de ce traitement. À l’heure actuelle, on ne recommande pas les traitements endovasculaires dans la prise en charge courante de la TVP iliofémorale non gangréneuse, mais dans des cas exceptionnels, comme le SMT ou autres syndromes de compression, ils peuvent être envisagés pour obtenir une perméabilité veineuse et prévenir les cas graves de SPP.

References 1. Mazzone PJ, Silvestri GA, Patel S, et al. Screening for lung cancer: CHEST Guideline and Expert Panel Report. Chest. 2018;153(4): 954-985. 2. Delva F, Margery J, Laurent F, et al. Medical follow-up of workers exposed to lung carcinogens: French evidence-based and pragmatic recommendations.