Progressive Spasticity With a Single Magnetic Resonance Imaging Lesion

A 59-year-old White man with a history of excised basal and squamous cell skin cancers was evaluated for gait difficulties. He had erectile dysfunction but no bowel or bladder dysfunction. He also reported fatigue. He began using a cane for ambulation 2 weeks before evaluation at our facility. His medications included vitamin D and sildenafil. He was a lifelong nonsmoker and had no family history of multiple sclerosis. Neurologic examination at the time of our evaluation 3 years after onset was notable for a positive Hoffman sign on the right and mild weakness of the right triceps but preserved strength elsewhere. He had a spastic gait with moderate spasticity in both lower extremities, hyperreflexic patellar and ankle jerks bilaterally, and bilateral positive Babinski sign. The remainder of the examination was essentially normal. Magnetic resonance imaging of the brain showed a single lesion at the cervicomedullary junction and medullary pyramids, more prominent on the right. There was also some accompanying atrophy that was also visible on cervical spine magnetic resonance imaging. Results of cerebrospinal fluid analysis showed a normal white blood cell count, increased protein concentration (108 mg/dL), and positive oligoclonal bands. The progressive nature of his symptoms, spinal fluid results, and lesion appearance were all consistent with a diagnosis of progressive solitary sclerosis. At the time this patient was seen, no immunomodulatory medications for progressive solitary sclerosis were approved, so no immunomodulatory medication was tried. Ongoing symptomatic management was recommended. Progressive solitary sclerosis is a rare variant of multiple sclerosis in which patients have a single central nervous system demyelinating lesion and development of motor progression attributable to that lesion. Patients can initially have a clinical episode followed by progression or can have a progressive course without an initial relapse.

SP3.2.9 The concordance between emergency CT reporting in non-traumatic abdominal pain with surgical findings at laparotomy

Aims Abdominal CT imaging is commonly used to assess the acute abdomen, and is relied upon by clinicians in decision making, often influencing the timeliness of intervention. Increased demand for CT imaging has led to departments out-sourcing reporting out of hours. The aim of this audit was to evaluate the concordance between emergency laparotomy findings and pre-operative CT reports. Methods 115 patients underwent emergency laparotomy with a pre-operative CT scan pertinent to the clinical episode (May 2019-October 2020). 2 surgical assessors independently assessed the CT reports and laparotomy findings to determine discrepancies. Using published audit standards, discrepancies were defined as major-felt to affect patient treatment- and further classified as false positive, false negative, misdiagnosis, indeterminate; or minor and unlikely to change course of patient care. Results 32/115 had discrepancies, 28/32 major (16/28 misdiagnosis, 4/28 false negative, 3/28 false positive, and 5/28 indeterminate). 71/115 reported by in house radiology. 19/71 discrepancies reported in house (16 major, 3 minor), 13/32 discrepancies reported by out of hours service (12 major, 1 minor). Relative risk of major discrepancies between in house radiology and out of hours service was 1.2 (p = 0.5). Conclusions Published audit standards are that CT reports should have >90% concordance with laparotomy findings; this audit found concordance in 76%. Further analysis comparing gastrointestinal vs. non-gastrointestinal specialist radiologist to assess the impact on concordance will be performed. We aim to explore the discrepancies, and seek to identify if our imaging and operating practices can be improved.

Individual-level variations in malaria susceptibility and acquisition of clinical protection

After decades of research, our understanding of when and why individuals infected with Plasmodium falciparum develop clinical malaria is still limited. Correlates of immune protection are often sought through prospective cohort studies, where measured host factors are correlated against the incidence of clinical disease over a set period of time. However, robustly inferring individual-level protection from these population-level findings has proved difficult due to small effect sizes and high levels of variance underlying such data. In order to better understand the nature of these inter-individual variations, we analysed the long-term malaria epidemiology of children ≤12 years old growing up under seasonal exposure to the parasite in the sub-location of Junju, Kenya. Despite the cohort’s limited geographic expanse (ca. 3km x 10km), our data reveal a high degree of spatial and temporal variability in malaria prevalence and incidence rates, causing individuals to experience varying levels of exposure to the parasite at different times during their life. Analysing individual-level infection histories further reveal an unexpectedly high variability in the rate at which children experience clinical malaria episodes. Besides exposure to the parasite, measured as disease prevalence in the surrounding area, we find that the birth time of year has an independent effect on the individual’s risk of experiencing a clinical episode. Furthermore, our analyses reveal that those children with a history of an above average number of episodes are more likely to experience further episodes during the upcoming transmission season. These findings are indicative of phenotypic differences in the rates by which children acquire clinical protection to malaria and offer important insights into the natural variability underlying malaria epidemiology.

An updated review of teriflunomide's use in multiple sclerosis

Teriflunomide, a once daily, oral disease-modifying therapy, has demonstrated consistent efficacy, safety and tolerability in patients with relapsing forms of multiple sclerosis (MS) and with a first clinical episode suggestive of MS treated up to 12 years. This review is an update to a previous version that examined data from the teriflunomide core clinical development program and extension studies. Data have since become available from active comparator trials with other disease-modifying therapies, treatment-related changes in brain volume (analyzed using structural image evaluation using normalization of atrophy) and real-world evidence including patient-reported outcomes. Initial data on the potential antiviral effects of teriflunomide in patients with MS, including case reports of patients infected with the 2019 novel coronavirus (SARS-CoV-2), are also presented.

Persistent sub-microscopic Plasmodium falciparum parasitaemia 72 hours after treatment with artemether-lumefantrine predicts 42-day treatment failure in Mali and Burkina Faso

A recent randomised controlled trial, WANECAM, conducted at seven centres in West Africa, found that artemether-lumefantrine, artesunate-amodiaquine, pyronaridine-artesunate and dihydroartemisinin-piperaquine all displayed good efficacy. However, artemether-lumefantrine was associated with a shorter interval between clinical episodes than the other regimens. In a further comparison of these therapies, we identified cases of persisting sub-microscopic parasitaemia by qPCR at 72h post-treatment among WANECAM participants from 5 sites in Mali and Burkina Faso, and compared treatment outcomes for this group to those with complete parasite clearance by 72h. Among 547 evaluable patients, 17.7% had qPCR-detectable parasitaemia at 72h during their first treatment episode. This proportion varied among sites, reflecting differences in malaria transmission intensity, but did not differ among pooled drug treatment groups. However, patients who received artemether-lumefantrine and were qPCR positive at 72h were significantly more likely to have microscopically-detectable recurrent Plasmodium falciparum parasitaemia by day 42 than those receiving other regimens, and experienced on average a shorter time-interval before the next clinical episode. Haplotypes of pfcrt and pfmdr1 were also evaluated in persisting parasites. These data identify a possible threat to the parasitological efficacy of artemether-lumefantrine in West Africa, over a decade since it was first introduced on a large scale.

Individual-level variations in malaria susceptibility and acquisition of clinical protection

After decades of research, our understanding of when and why individuals infected with Plasmodium falciparum develop clinical malaria is still limited. Correlates of immune protection are often sought through prospective cohort studies, where measured host factors are correlated against the incidence of clinical disease over a set period of time. However, robustly inferring individual-level protection from these population-level findings has proved difficult due to small effect sizes and high levels of variance underlying such data. In order to better understand the nature of these inter-individual variations, we analysed the long-term malaria epidemiology of children ≤12 years old growing up under seasonal exposure to the parasite in the sub-location of Junju, Kenya. Despite the cohort’s limited geographic expanse (ca. 3km x 10km), our data reveal a high degree of spatial and temporal variability in malaria prevalence and incidence rates, causing individuals to experience varying levels of exposure to the parasite at different times during their life. Analysing individual-level infection histories further reveal an unexpectedly high variability in the rate at which children experience clinical malaria episodes. Besides exposure to the parasite, measured as disease prevalence in the surrounding area, we find that the birth time of year has an independent effect on the individual’s risk of experiencing a clinical episode. Furthermore, our analyses reveal that those children with a history of an above average number of episodes are more likely to experience further episodes during the upcoming transmission season. These findings are indicative of phenotypic differences in the rates by which children acquire clinical protection to malaria and offer important insights into the natural variability underlying malaria epidemiology.

A Cross-Cultural Values-Based Approach to the Diagnosis and Treatment of Dissociative (Conversion) Disorders

This case report presents the story of a young woman of Romani descent with a mixed dissociative (conversion) disorder within the contextual evidence-based and value-based medical framework. By painting the picture illustrating the course of her illness and the circumstances leading to the last clinical episode, compelling her most recent hospitalization, we delineate the contrast between common clinical phenomenology and the additional layers of the patient’s beliefs and values. Thus, we emphasize the importance of expanding the one-dimensional mainstream evidence-based approach, not only in cases of cross-cultural doctor-patient interactions but also in general medical practice, since the health attitudes and illness behaviors of every individual are influenced by their values and beliefs. In addition, the contemporary notion of medicine as a factual science requires a paradigm shift toward integrative multifaceted approaches if we as doctors are to treat human beings and not merely diseases.

Impact of 12 months of immunotherapy for metastatic cancer patients on oncology workload.

279 Background: In the last years, the introduction of immune checkpoint inhibitors (ICI) in clinical practice translated into major changes in oncology workload. We conducted a study aimed to estimate the shift in workload generated, within 1 year of first consultation, by any new metastatic cancer patient receiving ICI at the Oncology Department of the Academic Hospital of Udine, Italy. Methods: We collected from our electronic accountability system data all new cases of metastatic cancer between 01.01.2017 and 31.12.2018, leading to at least a second clinical episode (treatment sessions, unplanned presentations, hospitalizations, re-evaluations, follow-up, and inpatient oncology advices) during the following year. Patients (pts) were divided into those receiving ICI (anti-CTLA4/PD1/PDL1) versus pts receiving other treatments. Mean number per patient and standard deviation were calculated for clinical episodes, and the mean numbers in each group were compared using Student’s t-test (significance p<0.05). Follow-up continued until 31.12.2019. Results: 969 pts were included: 115 were treated with ICI, 854 received other treatments. In the first group a greater number of treatment sessions, re-evaluations and unplanned presentations was generated, with a statistically significant increased workload. On the other hand, pts receiving other treatments generated a greater workload in terms of follow-up. In detail, data are reported in Table. Conclusions: ICI have transformed the oncology landscape, leading to longer lasting treatment period with emerging toxicities. Estimating the workload generated by ICI is crucial for the implementation of more sustainable systems and for planning clinical activities. Mean number of clinical episodes in the first year of treatment with ICI for metastatic disease. Mean number per patient is represented by mean value and standard deviation (SD). Total number of clinical episodes is shown (N=). Data are reported for ICI versus other treatments group. [Table: see text]

Development of Arthritis as the Initial Involvement in Adult-Onset Cutaneous Polyarteritis Nodosa: Two Cases and Literature Review

Articular symptoms are commonly present in polyarteritis nodosa (PAN). Meanwhile, they may occur as the initial and main involvement of PAN, raising a concern of a delay in a definitive diagnosis of disease unless the histological evidence is obtained. Herein, we report two cases of cutaneous PAN (c-PAN) in which arthritis developed as the initial clinical episode of disease and we argued, through a review of the literature, the clinical feature of patients presenting with arthritis as the initial symptom of PAN. To our knowledge, only six cases have been reported in the English literature, and all six patients were categorized as having c-PAN. Of those patients, four had arthritis with indicating destructive changes. A median of 9 years elapsed prior to the induction of immunosuppressive treatment despite the fact that the other reviewed cases as well as our two patients, who received treatment significantly earlier, showed no evidence of joint destruction. Taken together, this report suggests that the early induction of therapy based on the definitive diagnosis of PAN may be required for preventing joint disruption even though it is not easy to make a diagnosis of PAN unless biopsied tissue can provide the evidence of necrotizing vasculitis.

Should I stop or should I go on? Disease modifying therapy after the first clinical episode of multiple sclerosis

Introduction Treatment with disease-modifying therapies (DMT) in patients with clinically isolated syndrome (CIS) represents standard care in multiple sclerosis (MS) patients nowadays. Since a proportion of patients may show no evidence of disease activity (NEDA) after some time of treatment, the question might arise about the risks of stopping DMT. Methods We present a cohort of 49 patients who started DMT immediately after CIS and had no evidence of disease activity (NEDA-3) for at least five years before discontinuation of therapy. Thereafter, patients underwent clinical and MRI follow-up for at least five consecutive years. Results Of 49 patients discontinuing DMT, 53% (n = 26) had NEDA for at least further five years, while 47% (n = 23) showed either a relapse/disease progression (18.4%, n = 9), MRI activity (14.3%, n = 7) or both (14.3%, n = 7). The main predictive factor for sustained NEDA was age at DMT termination. Patients aged > 45 years had a significantly lower risk of disease reactivation (13% vs. 54% in patients aged < 45 years, p < 0.001) after DMT discontinuation. Discussion In CIS patients with immediate DMT after their first clinical episode, older age at the time of DMT discontinuation is the main predictive factor for sustained NEDA status.