Role of hyperhomocysteinemia and Vitamin B12 deficiency in central and hemi-central retinal vein occlusion: A case-control study.

BACKGROUND: Retinal venous occlusive diseases have been recognized as a major cause of ocular morbidity. Hyperhomocysteinemia could be a potentially modifiable risk factor. OBJECTIVE: To determine the association of hyperhomocysteinemia with central and hemi-central retinal vein occlusion (CRVO and HCRVO), the correlation of serum levels of homocysteine with Vitamin B12 and folate levels and the association of Vitamin B12 deficiency with hyperhomocysteinemia. METHODS: In this case-control study, patients with CRVO and HCRVO, and age- and gender-matched controls without CRVO and HCRVO, who met the eligibility criteria, were enrolled after obtaining informed consent. Data obtained from participants using a questionnaire, complete ophthalmological examination and relevant investigations, including estimation of serum homocysteine, Vitamin B12 and folate levels, were collated and analyzed. RESULTS: Thirty-nine cases with CRVO and HCRVO and 39 age- and gender-matched controls were studied. We found a significant association of hypertension (P < 0.01), hyperlipidemia (P = 0.01), and abnormal blood profile (P < 0.01) with retinal vein occlusion. There was no statistically significant association of hyperhomocysteinemia with CRVO and HCRVO (P = 0.81). However, we found a high prevalence of both hyperhomocysteinemia (43.58% of cases and 53.84% of controls; P = 0.81) and Vitamin B12 deficiency (23.08% of cases and 38.46% of controls; P = 0.14) in cases and controls, without a statistically significant difference between the two groups with respect to both parameters. Our study also found a negative correlation of serum levels of homocysteine with Vitamin B12 (Pearson correlation co-efficient - 0.3874, P = 0.0005), and folate (Pearson correlation coefficient - 0.3886, P = 0.0004) of the study participants. Among the study participants (n = 78), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 7.0 (2.26-21.72) times those of patients without Vitamin B12 deficiency (P = 0.001). Similarly, among the cases (CRVO, n = 39), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 7.0 (1.22-40.09) times those of patients without Vitamin B12 deficiency (P = 0.029). In the control group also (non-CRVO, n = 39), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 6.67 (1.47-30.21) times those of patients without Vitamin B12 deficiency (P = 0.014). CONCLUSION: Hyperhomocysteinemia was not found to be an independent risk factor for retinal vein occlusion in our study. However, we found a high prevalence of hyperhomocysteinemia and Vitamin B12 deficiency in both cases and controls, without a statistically significant difference between the two groups with respect to both parameters. We also found a negative correlation of serum homocysteine levels with Vitamin B12 and folate levels. The odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were seven times those of patients without Vitamin B12 deficiency. Hypertension, hyperlipidemia, and abnormal blood profile had a significant association with CRVO and HCRVO. Many of the systemic risk factors for retinal vein occlusions are found to be associated with elevation of serum homocysteine levels, which may be part of a final common pathway in bringing about a state of accelerated atherosclerosis, leading to CRVO or HCRVO. Therefore, lowering serum levels of homocysteine by Vitamin B12 and folate supplementation could have a role in the prevention of these diseases.

Dietary pattern characterisation among subfertile South Asian women and the impact of vitamin B12 intake on frozen embryo transfer outcomes: a cross-sectional study.

STUDY QUESTION: Is there a difference in dietary patterns among subfertile South Asian women undergoing frozen embryo transfer (FET)? SUMMARY ANSWER: Significant regional differences in dietary pattern exist among subfertile South Asian women undergoing FET. WHAT IS KNOWN ALREADY: Preconception consumption of certain food groups or adopting specific dietary patterns, such as the 'Mediterranean diet', and its level of adherence have been shown to enhance the odds of achieving a successful pregnancy in women undergoing ART. However, differences in geographic location, individual preference, cultural beliefs and local availability contribute to such dietary choices. There is also a predisposition to a vitamin B12 deficiency in those of South Asian ethnicity and a predominant pattern of vegetarian food intake. There is a paucity of studies analysing the type of dietary pattern followed by South Asian women, their vitamin B12 levels and the potential impact on ART treatment outcomes. STUDY DESIGN SIZE DURATION: This is a cross-sectional study of 159 South Asian women aged 21-37 years, belonging to the Eastern (n = 75) and Southern (n = 84) regions of India plus Bangladesh, and undergoing a FET cycle at a tertiary level infertility clinic between February 2019 and March 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Women underwent dietary assessment using '24-hour dietary recall' to capture daily nutrient consumption. A 'Food Frequency Questionnaire' listing commonly consumed foods was used to record frequency of intake. The primary outcome was the characterisation of regional dietary patterns in the cohorts using principal component analysis (PCA). Secondary outcomes included association of vitamin B12 intake and serum levels with clinical and ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Four components contributing to overall variance in dietary pattern were identified, namely: meat, poultry and seafood; green leafy vegetables and root tubers; fruits, dairy and sugar; nuts and oilseeds. PCA analysis showed a significantly higher consumption of two components in the East-meat, poultry and fish (P < 0.001); green leafy vegetables and root tubers (P < 0.001). All women reported taking preconception oral folic acid supplementation. The dietary intake of vitamin B12 and serum concentration correlated, showing a good validity of measured dietary intake (r = 0.398; P ≤ 0.001). Compared to the Southern region, participants from the East showed a higher daily median intake of vitamin B12 (1.11 versus 0.28 mcg, respectively; P < 0.001) and a higher serum vitamin B12 levels (441 versus 239 pg/ml, respectively; P < 0.001). Ongoing pregnancy showed no association with dietary vitamin B12 intake (relative risk 0.90; 95% CI, 0.68 to 1.19) or serum vitamin B12 levels (relative risk 0.99; 95% CI, 0.73 to 1.33) after adjustments for female age, body mass index (BMI) and geographic differences. Women belonging to different quartiles of serum vitamin B12 concentration had a similar likelihood of ongoing pregnancy. LIMITATIONS REASONS FOR CAUTION: Self-reported dietary assessment is prone to measurement errors owing to its subjective nature and recall bias. The study was not adequately powered to detect the impact of geographic differences in vitamin B12 intake and serum levels on FET treatment outcomes, the second objective. We adjusted for potential confounders, such as female age and BMI, but it is possible that residual confounders, such as physical activity, stress and use of dietary supplements, may have influenced the results. Extrapolation of the study findings to women undergoing ART in other populations should be made with caution. WIDER IMPLICATIONS OF THE FINDINGS: Our study findings suggest important differences in local dietary patterns within the South Asian region. Hence a personalised approach to dietary assessment and intervention when undergoing ART based on population dynamics is warranted. The geographic differences in the vitamin B12 intake or serum levels did not have an impact on the FET outcomes. There is also a need to further investigate the impact of such dietary differences on ART treatment outcomes in a large study population. STUDY FUNDING/COMPETING INTERESTS: No grant from funding agencies in the public, commercial, or not-for-profit sectors was obtained. The authors have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

The proposed systemic thermogenic metabolites succinate and 12,13-diHOME are inversely associated with adiposity and related metabolic traits: evidence from a large human cross-sectional study.

AIMS/HYPOTHESIS: Circulating succinate and 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) were recently shown to promote brown adipocyte thermogenesis and protect against metabolic disorders in rodents. This study aimed to evaluate the associations between plasma levels of these metabolites and adiposity and metabolic profile in humans. METHODS: Fasting plasma succinate and 12,13-diHOME levels were quantified using ultra HPLC-tandem MS in 2248 individuals (50% female, mean age 41.3 ± 5.9 years, mean BMI 26.1 ± 4.6 kg/m2) in addition to fasting plasma biochemistry. Total and regional adiposity were assessed with dual-energy x-ray absorptiometry. An age- and sex-adjusted linear regression model was used to determine the associations between succinate and 12,13-diHOME levels and body composition and metabolic profile. Two-sample Mendelian randomisation was used to assess the associations between genetically determined BMI and metabolic traits with circulating plasma succinate and 12,13-diHOME. RESULTS: A one-SD higher plasma succinate and 12,13-diHOME concentration was associated with a 0.15 SD (95% CI 0.28, 0.03) and 0.08 SD (0.15, 0.01) lower total fat mass respectively. Additionally, a one-SD higher plasma 12,13-diHOME level was associated with a 0.09 SD (0.16, 0.02) lower fasting plasma insulin and 0.10 SD (0.17, 0.04) lower plasma triacylglycerol. In Mendelian randomisation analyses, genetically determined higher BMI, fasting hyperinsulinaemia and elevated lipid levels were not associated with changes in either plasma succinate or plasma 12,13-diHOME concentrations. No indications of bias due to directional pleiotropy were detected in the Mendelian randomisation analyses. CONCLUSIONS/INTERPRETATION: Our findings tentatively suggest that plasma succinate and 12,13-diHOME may play a role in the regulation of energy metabolism and brown adipose tissue activation in humans. Further studies encompassing direct assessment of brown adipose tissue activity and dietary supplementation are necessary to investigate the potential beneficial effects of these metabolites on systemic metabolism.

A phase 2 randomized controlled trial of oral resistant starch supplements in the prevention of acute radiation proctitis in patients treated for cervical cancer.

BACKGROUND: Radiation induced proctitis is frequently encountered during the radiation therapy of cervical and prostate cancers that causes pain and occasionally with bleeding and may affect the continuity of radiation therapy. AIMS AND OBJECTIVES: The purpose of the study is to look at the benefit of administration of an oral prebiotic amylase resistant starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix. MATERIAL AND METHODS: The study was conducted between 2011 and 2014 in 104 patients receiving radical chemo-radiotherapy for carcinoma cervix. Patients were randomized in to two arms, one receiving 30 gm of resistant starch and the other digestible starch on a daily basis throughout the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. At completion of external beam radiotherapy, all patients underwent LDR/HDR brachytherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two groups and analyzed. Stool short chain fatty acid concentrations were measured at baseline at 2nd and 4th week and after 6 weeks of completion of radiotherapy in both study placebo arms and reported. The pattern of microbiota in the stool were also estimated in all patients at 4 time points. Two patients who progressed during therapy were not included in the analyses and two patients discontinued the intervention. A per protocol analyses was done. RESULTS: At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the resistant starch group. This difference was seen at 4th week and continued in the subsequent weeks till the end of radiation. Both groups had similar reported toxicity at 6 weeks post intervention and similar incidence of grade 2 and above diarrhea. The resistant starch group was found to have 8% incidence as compared to 2% in the other group at the 5th and 6th week. The short chain fatty acid concentrations were not significantly different in the groups at any point. CONCLUSION: The study did not demonstrate a significant benefit in administering resistant starch over and above normal diet to patients receiving pelvic radiotherapy. The reasons may be attributed to concurrent use of chemotherapy and decrease in intestinal probiotics. The use of digestible starch in the control arm may have contributed to lower incidence of the toxicity endpoints as well.

The Role of Magnesium in Post-thyroidectomy Hypocalcemia.

BACKGROUND: The purpose of this study was to determine the prevalence of hypomagnesemia in patients undergoing thyroidectomy and evaluate the relationship of hypomagnesemia with transient and severe hypocalcemia. MATERIALS AND METHODS: This was a prospective observational study of 50 patients undergoing thyroidectomy. Blood samples were collected pre- and postoperatively for calcium, albumin, magnesium, phosphorous and parathormone (PTH). Signs, symptoms of hypocalcemia and volume of intravenous fluids used perioperatively were documented. The statistical analysis was performed using STATA I/C 10.1. RESULTS: Preoperatively, twelve patients (24 %) had hypomagnesemia and one (2 %) hypocalcemia. On the first postoperative day, hypomagnesemia was seen in 70 % and hypocalcemia in 30 %. A similar trend was observed in the fall and rise of postoperative calcium and magnesium values (p = 0.41). Severe hypocalcemia was present in three patients (6 %). All three patients had a very low postoperative PTH (<2 pg/ml). Among them, two patients (66 %) had hypomagnesemia and their hypocalcemia responded to intravenous magnesium correction. Significant risk factors for postoperative hypocalcemia include a higher volume of fluid used perioperatively and low postoperative PTH (<8 pg/ml) (p = 0.01 and 0.03, respectively). CONCLUSION: Preoperative hypomagnesemia (24 %) was prevalent in this cohort of patients. Postoperative hypomagnesemia is a common event (70 %) following total thyroidectomy, and magnesium levels tend to mimic the calcium levels postoperatively. The cause of hypocalcemia post-thyroidectomy in this study is mainly a factor of parathyroid function and fluid status. Severe hypocalcemia is a rare event, and hypomagnesemia is associated in the majority of these patients. The role of magnesium correction to alleviate severe hypocalcemia needs to be further studied.