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Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.
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Introduction: Congenital choledochal cyst (CCC) is a rare cystic dilatation of intrahepatic or extrahepatic biliary ducts. We present a case of a type IVb choledochal cyst presenting as recurrent acute pancreatitis in a young healthy female with initial negative screenings. Case Description/Methods: An 18-year-old-female with a history of COVID-19 presented to the emergency department with one month of persistent abdominal pain, nausea, and vomiting. She was hospitalized once prior for similar symptoms and was diagnosed with acute pancreatitis. This admission, blood work showed elevated lipase, elevated liver enzymes, mild bilirubinemia with a normal lipid panel and urine was significant for infection. She received fluids, antiemetics and was started on prophylactic antibiotics for ascending cholangitis. A right upper quadrant ultrasound ruled out cholelithiasis or acute cholecystitis, but showed dilation of the common bile duct. MRCP confirmed dilation with bulbous termination in the periampullary region diagnosed as type IVb choledochal cyst. Discussion(s): CCCs are rare in Western countries with an incidence between 1 in 100,000 to 150,000. 80% of these cysts are diagnosed in patients under the age of 10. They are difficult to diagnose due to variable clinical presentations. A study of 214 CCC patients demonstrated the most common symptom was abdominal pain, followed by jaundice and fever. When cysts are found in adults, symptoms resemble atypical acute biliary tract disease. Surgical cyst removal may be needed for patients with significant risk factors such as older age and age of symptom onset, due to increased risk of malignant transformation. Longer periods of observation have been documented to be associated with an increased chance of developing late complications, such as anastomotic stricture, biliary calculi and recurrent cholangitis. Type IVb CCCs, as seen in this case, consist of multiple extrahepatic cysts and hepaticojejunostomy is the treatment. This patient's young age and recurrent acute pancreatitis combined with her lab and imaging findings strongly suggest the diagnosis of CCC. The anatomical location of the CCC impeded flow of pancreatic enzymes through the ampulla of vater, leading to recurrent pancreatitis in an otherwise healthy young female. CCC, although very rare, should be considered in the differential of acute pancreatitis when other causes such as gallstones and heavy alcohol consumption cannot be identified, as prompt diagnosis and surgical removal is imperative.
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Objective To assess the case-based malaria surveillance and response during the period of COVID-19 outbreak in China, in order to provide reference for malaria elimination under the COVID-19 pandemic. Methods Information of malaria cases reported during the four months pre - and post-COVID -19 outbreak (December 1, 2019-March 31, 2020) and in the same time period of past two years in China (excluding Hong Kong, Macau and Taiwan regions) was obtained from the Parasitic Disease Control Information Management System. Cross-sectional survey and comparison were conducted for malaria surveillance and response data in 3 four-month time periods (December 1, 2019 to January 22, 2020;January 23 to March 17, 2020;and March 18-31, 2020). The number of malaria cases including deaths, the median and average time interval from disease onset to the first visit, the median and average of time interval from the first visit to the confirmed diagnosis, the completion status of the #1-3-7$ task and the source of infections in each period were analyzed and compared to the same times in the past two years. Results From December 1, 2019 to March 31, 2020, a total of 750 malaria cases, which were all imported cases, were reported in China, decreased by 9.2% from that reported during December 2018 and March 2019 (826 cases) and by 13.1% from that reported during December 2017 to March 2018 (863 cases). The decrease mainly occurred in February and March in 2020;there were no statistical differences in the time interval from onset to first visit (median 1 day, mean 2.0 days), time interval from first visit to confirmed diagnosis (median 1 day, mean 1.8 days), case reporting rate within 1 day (100%), case epidemiological investigation rate within 3 days (98.4%), epidemic site disposal rate within 7 days (100%) between the time period of COVID-19 outbreak and the same time in the past year (December 2018 to March 2019). In addition, no statistical difference (! > 0.05) was found in the time intervals from onset to first visit among the first period [median 1 d, average (1.9 +/- 0.2) d], the second period [median 1 d, average (2.1 +/- 0.3) d] and the third period [median 1 d, mean (1.5 +/- 0.3) d], while the time interval from the first visit to the confirmed diagnosis was statistically different (! X 0.05) among the first period [median 0 d, average (1.5 +/- 0.2) d], the second period [median 1 d, mean (2.3 +/- 0.3) d] and the third period [median 0.5 d, average (1.5 +/- 0.4) d], where the time interval in the second period was longer than that in the first period (! X 0.01). Conclusion China' s core measures to eliminate malaria have been carried out as planned, although the timely malaria diagnosis was slightly affected in the second time period (January 23 to March 17, 2020).Copyright © 2021, National Institute of Parasitic Diseases. All rights reserved.
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Background: The interpretation of the evidence from randomized clinical trials (RCTs) on remdesivir for hospitalized patients with coronavirus disease 2019 (COVID-19) is conflicting. We conducted a systematic review and individual patient data meta-analysis (IPDMA) of RCTs to assess the benefit and harm of remdesivir compared to placebo or usual care in hospitalized patients and whether treatment effects differed between prespecified subgroups. Method(s): We systematically searched electronic databases and registries through April 11th 2022 and contacted authors of eligible trials to share individual patient data. The primary outcome was all-cause mortality at day 28. We used multivariable hierarchical regression adjusting for respiratory support, age, and enrollment period to investigate effect modifiers. The study was registered in PROSPERO (CRD42021257134). Result(s): Out of nine eligible RCTs, eight provided individual data for 10480 hospitalized COVID-19 patients (99% of global IPD) recruited between February 2020 and April 2021. Within 28 days of randomization, 662 of 5317 patients (12.5%) assigned to remdesivir and 706 of 5005 (14.1%) assigned to no remdesivir died (adjusted odds ratio [aOR] 0.88;95% confidence interval [CI], 0.78-1.00;p=0.045). We found evidence for a credible subgroup effect according to respiratory support at baseline (interaction p=0.019). Of those ventilated including high-flow oxygen, 253/844 (30.0%) assigned to remdesivir died versus 241/846 (28.5%) assigned to no remdesivir (aOR 1.10 [0.88-1.38];low certainty evidence). Of those receiving no or low flow oxygen, 409/4473 (9.1%) assigned to remdesivir died versus 465/4159 (11.2%) assigned to no remdesivir (aOR 0.80 [0.70-0.93];high certainty evidence). There was no credible subgroup effect with respect to time to start of remdesivir after symptom onset, age, presence of comorbidities, enrollment period or corticosteroid use. Remdesivir did not increase the frequency of severe or serious adverse events. Table 1 summarizes the findings according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Conclusion(s): This IPDMA, summarizing the evidence of 99% patients ever randomized on the topic, demonstrated that remdesivir reduced mortality in hospitalized COVID-19 patients requiring no or conventional oxygen support, but patients requiring more respiratory support may not benefit. These findings may inform clinical guidelines, especially due to increasing resistance to current monoclonal antibodies.
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Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, rare demyelinating disease of the central nervous system characterized by recurrent attacks which usually involve optic nerves and spinal cord. Although the most common symotoms are myelitis and optic neuritis, it can be presented as cerebral syndromes mainly those related to the brain stem and diencephalon. Since NMOSD is a rare disease and the epidemiological data on this disorder is still insufficient, the establishment of registry and long-term follow up studies are needed to assess the disease course and behavior over a period of time. Material(s) and Method(s): We stablished an electronic registry system for NMOSD patients in the MS center of Kashani hospital, Isfahan, Iran, since spring 2016. Every patient suspected for NMOSD and documented in our database was included in a follow up study to monitor their disease course and progression. Anti AQP4 antibody and Anti MOG antibody were checked for all patients in a unique lab by cell based assay method. Demographic data and clinical characteristics such as family history, comorbidities,education, number of relapses, presentation signs and radiological findings were recorded. Moreove, relapses, treatment change, triggers, and COVID-19 infection were documented. We investigated the effect of the COVID19 pandemic and vaccination on NMOSD patients. Result(s): This study included 173 cases with definite diagnosis of NMOSD, and 56 ones were seropositive for AQP4 Ab. 142 were females of which 46 were in the seropositive group. Their mean age was 40.02+/-11.11 years (45.78+/-12.88 in AQP4Ab positive group). The mean of age at disease onset was about 30.16+/-11.90 years. The mean time of follow up was 55.84+/-18.94 months until today. In 76 patients, there were LETM in the first cervical MRI. 123 patients revealedbabnormality in the first brain MRI. 27 patients had hypothyroidism as the most common comorbidity. 36 cases reported positive family history of multiple sclerosis and also 4 had a family history of NMOSD. Conclusion(s): The mean age of onset did not differ between seropositive and seronegative group but it was higher than MS patients. Brain MRI showed abnormality in NMOSD patients. Female/male was 4.4/1 which is lower than other studies.Copyright © 2022
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Background: Acute cerebellitis is the most frequent cause of acute ataxia in children. A clear definition of infectious versus post infectious cerebellitis is lacking in the literature. The outcome is usually favorable although the initial clinical picture varies greatly between patients. The aim of this study was to compare infectious versus post-infectious cerebellitis in terms of clinical features, imaging and outcome. Material(s) and Method(s): We conducted a retrospective descriptive study including patients who were hospitalized at the neuropediatrics department at the national Institute of Neurology of Tunisia, between 2005-2022, having a diagnosis of acute cerebellitis at discharge and a minimal follow-up period of six months. The SARA (Scale for Assessment and Rating of Ataxia) was used to evaluate ataxia at onset and follow-up. Symptoms of ataxia occurring alongside infectious symptoms were considered para-infectious. Result(s): A total of 37 patients were included with a sex ratio of 1,17. Post infectious cerebellitis represented 76% (28 cases). Mean age of onset was 5,79 +/- 3,74 years with no significant difference between groups. A history of infection was found in 84% of patients (31 cases) with a mean time of 7,43 +/- 6,31 days. Mean time of onset from infection was shorter in the para-infectious group (p=0,001) and concomitant fever was more frequently found (p=0,02). Onset was acute in 89% of cases in both groups. Mean SARA score at onset was 9,35 +/- 4,14 with no significant difference between groups. Aetiology was unknown in 51% of cases (19 patients). Two covid-19 related cerebellitis were noted both in the para-infectious group. No difference between groups in terms of imaging or cerebral spinal fluid analysis was noted. There were no sequalae in 78% and 89% of cases in the post-infectious and para-infectious groups respectfully and no difference in terms of outcome or SARA score at follow-up was noted. Conclusion(s): In our cases series, significant differences were noted between the post-infectious and para-infectious cerebellitis subgroups. Mean time of onset from infectious episode was shorter and fever was more frequent in the para-infectious group. A clear definition of para-infectious cerebellitis is needed in order to determine the real proportion of this entity and allow a better management.Copyright © 2022
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Background: Diabetes mellitus (DM) represents one of the most common metabolic diseases in the world, with rising prevalence in recent decades. Most cases are generally classified into two major pathophysiological categories: type 1 diabetes mellitus (DM1), which progresses with absolute insulin deficiency and can be identified by genetic and pancreatic islet autoimmunity markers, and type 2 diabetes mellitus (DM2), which is the most prevalent form and involves a combination of resistance to the action of insulin with an insufficient compensatory response of insulin secretion. In the last two decades, in parallel with the increase in childhood obesity, there has also been an increase in the incidence of DM2 in young people in some populations. Other forms of diabetes may affect children and adolescents, such as monogenic diabetes (neonatal diabetes, MODY – maturity onset diabetes of the young, mitochondrial diabetes, and lipoatrophic diabetes), diabetes secondary to other pancreatic diseases, endocrinopathies, infections and cytotoxic drugs, and diabetes related to certain genetic syndromes, which may involve different treatments and prognoses. DM1 is considered an immuno-mediated disease that develops as a result of gradual destruction of insulin-producing pancreatic beta cells that eventually results in their total loss and complete dependence on exogenous insulin. Clinical presentation can occur at any age, but most patients will be diagnosed before the age of 30 years
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Functional tic-like movements or functional tic-like behaviours are functional symptoms that look like tics. There has been a sudden rise in these movements coinciding with the COVID-19 pandemic, prior to which functional tic-like movements were considered very uncommon. As a tertiary specialist Tourette clinic, we have seen our referrals multiply. The referring clinicians often diagnose these young people with Tourette syndrome. We want to describe the differentiating features between Tourette-related (typical) tics and functional tic-like movements based on our experience in London, with the help of data we have collected in a large number of adolescents and through the help of videos (both of typical tics and those of functional tic-like movements). We will also discuss some of the underlying factors that explain the rise of functional tic-like movements in young people. The main differentiating features of functional tics in our clinic (similar to other international specialist tic centres whom we collaborate with) are: (1) The comparatively late age of onset of functional movements (in adolescence) instead of (age 4-7 years) in Tourette-related/typical tics. (2) Change in prevalence by sex (F > M);majority cases are females in our clinic, in contrast the sex ratio in typical tics/Tourette is M > F (4:1). (3) A very abrupt onset over one to a few days in most cases. (4) Presence of complex motor and vocal behaviours, in fact complex tics being more common than typical tics (which is not the case in typical Tics). (5) Prominent involvement of the upper limbs (as opposed to movements starting in the eyes or face or minor sniffing or throat clearing). (6) A significant variability in movements and other symptoms depending upon the environment. We will discuss phenomenology of movements and why it may be better to describe these presentations as functional tic-like movements or behaviours rather than as functional-tics.
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Introduction: The influence of environmental factors on central nervous system demyelinating conditions have been recently studied. In MOG antibody associated disease (MOGAD), a seasonal distribution of relapses is not yet well-defined. Objective(s):: To investigate the presence of seasonal distribution of MOGAD relapses. Method(s): Prospective data from consented MOGAD patients within the Oxford National NMO Highly Specialised Service were analysed until April 2022. Demographic and clinical characteristics, including relapse date and phenotype, were recorded. All relapses with month-defined dates were used to calculate observed monthly frequencies. Expected frequencies were calculated assuming an uniform distribution throughout the year, adjusting for month's length and patient numbers under follow up. Any deviation from a uniform distribution was analysed, and seasonal peaks were assessed using Friedman's, Edward's, Ratchet circular scan and Hewitt's rank-sum tests. Result(s): Three-hundred-four MOGAD patients were included, 190 (62.5%) females, mean age at onset 31 years (SD 16.9), median disease duration 3.0 (IQR 5.0) years, 77 (25.3%) with paediatric age onset. No significant seasonal pattern was identified when analysing all relapses (n=691), or onset relapses (n=286). Regarding age of disease onset, no seasonal pattern was found in onset under 18 (n=483) or over 18 years old (n=208). Regarding phenotype, no seasonal pattern was found in optic neuritis (n=483), transverse myelitis (n=180) or brain and brainstem relapses (n=125). Analysing all the relapses from the start of the COVID-19 pandemic (March 2020 - February 2022, n=112), a seasonal peak was identified from March to May (V(N)=0.132, p<0.05). Conclusion(s): No seasonal pattern of relapses in MOGAD was noted until the COVID-19 pandemic started in the UK. Seasonal infection peaks during winter and subsequent lockdowns could have influenced MOGAD relapse rates in the past two years.
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Background and Aim: Cardiac involvement in multisystem inflam-matory syndrome in children (MIS-C) associated with Coronavirus 2019 disease (COVID-19) is often observed with high risk of hearth failure. Early diagnosis and treatment are man-datory for a good outcome. The aim is to describe cardiovascular involvement, management and early outcome for patients with MIS-C and to analyze the differences in cardiovascular manifesta-tions between two groups: younger and older than 6 years old. Method(s): This retrospective observational study describes cardio-vascular clinical manifestations, laboratory findings, cardiac imag-ing, according to different age groups, and treatment in patients with diagnosis of MIS-C admitted to the Pediatric Istitute Giannina Gaslini between March 2020 and September 2021. Result(s): We collected 25 patients. Median age at onset of symptoms was 5 years old (interquartile range IQR, 3-12 y), 12 boys (56%). Immunoglobulin G antibodies were positive in 70% cases, Polymerase chain reaction (PCR) nasal/throat swab test for COVID-19 was positive in 15% cases, at the admission. The remaining cases had close contacts of COVID-19 positive cases. Predominant coronary artery abnormalities were observed in age group up to 6 years old (n.13) with development of small and medium aneurysms in half of cases and low rate of mild ventricular dysfunction. While children between 7-18 years of age present myopericardial involvement with ventricular dysfunction in 67% cases, from mild to moderate. Only two cases of transient coronary dilatation. Frequent electrocardiogram abnormalities: ventricular repolarization anomalies and reversibile QTc prolon-gation interval. Laboratory findings showed rised inflammatory markers and only mild elevation of cardiac enzymes compared to an early and significant NT-pro-BNP increase. All patients were treated with intravenous immunoglobulin and corticosteroids. Some cases needed anakinra. Aspirin and heparin was adminis-trated. No inotropes requied but only cardioprotective therapy. No need of Intensive Care Unit. Conclusion(s): This case-series shows the frequent cardiovascular involvement in MIS-C with a peculiar distribution, according to differents age's group: coronary artery anomalies in young ones, myopericardial disease in old ones. Prompt multi target anti-inflammatory therapy could have an effect to favorable outcome.
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SESSION TITLE: Critical Diffuse Lung Disease Cases 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Recurrent episodes of community acquired pneumonia (CAP) have been shown to be common in elderly patients. Cryptogenic organizing pneumonia (COP) is an interstitial lung disease that is often mistaken for pneumonia, especially in the older population. Here, we present a 100-year-old woman diagnosed with COP after multiple failed courses of antibiotics for CAP. CASE PRESENTATION: A 100-year-old female with a history of cardiomyopathy, pulmonary hypertension, and autoimmune hemolytic anemia previously on prednisone, who presented with shortness of breath and non-productive cough. CT of the chest showed dense left upper and lower lobe consolidations. She was admitted 2 months prior with similar symptoms and found to have extensive right sided consolidations with concerns of CAP. She was treated with antibiotics without resolution of her symptoms. CXR from two years prior revealed right upper and right lower lobe consolidations. This admission, she was started on antibiotics with no improvement and required supplemental oxygen. She had no leukocytosis. COVID-19 testing was negative and she was unable to produce any sputum for culture. The patient declined bronchoscopy. She was seen by speech and swallow with no concern for aspiration. Prednisone was started empirically for COP and the patient experienced rapid improvement in symptoms and oxygenation. Ultimately, she was discharged on 20 mg of prednisone daily as well as Bactrim for PCP prophylaxis. She continued a slow taper as an outpatient with overall improvement in her clinical symptoms. Serial CT scans demonstrate complete resolution of the infiltrates with no recurrence or new infiltrates. DISCUSSION: Cryptogenic organizing pneumonia is a rare interstitial lung disease known to affect bronchioles and alveoli. Its etiology is unclear and symptoms often mimic other types of infectious pneumonia leading to frequent mis-diagnosis. The average age of onset is typically 50-60. Establishing this diagnosis can be difficult due to the non-specific symptomatology of dry cough and dyspnea. Bronchoscopy with lavage and transbronchial biopsies can be performed to rule out infectious and non-infectious etiologies but is not necessary for diagnosis. The most common radiographic pattern is multifocal asymmetrical parenchymal consolidations with air bronchograms that tend to migrate and appear in different sites over time. Less common presentations include ground glass opacities, nodular densities, and progressive fibrotic patterns. Steroids with a slow taper as outpatient are mainstay of therapy and the majority of patients respond with symptom and radiographic improvement. CONCLUSIONS: While elderly patients are particularly susceptible to recurrent CAP, the diagnosis of COP should be considered part of the differential diagnosis in those with recurrent unexplained consolidations on chest radiography without an infectious etiology. Reference #1: Hedlund J, Kalin M, Ortqvist A. Recurrence of pneumonia in middle-aged and elderly adults after hospital-treated pneumonia: aetiology and predisposing conditions. Scand J Infect Dis. 1997;29(4):387-92. doi: 10.3109/00365549709011836. PMID: 9360255. Reference #2: Tiralongo F, Palermo M, Distefano G, et al. Cryptogenic Organizing Pneumonia: Evolution of Morphological Patterns Assessed by HRCT. Diagnostics (Basel). 2020;10(5):262. Published 2020 Apr 29. doi:10.3390/diagnostics10050262 Reference #3: Lee JW, Lee KS, Lee HY, Chung MP, Yi CA, Kim TS, Chung MJ. Cryptogenic organizing pneumonia: serial high-resolution CT findings in 22 patients. AJR Am J Roentgenol. 2010 Oct;195(4):916-22. doi: 10.2214/AJR.09.3940. PMID: 20858818. DISCLOSURES: No relevant relationships by Vincent Chan No relevant relationships by Mackenzie Kramer No relevant relationships by John Madara No relevant relationships by Stephanie Tzarnas No relevant relationships by Laura Walters
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The FDA has approved tirzepatide (Mounjaro - Lilly), a peptide hormone with activity at both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, to improve glycemic control in adults with type 2 diabetes. Tirzepatide, which is injected subcutaneously once weekly, is the fi rst dual GIP/GLP-1 receptor agonist to become available in the US. Selective GIP receptor agonists are not available in the US;GLP-1 receptor agonists have been available for years. Copyright © 2022, Medical Letter Inc.. All rights reserved.
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Specific clinical, electrophysiological and serological features are used to recognise a phenotype fitting the atypical chronic inflammatory demyelinating (CIDP) variant spectrum. We report a 28-year-old male patient, without any significant history apart from a recent asymptomatic COVID-19 infection, presenting at first with bilateral facial nerve palsy, subsequently -three months later- developing an subacute onset symmetric sensory ataxia and arefl exia, and thirdly experiencing diffuse rapidly progressive motor deficits. Additional investigations suggested an autoimmune polyneuropathy: Liquor analysis showed cytoalbuminologic dissociation. Cerebrospinal fluid protein elevation was remarkable: 631 mg/dL. Nerve conduction studies showed prominent distal latencies prolongation and dispersion of the potentials, meeting the electrodiagnostic criteria of the European Federation of Neurological Societies/Peripheral Nerve Society for CIDP (2021). Full spine magnetic resonance imaging depicted pathological thickening and enhancement of the roots of the cauda equina as seen in radiculitis. There was no or poor response to conventional treatment, i.e. immunoglobulins (IVIG), corticosteroids and even plasmapheresis. Muscle weakness deteriorated. Presence of serum IgG4 anti- contactin-1 (CNTN1) antibodies was found by ELISA identifi- cation and titration, and the patient improved substantially after rituximab treatment. While contributing to the expanding confidence in nodal and paranodal antibodies as valuable biomarkers in clinical practice, our case entails several peculiarities: 1/ SARS-CoV2 positivity as a possible trigger of this auto-immune polyneuropathy 2/ A considerably younger age of onset than in the patients already described (range 33-76 years). 3/ The clinical course progressed in an atypical manner even for atypical CIDP: Initial presentation with bilateral asymmetric facial palsy, followed by sensory ataxia, which prompted the initial diagnosis of Miller-Fisher syndrome, and later development of severe motor impairment. 4/ Proteinorachy was so pronounced that we considered neuroborreliosis as a potential associated disorder. Borrelia seroconversion occurred after the first IVIG-treatment, and could be false positive. However, the patient was treated with intravenous ceftriaxone, which had no effect on the clinic. 5/ Antibodies against CNTN1 were undetectable after 2 months of rituximab. Emphasising the both diagnostic and therapeutic importance of recognising a phenotype compatible with atypical CIDP, an underrecognized and consequently undertreated disease where early diagnosis and prevention of axonal damage is crucial in.
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Myasthenia gravis (MG) is an acquired autoimmune disorder of the neuromuscular junction, caused by antibodies that target the post-synaptic membrane. These antibodies most commonly bind to the nicotinic acetylcholine receptor (AChR), but in a smaller proportion of cases, antibodies to muscle specific tyrosine kinase (MuSK)(1-10%) or to lipoprotein receptor-related protein 4 (Lrp-4)(1-3%) can be present instead. These antibodies act on the receptors, prevent neuromuscular transmission and induce weakness of skeletal muscles. In 10-15% of MG patients, no antibodies are detected and these patients are designated as seronegative. Weakness can be generalized or localized, is usually more proximal than distal, and nearly always includes eye muscles, causing diplopia and/or ptosis. The pattern of involvement is usually symmetric, except for the eye involvement, which is mostly markedly asymmetric. The muscle weakness typically increases with exercise and repetitive muscle use (fatigue) and varies over the course of a day and from day to day. Patients commonly present first with ocular manifestations, however, the majority develop generalized muscle weakness, involving the facial and bulbar muscles (dysarthria, dysphagia), the limbs, the neck and axial muscles (dropped head, bent spine), and in severe cases the diaphragmatic and intercostal muscles. MuSK-MG predominantly appears in women, who show weakness in mostly cranial and bulbar muscles, commonly with an acute onset and a tendency to rapid progression in comparison to AchRMG. Myasthenic crisis (MC), the severe end of the disease spectrum, can occur at any age and is potentially life-threatening. This is a clinical emergency that requires management in an intensive care setting. MC is mostly provoked by infections or inadequate treatment. In 15-40% of the reported patients with COVID-19 infection a MC occurred. MC appears in around 15-20% of MG patients in the first 2 years after diagnosis. MC can be the first manifestation of MG. Up to a half of MuSK-MG patients develop a MC in their disease course and it is also common in patients with thymoma-associated disease, or AChR-positive late-onset disease;after surgery (including thymectomy);during or after childbirth;in patients taking a contraindicated medication;at the start of corticosteroid treatment or during the tapering of immunosuppression. In approximately 20% the cause of an exacerbation remains unknown. Characteristic symptoms for the impending MC include rapidly progressive muscle weakness, 'inverse aspiration', dysphagia with choking, and dyspnoea associated with orthopnoea and/or tachypnoea which can result in respiratory insufficiency. The clinical management of MC with mechanical ventilation, extended intensive care management and intravenous immunoglobulins (IVIg) or plasmapheresis (PLEX) or in case of persistent MC escalation with rituximab has led to a significant decline in mortality from around 40% in the early 1960s to 5-22% in recent studies with negative prognostic factors including older age at onset, prolonged intubation, and associated comorbidities. At present IVIg and PLEX are considered the gold standard treating MC. However, it may be conceiv- able that newly developed monoclonal antibody therapy (eculizumab, efgartigimod), could be used as rescue therapy to achieve a significant and rapid clinical improvement.
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Background: According to 2019 updated EULAR recommendations, therapy of Early Rheumatoid Arthritis (ERA) with biological disease-modifying antirheu-matic drugs(bDMARDs) is adviced in presence of poor prognostic factors,I.e. persistently moderate/high disease activity, high acute phase reactants, high swollen joint count, autoantibody positivity, presence of early erosions, failure of two/more conventional synthetic DMARD. Objectives: To evaluate over time prevalence of bDMARD therapy and factors associated to rapid initiation in our EA Clinic (EAC), comparing two different periods: from 2004 to 2012 and from 2012 to 2020. The last two years were not considered because of the adverse influence of COVID19 pandemia on early access to EAC and on timely scheduled visits. Methods: A total of 281 ERA patients with less than 12 months of disease duration (53.9 years mean age, 75% female, 77% seropositive), followed according to the treat-to-target (T2T) strategy, were enrolled in the study. At baseline, and every three months, the ACR/EULAR core data set variables were recorded. At baseline and every year, hand and foot radiographs were examined according to modifed Total Sharp score (mTSS). At each visit, clinical improvement and remission were evaluated according to EULAR criteria. The achievement of Comprehensive Disease Control (CDC) (28-joint Disease Activity Score using C reactive protein <2.6, Health Assessment Questionnaire <0.5 and change from baseline in mTSS ≤0.5) was assessed every year. Results: We examined 164 patients from 2004 to 2012 and 117 subjects from 2012 to 2020. In the frst group 72 patients (43.9%) initiated bDMARDs during the 8-year FU, with a mean delay of 41.8 months. In the second group 37 patients (31.6%) started biotechnological drugs over time, with a mean delay of 50.4 months. Analyzing the period from 2004 to 2012, ERA patients starting bDMARDs were younger (p<0.0001), had longer disease duration (p=0.02) and higher body mass index (BMI) (p=0.01) compared to subjects not undergoing to biological therapy. Moreover, ERA patients in bDMARDs were in higher percentage anti-citrullinated peptide antibody (ACPA) positive (80.6%) and reached to a lesser extent CDC at 12months of FU (26.1%) compared to patients that didn't initiate bDMARDs (60.9% ACPA positive, p=0.01;63% achieving CDC, p<0.0001, respectively). Examining the period from 2012 to 2020, bDMARD-treated ERA patients were younger (p=0.06),in higher percentage ACPA positive (81.1%) and erosive at baseline (35.1%) compared to patients that didn't initiate bDMARDs (64% ACPA positive, p=0.02;17.5% erosive, p=0.04, respectively). As previously, patients in bDMARD reached to a lesser extent CDC at 12 month of FU (35.1%) compared to subjects not undergoing to biological therapy (55% achieving CDC, p=0.05). On multivariate analysis, ACPA positivity was associated with initiation of bDMARD in both patient groups (p=0.02), whereas older age at onset and reaching CDC at 12 month were inversely associated (p=0.001;p<0.0001, respectively). Conclusion: Despite the widest choice of bDMARDs currently available in the last 8 years, we did not observe an increase in the prescription of these drugs from 2012 to 2020. As in other ERA cohorts, bDMARD initiation is associated to poor prognostic factors, in particular ACPA positivity, presence of erosions at baseline and not achieving CDC at 12 months of FU. In the last 8 years, the decreased influence of disease duration at onset and of BMI could be a consequence of the improvement in strategies of early referral and control of modifable risk factors.
ABSTRACT
Background: Dermatomyositis (DM) is a rare idiopathic infammatory myopathy that can present with a variable spectrum of cutaneous and systemic manifes-tations1. Correlations between myositis-specifc autoantibodies (MSAs) and disease phenotype have been documented in DM in particular in association with the development of interstitial lung disease (ILD). Ongoing studies focus on the potential role of MSAs in similarities of the pathophysiological mechanisms of COVID-19 associated ILD and that related to DM suggesting an intriguing cross talk between autoimmunity and COVID-192. Objectives: To explore clinical patterns including ILD and MSAs profile in DM patients from a population-based single-center study carried out in a Tertiary Referral Rheumatologic Clinic. SARS-CoV-2 infections and vaccination were also analysed. Methods: We enrolled patients affected by DM classified according to 2017 EULAR/ACR criteria1 with a disease onset at ≥18 years referring to the Rheumatologic Clinic of Tor Vergata University Hospital in Rome (Italy). Clinical data were collected from medical records: gender, age of onset of symptoms and diagnosis, clinical features, auto-antibodies patterns (ANA, MSAs including anti-tRNA synthetase,-Jo1,-PL7,-EJ,-MDA5,-NXP2, SAE, Mi2, and myositis-associated antibodies comprising anti-PM/Scl,-Ro-52,-Ku, U1RNP), pattern of lung abnormalities at thoracic CT scans, and treatments. The prevalence of SARS-CoV-2 infection and vaccination profile were also investigated. Results: Among eligible cases (n=30), patients who completed the study (n=19) included almost entirely women (F=73.7%). The median age at disease onset was 57.4±12.4 yrs while the mean diagnostic delay resulted as 12±10 months. Skin manifestations and myalgia were the prevalent symptoms (79% and 63%, respectively) whereas dyspnea and cough occurred in a third of the cohort at DM onset. Besides the skin involvement, the decrease in pulmonary function was the main clinical manifestation at the frst rheumatological referral (52.6% of cases) followed by joint pain (36.8%) and cardiovascular events (10.6%). ANA titer≥1:160 occurred in 79% of patients. All patients showed MSAs positivity with a similar distribution: a single case of double positivity was registered in a man with anti-MDA5 and-NXP2. The most common CT fndings were ground-glass opacity and parenchymal band in a third of patients (32%). The entire cohort had undergone cycles of steroids from the onset of DM and during the follow-up, according to disease severity. The main used therapies were methotrexate (47%), intravenous immunoglobulin (42%) and mofetil micofenolate (31.6%). None of patients had SARS-CoV-2 infection (until December 2021). The 63% of the cohort received at least one dose of the anti-SARS-CoV-2 mRNA vaccine (BNT162b2), of which 10% had completed with the booster dose. No adverse reactions or post-vaccination DM fare were registered. A third of the cohort had not been vaccinated due to concomitant disease activity or therapies. No cases of post-COVID19 new-onset DM were diagnosed. Conclusion: Our preliminary findings support the relevant impact of lung involvement in DM. The availability of MSAs can help to stratify patients with DM for outcome and risk of potential disease complications. The impact of MSAs on ILD associated or not to COVID-19 deserve further investigations in a larger DM cohort and for a longer post-COVID-19 pandemia follow-up time.
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Background and aims: COVID-19 infections are reported in numerous case-reports as a trigger for development of Parkinson's disease (PD). We report 4 patients with symptoms of PD developed or exagerated after SARSCoV2 infection. Methods: Patients were retrospectively recruited in an outpatient clinic of Department of Neurology, Faculty of Health Science, Medical University of Warsaw. Patients were independently assessed by 2 neurologists experienced in movement disorders. Results: We identified 4 patients with rapid onset of PD symptoms following COVID-19. All patients were female. Symptoms of COVID-19 included headache in 4/4 cases and anosmia in 3/4 cases. PCR test confirmed SARS-CoV2 infection in all cases. The age of onset was between 28 and 62 years old. The rest tremor was present in all patients, ridgidity in 3/4 patients. Non-motor symptoms included RBD in 2/4 patients. Two patients were treated with levodopa with good response. MRI findings were nonsignificant. The SPECT-DatScan was performed in one patient and was typical for parkinsonian disorders. The positive family history was present in two patients. Conclusion: We conclude that COVID-19 may trigger development of parkinsonian motor symptoms or exaggerate the slight disease progression. The cause is unknown. Involvement of olfactory bulb could trigger neuroinflammation in line with Braak's hypothesis. COVID-19 may also induce parkinsonism in patients with genetic predisposition.
ABSTRACT
Introduction: Sleep problems can actively contribute to the onset, maintenance and worsening of mental disorders. Beyond insomnia, several other sleep pathologies may be associated with adverse mental health outcomes, and having multiple sleep disorders may be an aggravating factor. This study aimed to delineate the current landscape of sleep difficulties and symptoms of sleep disorders linked to poor mental health, investigate associations between the age at onset of sleep problems and subsequent mental health, and assess the perceived impacts of sleep problems. Materials and Methods: A representative sample of 1,200 Canadians (16 to 88 years old, 53% females) completed an online survey on sleep and mental health between 21 and 24 September 2021 (i.e. after the acute phase of the COVID-19 pandemic in Canada). The survey included questions inspired form the Sleep Disorders Questionnaire, Sleep Disorders Symptom Checklist-25, Pittsburgh Sleep Quality Index, STOP-Bang, and Insomnia Severity Index. The sample was stratified in two groups based on self-reported current mental disorder diagnosis: mental disorder diagnoses [219 (18.2%)] vs no diagnosis [960 (80.0%)]. Total scores on the General Anxiety Disorder-7 and Patient Health Questionnaire were used to determine anxiety and depression symptoms severity. Results: Of those with mental disorder diagnoses, 80.4% (176/219) endorsed symptoms of at least one sleep disorder, a proportion significantly higher compared to the 42.7% observed in the rest of the sample (p<.001, V=.29). The mental disorder diagnoses group included higher proportions of respondents endorsing symptoms of insomnia disorder, sleep apnea, bruxism, restless legs syndrome, nightmare disorder, hypersomnia and somnambulism. After adjusting for age, sex, income level and total sleep time, having a mental disorder diagnosis was associated with: insomnia (OR=3.52, p<.001), obstructive sleep apnea (OR=1.95, p=.006) and bruxism (OR=2.77, p<.001). Half of those with mental disorders diagnoses endorsed symptoms of multiple sleep disorders, a proportion significantly higher than what was observed in the rest of the sample (p<.001, V=.35). Endorsing symptoms of insomnia, sleep apnea, bruxism, restless legs syndrome, and hypersomnia were associated with more severe anxiety and depression symptoms after adjusting for age, sex, income level, total sleep time, and mental disorders diagnoses (B>.98, p<.012). Younger age at onset of sleep problems was a significant independent predictor for current self-reported diagnosis of mental disorders (OR=.96, p<.001). Compared to the rest of the sample, the mental disorder group reported significantly worse impacts of sleep problems on mental health, family relationships, physical health, cognitive functioning, productivity level, and global daily functioning. Conclusions: These results reinforce the transdiagnostic nature and cumulative impacts of the various profiles of sleep problems associated with mental health issues. These findings also suggest that the relationship between sleep and mental health is not solely driven by short sleep duration or insomnia. There is a need to enhance awareness about the diverse profiles of sleep issues linked to poor mental health and the relevance of early intervention, notably during youth. Should future longitudinal studies based on objective measures confirm these observations, this may inform further development of transdiagnostic sleep interventions for people with mental disorders.