Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Canal of Nuck Abnormalities in Pediatric Female Patients.

A groin lump is not an uncommon condition in girls and female infants, and US plays a fundamental role in its exploration. The main pathologic conditions are related to the failure of obliteration of the canal of Nuck. Radiologists should gain a full understanding of the embryology and US anatomy of the inguinal canal before assessing this entity for the first time. An optimal age-adjusted US technique-including examinations at rest and during straining-is essential to help assess the canal of Nuck, diagnose a hernia, and analyze its content. The radiologist must be aware of the various types of hernial content depending on the patient's age, including intestinal, omental, ovarian, or tubouterine hernia, and the US features of each. Incarcerated hernias are common in girls and mostly contain an ovary. In such cases, it is crucial to screen for US signs suggestive of ovarian ischemic damage, thereby calling for urgent surgery. US can also depict a cyst or hydrocele of the canal of Nuck and its complications. Moreover, other rare pathologic conditions involving the inguinal area may be depicted at US, which helps guide appropriate treatment. US is the ideal modality for evaluating an inguinal lump in girls and female infants. Online supplemental material is available for this article. ©RSNA, 2022.

Anti-programmed death ligand 1 immunotherapies in cancer patients with pre-existing systemic sclerosis: A postmarketed phase IV safety assessment study.

OBJECTIVES: Cancer patients with pre-existing autoimmune disease, such as systemic sclerosis (SSc), are excluded from clinical trials, so the data on tolerability and efficacy of immune checkpoint inhibitors in these patients are limited. This study investigated the tolerability and efficacy of anti-programmed death ligand 1 (PD (L)1) immunotherapies in patients with pre-existing SSc. METHODS: Scleronco-01 was a multicentre, nationwide, open-label, phase IV observational study, from 2019 to 2021. RESULTS: Seventeen SSc patients receiving treatment for lung carcinoma (n = 13, 77%), head and neck cancer (n = 2, 12%), melanoma (n = 1, 6%), and colorectal carcinoma (n = 1, 6%) were included. The median (interquartile range) patient age was 60 (34-82) years. Fifteen (88%) patients received anti-PD1 (nivolumab and pembrolizumab) and two (12%) anti-PD-L1 (durvalumab). The median follow-up duration was 12 (range, 2-38) months. Four patients (24%) experienced flare-up of SSc symptoms. Ten patients (59%) developed an immune-related adverse event (grade I-II in 11 patients [65%], grade III-IV in one [6%]) without grade V. The overall response rate was 41% (7/17 patients). The median overall survival was 15.8 (95% confidence interval: 7.3 to not reached) months. CONCLUSION: Anti-PD1 or PD-L1 immunotherapies are suitable options for cancer patients with pre-existing SSc. Longer follow-up periods are required for long-term safety analyses.

Longitudinally Extensive Myelitis Associated With Immune Checkpoint Inhibitors.

OBJECTIVE: To define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs). METHODS: We performed a retrospective research in the databases of the French Pharmacovigilance Agency and the OncoNeuroTox network for patients who developed myelitis following treatment with ICIs (2011-2020). A systematic review of the literature was performed to identify similar cases. RESULTS: We identified 7 patients who developed myelitis after treatment with ICIs (anti-PD1 [n = 6], anti-PD1 + anti-CTLA4 [n = 1]). Neurologic symptoms included paraparesis (100%), sphincter dysfunction (86%), tactile/thermic sensory disturbances (71%), and proprioceptive ataxia (43%). At the peak of symptom severity, all patients were nonambulatory. MRI typically showed longitudinally extensive lesions, with patchy contrast enhancement. CSF invariably showed inflammatory findings. Five patients (71%) had clinical and/or paraclinical evidence of concomitant cerebral, meningeal, caudal roots, and/or peripheral nerve involvement. Despite the prompt discontinuation of ICIs and administration of high-dose glucocorticoids (n = 7), most patients needed second-line immune therapies (n = 5) because of poor recovery or early relapses. At last follow-up, only 3 patients had regained an ambulatory status (43%). Literature review identified 13 previously reported cases, showing similar clinical and paraclinical features. All patients discontinued ICIs and received high-dose glucocorticoids, with the addition of other immune therapies in 8. Clinical improvement was reported for 10 patients. CONCLUSION: Myelitis is a rare but severe complication of ICIs that shows limited response to glucocorticoids. Considering the poor functional outcome associated with longitudinally extensive myelitis, strong and protracted immune therapy combinations are probably needed upfront to improve patient outcome and prevent early relapses.

Coatomer-associated protein subunit alpha syndrome: abnormal trafficking between the Golgi complex and the endoplasmic reticulum.

A 25-year-old woman with a history of juvenile idiopathic arthritis and rheumatoid factor-positive polyarthritis developed dyspnoea. Progressive cystic lung disease was diagnosed. Biomarkers of autoimmunity, such as antinuclear antibodies, antiextractable nuclear antigen antibodies, anti-SCL-70, rheumatoid factor, cyclic citrullinated peptide antibodies, c-antineutrophil cytoplasmic antibody and MPO, were found. No familial disease was reported. Despite lack of kidney manifestations, coatomer-associated protein subunit alpha syndrome was suggested. Type 1 interferon signature score was 40.8 (range, <2.3). A class 4 heterozygous mutation (c.725T>G, p.Val242Gly) was confirmed. Due to abnormal trafficking between the Golgi complex and the endoplasmic reticulum, a Mendelian monogenic autosomal dominant syndrome associating inflammatory arthritis with interstitial lung disease, with several high-titre autoantibodies, was identified. Treatment with tyrosine kinase inhibitors, Janus kinases-signal transducers and activators of transduction, may be beneficial.

Respiratory Distress in SARS-CoV-2 without Lung Damage: Phrenic Paralysis Should Be Considered in COVID-19 Infection.

We describe an overweight COVID-19 patient with respiratory distress preceded by anosmia/dysgeusia with no lung injury shown on CT, angio-CT or ventilation/perfusion scans. Orthopnoea and paradoxical abdominal respiration were identified. Phrenic paralysis, demonstrated by examination of patient breathing, and on x-ray while standing breathing in and out, explained the respiratory distress. This is a rare and previously undescribed neurological complication of COVID-19 infection caused by vagus nerve injury. LEARNING POINTS: Phrenic paralysis must be kept in mind as a rare neurological complication of COVID-19.Vagus nerve palsy is a neurological manifestation as anosmia and dysgeusia, that were already identified in the olfactory system of COVID-19 patients.

Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study.

BACKGROUND: Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy. METHODS: We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively. FINDINGS: Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1. INTERPRETATION: Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

[Impact of COPD: from disability to exacerbations]. / Impact de la BPCO: du handicap aux exacerbations.

COPD is a common disease characterized by health status impairment and disability that is usually progressive. Exacerbations of COPD, an acute event in the course of the disease, have effects on symptoms and patient's quality of life. Assessment of symptoms and risk of exacerbations is useful to guide strategy management of the disease. COPD disability includes different aspects. Its assessment needs to consider the classification of severity of airflow limitation, symptoms, comorbidities and impairment of patient's health-related quality of life. The rate at which exacerbations occur varies between patients. History of previous exacerbations and severity of airflow limitation are the best predictors of the frequency and severity of exacerbations. Severity of the symptoms is associated with an increased risk of exacerbations. Exacerbations increase deterioration in health status and leads to severe disability, inducing a vicious circle from disability to exacerbations. At an individual patient level, an understanding of the impact of COPD requires to assess the patient's disability, the risk of future exacerbations, and the identification of comorbidities.

Cutaneous metastasis revealing a relapse of gastric linitis: Another case.

INTRODUCTION: Cutaneous metastasis from gastric cancer is a rare occurrence. The linitis gastric carcinoma accounts only 8.7% of all gastric cancers. PRESENTATION OF CASE: We report a case of female patient who was followed for linits cancer with peritoneal metastasis treated by six cycles of chemotherapy. After seventeen months of control, the relapse of the disease revealed by occurrence of cutaneous metastatsis. DISCUSSION: Cutaneous metastasis from linit gastric is rare and the prognostic remains poor. The treatment is palliative. CONCLUSION: This rare presentation should encourage the practitioners to biopsy any suspicion skin lesion.

Effectiveness of paramedic practitioners in attending 999 calls from elderly people in the community: cluster randomised controlled trial.

OBJECTIVE: To evaluate the benefits of paramedic practitioners assessing and, when possible, treating older people in the community after minor injury or illness. Paramedic practitioners have been trained with extended skills to assess, treat, and discharge older patients with minor acute conditions in the community. DESIGN: Cluster randomised controlled trial involving 56 clusters. Weeks were randomised to the paramedic practitioner service being active (intervention) or inactive (control) when the standard 999 service was available. SETTING: A large urban area in England. PARTICIPANTS: 3018 patients aged over 60 who called the emergency services (n=1549 intervention, n=1469 control). MAIN OUTCOME MEASURES: Emergency department attendance or hospital admission between 0 and 28 days; interval from time of call to time of discharge; patients' satisfaction with the service received. RESULTS: Overall, patients in the intervention group were less likely to attend an emergency department (relative risk 0.72, 95% confidence interval 0.68 to 0.75) or require hospital admission within 28 days (0.87, 0.81 to 0.94) and experienced a shorter total episode time (235 v 278 minutes, 95% confidence interval for difference -60 minutes to -25 minutes). Patients in the intervention group were more likely to report being highly satisfied with their healthcare episode (relative risk 1.16, 1.09 to 1.23). There was no significant difference in 28 day mortality (0.87, 0.63 to 1.21). CONCLUSIONS: Paramedics with extended skills can provide a clinically effective alternative to standard ambulance transfer and treatment in an emergency department for elderly patients with acute minor conditions. TRIAL REGISTRATION: ISRCTN27796329 [controlled-trials.com].

Developing assessment of emergency nurse practitioner competence--a pilot study.

AIM: This paper reports a study evaluating baseline competence levels among Emergency Nurse Practitioners using an Objective Structured Clinical Examination. The study also aimed to document change in competence over time and following an educational intervention. BACKGROUND: Emergency Nurse Practitioners form an increasingly established part of the minor injury service workforce in the United Kingdom (UK). At present, there is no national requirement for them to undergo formal preparation, gain a formal qualification, have continuing professional development or revalidate. Given that it is certain that the use of these professionals to deliver unplanned emergency care will increase in the UK, skill maintenance and extension of skills need to be considered in order to ensure the continued delivery of a quality service. Objective Structured Clinical Examinations aim to test a wide range of knowledge and skills in an objective fashion and can be developed to serve a number of educational requirements. METHODS: A competence assessment was planned using an Objective Structured Clinical Examination. It was developed following questionnaire consultation with Emergency Nurse Practitioners and also in conjunction with Emergency Department specialists and experts in medical education. The Objective Structured Clinical Examination was piloted with Emergency Department junior doctors. Baseline Objective Structured Clinical Examination assessment was conducted in 2001. An educational intervention followed and then a further Objective Structured Clinical Examination assessment took place in 2002. RESULTS: A total of 17 of 20 Emergency Nurse Practitioners consented to involvement in the study. Comparison of their performance showed a statistically significant overall improvement in performance between the two assessment periods (P < 0.05). Participant feedback on the experience of undertaking an Objective Structured Clinical Examination assessment was very positive. CONCLUSIONS: The assessment process worked well, and provides a framework for competence assessment that can be compared over time, between practitioners and between departments.

Efficient access to 2-aryl-3-substituted benzo[b]thiophenes.

[reaction: see text] Benzo[b]thiophene derivatives are important in part because of their use as selective estrogen receptor modulators. They are usually synthesized by intramolecular cyclization. Here, we propose a method for the synthesis of 2-arylbenzo[b]thiophenes with heteroatoms at the 3-positions directly from the benzo[b]thiophene core by using an aromatic nucleophilic substitution reaction and Heck-type coupling. This methodology provides 2-aryl-3-amino or phenoxybenzo[b]thiophenes in about 35% overall yield in 5 steps.