Periods Of Relapse Research Articles

JAK inhibitors in systemic lupus erythematosus: Translating pathogenesis into therapy.

Systemic lupus erythematosus (SLE) is a complex multi-organ autoimmune disease marked by the production of autoantibodies against nuclear structures, formation of immune complexes, and chronic inflammation triggered by their tissular deposition. SLE is characterized by alternating periods of relapse and remission and each flare has the potential to cause new organ damage related to either the disease process or the medication toxicity. Despite remarkable progress across its multiple domains, SLE is still an area with many unmet needs, calling for innovative and practical solutions. The efforts of the drug development programme in lupus have led to considerable growth in the last decade, owing to the approval of belimumab, anifrolumab, and voclosporin. The increasing understanding of the pathogenesis of the disease has enabled the exploration of novel therapeutic strategies. New discoveries in the intricate cytokine kaleidoscope of lupus have made the concept of targeted therapy an attractive and promising research focus. JAK inhibitors are oral targeted therapies approved for a wide variety of diseases across the Rheumatology, Gastroenterology, Dermatology, and Haematology fields. Multiple JAKis are currently being investigated in SLE. This paper aims to summarize existing data coming from both clinical trials and case reports regarding the use of JAK inhibitors in SLE.

Papillary microcarcinoma in three generations of the first degree relatives

Family papillary microcarcinoma of the thyroid gland is observed in 3–10 % of patients with cancer from follicular epithelial cells. Diagnosis and treatment are controversial. Three patients from the same family of the first degree of kinship were operated for family papillary microcarcinoma of the thyroid gland in Voronezh Regional Clinical Hospital No. 1. Only the first patient complained of the neck deformity, her son and granddaughter had an asymptomatic course of the disease. Metastases to the lymph nodes of the neck and bilateral localization of the tumor were not revealed. In the third generation, multifocal tumor growth was diagnosed at the age of 19. All patients underwent thyroidectomy. In the first patient, the period of relapse–free follow-up after surgery was 18 years, in the second and third – 5 years. In the family form of papillary thyroid carcinoma, we consider active screening of relatives justified since the disease in the new generation may develop at a younger age and with the risk of multifocal thyroid damage even in microcarcinomas.

Functional movement disorder similar to Parkinson’s disease: a case report

IntroductionFunctional neurological disorder challenges conventional medical understanding, presenting neurological symptoms without organic explanations. This report delves into the intricate interplay between psychological and physical manifestations, emphasizing the importance of timely diagnosis and intervention and its impact on a patient’s mental health and quality of life.Case presentationA 40-year-old single Iranian man was admitted for the third time owing to exacerbation of mood symptoms, including depression, irritability, aggression, suicidal ideation, and movement and sensory problems. The patient’s symptoms began with psychological stressors and family conflict, leading to muscle weakness and tremors in the left hand. Over a year, muscle weakness escalated, leading to slow movement, motor impairment in the lower limbs, and reliance on a cane for walking. The patient still exhibited symptoms, such as a mask-like face, stooped walking posture, and a relative improvement of symptoms periodically. At first, the patient was suspected of Parkinson’s disease and was placed on levodopa and amantadine. However, the medication was discontinued owing to an unsatisfactory response and the lack of strong evidence in favor of neurological problems on frequent examinations and reviews. Despite multiple hospitalizations, the patient’s symptoms remained unresolved. Finally, after years of investigations, based on specialists’ recommendations, he was admitted to the psychosomatic ward for diagnostic evaluationele, and he was diagnosed with functional neurological disorder (psychogenic parkinsonism). He underwent pharmacotherapy, electroconvulsive therapy, and psychotherapy. He was discharged with partial improvement of symptoms, but showed periods of relapse and remission during the following years.ConclusionThis case study illuminates functional neurological disorder complexities, emphasizing the need for a holistic diagnostic approach. Timely interventions, including psychological support, can alleviate symptoms, reduce healthcare costs, and improve the overall prognosis. The report contributes to evolving functional neurological disorder understanding in psychiatry and neurology. The report underscores early recognition, advocating for comprehensive interventions involving psychiatric support, cognitive-behavioral therapy, and patient psychoeducation.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Initially Presenting as Septic Meningoencephalitis in a 16-Year-Old Male.

We describe a case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in a 16-year-old patient who initially presented with clinical features of septic meningoencephalitis. This case outlines the importance of considering a diagnosis of MOGAD in patients who fail to improve with appropriate antimicrobial therapy or show a positive clinical response to glucocorticoids (often used in treatment of meningococcal meningitis). We emphasise the importance of recognising that an infectious prodrome can precede MOGAD. A 16-year-old male was admitted with vomiting, fever, headache, photophobia and altered mental state. He was treated for meningoencephalitis with initial clinical improvement. Lumbar puncture findings were suggestive of viral meningoencephalitis. During admission the patient went through several periods of transient clinical and biochemical improvement, alternating with periods of symptomatic relapse. On day 17 of admission, he was transferred to a tertiary centre for suspected autoimmune disseminated meningoencephalitis (ADEM) and two days later, he suffered a catastrophic neurological decline with new dysarthria, dysphagia, aphasia, horizontal nystagmus and facial paralysis. He made a remarkable neurological recovery after commencing treatment with IV immunoglobulin, IV methylprednisolone and plasma exchange, with complete resolution of symptoms. MOGAD can run a variable course and present soon after a central nervous system infection, making the diagnosis more challenging. Nonetheless, patients can achieve a full neurological recovery with early recognition, diagnosis and treatment of this rare entity. Autoimmune encephalitis can be preceded by an infectious prodrome which makes the diagnosis more challenging.Autoimmune encephalitis can run a subacute and fluctuating course with transient periods of symptomatic improvement preceding a rapid neurological decline.Glucocorticoids often used in treatment of patients with meningococcal meningitis may lead to transient symptomatic improvement in patients with autoimmune encephalitis, masking the diagnosis.MRI findings of demyelination in autoimmune encephalitis may lag behind clinical symptoms by days to weeks.

Oral lichen planus – an oral potentially malignant disorder (OPMD) of the oral cavity

Introduction. Oral lichen planus is a chronic inflammatory disease of unknown etiology, characterized by recurrent lesions, presenting as reticular lesions, sometimes accompanied by atrophic, erosive, and/or ulcerative areas. Despite being one of the most common conditions affecting the oral mucosa, oral lichen planus remains an ailment with undefined etiology and unclear pathogenesis, imprecise management, and uncertain premalignant potential. Materials and methods. A narrative literature review study was conducted. A bibliographic search was carried out in databases such as PubMed, Hinari, SpringerLink, the National Center of Biotechnology Information, and Medline. Articles published from 1990 to 2023 were selected using various combinations of keywords: “oral lichen planus,” and “epidemiology,” “etiology,” “pathogenesis,” “symptoms,” “management,” “histopathology,” and “malignant transformation.” After processing the data from these databases, 475 full articles were found. The final bibliography comprised 50 relevant sources, considered representative of the materials published on the topic of this synthesis article. Results. Oral lichen planus is an inflammatory condition associated with T-cell-mediated immune dysfunction. Triggers include autoimmune responses to local antigens, microorganisms, and stress. The disease results from a complex interplay of host factors, lifestyle, and environmental factors leading to T-cell-mediated immune dysregulation. Diagnosis of oral lichen planus is based on clinical features (multiple, bilateral, symmetrically distributed lesions, occurring most commonly on the buccal mucosa, dorsal tongue surface, and gingiva), histopathological findings (predominantly lymphocytic bandlike infiltrate in the lamina propria, presence of apoptotic cells in the basal cell layer, absence of epithelial dysplasia), and immune-related changes (deposition of fibrinogen along the basement membrane zone, presence of granular fluorescent deposits containing IgA, IgG, and IgM in colloid bodies). Conclusions. Oral lichen planus is a chronic inflammatory condition mediated by T-cells in response to various extrinsic antigens, modified autoantigens, or superantigens, with periods of remission and relapse and the potential for malignant transformation. The etiology and pathogenesis of this condition are complex, diagnosis relies on clinical features, histopathological findings, and immunological data, patient treatment is symptomatic, and the potential for malignant transformation varies. Nevertheless, prospective studies with large sample sizes, adequate treatment duration, and long-term follow-up are needed.

Cognition as a parameter in monitoring the effect of multiple sclerosis relapse treatment: A prospective controlled study

BackgroundCognitive evaluation was considered to be very important in the relapse period, on the basis of the presence of isolated cognitive attacks and the necessity of monitoring the patient both physically and cognitively. Materials and methodsPeople with MS (pwMS) who were hospitalized during relapse were included in the study. All MS patients were evaluated by the neurologist with Expanded Disability Status Scale (EDSS), The 9 Hole Peg Test (9HPT) and the Timed 25-Foot Walk Test (T25-FWT). Additionally, all participants were examined cognitively with the Turkish version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Also, schedules were indicated as during relapse before the treatment (pre-treatment) and the first month after relapse (1-month follow-up). ResultsA total of 140 MS patients (mean age; 34.98±10.09, mean disease duration; 6.05±5.29 years) and 86 healthy controls (mean age; 36.94±10.83) were included to the present study. The mean EDSS scores in pre-treatment in MS patients was 2.74±1.14 and decreased significantly in the 1-month follow-up (1.74±1.24; p<0.001). The mean SDMT score was lower by 8.76 points in MS patients than in HCs) in pre-treatment and 7.66 points in 1-month follow-up (p<0.001). The mean SDMT scores of all participants increased with measurement time gradually (p<0.001). ConclusionIn this study, it was detected which cognitive domains were affected after relapse treatment and cognitive changes in pwMS during relapse and remission periods compared to the healthy controls. All three BICAMS test scores significantly increased in one-month follow-up than the pre-treatment period. The results showed that CVLT-II and BVMT-R scores improved more in pwMS than in HCs, and also SDMT scores of pwMS showed a trend of increase, but was not a significant improvement.

Impact of probiotics on inflammatory bowel disease - a systematic review

Introduction: Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory disease of the gastrointestinal tract that includes ulcerative colitis (UC) and Crohn's disease (CD). Both disease entities have many features in common, such as a basis of chronic inflammation, similar clinical symptoms as well as periods of remission and relapse. The difference between them lies in the lesions location. Treatment of IBD is primarily based on reducing inflammation and maintaining as long a remission time as possible. Increasing evidence is being attributed to the therapeutic potential of probiotics in IBD.&#x0D; Purpose: This review aims to present the preventive and therapeutic effects of probiotic use in IBS through an analysis of recent studies.&#x0D; Methods: A review of recent literature was conducted to investigate the impact of probiotic use on the treatment of IBD.&#x0D; Results: In studies, probiotics help induce and maintain remission in patients with mild to moderate ulcerative colitis, especially when used in combination therapy. In contrast, the usage of probiotics in Crohn's disease does not provide due benefit: it does not induce or prolong remission.&#x0D; Conclusions: In conclusion, the effect of probiotics on IBD is inconclusive. Some probiotics, particularly the VSL#3 probiotic blend, have shown decent effects on induction and remission in patients with mild to moderate UC. However, no therapeutic effect has been demonstrated in patients with Crohn's Disease. Therefore studies under more restrictive and standardized conditions are required.

P415 The influence of bowel urgency on the quality of life in individuals with ulcerative colitis

Abstract Background Ulcerative colitis (UC) is a persistent inflammatory condition marked by periods of relapse and remission, significantly impacting overall quality of life (QoL). Among the various symptoms influencing this quality, bowel urgency (BU) stands out as particularly distressing. BU manifests with profound negative implications on physical health, psychological well-being, and social aspects. Furthermore, bowel urgency (BU) is often omitted from the majority of disease activity scoring systems and is not consistently considered as a treatment outcome. Our objective was to explore the impact of BU on specific subgroups of QoL measures and its correlation with the partial Mayo score. Methods During this cross-sectional study, patients were categorized based on both BU and the concurrent partial Mayo score. The patients completed the Whoqol Bref questionnaire for assessing their QoL. Long-term outcomes, such as steroid use, hospitalization and colectomy, were evaluated at the 6-month follow-up. Results The study included 154 patients diagnosed with UC. When comparing BU with the partial Mayo score in terms of QoL, significant differences were found in the physical health domain (p&amp;lt;0.001), psychology domain (p&amp;lt;0.001), social relationship domain (p&amp;lt;0.014), and environmental domain (p&amp;lt;0.001). Among patients in remission according to the partial Mayo score (25/117, 21.3%), a notable proportion experienced bowel urgency (BU). BU was identified as a predictor for both steroid requirement (OR: 4.7; 95% CI [2.3-9.7], p&amp;lt;0.001) and hospitalization (OR: 4.7; 95% CI [2.3-9.7], p&amp;lt;0.001) during the six-month follow-up period. None of the patients required surgical intervention. Notably, even among patients in remission according to the partial Mayo score (25/117, 21.3%), bowel urgency (BU) persisted. Conclusion We noted that the existence of BU significantly impairs the quality of life for individuals with UC. Moreover, it is associated with an increased probability of future steroid use and hospitalization. Notably, some patients still experienced BU even while in remission. Further investigations are necessary to elucidate the mechanisms contributing to the persistence of these symptoms in these individuals.

ECCO Grant Untangling the gut phagosome dynamics of the relapse/remission cycle in ulcerative colitis

Abstract Background and Aims The course of ulcerative colitis (UC) is usually characterized by intertwining periods of remission and relapse. Most microbiome UC studies focus on the gut bacteriome. However, recent studies on animal models suggest that phage-mediated bacterial cell lysis may play a role in sustaining gut inflammation, proving the phageome (collection of bacteriophages) should not be ignored in this disease. Therefore, this project aims to: 1) characterize the gut phageome of patients with UC who suffer from frequent relapses, 2) compare temporal dynamics of gut the phageome between patients and healthy controls, 3) To model interactions between bacteriome, mycobiome, phageome on one hand, and lifestyle factors (diet, stress levels, medication) on the other 4) To infer host status (relapse versus remission of the disease) based on phageome composition, and using interactions inferred in Objective 3. Methods The cohort comprises 24 patients with UC (14 of whom suffered from relapse) and 10 healthy controls, with stool samples collected monthly for a year. Phageome profiling will be achieved via shotgun sequencing of phage genomes from the same stool samples. This dataset will be interrogated together with bacterial (16S rRNA) and fungal (ITS) amplicon data, which have just been generated. Available metadata include disease symptoms, diet, stress levels, work productivity, medication, and faecal calprotectin. Dynamic time-wrapping algorithms will be used to align time series of microbial members with similar temporal dynamics. Dynamic Bayesian Network modelling will infer interactions between microbiome members and predict future relapse. Anticipated Impact The phageome is the often neglected (“dark matter”) part of the microbiome, but has defining interactions with bacteria. We will expand knowledge on inter-species dynamics during relapse and remission cycles of UC. This will potentially lead to new microbiome-related relapse predictors, which may contribute to new prognostic tools in UC, and potentially inform therapeutic avenues.

P021 Higher TNFα and IL-6 mucosal levels in ulcerative colitis patients with more severe endoscopic activity

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterised by colonic mucosa inflammation. Its clinical course is marked by alternating periods of relapse and remission that impair patients' quality of life. In the last decades, novel therapies have shown to be effective for UC resulting in lower rates of colectomy. However, there is still a significant proportion of non-responding patients that change from one treatment to another, being exposed to its potential adverse events. Thus, predictive factors of response to available drugs are needed to tailor the best treatment strategy for each patient. The aim of our study was to measure TNFα and IL-6 levels in colonic biopsies from patients with UC with moderate to severe endoscopic activity. Methods A prospective, observational single-centre study was designed and it is currently on going. Adult UC patients with moderate to severe endoscopic activity (Mayo Endoscopic Score (MES) &amp;gt; 1) in a routine colonoscopy were included. Biopsies from inflamed (MES&amp;gt;1) and non-inflamed (MES=0) colon of each patient were homogenised and processed by using RIPA buffer and ultrasounds to obtain cell lysates. Human Luminex Discovery Assay (2 plex) was used for the simultaneous detection and quantitation of IL-6 and TNFα. Data are shown as percentage, median, interquartile range (IQR) and mean ± standard deviation (SD) as appropriate. Results So far, 21 patients were consecutively included (mean age 53.8 years (SD 17.0), 52.4% female). About 43% of patients had left-sided UC, 28.5% extensive UC and 28.5% proctitis. Regarding endoscopic activity, 61.9% of patients showed MES=2 and 38.1% were MES=3. Fourteen patients (66.6%) were bio-naïve and 7 (33.3%) had been exposed to anti-TNFα. IL-6 was detected in biopsies from colon with MES ≥ 2 of 18 (85.7%) patients, of which 10 (55.6%) patients also TNFα was found. Neither IL-6 nor TNFα were detected in biopsies from non-inflamed colon (p=0.00). Median IL-6 in inflamed colonic samples from patients with MES-2 was 25.6pg/ml (IQR 0.2-74.3) and 92.2pg/ml (IQR 16.9-314.3) in those with MES-3 (p=0.09). Median TNFα in inflamed colonic biopsies from patients with MES-2 was 0.0pg/ml (IQR 0.0-20.0) and 22.2pg/ml (IQR 0.0-34.3) in patients with MES-3 (p=0.12) (Figure 1). No differences were found in TNFα levels between anti-TNFα naïve patients and those patients previously exposed to anti-TNFα (p=0.96). Conclusion IL-6 and TNFα are elevated in inflamed colonic mucosa, particularly in those patients with more severe endoscopic activity, while they are not found in non-inflamed colonic mucosa. The correlation between cytokine levels and endoscopic severity suggests their potential as biomarkers for treatment response.

Cocaine reward and reinstatement in adolescent versus adult rodents.

Adolescence is a critical juncture when initiation of drug use intersects with profound developmental changes in the brain. Adolescent drug use increases the risk to develop substance use disorders (SUDs) later in life, but the mechanisms that confer this vulnerability are not understood. SUDs are defined by cycles of use, abstinence, and relapse. Intense craving during drug-free periods is often triggered by cues and environmental contexts associated with previous use. In contrast to our understanding of stimuli that elicit craving and relapse in adults, the behavioral processes that occur during periods of abstinence and relapse in adolescents are poorly understood. The current mini-review will summarize findings from preclinical rodent studies that used cocaine conditioned place preference and operant cocaine self-administration to examine subsequent effects on reward, relapse and incubation of craving.

Current Pharmacologic Options and Emerging Therapeutic Approaches for the Management of Ulcerative Colitis: A Narrative Review.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder (IBD) with periods of relapse and remission. Current advancements in clinical research have led to the development of more refined and effective medical therapy for UC. Traditional therapeutic agents such as 5-aminosalicylates (5-ASAs), sulfasalazine (SASP), corticosteroids, and immunomodulatory drugs have remained the gold standard for decades. However, their novel formulations and dosage regimens have changed their sequences in the medical management of UC. Several other novel drugs are in the final phases of clinical development or have recently received regulatory approval designed to target specific mechanisms involved in the inflammatory cascade for UC. This narrative review sought to provide a comprehensive knowledge of the potential benefits of standard and emerging therapies, including novel formulations, new chemical entities, and novel therapeutic approaches in managing UC. Keywords: Ulcerative colitis, 5- Aminosalicylic acid, sulfasalazine, corticosteroids, biologics, immunomodulators, novel formulations.

RECURRENCE OF OVARIAN CANCER: POSSIBLE CAUSES, EARLY DETECTION

Relevance: Early detection of ovarian cancer relapses and their treatment is among the most difficult in practical oncogynecology. Early diagnosis of ovarian cancer recurrence increases the effectiveness of treatment and gives a more favorable survival prognosis.&#x0D; The study aimed to show the possible cause of ovarian cancer recurrence and methods for early detection of relapses.&#x0D; Materials and methods: We systematically analyzed 31 cases of recurrent ovarian cancer treated at the Zhambyl Regional Center of Oncology and Surgery (Kazakhstan) in 2021-2022. We divided them by age, stage, period of relapse, type of histology, tumor grade, sites of recurrence, and symptoms of recurrence.&#x0D; Results: Ovarian cancer is most often detected in the late stages since, in the early stages, the disease is asymptomatic. Patients with advanced stages showed more relapses and distant metastases. Most ovarian cancer and this disease’s relapses are detected at 50-70 years old. The late stages give more distant and multiple relapses than the early stages and in terms of earlier. Moreover, according to histology results, mesenchymal tumors are more significant than epithelial and G3.&#x0D; Conclusion: The recurrence of ovarian cancer is an aggressively occurring disease. Based on the analysis work carried out, more than 70% of patients with recurrent ovarian cancer were aged 50-70 years, and the recurrence rate was higher at later stages (St III) or with a low-grade form of the tumor. All patients received platinum-based combination therapy. Targeted therapy (Bevacizumab) was administered in generalization of the process. More than 20% of all patients are resistant to platinum, whose relapse occurred before six months; the rest are sensitive to platinum with a later relapse. Based on everything, there is an increase in distant and multiple relapses in the late stages of ovarian cancer. This indicates the need to introduce screening programs based on cancer markers (CA-125) and diagnostic instrumental examinations (MRI/CT) to detect ovarian cancer in the early stages. After the treatment, all patients with this disease should be under active supervision, especially patients with low-grade tumors and in late stages.

RECURRENCE OF OVARIAN CANCER:&#x0D; POSSIBLE CAUSES, EARLY DETECTION

Relevance: Early detection of ovarian cancer relapses and their treatment is among the most difficult in practical oncogynecology.&#x0D; Early diagnosis of ovarian cancer recurrence increases the effectiveness of treatment and gives a more favorable survival prognosis.&#x0D; The study aimed to show the possible cause of ovarian cancer recurrence and methods for early detection of relapses.&#x0D; Materials and methods: We systematically analyzed 31 cases of recurrent ovarian cancer treated at the Zhambyl Regional Center&#x0D; of Oncology and Surgery (Kazakhstan) in 2021-2022. We divided them by age, stage, period of relapse, type of histology, tumor grade,&#x0D; sites of recurrence, and symptoms of recurrence.&#x0D; Results: Ovarian cancer is most often detected in the late stages since, in the early stages, the disease is asymptomatic. Patients with&#x0D; advanced stages showed more relapses and distant metastases. Most ovarian cancer and this disease’s relapses are detected at 50-70&#x0D; years old. The late stages give more distant and multiple relapses than the early stages and in terms of earlier. Moreover, according to&#x0D; histology results, mesenchymal tumors are more significant than epithelial and G3.&#x0D; Conclusion: The recurrence of ovarian cancer is an aggressively occurring disease. Based on the analysis work carried out, more&#x0D; than 70% of patients with recurrent ovarian cancer were aged 50-70 years, and the recurrence rate was higher at later stages (St III)&#x0D; or with a low-grade form of the tumor. All patients received platinum-based combination therapy. Targeted therapy (Bevacizumab) was&#x0D; administered in generalization of the process. More than 20% of all patients are resistant to platinum, whose relapse occurred before six&#x0D; months; the rest are sensitive to platinum with a later relapse. Based on everything, there is an increase in distant and multiple relapses&#x0D; in the late stages of ovarian cancer. This indicates the need to introduce screening programs based on cancer markers (CA-125) and&#x0D; diagnostic instrumental examinations (MRI/CT) to detect ovarian cancer in the early stages. After the treatment, all patients with this&#x0D; disease should be under active supervision, especially patients with low-grade tumors and in late stages.

Multiple sclerosis: Unveiling current immunogenetic factors and their role in etiopathogenesis and clinical aspects

Multiple sclerosis (MS) is the most common cause of neurological deficits among the young population. While the prevalence of MS is increasing worldwide, the incidence rate of MS is also undergoing a similar trend in Lithuania. Globally, women are twice as likely to be affected by MS as men. Unilateral optic neuritis is the most common initial symptom of MS. The signs and symptoms of MS vary greatly from patient to patient and depend on the location and severity of the nerve fiber damage in the central nervous system. Most people with MS have a relapsing-remitting disease course or clinically isolated syndrome. They experience periods of new symptoms or relapses that develop over days or weeks and usually resolve partially or completely. These relapses are followed by quiet periods of disease remission that may last months or even years. Data accumulated over the years suggest a complex interplay between environment and immunogenetics (strong associations with a large number of immune and genetic markers), and an increasingly convincing role of an underlying degenerative process leading to demyelination (in both white and gray matter), axonal and neurosynaptic damage, and a persistent innate inflammatory response, with T-cell-mediated autoimmunity appearing to play a diminishing role as the MS develops and progresses. In the absence of clinically proven, accurate, and reliable biomarkers, the disease can take a progressive course in case of late treatment, signifying the critical need for early diagnosis. This article therefore discusses the etiopathogenesis and clinical aspects of MS.

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence. For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5-7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470. Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2-53·9) in 1470 patients treated without primaquine, 19·3% (16·9-21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0-9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17-0·27; p<0·0001) and high-dose primaquine (0·10, 0·08-0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5-7 were reported by 4·0% (95% CI 0·0-8·7) of 893 patients treated without primaquine, 6·2% (0·5-12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8-10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7-16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias. Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms. Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.

Effect of vitamin D deficiency on postorthodontic relapse: An animal study.

This study aims to evaluate the effect of vitamin D deficiency (VDD) on orthodontic tooth movement (OTM), retention, and relapse and to assess the effect of systemic administration of vitamin D (VD) in a rat model. A total of 32 male Wistar rats were divided into two groups, a control group of 11 rats and an experimental group of 21 rats with VDD, after enhancement using a custom diet. Of the VDD group, 11 rats were supplemented with systemic vitamin D3 and categorized as vitamin (VD supplement [VDS]) groups. The VDS group received 40,000 IU/kg via intramuscular injection on Days 1 and 15 of the orthodontic treatment period. A modified orthodontic appliance was fitted to apply 0.5 N of force to move the maxillary right first molars mesially for 14 days, followed by retention and relapse periods for 7 days. Space created during OTM was measured and reassessed after the retention and relapse periods. The relapse ratio was estimated, and histomorphometric analysis was performed to assess the number of osteoblasts, osteoclast bone cells, and bone area. A significant increase in the relapse ratio and a reduction in osteoblast cells and bone area were observed in the VDD group. By contrast, the amount of tooth movement was significantly higher together with osteoblast cells and bone marrow in VDS with a significant reduction in relapse ratio. VDD was associated with a significant reduction in osteoblast cell count and total bone area in addition to a significant increase in relapse ratio. Routine screening of VD may be beneficial before commencing orthodontic treatment.

Intensive Counseling of Smokers for Nicotine Addiction Cessation and Health Benefits of Smoking Cessation

Abstract Smoking is a chronic disease with a recurring character, one of the oldest habits on the globe but also a problem of modern society, which kills more than 8 million people each year. More than 50% of those deaths are the result of direct tobacco use, while around 1.2 million are the result of non-smokers being exposed to second-hand smoke(1). Nicotine addiction must be seen as a chronic disease, with numerous periods of relapse and remission, and is mandatory that the clinician must treat it properly. Smoking cessation is of critical importance to public health, various studies indicate that smoking is a major risk factor for a variety of serious health conditions, including cancer, heart disease, stroke, and chronic obstructive pulmonary disease (COPD). The risk of developing these conditions is directly related to the amount and the duration of smoking and is higher for those who start smoking at a younger age. While counseling is likely to be successful in helping individuals quit smoking, there are also other methods to reach the goal, including medication, nicotine replacement therapy, and lifestyle changes. However, these methods may not be as effective as counseling in helping individuals quit smoking. Otherwise, other methods, such as reducing the amount of smoking or switching to a less harmful form of tobacco, may reduce the risk of developing some of the conditions associated with smoking, but they do not reduce the risk to the same level as quitting smoking.

Idiopathic autoimmune encephalitis with a recurrent course. A case report

We presented a clinical case of idiopathic autoimmune brainstem encephalitis in a 12-year-old female patient. At the onset of the disease, which developed after a respiratory infection, the clinical picture was accompanied by oculomotor and bulbar syndromes. The diagnosis of Bickerstaff brainstem encephalitis was made based on clinical diagnostic criteria and the positive effect of the course of intravenous immunoglobulin therapy. During 3 years of follow-up, there were periods of relapse of the disease, during which symptoms not typical for Bickerstaff stem encephalitis appeared. Against the background of long-term immunosuppressive therapy, there was a long-term remission of about 2 years. The clinical picture, the presence of relapses, the data of additional methods forced to reconsider the diagnosis in favor of idiopathic autoimmune brainstem encephalitis.

Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation: a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

BackgroundThe World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance.MethodsUncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/µL and age-stratified values) using estimates derived from the measured WBC value as reference.ResultsEighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (× 1000 cells/µL) in age groups < 1, 1–4, 5–14 and ≥ 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/µL resulted in parasite density underestimation by a median (IQR) of 26% (4–41%) in infants < 1 year old but an overestimation by 50% (16–91%) in adults aged ≥ 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve precision of parasitaemia estimation. Imprecision of parasite clearance estimates was only affected by the within-patient WBC variability over time, and remained < 10% for 79% of patients.ConclusionsUsing an assumed WBC value for parasite density estimation from a thick smear may lead to underdiagnosis of hyperparasitaemia and could adversely affect clinical management; but does not result in clinically consequential inaccuracies in the estimation of the prevalence of prolonged parasite clearance and artemisinin resistance.