Adequate Vitamin Supplementation Research Articles

Osteoporosis in Rheumatology.

Osteoporosis is a common diagnosis and comorbidity observed in patients with rheumatic diseases. It is frequently associated with conditions such as rheumatoid arthritis, spondyloarthropathy, systemic lupus erythematosus, and other autoimmune rheumatic diseases. The incidence of osteoporosis is influenced by factors such as uncontrolled disease, prolonged and higher doses of steroid use, immobility, advanced age, and postmenopausal status. Achieving good control of the underlying disease, minimizing or avoiding the use of steroids for extended periods, and ensuring adequate supplementation of vitamin D and calcium are crucial in reducing the incidence of osteoporosis. Regular screening and appropriate management of osteoporosis can significantly decrease the associated morbidity and mortality.

Performance and bone characteristics of broilers fed diets supplemented with vitamin A at different concentrations.

This work evaluated the influence of vitamin A on performance, organ weight, and bone and skin characteristics in broilers (Cobb 500) at 21 and 42 days of age. A total of 1920 chickens were distributed in a randomised design, considering six vitamin A supplementation levels (0, 6000, 16,000, 26,000, 36,000, and 46,000 IU kg-1 ), with 16 replicates and 20 chickens per experimental unit, established due to rising the range of vitamin levels observed in the literature to evaluate the effect of vitamin A on broilers. At 22 days, half of the replicates from each treatment continued receiving the initial diet, and the other eightrepetitions received diets without vitamin A (0 IU kg-1 ) until 42 days. The level of vitamin A influenced feed intake (FI) and body weight gain (BWG) until 21 days for all treatments. Broilers at 21 days of age had a more significant BWG at a vitamin A supplementation level of 28,209 IU kg-1 . At 42 days, vitamin A influenced the BWG and FI of broilers at treatments that were not supplemented after 21 days. Treatments supplemented up to 42 days showed quadratic responses to vitamin A for BWG, FI, and feed conversion. The vitamin A levels influenced the relative weights of the small intestine, pancreas, gizzard, abdominal fat, Seedor index, and breaking strength at 42 days, where the adequate supplementation of vitamin A improved these characteristics in broilers. Vitamin A supplementation from 22 to 42 days old did not affect broiler performance. An increased BWG was obtained when vitamin A supplementation occurred until 42 days, with supplementation of 29,375 IU kg-1 and a lower response of feed conversion with the addition of 27,775 IU kg-1 .

Decreased vitamin D levels in the pediatric population after COVID-19 lockdown

BackgroudSARS-Cov2 infection began to spread worldwide since December 2019; on March 2020, the World Health Organization characterized its related disease, named COVID-19, as a pandemic. In Italy, to contain the spread of infection a severe lockdown in the spring 2020 was instituted. Other less severe restrictions were imposed in the winter 2020–2021 and in the spring 2021. The containment measures caused a series of consequences for the population and, in particular, for children and adolescents that presented psychophysical problems.The aim of this manuscript is to investigate the serum levels of vitamin D in children and adolescents before, during and after the lockdown consequent to COVID-19 pandemic.MethodsThis is a retrospective cross-sectional study, including all children and adolescents between 1 to 18 years referring to the Pediatric Endocrinology Service of the University Hospital of Verona, Italy, between January 2019 and December 2021. All patients affected by clinical conditions that involve vitamin D metabolism or assuming vitamin D supplementation were excluded.ResultsIn total, 491 children (36.7% males and 63.3% females) were enrolled in this study. The vitamin D levels decreased over time: 28.3 ± 10.2 ng/mL in 2019; 28.2 ± 11.4 ng/mL in 2020 and 24.9 ± 10.1 ng/mL in 2021 (p < 0.05). The vitamin D levels are significant higher in summer and in autumn in comparison with the levels of winter and spring, regardless of the examined years.ConclusionsThe measures adopted to contain the COVID-19 pandemic led to a reduction of serum levels of vitamin D in pediatric population, probably due to the reduced solar exposure. This may have severe consequences on the bone metabolism of those children who did not present optimal vitamin D levels even before the lockdown. Therefore, an adequate supplementation of vitamin D is necessary from the end of fall to the beginning of spring (November–April) in all children and adolescents living in Northern Italy.

Ischaemic stroke with multi-focal venous and arterial thrombosis due to hyperhomocysteinemia: anabolic androgenic steroid use and MTHFR c.667 C > T variant – a case report

BackgroundSeverely elevated serum homocysteine is a rare cause of ischaemic stroke and extra-cranial arterial and venous thrombosis. Several factors can lead to mild elevation of homocysteine including dietary folate and B12 deficiency, and genetic variants of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The use of Anabolic androgenic steroid (AAS) is under-reported, but increasingly linked to ischaemic stroke and can raise homocysteine levels.Case ReportWe present a case of a man in his 40s with a large left middle cerebral artery (MCA) territory ischaemic stroke and combined multifocal, extracranial venous, and arterial thrombosis. His past medical history was significant for Crohn’s disease and covert use of AAS. A young stroke screen was negative except for a severely elevated total homocysteine concentration, folate and B12 deficiencies. Further tests revealed he was homozygous for the methylenetetrahydrofolate reductase enzyme thermolabile variant (MTHFR c.667 C > T). The etiology of this stroke was a hypercoagulable state induced by raised plasma homocysteine. Raised homocysteine in this case was likely multifactorial and related to chronic AAS use in combination with the homozygous MTHFR c.677 C > T thermolabile variant, folate deficiency and, vitamin B12 deficiency.ConclusionIn summary, hyperhomocysteinemia is an important potential cause of ischaemic stroke and may result from genetic, dietary, and social factors. Anabolic androgenic steroid use is an important risk factor for clinicians to consider, particularly in cases of young stroke with elevated serum homocysteine. Testing for MFTHR variants in stroke patients with raised homocysteine may be useful to guide secondary stroke prevention through adequate vitamin supplementation. Further studies looking into primary and secondary stroke prevention in the high-risk MTHFR variant cohort are necessary.

Dietary Intake and Genetic Background Influence Vitamin Needs during Pregnancy.

Numerous approaches demonstrate how nutritional intake can be sufficient to ensure the necessary supply of vitamins. However, it is evident that not all vitamins are contained in all foods, so it is necessary either to combine different food groups or to use a vitamin supplement to be well-fed. During pregnancy, deficiencies are often exacerbated due to increased energy and nutritional demands, causing adverse outcomes in mother and child. Micronutrient supplementation could lead to optimal pregnancy outcomes being essential for proper metabolic activities that are involved in tissue growth and functioning in the developing fetus. In order to establish adequate vitamin supplementation, various conditions should be considered, such as metabolism, nutrition and genetic elements. This review accurately evaluated vitamin requirements and possible toxic effects during pregnancy. Much attention was given to investigate the mechanisms of cell response and risk assessment of practical applications to improve quality of life. Importantly, genetic studies suggest that common allelic variants and polymorphisms may play an important role in vitamin metabolism during pregnancy. Changes in gene expression of different proteins involved in micronutrients’ metabolism may influence the physiological needs of the pregnant woman.

Vitamin D Deficiency, Osteoporosis and Effect on Autoimmune Diseases and Hematopoiesis: A Review.

Vitamin D (VD) is essential for bone homeostasis, but it is also involved in pleiotropic effects on various organs and tissues. In adults, VD deficiency can cause or exacerbate osteoporosis and induce osteomalacia. However, every tissue and cell in the body has a VD receptor, including the brain, heart, stomach, pancreas, skin, gonads, and immune cells, and a deficiency may modify the function of these organs. Thus, the wide-ranging actions of VD help to explain why a reduction in VD amount has been correlated with numerous chronic diseases. In fact, VD deficiency increases the risk of osteoporosis and several other diseases and complications characterized by impaired bone metabolisms, such as autoimmune diseases, inflammatory bowel diseases, allergy, endocrinological diseases, hematological malignancies, and bone marrow transplantation. This review aims to investigate the link between VD deficiency, osteoporosis, and its concomitant diseases. Further epidemiological and mechanistic studies are necessary in order to ascertain the real role of hypovitaminosis in causing the reported diseases; however, adequate vitamin supplementation and restoration of metabolic normality could be useful for better management of these pathologies.

Multiple Insufficiency Fractures Related to Vitamin D Deficiency in a Young Lady

A young girl presented with increasing bilateral groin pain for the past 3 months (visual analog scale score 8/10) and inability to weight bear for the last 1 month. Plain X-rays showed bilateral fractures of the femoral neck, extending in the intertrochanteric and subtrochanteric regions on both sides. Laboratory investigations revealed severe Vitamin D deficiency with secondary hyperparathyroidism. The insufficiency fractures are subtypes of stress fractures with decreased mineralization and weakened zone calcification of the bone. Clinical awareness about the insufficiency fractures and a high index of suspicion is required to make an early diagnosis. The majority of insufficiency fractures due to Vitamin D deficiency can be managed conservatively with timely diagnosis, adequate supplementation of Vitamin D, and calcium.

Are Solid Organ Transplant Patients the New Unsuspecting Osteonecrosis Victims?

Purpose Bone disease is common in organ transplant recipients. Immunosuppressive regimens with glucocorticoids have shown to improve patient and graft survival rates following transplantation. As survival rates have improved, so has awareness of long-term complications of transplantation. Pre-existing bone disease combined with immunosuppressive agents serve as primary risk factors for osteoporosis and fractures. Recently, supplementation of the traditional medical regimen with bisphosphonates and denosumab has become necessary to counteract the adverse effects of long-term steroid use. Although it does enhance bone mineral density, bisphosphonate therapy has failed to result in a significant decrease in the fracture rate. We propose an individualized approach aimed at managing bone loss and fracture rates in transplant patients. Methods This study, an evidence-based review, aims to provide a better understanding of the risk factors associated with osteoporosis, incorporating the bone effects of glucocorticoids and antiresorptive medications. We first developed several specific research questions, assorted questions by category, devised an approach to identify appropriate sources in the organ transplant literature, and selected a list of possible articles to review. We completed an initial review to limit the set to 55 articles and then conducted a thorough review, including the current guidelines provided by the American College of Rheumatology for management of bone disease, and the American Association of Oral and Maxillofacial Surgeons for prevention and treatment of osteonecrosis of the jaw. Furthermore, we have summarized our findings to synthesize an improved patient-centered protocol to help limit the indiscriminate use of antiresorptive medications, and strategies for appropriate dental management pre- and post-transplantation. Results Bisphosphonates and other antiresorptive medications reduce excessive turnover of bone, resulting in enhanced bone mineral density (BMD). These medications have become part of the typical treatment regimen for patients in the post-transplantation period to counteract the negative effects of high-dose steroids, despite the lack of evidence that preservation in BMD translates to decreased fracture risk. Although the risk of medication-related osteonecrosis of the jaw (MRONJ) is low, the diagnosis and the sequelae can be devastating and difficult to treat in advanced stages. Conclusions The best method of prevention lies in an evidence-based multidisciplinary approach to ensure that the solid organ transplant patients administered these medications do not become the new MRONJ victims. This should include, but not be limited to, evaluation by a dental professional familiar with antiresorptive medications and bisphosphonates and their adverse effects on the craniofacial skeletal tissues, minimizing steroid use, adequate supplementation of vitamin D in patients with vitamin D deficiency, and careful targeted use of bisphosphonates and denosumab only in those patients where it is mandatory. Although the prevalence of MRONJ among transplant recipients remains to be studied, it behooves providers to help protect these patients from unnecessary harm.

0725 Effect of 2,4-thiazolidinedione treatment in the inflammatory response to induced subclinical mastitis in dairy goats receiving adequate vitamin supplementation

0725 Effect of 2,4-thiazolidinedione treatment in the inflammatory response to induced subclinical mastitis in dairy goats receiving adequate vitamin supplementation

Vitamin blood concentration and vitamin supplementation in bottlenose dolphins (Tursiops truncatus) in European facilities.

BackgroundAs fish eaters bottlenose dolphins (Tursiops truncatus) in human care need to receive daily vitamin supplementation, because whole thawed fish lacks certain vitamins. However, the exact concentration of supplementation has not been established and is a matter of discussion. To ensure adequate vitamin supplementation in pets, vitamin blood concentrations are measured. This is not a common practice in dolphins. The objective of the present study was to collect information about vitamin supplementation in bottlenose dolphins and on vitamin blood concentrations of healthy animals in European facilities. In addition, these results were compared with blood levels of wild animals. Conclusions on how to provide bottlenose dolphins in human care with an effective vitamin supplementation will then be drawn.Initially, fish-handling techniques and vitamin supplementation were evaluated by questionnaire, which was sent to 25 European facilities that house bottlenose dolphins. Secondly, blood samples from 57 dolphins living in 10 facilities were taken and sent by mail to a reference laboratory. They were analysed for retinol, thiamine pyrophosphate, cobalamin, calcidiol and tocopherol. The blood concentrations were then correlated with vitamin supplementation, fish handling techniques and pre-existing blood concentrations of free-ranging dolphins. Finally, the data was subjected to a standard analysis of variance techniques (ANOVA) and a linear model analysis.ResultsFish was mainly thawed in a refrigerator. Further, the 95 % confidence interval for retinol blood concentrations was 0.048 to 0.059 mg/l and for tocopherol 17.95 to 20.76 mg/l. These concentrations were 27 and 53 %, respectively, higher than those found in free-ranging animals. In contrast, calcidiol concentrations (143.9–174.7 ng/ml) of the dolphins in human care were lower than in blood found for free-ranging animals. Regarding thiamine pyrophosphate and cobalamin, concentrations ranged between 0.42 and 0.55 mg/l and 175.55 and 275.22 pg/ml respectively. No reference concentrations for free-ranging Tursiops truncatus were found.ConclusionsThese findings suggest an over-supplementation of retinol (vitamin A) and tocopherol (vitamin E) in bottlenose dolphins (Tursiops truncatus) housed in human care. Therefore, vitamin A supplementation should not exceed 50,000 IU per animal per day and vitamin E supplementation should be around 100 IU per kg fed fish per day.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0818-1) contains supplementary material, which is available to authorized users.

Vitamin D profile of patients with spinal cord injury and post-stroke hemiplegia: All in the same boat.

Patients with spinal cord injury (SCI) and hemiplegia are at risk of fractures partly due to decreased bone mineral density with relation to the low levels of vitamin D. The objective of this study is to evaluate the vitamin D profile of patients with SCI and post-stroke hemiplegia. 25(OH)D levels of patients with SCI and hemiplegia were obtained from the electronic medical record database and compared with age- and sex-matched non-disabled controls. Furthermore, the effect of Functional Ambulation Category (FAC), American Spinal Injury Association (ASIA) level and Brunnstrom's recovery stage, on vitamin D insufficiency, was studied. The study sample consisted of 173 individuals (118 patients and 55 controls). Vitamin D levels and sufficiency rates of the neurologically disabled patients was significantly lower than that of controls (p= 0.000 and p= 0.000, respectively). However, there was no difference between patients with SCI and hemiplegia regarding the 25(OH)D levels and vitamin D insufficiency (p= 0.303 and p= 0.952, respectively). There were no statistically significant differences in vitamin D status by American Spinal Injury Association (ASIA) level and Brunnstrom's score. However, regression analysis revealed that vitamin D insufficiency rate of non-functionally ambulatory (FAC = 0-2) patients was higher than that of functionally ambulatory (FAC = 3-5) ones (p= 0.044). Vitamin D status of patients with neurological disabilities was lower than that of controls. Non-functionally ambulatory patients had higher vitamin D insufficiency rate than functionally ambulatory patients. Preventative measures including adequate supplementation of vitamin D should be directed to neurologically disabled subjects, particularly those with non-functional ambulation.

Evaluating the Frequency of Vitamin D Deficiency in the Pediatric Age Group and Identifying the Biochemical Predictors Associated with Vitamin D Deficiency

Objective: To determine the frequency of Vitamin D deficiency in the Peadritic population Pakistan. To identify the biochemical predictors associated with Vitamin D deficiency. Method: A cross sectional study was conducted in an urban tertiary care hospital, on, infants and children up to the age of 15 years who were seen in inpatient and in the outpatient department. Serum Vitamin D levels were measured along with a biochemical profile which included Serum Calcium, Serum Phosphate, Serum Alkaline Phosphate and Serum Parathyroid Hormone. The results were then analyzed using SPSS 20. Results: Out of the 293 samples included in the study, frequency of children with Vitamin D deficiency was found out to be 77% (n = 227 ). 48% (N = 142) of the total sample had severe deficiency although showed no clinical signs of Rickets. Patients with Vitamin D deficiencies were also found out to have secondary hyperparathyroidism and hypophosphatemia although serum calcium levels were normal. Conclusion: Through our study we found out that Majority of the children coming to Ziauddin were deficient in Serum Vitamin D. We suggest that adequate supplementation of Vitamin D should be started from an early age to prevent clinical effects of the deficiency in the long term.

Autism spectrum disorder and low vitamin D at birth: a sibling control study.

BackgroundInsufficient vitamin D activity has attracted increasing interest as a possible underlying risk factor in disorders of the central nervous system, including autism.MethodsIn this study, 25-hydroxyvitamin D (25(OH)D) was analysed in 58 Sweden-born sibling pairs, in which one child had autism spectrum disorder (ASD) and the other did not. The study group consisted of two representative samples; 47 Gothenburg sibling pairs with mixed ethnicities and 11 Stockholm sibling pairs with Somali background. 25(OH)D levels were analysed in the stored dried blood spots taken in the neonatal period for metabolic screening.ResultsThe collapsed group of children with ASD had significantly lower vitamin D levels (M = 24.0 nM, SD = 19.6) as compared with their siblings (M = 31.9 nM, SD = 27.7), according to a paired samples t-test (P = 0.013). The difference was - most likely - not only accounted for by a difference in season of birth between ASD and non-ASD siblings since the mean 25(OH)D levels differed with similar effect size between the sibling pairs born during winter and summer, respectively. All children with African/Middle East background, both the children with ASD and their non-ASD siblings, had vitamin D deficiency.ConclusionsThe findings suggest that low prenatal vitamin D may act as a risk factor for ASD, however, there is a need for replication with larger samples. Future research should study whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD in the offspring.

The authors' reply.

We thank Dr. Kayadibi and colleagues (1) for their comments regarding our paper on hyperhomocysteinemia. (2) As it is known, vitamin B9, also called folate or folic acid, is one of the eighth forms of vitamin B. (3, 4) So, in the current study by Monfared et al. (2), folic acid is obviously considered as one of the forms of vitamin B, so the authors did not separately mention folic acid, and it is considered as an exclusion criteria. In addition, if despite adequate vitamin supplementation, adequately lowering plasma homocysteine has failed, the patients should be evaluated for vitamin deficiency, renal impairment, and thyroid dysfunction. It should be remembered that a (low) “normal” vitamin B12 level does not exclude intracellular vitamin B12 deficiency. Serum methylmalonic acid (MMA) and holotranscobalamin II levels are more reliable markers of vitamin B12 deficiency compared to the serum vitamin B12 concentration (5). Although Solomon demonstrated that high serum folate levels (>20 ng/mL) are associated with higher MMA, at the same time, homocysteine levels and cobalamin levels (201–300 pg/mL) are low normal. It should be mentioned that its effect is age dependent (≥60 years). In the case of having a normal range of serum folate, the effects would not progress (suggesting a threshold effect), but it would be reversed by cobalamin therapy (6). In our study, hyperhomocysteinemic patients had a mean folate level of 16.26±4.06 ng/mL (normal levels) with mid-normal cobalamin levels (405.56±169.28 pg/mL). It seems that, as Kayadibi et al. (1) proposed, evaluation of the functional deficiency of vitamin B12 by means of MMA, as an early functional marker of tissue vitamin B12 deficiency, could provide more accurate results. Further studies should consider this point. It is recommended by Kayadibi and colleagues (1) that multiple linear regression analysis should be performed with sex adjustment to eliminate tHcy differences that may be because of sex differences, so homogeneous distribution of sex would be achieved. As it is shown, in the univariate analysis, a significant association was found between tHcy and age (P=0.02), male sex (P=0001), serum creatinine (P=0.0001), blood urea nitrogen (P=0.0001), estimated creatinine clearance (P=0.001), the history of glomerulonephritis before transplantation (P=0.05), body mass index (P=0.02), serum uric acid (P=0.003), serum folate (P=0.0001), cyclosporine A dose (P=0.01), and CsA trough level (C0; P=0.02) (2). Then, in the multivariate analysis, multiple linear regression models were used by stepwise (entry=0.05, removal=0.1) method for determining associated factors of Hcy levels after adjusting all the demographic (including sex) and clinical variables (2). In response to tHcy analysis, fasting blood sample was collected into an ethylenediaminetetraacetic acid tube which was used for measuring plasma homocysteine of each patient. To separate the plasma, the blood sample was centrifuged immediately after collecting. Then the separated plasma was deeply frozen (−20°C). By this method, we tried to minimize the production and release of tHcy by red blood cells after obtaining the blood sample. (2) Congruent to the conclusion of Kayadibi and colleagues, we considered that measuring MMA, in addition to tHCY, folate, and vitamin B12, could reveal more accurate results. Ali Monfared 1 Seyyede Zeinab Azimi1 Ehsan Kazemnezhad1 Masoud Khosravi1 Mohammadkazem Lebadi1 Ebrahim Mirzajani2 Mohammad Najafi Ashtiani2 1 Urology Research Center School of Medicine Guilan University of Medical Sciences Rasht, Iran 2 School of Medicine Guilan University of Medical Sciences Rasht, Iran

Evaluation of risk factors associated with denosumab induced hypocalcemia.

144 Background: Denosumab is a monoclonal antibody that neutralizes RANKL preventing osteoclast activation. It has been shown to be superior to zoledronic acid in preventing skeletal-related events in breast cancer with bone metastases. Hypocalcemia has been reported as a common side effect. The aim is to evaluate the risk factors associated with denosumab induce hypocalcemia. Methods: Retrospective study in which 144 charts were reviewed. Baseline characteristics: age, gender, race, type of cancer, calcium, phosphate, vitamin D, PTH, creatinine levels, GFR and corrected calcium were obtained. Tumors were classified in hormone sensitive versus non-sensitive. Charts were reviewed to evaluate for the development and severity of hypocalcemia as defined by the international review criteria. A multivariant analysis to evaluate the relationship between hypocalcemia and the variables of interest was done. Results: Hypocalcemia was observed in 71 of 144 patients. Grade 2 hypocalcemia was the most common. Significantly lower levels of GFR at baseline were detected in patients withhypocalcemia. Hormone responsive tumors were significantly less likely to develop hypocalcemia. Conclusions: Despite adequate supplementation of vitamin D and calcium, hypocalcemia is a common side effect of Denosumab. Careful monitoring of calcium levels is necessary especially in chronic kidney disease and hormone insensitive tumors. [Table: see text]

The PARAMOUNT trial: Implications for Maintenance Therapy in Lung Cancer Patients

243 ISSN 1758-1966 10.2217/LMT.13.28 © 2013 Future Medicine Ltd Lung Cancer Manage. (2013) 2(4), 243–246 The maintenance strategic approach has been extensively investigated in hematologic malignancies and then in solid tumors. Among thoracic cancers, small-cell lung cancer has been the setting for several clinical trials of maintenance treatment. The most recent systematic review pooled the available trials evaluating maintenance therapy in small-cell lung cancer, producing a thorough picture of efficacy related to different pharmacological strategies. Despite an overall survival (OS) advantage reported for maintenance chemo therapy and interferon treatment, the results are not clinically relevant [1,2,101]. Maintenance therapy has only recently been accepted as a treatment strategy for advanced non-smallcell lung cancer (NSCLC) with the main goal of prolonging a favorable clinical state after induction first-line platinum-based combination chemo therapy in respect of an adequate tolerability and without impairing quality of life (QoL). This renewed interest has been raised with the availability of active and tolerable new drugs. Among these, pemetrexed, a new cytotoxic agent, is a potent inhibitor of thymidylate synthase and other folate-dependent enzymes. Based on its mechanism of action, pemetrexed was the first chemotherapeutic to be studied as a targeted agent. In fact, due to the evidence of the differential expression of thymidylate synthase between adenocarcinoma and squamous NSCLC, pemetrexed reported an increased efficacy in nonsquamous histology, and thus it is now registered only for the treatment of this histotype worldwide [3,4]. With adequate vitamin supplementation, pemetrexed was shown to be active and well tolerated, with grade ≥3 toxicities, when administered as a single agent, not exceeding 5–10% [5]. First, pemetrexed was tested as switch maintenance within the randomized Phase III trial JMEN. Advanced NSCLC patients of any histology not progressing after four cycles of platinum-based doublets, not including pemetrexed, were randomized to pemetrexed or placebo. Pemetrexed showed a statistically better progressionfree survival (PFS) and OS than placebo, which were more significant for nonsquamous histology [6]. These results led to the design of the PARAMOUNT study, a double-blind, multicenter, Phase III, randomized, placebocontrolled trial. The primary end point was PFS, chosen because this measure is not

Vitamin B1 in the treatment of Wernicke’s encephalopathy due to hyperemesis after gastroplasty

Wernicke’s encephalopathy (WE) is a severe brain disorder, first described in 1881, and is caused by a nutritional deficiency of thiamine (vitamin B1) found mostly in patients suffering from chronic alcoholism. In addition, WE can also complicate bariatric surgery if adequate vitamin supplementation is not insured. Without immediate treatment, the prognosis is poor and the mortality rate is high. Most patients present with atypical neurological symptoms, which hampers rapid diagnosis. We present a 40-year-old woman who underwent gastroplasty combined with gastric banding for severe obesity. She experienced repetitive vomiting and her diet was without vitamin supplementation. After three months she developed convergent strabismus, apathy and urinary incontinence, which was diagnosed as WE and treated as such. Six months later her recovery was incomplete, still showing gait difficulties and nystagmus. We aim to show that adequate vitamin supplementation in patients undergoing gastroplasty is necessary, especially considering the risk of permanent neurological deficits.

Wernicke's encephalopathy in a patient with short bowel syndrome on total parenteral nutrition: A case report

Summary Background Wernicke's encephalopathy is an acute disorder caused by thiamine deficiency. It can occur during total parenteral nutrition without adequate vitamin supplementation. Methods We report the case of a 20-year-old woman who was affected by Wernicke's encephalopathy while undergoing parenteral nutrition. After 3 weeks of daily infusions of industrial tricompartment bags, without multi-vitamin supplementation, the patient developed diplopia, ataxia, general muscle stiffness, a confusional state and severe anemia. Magnetic resonance scan showed pathological intensity changes in the medial thalamus, the floors of the third and fourth ventricles and the periaqueductal gray substance. Results All neurologic signs and anemia gradually normalized after intensive parenteral supplementation of thiamine (100 mg daily for 15 days). Forty days after thiamine supplementation, a magnetic resonance scan showed complete resolution of the brain alterations. Conclusions This report alerts physicians to the risk of incorrect management of total parenteral nutrition and to the need for regular supplementation of vitamins, particularly thiamine.

Interactions between drugs and vitamins at advanced age.

Drug consumption increases at advanced age due to increased morbidity. At the same time the state of repletion is reduced for several vitamins. Physiological and kinetic alterations in the elderly are reviewed in order to analyse possible interrelations between these two phenomena. At high age the status of all vitamins is compromised by reduced food intake. Decreased active intestinal transport and an increased propensity for atrophic gastritis may reduce the absorption of vitamins A, B1, folate and B12. Decreased exposure to sunlight and reduced cutaneous synthesis impair the vitamin D status. Studies on the state of vitamin repletion in hospital patients indicate a specific response of vitamins A, B1, B6 and C to drug administration at advanced age. Reduced food intake in the elderly is further compromised by drugs that impair appetite and absorption. Anticonvulsives and other drugs that induce hepatic microsomal enzymes accelerate vitamin D metabolism and aggravate post-menopausal osteoporosis. Acid inhibiting agents increase achlorhydria and reduce vitamin B12 absorption. Renal clearance of acidic drugs such as acetylsalicylic acid and barbituric acid, which is impaired at high age, is further reduced by high doses of vitamin C. Vitamin B6 reduces the therapeutic effect of L-dopa. When recognised, the negative effects of drug-vitamin interactions can be compensated by adequate vitamin supplementation and by adaptation of drug dosing.

Metabolic Acidosis and Thiamine Deficiency

We describe a 19-year-old patient who was receiving home parenteral nutrition in whom lactic acidosis developed. A review of her home parenteral nutrition formula revealed the absence of multivitamins, most significantly thiamine. After thiamine administration, the acidosis resolved, and the patient experienced pronounced clinical improvement. Clinicians must be aware that thiamine is essential for normal glucose metabolism and that thiamine deficiency can lead to lactic acidosis. Thiamine deficiency should be included in the differential diagnosis of lactic acidosis. The recent shortage of intravenous multivitamin preparations has led to documented cases of lactic acidosis as a result of thiamine deficiency, and a previous shortage led to several deaths due to lactic acidosis as a consequence of thiamine deficiency. All patients receiving parenteral nutrition must also receive adequate vitamin supplementation.