Recrudescence Of Symptoms Research Articles

The Role of Tofacitinib in the Treatment of Acute Severe Colitis in Children.

Acute severe colitis (ASC) occurs in up to 15 percent of children with ulcerative colitis, with a high index of morbidity and mortality. Treatment includes high-dose steroids, infliximab, and salvage therapies. Unfortunately, up to 20 percent of patients may need an urgent colectomy due to treatment failure. We report our experience using tofacitinib for the treatment of six patients. A retrospective review of our medical electronic records was conducted. We included every patient with ASC and treatment failure, in whom tofacitinib was used as a salvage therapy. Response, complications, and disease course were noted. Six patients were included with Pediatric Ulcerative Colitis Activity Index (PUCAI) scores ranging from 65 to 85 on admission, and 35 to 85 before tofacitinib was started (P 0.07). Median response time was 72 h. A median decrease of 40 points in PUCAI was noted (P 0.00001). Mean length of stay was 18 days with discharge 9 days after tofacitinib introduction. Haemoglobin, albumin, fecal calprotectin, and CRP improved after tofacitinib (P 0.02, P 0.02, P 0.025, and P 0.01, respectively). The mean follow-up was 8.5 months, four patients achieved complete remission and only one had a recrudescence of symptoms (P 0.01). One patient had a systemic Epstein-Barr virus infection prior to tofacitinib therapy, which resolved with rituximab treatment. No other complications were noted. Tofacitinib response is rapid and impressive in children suffering from ASC, and the safety profile appears comparable to or better than other available treatments. In the future, tofacitinib should be integrated into pediatric protocols.

Clinical Worsening in an Adolescent With Pleural Tuberculosis

A 17-year-old previously healthy female presented with unilateral chest pain and dyspnea. Chest radiographs demonstrated a unilateral pleural effusion and pneumonia. Pleural fluid bacterial cultures were negative; acid-fast cultures grew Mycobacterium tuberculosis. Two months after starting appropriate therapy, she had a recrudescence of symptoms and reaccumulation of the pleural fluid. Her tuberculosis antibiotic regimen was expanded, the effusion drained, and systemic corticosteroids initiated, resulting in rapid clinical improvement. Cultures of the second pleural fluid collection were negative. Her clinical deterioration was due to immune reconstitution inflammatory syndrome (IRIS). IRIS can be seen within the first several months of starting tuberculosis therapy and can result in paradoxical worsening of symptoms or radiographic findings in adolescents who are on the appropriate therapy. IRIS is a diagnosis of exclusion after drug resistance and medication malabsorption, intolerance, and nonadherence are excluded. Therapy includes nonsteroidal anti-inflammatory agents for milder reactions and systemic corticosteroids for more severe IRIS cases.

Acute Central Nervous System Demyelination Following COVID-19 Vaccination

Objective To describe features of central nervous system (CNS) demyelinating events following vaccination against coronavirus disease 19 (COVID-19). Background Several reports suggest a potential association between COVID-19 vaccines and acute CNS inflammation. Design/Methods A case series was performed at the BARLO MS Centre in Toronto, Ontario, Canada. Clinicians reported patients who experienced an acute CNS demyelinating event within 60 days after receiving at least one COVID-19 vaccination from March 2021 to January 2022. Clinical characteristics were evaluated. Results Twenty patients were identified (median age 39 years (range 25-82); 13 (65.0%) female). Two had pre-existing multiple sclerosis (MS). Individuals received the Pfizer (n = 14), Moderna (n = 5) or Astrazeneca (n = 1) COVID-19 vaccines. Within 1-53 days (median 12) of the first (n = 8) or second (n = 12) vaccine dose, patients developed transverse myelitis (TM) (n = 15), optic neuritis (n = 4) or brain demyelination (n = 4). Diagnoses at last follow up (median 114 days (range 39-255)) were relapsing remitting MS (n = 8), post-vaccine TM (n = 5), clinically isolated syndrome (n = 3), myelin oligodendrocyte glycoprotein antibody disease (n = 2), MS relapse (n = 1) and neuromyelitis optica spectrum disorder (n = 1). Thirteen patients received pulse corticosteroids, and of these, 4 received plasma exchange. Seven did not receive acute treatment. 20.0% returned to baseline (n = 4), 75.0% partially recovered (n = 15) and 5.0% worsened (n = 1). At last follow up, 11 were on disease modifying therapy and 9 were not. Nine patients received a subsequent COVID-19 vaccine. Of these, one experienced symptom recrudescence without radiologic evidence of a new demyelinating attack. Conclusions To our knowledge, this is the largest series to date describing acute CNS demyelination after vaccination against COVID-19. The rate of vaccination in the eligible general population was high during the time of the cases and we could not determine whether the number of demyelinating events was higher than expected. Repeat vaccination was not associated with recurrent adverse events in this small observational series.

First case of systemic fatal mycobacteriosis caused by Mycobacterium goodii in a pet Kenyan sand boa (Eryx colubrinus loveridgei)

BackgroundEnvironmental nontuberculous mycobacteria species that are not members of the M. tuberculosis complex, are ordinary inhabitants of a wide variety of environmental reservoirs and their role in human and animal diseases has been fully recognized. Even if spontaneous mycobacterial infections have been reported in a wide variety of reptiles, this is the first report of systemic fatal mycobacteriosis sustained by Mycobacterium goodii in a pet reptile. Case presentationAn adult, wild caught (WC), male Kenyan sand boa (Eryx colubrinus loveridgei) age unknown, was presented for clinical examination due to decreased activity level, decreased appetite and diarrhea. Blood tests showed unreliable results. Coprologic exam showed a moderate to severe presence of flagellates. X rays and ultrasound showed moderate presence of air and faeces in the large intestine. The snake was hospitalized and oral metronidazole was chosen as antiprotozoal agent in association with subcutaneous warm fluids. The snake was discharged after 2 weeks therapy in good clinical condition. Faecal exam resulted negative. One month after, the snake was quickly hospitalized again because of a recrudescence of symptoms. Biochemistry showed severe increase of AST, ALT and biliary acids. Severe leucocytosis and moderate to severe anemia were highlighted. Ultrasound examination revealed a severe diffused alteration of the liver parenchyma and a fine needle aspiration was performed. The cytological diagnosis was mixed inflammation, with a numerous of unstained rod-shaped bacteria both inside macrophages and free in the sample. The snake’s condition rapidly deteriorated and euthanasia was performed. The histology of the coelomic organs confirmed a systemic mycobacteriosis. Real-time PCR identified the mycobacteria as Mycobacterium goodii.ConclusionsSpecies from the genus Mycobacterium are among the most important micro-organism including the causative agents of tuberculosis. Even if the general incidence of disease in reptiles due to mycobacteria is comparatively low, they can serve as reservoirs of many ubiquitous mycobacteria species. Mycobacterium goodii is a rapidly growing non‐tuberculous mycobacterium that has recently been associated with severe infections in animals and humans. Although in this case the pathogenesis was not completely clear, we highlight the zoonotic risk of mycobacteriosis in exotic animals especially in WC specimens.

Extracranial-to-Intracranial Bypass for Distal Internal Carotid Artery and/or Proximal Middle Cerebral Artery Steno-Occlusive Disease: A Case Series of Clinical Outcomes at a Single, High-Volume Cerebrovascular Center.

Extracranial-to-intracranial (EC-IC) bypass was first described by Yasargil in the 1960s for treatment of symptomatic distal internal carotid artery (ICA) and/or proximal middle cerebral artery (MCA) steno-occlusive disease through direct anastomosis. Subsequent bypass trials failed to demonstrate benefit for overall outcomes and stroke rates compared with best medical therapy. However, the procedure remained in the neurosurgeon's armament, with studies showing benefits in select patient populations. With advancements in technology, patient selection has become more comprehensive. To provide a contemporary evaluation of EC-IC bypass from our high-volume cerebrovascular center, focusing on associated clinical outcomes. Consecutive patients who underwent direct EC-IC bypass surgeries for symptomatic distal ICA and/or proximal MCA steno-occlusive disease between April 2015 and September 2019 were identified retrospectively. Medical records were reviewed to collect demographics, clinical presentation, computed tomography perfusion imaging findings, transcranial Doppler results, procedure indication, donor vessel types, anastomosis site, bypass patency, periprocedural complications, postprocedural complications, symptom recrudescence, repeat or new interventions, subjective improvements, and modified Rankin Scale scores. We identified 27 patients who underwent 32 EC-IC bypass procedures. The rate of ipsilateral stroke was 9.4%, with a median follow-up of 8 months (IQR, 4-13 months). Patients experienced a 22.3% improvement in modified Rankin Scale scores, and 70.3% of patients reported subjective improvement and satisfaction at follow-up. Direct EC-IC bypass remains a viable option for revascularization in symptomatic patients with distal ICA and/or proximal MCA steno-occlusive disease.

SARS-CoV-2 Infection and Vaccination Outcomes in Multiple Sclerosis.

The effects of the SARS-CoV-2 vaccination and infection on clinical outcomes, including relapse risk, have been insufficiently explored in people with multiple sclerosis (PwMS). The objectives of this study were to determine the incidence of new neurologic symptoms or symptom recrudescence among PwMS who received the SARS-CoV-2 vaccine, characterize outcomes after SARS-CoV-2 infection, and assess MS-specific determinants of vaccine hesitancy. Online surveys that assessed incidence and severity of SARS-CoV-2 infection, vaccination status/type, reasons for vaccine deferral, and postvaccination symptoms were administered to PwMS. Medical charts were reviewed for consenting respondents. Associations between infection, postvaccination outcomes, and clinical characteristics were compared using χ2 tests, 2-sample t tests, and adjusted logistic regression models. In total, 292 of 333 respondents were vaccinated, of whom 58% reported postvaccination side effects, most commonly among mRNA vaccine recipients (p = 0.02), younger patients (p < 0.01), and people with relapsing-remitting MS (p = 0.03). Twelve percent endorsed recrudescence of existing MS symptoms, while 3% endorsed new neurologic symptoms postvaccination. Sixty-two participants reported SARS-CoV-2 infection since the start of the pandemic, more frequent in younger individuals (1-year odds ratio [OR] = 0.958, 10-year OR = 0.649, p < 0.01). Neither disease-modifying therapy nor B-cell therapies specifically were associated with vaccine side effects, neurologic symptoms, or SARS-CoV-2 infection. Twenty-one percent of unvaccinated cited a desire for provider guidance before vaccination. Our findings provide new data to suggest that among PwMS who received SARS-CoV-2 vaccination, clinical disease worsening is rare and mostly associated with symptom recrudescence, as opposed to new relapses. Postvaccination side effects may occur more often among mRNA vaccine recipients and in younger individuals.

Transvenous Coil Embolization of a Transverse-Sigmoid Sinus Dural Arteriovenous Fistula: 2-Dimensional Operative Video.

This case is a 66-yr-old woman with a 2-mo history of left-sided tinnitus. Workup with magnetic resonance angiography showed early opacification of the left sigmoid sinus and internal jugular vein as well as asymmetric and abundant opacification of the left external carotid artery branches, suspicious for a dural arteriovenous fistula (dAVF). Diagnosis was confirmed with cerebral angiography, consistent with a left-sided Cognard type I dAVF.1 Initial treatment attempt was made with transarterial 6% ethylene-vinyl alcohol copolymer (Onyx 18) embolization of feeders from the occipital and middle meningeal arteries. However, embolization was not curative and there was a recurrence of a highly bothersome tinnitus 3 wk following treatment. Angiography redemonstrated the transverse sinus dAVF with new recruitment arising from several feeders, including the left external carotid artery, middle meningeal artery, and superficial temporal artery, now Cognard type IIa. Definitive treatment through a transvenous coil embolization provided permanent obliteration of the fistula without recrudescence of symptoms on follow-up. In this video, the authors discuss the nuances of treating a dAVF via a transvenous embolization. Patient consent was given prior to the procedure, and consent and approval for this operative video were waived because of the retrospective nature of this manuscript and the anonymized video material.

Prolonged Viral Shedding in Patients with Mild to Moderate COVID-19 Disease: A Regional Perspective.

BackgroundThe risk of transmission of Coronavirus Disease 2019 (COVID-19) is increasingly understood to be greatest early after symptom onset, however, factors associated with prolonged and increased risk of transmission remain unclear. In settings where COVID-19 prevalence is low, there may be a benefit of extending the period that patients are isolated to decrease the risk of transmission. This study explored the duration of viral shedding in such a location, in patients with mild-moderate COVID-19 disease in Ballarat, Australia.MethodsPatients diagnosed with COVID-19 disease using a real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay from oropharyngeal and bilateral deep nasopharyngeal sampling and managed through Ballarat Health Services between March 1 and May 1, 2020 were included. Patients were retested if they were afebrile for >72 hours, asymptomatic and >14 days since symptom onset. If positive on retesting, patients were tested every 3 to 7 days thereafter.ResultsPatients underwent testing a median of 4 days (range 1-12) after initial symptom onset. Duration of symptoms ranged from 1 to 36 days. Positive tests were recorded up to a median of day 21 (range 6-38). Cycle thresholds were inversely correlated with time since symptom onset (P < .0001). Median time to the first negative test was 25 days (range 12-32). Two patients who had remained asymptomatic for >7 days after initial symptom onset had recrudescence of mild symptoms on day 13 and 14; both tested positive on follow-up tests at this time.ConclusionsThis study demonstrates prolonged shedding of COVID-19 in patients with mild-moderate disease. It suggests that some patients with mild disease may have recrudescence of symptoms a week or more after their initial symptoms resolved.

Atrial fibrillation ablation in athletes: 5-years experience of a single italian third-level center

Abstract Background The number of master athletes is increasing and treatment of AF is mandatory for sports continuation. However, few data exist about the effectiveness of catheter ablation (CA) in athletes and the feasibility of resuming vigorous exercise afterwards. Objectives Aim of our study was to analyze the efficacy and safety of AF CA in athletes and to evaluate the feasibility of resuming vigorous exercise. Methods We report a retrospective registry of athletes referred to our center for AF CA in the last five years. All athletes were previously declared non-eligible to competitive sport because of recurrences of AF or evidence of persistent asymptomatic AF. CA was performed as per practice and recurrences were defined as recrudescence of symptoms and/or any documentation of AF lasting more than 30 sec. At the end of the follow-up all pts were asked about resuming sport. Results We ablated 40 athletes (38 males, 95%) with a mean age of 48±13 years. Mean left atrium volume was 36±11 ml/m2 and mean ejection fraction was 61±5%. Distribution between AF characteristics was: 31 (78%) paroxysmal AF, 8 (20%) early-persistent AF, 1 (2%) long-persistent AF. After a median follow-up of 787 days, 62,5% of athletes were free from recurrences after one CA procedure and mostly without antiarrhythmic drugs (87%). 7 athletes underwent a redo procedure and all of them were then free of recurrences with an overall freedom from recurrences of 84%. No major complication was observed. Athletes practicing endurance sports showed a negative trend in terms of recurrences (p = ns). Most (72%) of the athletes resumed vigorous exercise after at least 3 months from the CA as per Italian sport protocols. Conclusions CA is safe and efficient in treating AF also in athletes. Resuming high intensity sports is often possible after 3 months from CA. Funding Acknowledgement Type of funding source: None

COVID-19 outcomes in MS: Observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center.

ObjectiveTo report outcomes on patients with multiple sclerosis (MS) and related disorders with coronavirus disease 2019 (COVID-19) illness.MethodsFrom March 16 to April 30, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by review of in-patient hospital records.ResultsWe identified 76 patients (55 with relapsing MS, of which 9 had pediatric onset; 17 with progressive MS; and 4 with related disorders). Thirty-seven underwent PCR testing and were confirmed positive. Of the entire group, 64 (84%) patients were on disease-modifying therapy (DMT) including anti-CD20 therapies (n = 34, 44.7%) and sphingosine-1-phosphate receptor modulators (n = 10, 13.5%). The most common COVID-19 symptoms were fever and cough, but 21.1% of patients had neurologic symptom recrudescence preceding or coinciding with the infection. A total of 18 (23.7%) were hospitalized; 8 (10.5%) had COVID-19 critical illness or related death. Features more common among those hospitalized or with critical illness or death were older age, presence of comorbidities, progressive disease, and a nonambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome.ConclusionsMost patients with MS with COVID-19 do not require hospitalization despite being on DMTs. Factors associated with critical illness were similar to the general at-risk patient population. DMT use did not emerge as a predictor of poor COVID-19 outcome in this preliminary sample.

Treatment of bypass failure in patients with chronic limb threatening ischemia - open surgery vs. percutaneous mechanical thrombectomy.

Background: Lower limb bypass occlusion in patients with chronic limb threating ischemia remains a challenge. We can choose between different treatment options: open surgery, local thrombolysis, thrombectomy/atherectomy devices. In this pilot study, we compare clinical outcomes and treatment costs between open surgery (OS) and percutaneous mechanical thrombectomy (pMTH). Patients and methods: This pilot study represents a retrospective analysis of hospital data of 48 occluded bypasses admitted from 2013 to 2018. Only patients presenting with severe ischemia and recrudescence of symptoms (Rutherford 4-6) were included in the current analysis. Two cohorts of patients were analysed: patients who underwent OS and patients that underwent pMTH. Primary clinical outcomes were one-year cumulative patency and limb salvage rates. Total cost was calculated as a sum of intra- and post-operative costs. To weigh clinical benefits against the economic consequences of OS versus pMTH a cost-effectiveness framework was adopted. Results: We analysed a series of 48 occluded bypasses 17 treated with open surgery and 31 with pMTH. Procedural success was 100% in both groups. When comparing one-year death rates (p-value=.22) and re-occlusion rates (p-value=.43), no statistically significant differences were observed between the two cohorts. Mean patency duration in the surgery cohort was significantly shorter (p-value<.05). Primary patency (OS 41.2% vs. pMTH 48.4%) and limb salvage rate (OS 88.2% vs. pMTH 90.3%) at one year are similar in both groups. The total cost of surgery was substantially higher (OS 10,159€ vs. pMTH 8,401€) Conclusions: This pilot study, although limited to 48 occluded bypasses, demonstrates that endovascular treatment with pMTH is less invasive, less time consuming and less expensive, and produces greater health benefits than traditional OS.

End of dose interval symptoms in patients treated with natalizumab: A role for serum cytokines?

BackgroundMany natalizumab treated patients experience end of dose interval (EDI) symptoms towards the end of the administration cycle. Natalizumab has previously shown to influence cytokine profiles in relapsing remitting MS patients. We hypothesize that EDI symptoms might be explained by variability in serum cytokine levels during natalizumab treatment. Methods42 relapsing remitting MS patients were included. Participants were evaluated before natalizumab administration (day 0) and 7 days afterwards (day 7). At both time points fatigue, depressed mood and cognition were evaluated using the fatigue severity scale (FSS), the visual analogue scale for fatigue (VAS-F), the symbol digit modality test (SDMT) and the inventory for depressive symptomatology (IDS-SR). Serum samples were tested for concentrations of IL-6, IFN-γ and TNF-α at both timepoints. On day 7 an additional EDI questionnaire was completed. Data were analyzed with SPSS by means of non-parametric tests. ResultsEDI symptoms were reported by 59.5%. Although fatigue was most frequently reported, fatigue scales did not significantly change from day 0 to 7 in (fatigued) EDI patients. Mood and cognition significantly ameliorated in both EDI and non-EDI patients. Cytokines remained stable at day 0 vs 7 except for a significant increase in IFN-γ. On day 0, IFN-γ concentration was positively correlated with a depressed mood in the whole cohort, and with mood and fatigue in the EDI group. Depressed mood positively whilst cognition negatively correlated with IFN-γ concentration on day 0 in the EDI subgroup reporting fatigue. No significant correlations between IL-6 nor TNF-α and symptom scores could be found. ConclusionIn our study EDI symptoms could not be objectified since EDI and non-EDI groups did not differ in terms of change in mood, cognition and fatigue between day 0 and 7 suggesting that symptom recrudescence could be a subjective experience. Although our results need to be interpreted cautiously, we found no clear correlation between studied serum cytokines concentrations and the occurrence of EDI symptoms.

Gastric Obstruction Secondary to an Unexplained Hyperinflation of an Intragastric Balloon

A 42-year-old-woman with medical history of cholecystectomy and obesity (1.63 m, 98 kg, body mass index 37 kg/m2) presented with suspicion of intestinal occlusion. Six months prior, an intragastric balloon (Orbera, Apollo Endosurgery, Austin, TX) had been placed to treat obesity, with a loss of 23 kg. For 2 months, the patient described progressive onset of abdominal pain, gastroesophageal reflux, and vomiting, with acute aggravation during the last 72 hours. Physical examination revealed a painful epigastric mass. Laboratory studies showed severe hypokalemia at 2.4 μmol/L. An abdominal computed tomography scan was performed, which showed the intragastric balloon with mixed content; liquid and gaseous; with a significant increase in volume to 1513 mL, contrasting to the 700 mL of water injected 6 months prior (Figures 1A and B). This hyperinflation seemed to be related to the unexplained appearance of the gas volume (about 800 mL) and caused gastric obstruction. Upper gastrointestinal endoscopy was performed, showing fluid stasis and allowing to empty and remove the balloon (Figures 1C–E). Some superficial ulcerations of the gastric mucosa were present. The patient was discharged 24 hours later. The prevalence of hyperinflation is estimated at 1% in large series. This complication may be caused by contamination of balloon by pathogens (fungal or bacterial). Appearance or recrudescence of symptoms, several months after balloon placement, should induce an abdominal x-ray to eliminate hyperinflation.

Varicella complicated by cellulitis and deep vein thrombosis

We report a 16-month-old girl with varicella complicated by cellulitis, invasive Group A Streptococcus (GAS) infection and deep vein thrombosis. She presented with varicella lesions, fever and a painful firm...

Selective Serotonin Reuptake Inhibitors and Operative Bleeding Risk: A Review of the Literature.

This study aimed to review the data on the effect of selective serotonin reuptake inhibitors (SSRIs) on bleeding during or after operative procedures and to offer guidelines for clinical management. Search of PubMed and MEDLINE for all articles in English from 1990-2016 with key words depression, antidepressants, bleeding, platelets, and operation. Studies were included if they reported information on bleeding complications during operative or childbirth procedures in patients taking antidepressants. Because of the limited number and heterogeneity of studies with respect to the range of operative procedures and definition of bleeding complications, a qualitative approach was taken to summarize results rather than abstracting and aggregating data. The weight of the evidence is that SSRI use increases the risk of bleeding complications during and immediately after surgery. However, given the limited data, we cannot estimate the risk for a given patient having a given procedure. Clinicians must consider the risk-to-benefit ratio of discontinuing an SSRI before an elective operative procedure. Discontinuing SSRI medications may result in discontinuation syndrome, symptom recrudescence, or relapse of depression, whereas continuing an SSRI during surgery exposes patients to significant bleeding risks. Antidepressant prescribers must be cognizant of and take responsibility for discussing this potential problem and considering different options. This issue must also be the responsibility of the doctor performing the procedure, but, frequently, it will be the prescribing physician who alerts the surgeon to the potential bleeding risk associated with SSRIs.

Review article: Role of magnesium sulphate in the management of Irukandji syndrome: A systematic review.

Signs of Irukandji syndrome (IS) suggest an underlying catecholamine storm with research demonstrating that Carukia barnesi venom causes a significant rise in adrenaline/noradrenaline serum levels. A systematic review was undertaken to ascertain the current evidence in treating IS with magnesium salts. A literature search was conducted using Scopus, Medline and ScienceDirect. Further articles were discarded via title description and/or abstract details. The remaining were read in full, and those identified as not having sufficient information regarding magnesium and patient outcomes were removed. Nine articles were identified. One article was a randomised controlled trial, which concluded that there appears to be no beneficial difference between those patients who received the magnesium sulphate (MgSO4 ) and those who received the placebo and recommended against the use of MgSO4 in IS. Of the remaining eight, one reported the failure of MgSO4 and the remaining seven were case series reporting varying success in its use. This systematic review found insufficient evidence to support any clear recommendation regarding the use of magnesium, but nor was there clear evidence to recommend against its use in IS. Two case series describe significant reduction in key symptoms and hypertension but are a non-randomised albeit prospective series with the limitations accompanying this. The reporting of recrudescence of symptoms with reduction of dose does suggest a dose-response relationship. The evidence for the use of MgSO4 is at best anecdotal, and further research is required to either confirm its benefit or confirm the randomised controlled trial.

The topographical model of multiple sclerosis: A dynamic visualization of disease course.

Relapses and progression contribute to multiple sclerosis (MS) disease course, but neither the relationship between them nor the spectrum of clinical heterogeneity has been fully characterized. A hypothesis-driven, biologically informed model could build on the clinical phenotypes to encompass the dynamic admixture of factors underlying MS disease course. In this medical hypothesis, we put forth a dynamic model of MS disease course that incorporates localization and other drivers of disability to propose a clinical manifestation framework that visualizes MS in a clinically individualized way. The topographical model encapsulates 5 factors (localization of relapses and causative lesions; relapse frequency, severity, and recovery; and progression rate), visualized utilizing dynamic 3-dimensional renderings. The central hypothesis is that, like symptom recrudescence in Uhthoff phenomenon and pseudoexacerbations, progression clinically recapitulates prior relapse symptoms and unmasks previously silent lesions, incrementally revealing underlying lesion topography. The model uses real-time simulation software to depict disease course archetypes and illuminate several well-described but poorly reconciled phenomena including the clinical/MRI paradox and prognostic significance of lesion location and burden on disease outcomes. Utilization of this model could allow for earlier and more clinically precise identification of progressive MS and predictive implications can be empirically tested.

Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening.

Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that >300,000 cases per annum are reported in USA alone. A total of 10%–20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with posttreatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved) that were screened are Library of Pharmacologically Active Compounds (LOPAC1280), the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150 unique compounds, which inhibited >90% of B. burgdorferi growth at a concentration of <25 µM. These 150 unique compounds comprise many safe antibiotics, chemical compounds, and also small molecules from plant sources. Of the 150 unique compounds, 101 compounds are FDA approved. We selected the top 20 FDA-approved molecules based on safety and potency and studied their minimum inhibitory concentration and minimum bactericidal concentration. The promising safe FDA-approved candidates that show low minimum inhibitory concentration and minimum bactericidal concentration values can be chosen as lead molecules for further advanced studies.

Short-term course and outcome of late-life depression

Introduction: Despite a plethora of prevalence studies, research on the course and outcome of late-life depression (LLD) have received little attention in India. Thus, the present study was undertaken to explore the course and outcome of LLD. Materials and Methods: A retrospective case note review of outpatient clinic was undertaken. Only those patients having completed the baseline Mini-Mental State Examination (MMSE) and Hamilton Rating Scale for Depression (HAMD) on the first visit were included in the study. Other relevant information was collected from the case notes. Results: Forty-eight patients fulfilled the selection criteria. The mean age of the sample was 67.3 years, with male preponderance (72%). There was no significant difference in demographic variables between genders, urban/rural domicile, and early/late onset depression (EOD/LOD). The EOD and LOD cases (cut-off age 60 years for the groups) were similar except that the former had more severe illness and longer duration of untreated illness at the baseline. Sixty-five percent patients (n = 31) attended at least one follow-up visit. The mean intervals of the first, second, and third follow-up visits were 3.7 ± 5.1 weeks, 5.1 ± 4.5 weeks, and 8.4 ± 5.7 weeks, and >50% improvement on HAMD was noted in 19%, 21% and 21% patients respectively. However, those who responded at earlier times either dropped out or showed recrudescence of symptoms. While those who responded at later times maintained the benefit. Conclusions: This is the first study to look at short-term outcome of LLD in India. The response rates were low and patients showed a fluctuating degree of improvement.

Multiple sclerosis symptom recrudescence at the end of the natalizumab dosing cycle.

This study was undertaken to determine how frequently patients receiving natalizumab for multiple sclerosis (MS) experience recrudescence of their MS symptoms at the end of the dosing cycle. One hundred consecutive MS patients receiving natalizumab completed a survey evaluating changes in symptoms during the natalizumab dosing cycle. Ninety-one patients also completed questionnaires at two time points: the first week after natalizumab infusion and the last week of the dosing cycle. These included the Multiple Sclerosis Quality of Life-54 (MSQOL-54), Fatigue Visual Analog Scale (VAS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-II (BDI-II). End of dosing interval (EDI) symptoms were reported as currently being experienced by 57% of respondents. An additional 10% reported that they previously experienced that phenomenon, but not currently, and 33% reported never experiencing this. In those with EDI symptoms, they began to occur a median of 21 days after infusion and improved again a median of 1 day after infusion. The most common symptoms reported were fatigue, weakness, walking impairment, and cognitive difficulties. No specific demographic or disease characteristics were associated with this phenomenon. In the subgroup with EDI symptoms, the MSQOL-54, Fatigue VAS, FSS, and BDI-II scores were all significantly worse in the last week of the dosing cycle when compared with the first week. No difference was seen in these scores between first and last week in the subgroup not experiencing symptom recrudescence. Recrudescence of fatigue, weakness, walking impairment, or cognitive difficulties at the end of the dosing cycle occurs in about two-thirds of MS patients receiving natalizumab.