The Effect of Vitamin K2 Supplementation on PIVKA-II Levels in Patients with Severe Motor and Intellectual Disabilities Undergoing Long-Term Tube Feeding.

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

Isolated neutropenia caused by copper deficiency due to jejunal feeding and excessive zinc intake: A case report.

BACKGROUND: Percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) is often used to treat patients with neurological impairment and difficulty in swallowing. However, these patients often develop copper deficiency. This report describes a case of isolated neutropenia, which is a rare manifestation of copper deficiency. CASE SUMMARY: Our patient was a 19-year-old boy with neurological impairment and gastroesophageal reflux. He received PEG-J feeding, including an enteral supplement containing copper and zinc. However, as his serum zinc level was low (53 µg/dL) at the age of 19 years and 2 mo, we changed to a zinc-rich supplement containing 22 mg/d of zinc and 1.0 mg/d of copper. The supplement comprised a mixture of isocal 1.0 junior (5 packs/d), Tezon [2 packs (250 mL)/d], and cocoa powder. Seven months later, he had neutropenia (606/mm3) with a serum copper level of 16 µg/dL. There were no other manifestations of copper deficiency, including anemia. Copper deficiency and neutropenia both improved following the administration of cocoa powder and Tezon. CONCLUSION: In patients receiving long-term PEG-J feeds, white blood cell counts, hemoglobin, and serum levels of copper and zinc should be regularly monitored.

Nutritional Therapy with Vitamin K1 Is Effective in the Improvement of Vitamin K Status and Bone Turnover Markers in Patients with Severe Motor and Intellectual Disabilities.

We have previously reported that patients with severe motor and intellectual disabilities (SMID) have a high prevalence of vitamin K deficiency both in the liver and bone. Thus, vitamin K therapy for SMID patients should be considered. In the present study, we have studied the efficacy of nutritional therapy with vitamin K1 for improving their vitamin K status and bone metabolism markers in patients with SMID. During the 3-mo period, 19 patients under enteral feeding received vitamin K1 treatment, the dose of which was determined to meet each subject's energy requirement. Biomarkers of vitamin K insufficiency; protein induced by vitamin K absence or antagonist-II (PIVKA-II), undercarboxylated osteocalcin (ucOC), intact osteocalcin (intact OC) and bone turnover markers (tartrate-resistant acid phosphatase-5b: TRACP-5b and bone alkaline phosphatase: BAP) were measured at baseline and post treatment. The ucOC/OC ratio was calculated as a more sensitive index than ucOC for vitamin K status in the bone. After treatment, the median vitamin K intake increased from 66 to 183 µg/d, and serum levels of PIVKA-II and ucOC/OC ratio were significantly decreased. Decrements of serum ucOC level and ucOC/OC ratio were significantly associated with vitamin K intake, indicating that both markers well reflect the dose-dependent vitamin K effects. Serum levels of BAP and TRACP-5b were significantly increased after vitamin K1 therapy. Nutritional therapy with vitamin K1 effectively improved the markers for vitamin K status and bone turnover, and was considered to be a good candidate for treatment in SMID patients.

Deep Vein Thrombosis in Severe Motor and Intellectual Disabilities Patients and Its Treatment by Anticoagulants of Warfarin Versus Edoxaban.

Objective: Patients with severe motor and intellectual disabilities (SMID) often develop complications, including paralysis of the extremities due to abnormal muscular tonicity. Furthermore, the incidence of sudden death, which may be caused by pulmonary thromboembolism (PTE), is approximately 4.2%. Deep vein thrombosis (DVT) is attracting attention as an embolic source. In this study, DVT was confirmed in SMID patients by lower extremity venous ultrasound. The oral anticoagulant, warfarin, and novel oral anticoagulant, edoxaban tosilate hydrate, were administered, and their efficacies and safeties were evaluated. Materials and Methods: DVT patients were randomly allocated to warfarin and edoxaban groups. The frequency of hemorrhagic events and incidence of adverse events were investigated to evaluate efficacy and safety. Results: DVT was detected in 14 (8.4%) out of 167 patients. Four (0.067/person-month) hemorrhagic events occurred in the warfarin group from subcutaneous hemorrhage due to bruises caused by postural changes. Three (0.042/person-month) events occurred in the edoxaban group due to nasal hemorrhage caused by tracheal aspiration. There was no significant difference (p=0.5383) between groups. Conclusion: No significant differences were observed in hemorrhagic events between SMID patients with DVT treated with warfarin and edoxaban.

Gastric and Jejunal Enteral Feeding Differently Affect Vitamin B12 Status in Subjects with Severe Motor and Intellectual Disabilities.

The absorption of vitamin B12 is a complex process involving gastric acid and intrinsic factor as the indispensable components. In this study, we have investigated the effects of the administration site in enteral feeding on vitamin B12 status in subjects with severe motor and intellectual disabilities (SMID). This is a cross-sectional study conducted from January to June 2016. Blood concentrations of vitamin B12, folate, vitamin B6, and homocysteine (Hcy) were measured in a total of 82 subjects (38 men, 44 women). Also, nutrients intake was assessed. Subjects with enteral feeding (EF) had significantly higher intakes of vitamin B12, folate, and vitamin B6 than those with oral ingestion (OI). Serum folate and vitamin B6 concentrations in subjects with EF were significantly higher than those with OI. Among the EF subjects, serum vitamin B12 concentration was significantly higher in those fed with gastric tube than those fed with jejunal tube in spite of similar vitamin B12 intakes. No significant difference was observed between the two groups regarding the circulating concentrations of folate, vitamin B6, or Hcy. Although each administration route has its own benefit, gastric tube is advantageous in the absorption of vitamin B12.

Multicenter, Open-Label, Randomized Controlled Trial of Warfarin and Edoxaban Tosilate Hydrate for the Treatment of Deep Vein Thrombosis in Persons with Severe Motor Intellectual Disabilities.

Sudden death in patients with severe motor and intellectual disabilities (SMID) is sometimes caused in part by pulmonary thromboembolism (PTE), and deep venous thrombosis (DVT) has drawn attention as a possible embolic source. Warfarin, which is a conventional therapeutic agent, is not easy to control appropriately, and daily management can be especially difficult in SMID patients. On the other hand, edoxaban tosilate hydrate, which has been newly approved for insurance coverage for the treatment of DVT, is not listed in the Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism and Deep Vein Thrombosis (DVT-PTE guidelines). The aim of this study is to evaluate the efficacy and safety of anticoagulation therapy (warfarin vs. edoxaban) in DVT treatment in SMID patients by means of an open-label, randomized controlled trial. The primary endpoint is the incidence of hemorrhagic events during 12 months of follow up.

[Management of nutrition in children and adults with severe motor and intellectual disabilities].

In children and adults with severe motor and intellectual disabilities (SMID), management of nutrition is very important. We investigated the problem of long-term use of tube feeding on which many of them depend because of swallowing dysfunction. Trace elements such as copper, zinc, selenium and long chain unsaturated fatty acid (omega-3 fatty acid) were often deficient. To evaluate their nutritional condition, we calculated the body fat mass by the method of Bioelectrical Impedance Analysis and measurement of subcutaneous fat thickness. Patients with the athetotic type of cerebral palsy had a lower level fat mass than those with the spastic type. Patients with a low body fat mass tended to require more energy than those with a high body fat mass. To improve the quality of life of persons with SMID, it is important to find clinical dysfunction related to the nutrition and to improve the nutritional condition immediately.