Hematological parameters in patients with recurrent Aphthous Stomatitis: a systematic review and meta-analysis.

OBJECTIVES: Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological parameters seems to be considered as an etiologic factor. So, this meta-analysis and systematic review was aimed to examine the relationship between RAS and hematological parameters. METHODS: Relevant studies were found using online international databases including Scopus, Science direct, Web of science (ISI), PubMed, and Google Scholar search engine between 2000 and October 2023. The quality of all papers was determined by NOS checklist. Heterogeneity between the results of primary studies was evaluated with I-square index and publication bias was performed by Egger's test and funnel plots. Also, sensitivity analysis was done to check the effect of each of the primary studies on the overall estimate. Also, the statistical analyses were done using Stata software Ver. 11. RESULTS: By combining the results of primary studies, the standardized mean difference (SMD) of vitamin B12, ferritin, folic acid, hemoglobin, iron and zinc indices with a 95% confidence interval (CI) between the case (patients with RAS) and control (Healthy) groups were estimated -0.52(-0.89, -0.14), -0.20(-0.51, 0.11), -0.42(-0.95, 0.11), -0.58(-0.90, -0.27), 0.01(-0.12, 0.15), -0.33(-0.81, 0.14) respectively. The patients with vitamin B12, ferritin, folic acid, and iron deficiencies and reduced hemoglobin (Hb) level reported 2.93(2.28, 3.78), 2.50(1.48, 4.22), 1.51(0.53, 4.29), 1.46(0.70, 3.03), and 2.14(1.38, 3.32), times more susceptible to develop RAS than healthy individuals. CONCLUSION: The results of the meta-analysis indicated that the SMD of vitamin B12 serum and Hb levels in the case group was 52%. Our result have also showed that the odds ratio of vitamin B12, ferritin deficiencies, and decreased Hb level in case group was 2.93, 2.50, and 2.14 times more than healthy group.

Iron deficiency in pernicious anemia: Specific features of iron deficient patients and preliminary data on response to iron supplementation.

BACKGROUND & AIMS: While vitamin B12 (B12) deficiency is considered as the hallmark of pernicious anemia (PA), iron deficiency (ID) is also prevalent. Indeed, this auto immune gastritis is responsible for parietal cell atrophy and increase in gastric pH, leading to impaired iron absorption. We compared PA patients' features according to their iron status at PA diagnosis, and we assessed the iron status recovery after oral or intravenous iron supplementation. METHODS: We prospectively included patients presenting with a newly diagnosed PA in a tertiary referral hospital between November 2018 and October 2020. Iron status was assessed at PA diagnosis then regularly during a standardized follow-up. In case of ID, the decision of treatment with oral and/or intravenous iron supplementation was left to the clinician convenience. RESULTS: We included 28 patients with newly diagnosed PA. ID was observed in 21/28 (75.0%) patients: from the PA diagnosis in 13 patients, or during the follow-up in 8 patients. Iron deficient PA patients had higher plasma B12 (p = 0.04) and lower homocysteine levels (p = 0.04). Also, ID was independently associated with the 'APCA (anti-parietal cell antibodies) alone' immunological status (absence of anti-intrinsic factor antibodies) after adjustment for age, gender and B12 level (aOR 12.1 [1.1-141.8], p = 0.04). High level of APCA was associated with lower ferritin level. After 3 months of supplementation, 3/11 PA patients normalized the iron status with oral iron supplementation, versus 7/8 with intravenous iron supplementation (p = 0.02). CONCLUSION: The high frequency of iron deficiency in PA highlights the interest of regular assessment of iron status in this condition. ID was associated with a profile including APCA alone and less pronounced B12 deficiency. Intravenous iron supplementation seemed to be more efficient than an oral supplementation in these preliminary data.

Severe Hemolytic Anemia: Atypical Presentation of Cobalamin Deficiency.

Two severe cases of hemolytic anemia are described in different pediatric age groups, both linked to severe cobalamin deficiency from distinct causes. The first case refers to an exclusively breastfed infant with vitamin deficit secondary to maternal impaired absorption. Apart from the neurological deficits present at diagnosis, he also presented with infantile epileptic spasms syndrome a few months after treatment while having normal cobalamin serum levels. The second case refers to an adolescent with long-term inadequate intake. The occurrence of severe hemolytic anemia in cobalamin deficiency is exceptionally rare.

Nitrous oxide induced subacute combined degeneration of the spine cord: A case report.

RATIONALE: In recent years, recreational use of inhaled nitrous oxide (N2O) is on the increase among young people, accompanied by a corresponding rise in reports about its toxicity. Subacute combined degeneration of the spine cord (SCD) is the typical clinical picture of the nervous system disorder caused by N2O intoxication, as a result of metabolic disturbance of vitamin B12. PATIENT CONCERNS, DIAGNOSES, INTERVENTIONS AND OUTCOMES: We report a 28-year-old female of SCD due to prolonged use of N2O, presented with paresthesia and unsteady in walking progressing within 1 month. Symptoms gradually improved with the treatment of intramuscular injections of hydroxocobalamin combined with N2O abstinence, and the patient recovered completely with normal neurological examination after 4 months of follow-up. LESSONS: Clinicians should be aware of the clinical features and pathogenesis of SCD caused by N2O intoxication in order to lead effective treatment as soon as possible. Recreational N2O use should always be considered as an etiology when dealing with patients presented with myelopathy and/or neuropathy suspected of vitamin B12 deficiency.

Iron and Vitamin B12 Deficiency in Patients with Autoimmune Gastritis and Helicobacter pylori Gastritis: Results from a Prospective Multicenter Study.

INTRODUCTION: Iron and vitamin B12 deficiencies are common in patients with atrophic gastritis, but there are limited data on the prevalence of these deficiencies in different types of atrophic gastritis. METHODS: This multicenter, prospective study assessed micronutrient concentrations in histologically confirmed autoimmune gastritis (AIG, n = 45), Helicobacter pylori-related non-autoimmune gastritis (NAIG, n = 109), and control patients (n = 201). A multivariate analysis was performed to determine factors influencing those deficiencies. RESULTS: The median vitamin B12 concentration was significantly lower in AIG (367.5 pg/mL, Q1, Q3: 235.5, 524.5) than in NAIG (445.0 pg/mL, Q1, Q3: 355.0, 565.0, p = 0.001) and control patients (391.0 pg/mL, Q1, Q3: 323.5, 488.7, p = 0.001). Vitamin B12 deficiency was found in 13.3%, 1.5%, and 2.8% of AIG, NAIG, and control patients, respectively. Similarly, the median ferritin concentration was significantly lower in AIG (39.5 ng/mL, Q1, Q3: 15.4, 98.3 ng/mL) than in NAIG (80.5 ng/mL, Q1, Q3: 43.6, 133.9, p = 0.04) and control patients (66.5 ng/mL, Q1, Q3: 33.4, 119.8, p = 0.007). Iron deficiency and iron deficiency adjusted to CRP were present in 28.9% and 33.3% of AIG, 12.8% and 16.5% of NAIG, and 12.9% and 18.4% of controls, respectively. Multivariate analysis demonstrated that AIG patients had a higher risk of developing vitamin B12 deficiency (OR: 11.52 [2.85-57.64, p = 0.001]) and iron deficiency (OR: 2.92 [1.32-6.30, p = 0.007]) compared to control patients. Factors like age, sex, and H. pylori status did not affect the occurrence of vitamin B12 or iron deficiency. CONCLUSION: Iron and vitamin B12 deficiencies are more commonly observed in patients with AIG than in those with NAIG or control patients. Therefore, it is essential to screen for both iron and vitamin B12 deficiencies in AIG patients and include the treatment of micronutrient deficiencies in the management of atrophic gastritis patients.

Subacute Combined Degeneration of the Spinal Cord Induced by Nitrous Oxide Abuse: A Rare Patient Presentation to a Spine Surgery Clinic: Illustrative Case.

Subacute combined degeneration (SCD) of the spinal cord is a disease involving the lateral and posterior columns of the spinal cord that can manifest in patients with vitamin B12 deficiency. Nitrous oxide (N2O)-induced SCD of the spinal cord is a result of N2O interfering with the metabolism of vitamin B12 and results in nervous system demyelination. This is an infrequent complication of N2O anesthesia; however, cases are rising with recreational N2O use. This case report describes a patient with SCD of the spinal cord induced by recreational N2O abuse. The patient presented to a spine surgery clinic with a 3-week history of progressive global weakness and paresthesias. After a detailed history and physical examination, the diagnosis was made and supported by various tests and imaging findings. Despite marked neurologic deficits, the patient's symptoms improved markedly with therapy and vitamin B12 supplementation. Spine surgery clinicians may be confronted with these cases and should be aware of this atypical presentation of SCD. As in our case, patients may present with neurologic deficits of unclear etiology. Neurologic dysfunction may be irreversible; therefore, accurate diagnosis, medical treatment, and complete neurologic evaluation are of the utmost importance to prevent additional progression.

Not a Laughing Matter: When Nitrous Oxide Causes Functional Vitamin B12 Deficiency.

Subacute combined degeneration (SCD) is an acquired neurologic complication from prolonged vitamin B12 deficiency. As a result of dorsal and lateral spinal cord column degeneration, patients present with a range of neurological symptoms, including paresthesias, ataxia, and muscle weakness. Without prompt treatment, irreversible nerve damage occurs. Here we present a young man who developed progressive ascending paresthesias and lower extremity weakness after escalated nitrous oxide use. This case highlights the importance of considering SCD from nitrous oxide toxicity when patients present with progressive ataxia, paresthesia, and lower extremity weakness.

A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration.

Concurrent Cobalamin C and Plasminogen Deficiencies in a Patient with Chronic Thrombotic Microangiopathy.

BACKGROUND: Although most patients with atypical hemolytic uremic syndrome (aHUS) have variants in genes participating in alternative complement pathways, rare variants in non-complement pathway-related genes, including DGKE, INF2, MMACHC, PLG, and THBD, have also been described. CASE PRESENTATION: We report an 18-year-old male patient with renal biopsy-proven chronic thrombotic microangiopathy that raised suspicion of aHUS. Whole-exome sequencing revealed a novel pathogenic homozygous MMACHC c.484G>T (p.Gly162Trp) variant. Subsequently, clinical and laboratory findings confirmed cobalamin C (Cbl C) deficiency. Also, homozygous missense c.1112C>T PLG (p.Thr371Ile) variant was detected (it had been reported as a variant of unknown significance). However, the low serum plasminogen (PLG) activity proved the pathogenicity of c.1112C>T. Hence, the patient was diagnosed with concurrent Cbl C and PLG deficiencies. Segregation analysis revealed that the mother and father had the same heterozygous PLG and MMACHC variants. PLG variants have generally been described in aHUS patients concomitant with complement gene variants in the literature; therefore, the association between aHUS and PLG variants is controversial. The possible contribution of PLG deficiency to thrombotic microangiopathy was also discussed in this case. CONCLUSION: Non-complement-mediated aHUS is an exceptional disorder. A limited number of genes are involved in this entity. To our knowledge, this is the first aHUS patient diagnosed with both Cbl C and PLG deficiencies in the literature.

Evaluation of vitamin B12 levels among severe obese and obese adolescents.

Obesity, whose prevalence is increasing globally, is malnutrition that causes micro/macronutrients and vitamin deficiencies in adolescents. Vitamin B12 plays a prominent role in the body systems such as remethylation, deoxidation, and DNA synthesis. We aimed to examine the relationship between severe obese/obese adolescents and vitamin B12 levels in this study. This study was conducted as a case-control study consisting of 44 obese and 40 healthy control adolescents aged 11-17 years. Obesity was diagnosed using body mass index (BMI) charts defined by the World Health Organization according to age and gender. Vitamin B12 deficiency was found to be 34.1% in the patient obesity group, while it was 12.5% in the control group (p = 0.02). Homeostatic Model Assessment for Insulin Resistance levels were found to be 3.09 (1.9-5.29) higher in the severely obese group (p < 0.001). The median level of vitamin B12 in the obese group was 173 (122.5-220.7) in the severe obese group, 197 (146.5-302.7) in the obese group, and 252.5 (192.8-302) in the control group (p = 0.021). We found that obesity has a 1.6-fold decreasing effect on vitamin B12 levels. This study shows the clinician the importance of monitoring BMI and vitamin B12 levels in obese adolescents, given the effects of vitamin B12 on neuronal migration, metabolic reactions, and many systems in the body. Further researches are needed to investigate the pathophysiology and effect of low vitamin B12 levels in obese adolescents.

Evaluation of Neurodevelopmental Screening Test Scores in Children with Vitamin B12 Deficiency.

INTRODUCTION: Vitamin B12 deficiency can lead to hematological findings, neurological symptoms, and neurodevelopmental delay. The aim of this study was to investigate the impact of vitamin B12 deficiency on the neurodevelopment of children. MATERIALS AND METHODS: This study included 89 children aged between 6 and 24 months without any complaints; 44 of these were evaluated in the study group (serum vitamin B12 <300 pg/mL) and 45 in the control group (serum vitamin B12 ≥300 pg/mL). Denver Developmental Screening Test II (DDST-II) and the Social Communication Area Screening Test (SCAST) were evaluated in each participant. RESULTS: The mean vitamin B12 level in the study group was 206.11 ± 9.1 pg/mL, and in the control group, it was 540.65 ± 24.1 pg/mL. When DDST-II results were analyzed, the rate of getting suspicious and abnormal results in the study group was significantly higher compared with the control group (p = 0.001). The rate of the "risky" SCAST results of the cases was found to be statistically significantly higher in the study group than in the control group (p = 0.003). Vitamin B12 values of patients with suspicious or abnormal DDST-II results and with risky SCAST results were found to be statistically significantly lower than those with normal neurodevelopmental screening tests results (p = 0.001 and p = 0.001, respectively). CONCLUSION: Vitamin B12 deficiency can lead to neurodevelopmental delay in children, even in the absence of neurological and hematological symptoms or complaints, which highlights the importance of early detection and intervention of vitamin B12 deficiency.

Coexistence and clinical implications of anemia and depression in the elderly population. / Wspólwystepowanie i implikacje kliniczne anemii i depresji u osób w podeszlym wieku.

Anemia and depression are common in the elderly and they are important medical, social and economic problems for the world. Both disorders are associated with a lower quality of life, multimorbidity and a higher risk of death. The connections between anemia and depression have been reported, but the mechanism and clinical consequences of their co-existence are not fully understood. Several links can be found between anemia and depression in the elderly: common etiological factors, low socioeconomic status of patients, poor education and less physical activity. Both conditions are associated with the occurrence of the same pathological changes: age-related (especially with the presence of inflammation, oxidative stress, degenerative changes in organs and tissues), nutritional deficiencies (iron, vitamin B12, folic acid) and hormonal disorders (especially thyroid gland disorders, sex hormone deficiencies). Anemia and depression are not sufficiently diagnosed in the elderly and, as a result, are often left untreated. The diagnosis and treatments of these conditions in the elderly differ from those in other age groups. The study provides an overview of the literature regarding the co-existence of anemia and depression in elderly patients and clinical recommendations.

Neuropsychiatric disorders associated with recreational nitrous oxide use.

BACKGROUND: Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. PURPOSE: This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians' awareness of this public health problem. METHODS: We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. RESULTS: There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted "V" sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. CONCLUSION: Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.

Subacute combined degeneration of the spinal cord in a patient with nitrous oxide use and autoimmune atrophic gastritis.

Nitrous oxide is among the most common drugs used by adolescents and young adults, and its neuropsychiatric sequelae are severe but reversible with timely treatment. The causal mechanism relates to impaired metabolism of vitamin B12, which is necessary for the development and maintenance of the myelin sheath. Individuals most susceptible to neuropsychiatric manifestations are those with a secondary cause of vitamin B12 deficiency, including nutritional deficiency and impaired absorption, or an alternative cause of impaired metaboclism. We describe the case of a man in his thirties who developed subacute combined degeneration of the spinal cord and polyneuropathy in the setting of recreational nitrous oxide use and autoimmune atrophic gastritis. Our case highlights clinical pearls for diagnosis and treatment, differential diagnosis, common concomitant aetiologies and the importance of screening for substance use disorder and psychiatric comorbidities.

Methylmalonic acid, vitamin B12, and mortality risk in patients with preexisting coronary heart disease: a prospective cohort study.

BACKGROUND: The inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD. METHODS: The data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk. RESULTS: Overall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31-2.20) for all-cause mortality, and 2.00 (1.39-2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001). CONCLUSION: MMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.