Rare association between rheumatoid arthritis and Vogt-Koyanagi-Harada syndrome: A case-based review

IntroductionVogt-Koyanagi-Harada (VKH) syndrome is a systemic autoimmune disorder that targets tissues containing melanocytes such as the eye, inner ear, meninges and skin. Despite a common genetic susceptibility, the association between VKH syndrome and rheumatoid arthritis (RA) has been rarely reported.Aim of the workTo report a rare case with RA who developed incomplete VKH syndrome. The case is described and a review of the literature on similar cases is presented.Case reportA 26 year-old Tunisian woman, with a medical history of Hashimoto’s thyroiditis, was diagnosed on 2011 with seropositive and erosive RA treated with Leflunomide. She presented to the emergency department on June 2018 with bilateral blurred vision associated with photophobia, vomiting and severe headache that had gradually progressed over the preceding five days. Ophthalmological examinations showed typical findings of VKH syndrome. The patient received intravenous infusions of methylprednisolone at a daily dose of 1000 mg for 3 days that was followed orally with 2 mg/kg of prednisone equivalent. Given the lack of improvement in visual acuity after 3 weeks of treatment, azathioprine was added and VKH remission was achieved on September 2018 as confirmed on optical coherence tomography. However, the patient passed away on October 2018 due to infectious complications of the immunosuppressant agents.ConclusionTreatments and outcomes of VKH are variable. Pharmacological management of such an association between RA and VKH may be challenging, so care must be taken to balance treatment escalation with adverse events in patients at risk.     

Exploring Mentoring Experiences,Perceptions, and Needs of General Internal Medicine Clinician Educators Navigating Academia: a Mixed-Methods Study

BackgroundFew studies examined specific mentoring needs and preferences of clinician educators (CEs). Further research on CEs’ perceptions of mentoring adequacy, as related to educational development and career advancement, is needed.ObjectiveThe study aims were to (1) explore general internal medicine CEs’ experiences as mentees within various mentoring models; (2) examine the perceived quality, nature, and impact of mentoring on career development; and (3) determine whether specific models of mentoring impact their attitudes towards mentoring.DesignSequential mixed methods study design answered the study questions.ParticipantsSociety of General Internal Medicine members identifying themselves as CEs.Main measures/ApproachParticipants completed an anonymous online survey and a subsample participated in two semi-structured focus group discussions. Outcomes of interest were perceptions of mentoring experiences, and perspectives on quality of mentoring as well as mentoring needs specific to clinician educators.Key ResultsOne hundred thirty-nine participants completed the survey (37% response rate) with 20 participants in focus group discussions. Among CEs with perceived high-quality mentor relationships (e.g., reporting strongly agree), peer mentorship was viewed as adequate mentorship (45% (n = 17) vs 24% (n = 24), p < 0.05), as beneficial for career development (77% (n = 40) vs 48% (n = 41), p < 0.01) and as being challenged to become a better CE (58% (n = 30) vs 35% (n = 29), p < 0.05), compared to reporting agree or lower. Qualitative analysis generated four themes: (1) A mentoring team promotes career advancement, (2) peer mentors are important at every stage of a CE’s career, (3) there is inadequate mentoring specific to CE needs, and (4) mentoring needs protected time and skill development.ConclusionsThe traditional dyadic mentoring relationship may not adequately address all professional needs of CEs. A mentoring team can provide valuable perspectives on career goals. Peer mentoring can be powerful for professional growth. Mentoring needs change at different career stages and training in mentoring skills is essential.KEY WORDS: clinician educator, mentoring experiences, peer mentor, mentee, mentor     

Von Economo neuron density in the anterior cingulate cortex is reduced in early onset schizophrenia

The anterior cingulate cortex (ACC) represents a phylogenetically ancient region of the mammalian brain that has undergone recent adaptive changes in humans. It contains a large spindle-shaped cell type, referred to as von Economo neuron (VEN) that has been shown to be involved in the pathophysiology of various neuropsychiatric disorders. Schizophrenia is a group of disorders that is, in part, characterised by a disruption of neuronal migration in early ontogeny and presumably secondary degeneration after the first psychotic episode in some patients. Accordingly, we tested the hypothesis that the density of VENs is reduced in a neurodevelopmental subtype of schizophrenia, which we defined by an early onset of the disorder. The density of VENs was estimated in layer Vb of Brodmann’s area 24 in 20 subjects diagnosed with schizophrenia. The results were compared with 19 specimens from patients with bipolar disorder as a clinical control and 22 non-psychiatric samples. The density of VENs did not differ between the three groups. However, the VEN density in the right ACC correlated with the age at onset, and inversely with the duration of the illness in schizophrenia, but not in bipolar disorder. Thus, patients with early onset schizophrenia (and longer duration of illness) had a reduced VEN density. Age, sex, postmortem interval, brain weight, and cortical thickness had no significant impact on the results. These findings suggest that VENs in the ACC are involved in neurodevelopmental and perhaps neurodegenerative processes specific to schizophrenia.     

Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex

We have recently found that in the mouse cortex, activation of delta-opioid receptor (DOR) attenuates the disruption of K(+) homeostasis induced by hypoxia or oxygen-glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K(+) homeostasis because the disruption of K(+) homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na(+) influx and thus stimulates K(+) leakage, we investigated whether DOR protects the cortex from anoxic K(+) derangement by targeting the Na(+)-based K(+) leakage. By using K(+)-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na(+) concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K(+) derangement; 2) lowering Na(+) concentration by substituting with permeable Li(+) tended to potentiate the anoxic K(+) derangement; and 3) the DOR-induced protection against the anoxic K(+) responses was largely abolished by low-Na(+) perfusion irrespective of the substituted cation. We conclude that external Na(+) concentration greatly influences anoxic K(+) derangement and that DOR activation likely attenuates anoxic K(+) derangement induced by the Na(+)-activated mechanisms in the cortex.     

Preoperative staging of patients with rectal tumors suitable for transanal endoscopic microsurgery (TEM): comparison of endorectal ultrasound and histopathologic findings

Background  Accurate preoperative staging is the key to correct selection of rectal tumors for local excision. This study aims to assess the accuracy of endorectal ultrasound (ERUS) at our institution. Patients and methods  Retrospective analysis was carried out of patients treated by transanal endoscopic microsurgery (TEM) from 1996 to 2008. TEM was considered the treatment of choice for uT0-1/N0 lesions located between 2 and 12 cm from the anal verge. It was also proposed in selected uT2-3 patients. Preoperative staging was compared with histopathologic findings. Results  Eighty-one patients (46 males, mean age 66 years) underwent TEM. Mean distance of the tumor from the anal verge was 6.6 cm (range 2–12 cm). ERUS staged 15 of 27 adenomas (55%) as uT1. Of 54 carcinomas, 5 were pT0 because TEM was performed to remove resection margins of a malign polyp already snared. Five of 19 pTis (26%) were overstaged uT1, while 7 of 17 pT1 (41%) were understaged. Overall, ERUS enabled distinction between early and advanced rectal lesion with 96% sensitivity and 85% specificity, giving accuracy of 94% (65/67). Thirteen patients had advanced lesions (eight pT2 and five pT3). Only in two of them (15%) was depth of invasion underestimated by ERUS (one uT0, one uT1) and thus was subsequent salvage surgery necessary. Conclusions  ERUS is useful to confirm the diagnosis of adenoma and predict depth of mural invasion in early rectal cancer. Differentiation between T0/is and T1 lesions remains challenging, however this does not usually influence surgical strategy.     

Hemorrhagic shock after experimental traumatic brain injury in mice: effect on neuronal death

Traumatic brain injury (TBI) from blast injury is often complicated by hemorrhagic shock (HS) in victims of terrorist attacks. Most studies of HS after experimental TBI have focused on intracranial pressure; few have explored the effect of HS on neuronal death after TBI, and none have been done in mice. We hypothesized that neuronal death in CA1 hippocampus would be exacerbated by HS after experimental TBI. C57BL6J male mice were anesthetized with isoflurane, mean arterial blood pressure (MAP) was monitored, and controlled cortical impact (CCI) delivered to the left parietal cortex followed by continued anesthesia (CCI-only), or either 60 or 90 min of volume-controlled HS. Parallel 60- or 90-min HS-only groups were also studied. After HS (+/-CCI), 6% hetastarch was used targeting MAP of > or =50 mm Hg during a 30-min Pre-Hospital resuscitation phase. Then, shed blood was re-infused, and hetastarch was given targeting MAP of > or =60 mm Hg during a 30-min Definitive Care phase. Neurological injury was evaluated at 24 h (fluorojade C) or 7 days (CA1 and CA3 hippocampal neuron counts). HS reduced MAP to 30-40 mm Hg in all groups, p < 0.05 versus CCI-only. Ipsilateral CA1 neuron counts in the 90-min CCI+HS group were reduced at 16.5 +/- 14.1 versus 30.8 +/- 6.8, 32.3 +/- 7.6, 30.6 +/- 2.2, 28.1 +/- 2.2 neurons/100 mum in CCI-only, 60-min HS-only, 90-min HS-only, and 60-min CCI+HS, respectively, all p < 0.05. CA3 neuron counts did not differ between groups. Fluorojade C staining confirmed neurodegeneration in CA1 in the 90-min CCI+HS group. Our data suggest a critical time window for exacerbation of neuronal death by HS after CCI and may have implications for blast injury victims in austere environments where definitive management is delayed.     

Changes in pulmonary function in patients with ulcerative colitis

OBJECTIVES: Information on the occurrence and frequency of pulmonary involvement in patients with ulcerative colitis (UC) is inconsistent. Some authors reported pulmonary impairment with UC by standard pulmonary function tests (PFTs) and documented a reduced diffusing capacity for carbon monoxide (DLCO) especially in patients with active disease, whereas others could not detect differences in routine PFTs between UC patients and controls. AIM: The aim of this prospective study was to determine the frequency and type of pulmonary dysfunction in patients with UC with respect to disease activity. Furthermore, to evaluate the influence of smoking, nutritional status, sputum cytology and sulphasalazine therapy on PFT parameters. PATIENTS AND METHODS: Twenty-six patients with UC (20 with active disease, 6 inactive) and 16 age and sex matched healthy controls were investigated with respect to the following pulmonary function tests, forced vital capacity (FVC), forced expiratory volume in the 1s (FEV(1)%) and their ratio (FEV(1)/FVC) and forced expiratory flow 25-75% (FEF25-75%) as well as oxygen saturation. For UC patients, colonoscopy and biopsy were done. Disease activity was assessed by Truelove index for UC. Induced sputum was sampled for cytology. Smoking habit, body mass index (BMI) and medications were recorded. RESULTS: Fifteen out of 26 patients with UC (57.6%) exhibited at least one pathological pulmonary function test (<80% of predicted value). Small airway obstruction was reported in the 15 patients, restrictive dysfunction in 30.7% and obstructive dysfunction in 11.5%. The impairment of PFTs was significant and more pronounced in patients with active disease, FVC (-14% of predicted), FEV(1) (-9% of predicted) and FEF25-75% (-32% of predicted), P<0.01, 0.05 and 0.01, respectively. There was no significant influence of smoking and medications on PFTs. CONCLUSIONS: UC patients show significantly decreased lung function tests in comparison to healthy controls. The impairment in active disease exceeded that during the remission. Early recognition is important, as they can be strikingly steroid responsive.