A straightforward electrochemical hydrogenation of benzo[b]thiophene 1,1-dioxides with HFIP as the hydrogen donor has been re-ported in an undivided cell under metal-free conditions. Moreover, the tolerance of various functional groups and scaled-up experi-ments showed the practicability and potential applications of this methodology.
Alemtuzumab‐induced petechiae and epistaxis in a patient with relapsing remitting multiple sclerosis; A case report Farhad Mahmoudi1*, Sayed Ali Emami1, Farid Masaeli1, Najmeh Rayatpisheh21 School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran2School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, IranCorresponding author*Farhad MahmoudiSchool of Medicine,Isfahan University of Medical Sciences,Isfahan, IranEmail: [email protected]: This case report presents a 58-year-old woman with Multiple Sclerosis (MS) who developed petechiae and epistaxis, rare side effects following Alemtuzumab treatment. While these reactions are infrequent, heightened awareness among healthcare providers is essential as Alemtuzumab gains popularity in MS treatment. Recognizing and managing such hypersensitivity reactions promptly is crucial for improved patient care. 1.Introduction Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system. The course of the disease varies among individuals, leading to a wide range of symptoms and patterns of presentation. Additionally, there are other conditions, such as radiologically isolated syndrome, which can progress to MS(1). While there is no curative therapy for this condition, certain drugs can modify the course of the disease and improve the prognosis and quality of life for patients.Disease-modifying treatments (DMTs) are the preferred treatment option for patients with MS. Alemtuzumab is an intravenously administered DMT drug that has been available since 2014 for the treatment of patients with multiple sclerosis who have not responded adequately to two or more DMTs. It is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to the CD52 antigen on B and T lymphocytes, depleting them from the bloodstream. This drug has been described as a safe and effective treatment with minimal side effects for patients with relapsing-remitting multiple sclerosis.(2)While there are few studies on the cutaneous adverse effects of Alemtuzumab, in this study, we report the first case of an MS patient treated with Alemtuzumab who developed drug-induced petechiae and epistaxis.2. Case presentationA 58-year-old Caucasian woman with relapsing-remitting multiple sclerosis, who had no previous medical conditions, presented to the emergency department due to muscle spasms and stiffness in her right foot. Neurological examination revealed weakness in her right lower limb with 3/5 muscle strength. She was diagnosed with MS at the age of 26 through an MRI and had previously been on weekly Interferon-beta (IFNb) treatment. During acute MS attacks, she received intravenous corticosteroids. Despite being on disease-modifying therapies (DMTs), she experienced more relapses in the last year, and her Expanded Disability Status Scale (EDSS) was 3. During the current hospitalization, the patient underwent brain and cervical spinal MRI, which revealed the appearance of new periventricular white active plaques in addition to previous black old lesions.Considering the progression of her disease condition, she was started on treatment with Alemtuzumab at a dose of 12mg/day IV. There were no drug reactions, and after completing the treatment, her muscle spasms and stiffness resolved, and the patient was discharged from the hospital.The day after, the patient came to the hospital to receive the second dose of the drug. While receiving the treatment, her condition remained stable, and she did not experience any notable symptoms. However, one day after finishing the first dose, the patient started to experience a gradual appearance of petechiae on her upper and lower limbs, chest, shoulders, and back. Moreover, a few minutes later, she developed epistaxis. Her blood pressure and heart rate were 127/73 and 87, respectively. The patient denied any previous history of eczema, skin issues, or respiratory allergies.Dermatology was consulted to investigate the possible causes of petechiae, and ENT was consulted to manage and evaluate the epistaxis. Despite applying pressure to the nostrils and placing ice on the forehead, the epistaxis did not cease. Consequently, the patient underwent posterior nasal packing, which successfully halted the bleeding.
Millions of people suffer from dopamine-related disorders spanning disturbances in movement, cognition and emotion, often attributed to changes in striatal dopamine function. Understanding how dopamine signaling in the striatum and basal ganglia shapes human behavior is fundamental to advancing the treatment of affected patients. Dopaminergic neurons innervate large scale brain networks and many different roles for dopamine signals have been proposed, such as invigoration of movement and tracking of reward contingencies. The canonical circuit architecture of cortico-striatal loops sparks the question, whether dopamine signals in the basal ganglia serve an overarching computational principle which could provide new insights into symptom generation in psychiatry to neurology. Here, we review the perspective that dopamine could bidirectionally control neural population dynamics, increasing, or decreasing their strength and likelihood to reoccur in the future, a process previously termed neural reinforcement. We outline how the basal ganglia pathways could drive strengthening and weakening of circuit dynamics and discuss the implication of this hypothesis on the understanding of motor signs of Parkinson’s disease (PD), the most frequent dopaminergic disorder. We propose that loss of dopamine in PD may lead to a pathological brain state where repetition of neural activity leads to weakening and instability, possibly explanatory for the fact that movement in PD deteriorates with repetition, as defined by the sequence effect or decrement of movement. Finally, we speculate on how therapeutic interventions such as deep brain stimulation (DBS) may be able to reinstate reinforcement signals and thereby improve treatment strategies of PD in the future.
Background: Intracardiac echocardiography (ICE) is increasingly used during left atrial appendage occlusion (LAAO) as an alternative to transesophageal echocardiography (TEE) Aim: To evaluate the impact of ICE vs. TEE guidance during LAAO on procedural characteristics and acute outcomes, as well the presence of peri-device leaks and residual septal defects during follow-up. Methods: All studies comparing ICE-guided vs. TEE-guided LAAO were identified. The primary outcomes were procedural efficacy and occurrence of procedure-related complications. Secondary outcomes included lab efficiency (defined as a reduction in in-room time), procedural time, fluoroscopy time, and presence of peri-device leaks and residual interatrial septal defects (IASD) during follow-up. Results: Twelve studies (n=5637) were included. There were no differences in procedural success group (98.3% vs. 97.8%; OR 0.73, 95% CI 0.42-1.27, p=0.27; I2=0%) or adverse events (4.5% vs. 4.4%; OR 0.81 95% CI 0.56-1.16, p=0.25; I2=0%) between the ICE-guided and TEE-guided groups. ICE guidance reduced in in-room time (mean-weighted 28.6-minute reduction in in-room time) without differences in procedural time or fluoroscopy time. There were no differences in peri-device leak (OR 0.93, 95% CI 0.68-1.27, p=0.64); however, an increased prevalence of residual IASD was observed with ICE-guided vs. TEE-guided LAAO (46.3% vs. 34.2%; OR 2.23, 95% CI 1.05-4.75, p=0.04). Conclusion: ICE guidance is associated with similar procedural efficacy and safety, but could result in improved lab efficiency (as established by a significant reduction in in-room time). No differences in the rate of periprocedural leaks were found. A higher prevalence of residual interatrial septal defects was observed with ICE guidance.
In May 2022, a cluster of non-travel-related cases of human mpox were reported in the UK. The outbreak has since spread world-wide infecting over 85,000 patients and causing over 100 deaths. Recent data clearly suggest that patients infected with Human Immunodeficiency Virus (HIV) with CD4 counts less than 200 cells per mm 3 suffer significantly worse outcomes than immunocompetent patients. The available countermeasures lack robust clinical data and are deployed based on in vitro and animal studies as well as extrapolations from use against other poxviruses. In many cases, despite administration of these available treatments, initiation of antiretroviral therapy, and management of Immune Reconstitution Inflammatory Syndrome (IRIS), patients die. This review summarizes available data, identifies knowledge gaps and proposes recommendations on the management of severe mpox in PLWH.
Rhabdomyosarcoma (RMS) is a highly aggressive pediatric cancer known for its therapeutic challenges, particularly when it becomes metastatic or recurrent. Traditional treatment approaches have shown limited success, prompting a growing interest in targeted therapies. The emergence of next-generation sequencing (NGS) has revolutionized our ability to identify actionable mutations in RMS, offering the promise of personalized treatments and improved patient outcomes. A recent case involving a 3-year-old child diagnosed with embryonal RMS highlighted the potential of next-generation sequencing (NGS) in clinical practice. Despite receiving initial chemotherapy, the patient’s tumor showed progressive growth. What made this case particularly intriguing was the discovery of co-occurring somatic mutations in the RAS/MAPK pathway, specifically in BRAF and HRAS genes, which are traditionally believed to be mutually exclusive. Notably, the BRAF mutation identified in this case, N581I, is a non-classical (Class III) hotspot mutation that had not been previously reported in embryonal RMS. This novel finding underscores the critical importance of comprehensive genetic profiling in pediatric cancers and suggests the existence of potential therapeutic avenues that target BRAF alterations. In conclusion, the integration of NGS technologies in clinical practice holds great promise for identifying previously unrecognized mutations in pediatric cancers like RMS. These findings have the potential to open up new treatment options and improve outcomes for young patients facing this aggressive disease.
In the unique landscape of immunology research in New Zealand, this article explores the collaborative networks spanning the two main islands, through a conversation with Associate Professor Joanna Kirman and Dr. Robert Weinkove. The discussions delve into their dynamic collaborations with countries like Asia, Australia, and the United States from their labs at the University of Otago and the Malaghan Institute respectively, provides insight into the translational research landscape of New Zealand, and the integration of Māori culture into all aspects of scientific research and clinical practise. Kirman’s work in understanding immunological memory in tuberculosis and Weinkove’s research in cancer immunotherapies, particularly CAR-T cells, are highlighted. The natural beauty and accessibility of New Zealand supports it’s research diversity.
Emeritus Professor Margaret Baird forged a luminary career for her pioneering research investigating the role of dendritic cells (DCs) in cancer and infectious diseases, as an inspirational lecturer at the University of Otago and a role model to many. In this article celebrating the 100-year anniversary of ICB, we discuss Margaret’s career and life journey through the eyes of her family and co-authors, as we explore her many publications in ICB and beyond.
A Rare Case: IgG4-Related Chronic Inflammatory Disease with Kidney InvolvementFatos METE¹, Tuba MENGENECI¹, Emre ALBAYRAK¹, Yavuz AYAR2, Melike NALBANT3, Ilknur MUTLUCAN4, Zeliha Fusun BABA51Bursa City Hospital, Department of Internal Medicine, Bursa, Turkey2Bursa City Hospital, Department of Internal Medicine, Division of Nephrology, Bursa, Turkey3Bursa City Hospital, Department of Medical Pathology, Bursa, Turkey4Bursa City Hospital, Department of Radiology, Bursa, Turkey5Acıbadem International Hospital, Department of Medical Pathology, Istanbul, Turkey
BACKGROUND There is increasing concern that a significant proportion of randomised controlled trials (RCTs) included in Cochrane reviews may not be trustworthy. Applying a trustworthiness screening tool (TST) has already had a clinically important effect on several reviews published by the Cochrane Pregnancy and Childbirth Group. OBJECTIVES We wanted to assess the impact of removing untrustworthy RCTs from already- published Cochrane reviews on a defined clinical area (ante- and post-natal nutritional interventions). METHODS We applied the tool to 18 Cochrane reviews (375 RCTs). The tool had four domains: i) is the research governance trustworthy; ii) are the baseline characteristics trustworthy; iii) is the study feasible; iv) are the results plausible?). When additional information was needed, authors were contacted using a standard template. At least two attempts were made to contact the authors. At the end of the evaluation process each study was classified as: i) included (YES to all domains); ii) excluded (retracted study); or iii) awaiting classification (any NO to the TST questions). RESULTS 95/375 studies (25%) were removed, affecting 14/18 (78%) reviews. 13/18 reviews (72%) showed a difference in the Summary of Findings tables (direction and size of effects and/or GRADE ratings). 6/18 Cochrane reviews (33%) were judged to require updating because of important differences in either in their conclusions, implication for practice, and/or implication for research. CONCLUSIONS Formal assessment of trustworthiness and inclusion only of studies that satisfy prespecified criteria for trustworthiness affect conclusions in a relatively large number of Cochrane reviews, with potentially important clinical implications for practice and research. The lack of consensus regarding the best tool(s) for assessing trustworthiness cannot be an excuse for ignoring this issue in future Cochrane reviews.
Accuracy of outcome definitions in Mendelian randomization of maternal healthQian Yang,1,2 Maria Carolina Borges1,2 1 MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK2 Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKDear Dr Papageorphiou,We recently read the article by Dr Ardissino and colleagues entitled ‘Genetically predicted body mass index and maternal outcomes of pregnancy: A two-sample Mendelian randomization study’ , where 11 outcomes were investigated. To conduct Mendelian randomization (MR) analyses, this study extracted associations of selected genetic variants with those outcomes from publicly available GWAS (genome-wide association study) summary data from FinnGen (the sixth release, total N=147,061 women) – a national-wide network of Finish Biobank . We noticed that “postpartum depression” included in Ardissino et al was inconsistent with the commonly used definition of postnatal depression occurring within a year of delivery [3,4]. FinnGen defined this outcome based on the International Classification of Diseases 10th Revision (ICD-10) codes (ICD-10 F32, F33 and F53.0) among women with at least one episode of delivery (ICD-10 O80-O84), without considering the time interval between delivery and diagnosis of depression. Therefore, cases of “postpartum depression” could be ascertained at any time after giving birth and, therefore, could be unrelated to pregnancy. As a consequence, findings for “postpartum depression” in Ardissino et al should be interpreted with caution due to the unspecific outcome definition.The increasing availability of publicly available or accessible data from GWAS consortia (e.g. Early Growth Genetics) and large biobanks (e.g. UK Biobank and FinnGen), combined with the creation of automated pipelines (e.g. MR-Base  used by Ardissino et al), has supported an rapid increase in publications using two-sample MR. Though such a combination has great potential to promote open science and advance health research, including in maternal-child health, we cautioned that detailed understanding of procedures used to generate GWAS summary data underlying MR analyses is of major importance to obtain reliable evidence and interpretable findings.
INTRODUCTION:Tuberculosis (TB) is still one of the most prevalent infections, especially in the developing world. The World Health Organisation (WHO) estimates that there are 8 million new cases annually [1,2]. Cough, sputum with or without haemoptysis, fever, and constitutional symptoms are the hallmark manifestations of an active tuberculosis infection. In patients with pulmonary TB, an increase in haemoglobin levels is regarded as an indicator of a positive response to treatment. Furthermore, Omar et al. found that a fall in platelet count, white blood cell (WBC) count, and erythrocyte sedimentation rate (ESR) were strong indications of clinical response . Despite the possibility of an increase in white blood cells (WBC), which results in lymphocyte predominance, in clinical practice, eosinophilia is a usual finding that is self-limiting in moderate cases, but it is exceedingly infrequent in TB [4,5].Many allergic, viral, and neoplastic conditions may produce peripheral blood eosinophilia, necessitating a variety of examinations and subsequent therapy. Common causes of eosinophilia in children include infections with helminthic parasites, allergic diseases, malignancies, and adverse drug reactions [1,6]. One of the primary goals of the early evaluation is to identify an underlying cause that needs specific therapy. Even though difficulties linked with eosinophilia are more prevalent in individuals with higher eosinophil counts (>1500 eosinophils/uL), the peripheral blood eosinophil count does not accurately assess the risk of organ damage in each patient. A patient with modest peripheral blood eosinophilia may also have significant eosinophil organ involvement. Normal eosinophil counts in the human blood range between 0-350/mm3. This quantity accounts for between 1 and 3% of the differential leukocyte count . Most reports of eosinophilia in tuberculosis describe local eosinophilia as opposed to peripheral eosinophilia . To the best of our knowledge, reported cases are very rare. As a consequence, we describe one case of TB with considerable peripheral eosinophilia and the treatment outcome.