Nevin Manimala

Dev Med Child Neurol. 2022 Jul;64(7):915-923. doi: 10.1111/dmcn.15140. Epub 2022 Jan 31.

ABSTRACT

AIM: To study neurotransmitter status in children with early epileptic and developmental and epileptic encephalopathy (DEE) and to explore the clinical response to dopaminergic and serotoninergic therapies in a group of patients.

METHOD: Two hundred and five patients (111 males [54.1.%] and 94 females [45.9%], mean age 10 months at the onset of epilepsy [SD 1 year 1 month], range 0-3 year) with epileptic encephalopathy/DEE were recruited, including those with West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, myoclonic encephalopathy in non-progressive disorders, infantile spasms, Doose syndrome, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and those unclassified. Cerebrospinal fluid (CSF) neurotransmitter studies and patients’ medical records were reviewed. Additionally, we present clinical data of 10 patients with low CSF neurotransmitter levels who received dopaminergic/serotoninergic treatments.

RESULTS: Abnormal neurotransmitter values were identified in 68 (33%) patients. 5-Hydroxyindoleacetic acid (5-HIAA) deficit was the most prevalent alteration (91%). Low CSF 5-HIAA levels were significantly higher in 1- to 3-year-old children. A negative significant correlation was found between 5-HIAA levels and epilepsy duration before CSF study (Spearman’s ρ=-0.191, p=0.007). Abnormalities in deep grey matter were associated with low levels of CSF homovanillic acid and 5-HIAA. Ten patients with low CSF neurotransmitter levels received dopamine and/or serotonin therapies. Six of them showed initial decrease of seizure frequency and severity and maintained improvement in some neurodevelopmental skills.

INTERPRETATION: A considerable number of patients showed neurotransmitter abnormalities. Age at seizure onset and duration of epilepsy before CSF study were the principal factors related to neurotransmitter depletion. Early monoamine supplementation would seem advisable as a neuroprotective strategy.

WHAT THIS PAPER ADDS: 5-Hydroxyindoleacetic acid homeostasis is especially vulnerable in patients with epileptic encephalopathy/developmental and epileptic encephalopathy. Age of seizure onset and duration of epilepsy are determinants of neurotransmitter depletion.

PMID:35833444 | DOI:10.1111/dmcn.15140

Ann Surg. 2022 Jul 14. doi: 10.1097/SLA.0000000000005492. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of the present study was to compare the effect of radiotherapy (RT) on abdominal recurrence-free survival (ARFS) in patients with primary retroperitoneal sarcoma treated in the EORTC-STBSG-62092 (STRASS) phase 3 randomized controlled trial (STRASS cohort) and off-trial (STREXIT cohort) and to pool STRASS and STREXIT data to test the hypothesis that RT improves ARFS in patients with liposarcoma.

BACKGROUND: The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S).

METHODS: All consecutive adult patients not enrolled in STRASS and underwent curative-intent surgery for a primary retroperitoneal sarcoma with or without preoperative RT between 2012 and 2017 (STRASS recruiting period) among ten STRASS-recruiting centres formed the STREXIT cohort. The effect of RT in STREXIT was explored with a propensity score (PS)-matching analysis. Primary endpoint was ARFS defined as macroscopically incomplete resection or abdominal recurrence or death of any cause, whichever occurred first.

RESULTS: STRASS included 266 patients, STREXIT included 831 patients (727 after excluding patients who received preoperative chemotherapy, 202 after 1:1 PS-matching). The effect of RT on ARFS in STRASS and 1:1 PS-matched STREXIT cohorts, overall and in patients with liposarcoma, was similar. In the pooled cohort analysis, RT administration was associated with better ARFS in patients with liposarcoma [N=321, hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.42-0.89]. In particular, patients with well-differentiated liposarcoma and G1-2 dedifferentiated liposarcoma (G1-2 DDLPS, n=266) treated with RT+S had better ARFS (HR, 0.63; 95% CI, 0.40-0.97) while patients with G3 DDLPS and leiomyosarcoma had not. At the current follow-up, there was no association between RT and overall survival or distant metastases-free survival.

CONCLUSIONS: In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS.

PMID:35833413 | DOI:10.1097/SLA.0000000000005492

J Assoc Physicians India. 2022 Jul;70(7):11-12. doi: 10.5005/japi-11001-0051.

ABSTRACT

AIM: To study the efficacy of uptitrating the dose of Teneligliptin from 20 to 40 mg in patients with type II diabetes mellitus.

METHOD: A retrospective, comparative analysis was undertaken in 853 type II diabetes mellitus patients (499 males and 354 females) who had follow-up records for more than 6 months. These patients were uncontrolled after use of atleast three oral antidiabetic drugs (OADs) and Teneligliptin 20 mg was added as the fourth drug. Patients who remained uncontrolled with the addition of 20 mg of Teneligliptin at the end of 3 months and were switched to receive 40 mg of Teneligliptin daily were included in this study. Results were analyzed at 3 and 6 months to ascertain efficacy of high-dose (40 mg) Teneligliptin. All other OADs remained the same in both groups. In all patients, the fasting blood glucose, postprandial blood glucose, and hemoglobin A1c (HbA1C) were evaluated and compared.

RESULT: A total of 853 patients whose dose of Teneligliptin was increased from 20 to 40 mg were included in the study. At the end of 3 months after using Teneligliptin 40 mg, mean reduction in HbA1C was 0.5% (p-value 0.154). Similarly, mean reduction in fasting blood sugar (FBS) and postprandial blood sugar (PPBS) was 6.5 and 3.6 mg/dL, respectively (p-value 0.234 and 0.143). At the end of 6 months after using Teneligliptin 40 mg HbA1C showed no change but mean FBS and PPBS showed a modest reduction of 14.6 and 14 mg/dL, respectively (p-value < 0.001).

CONCLUSION: The results of our study show that there was no statistically significant improvement in glycemic parameters when dose of Teneligliptin was increased from 20 to 40 mg at 3 months. But at 6 months, the FBS and PPBS showed a modest reduction of 14.6 and 14 mg/dL, respectively (p-value < 0.001) but the HbA1C showed no change.

PMID:35833400 | DOI:10.5005/japi-11001-0051

J Assoc Physicians India. 2022 Jul;70(7):11-12. doi: 10.5005/japi-11001-0047.

ABSTRACT

BACKGROUND: Thyroid hormones have a crucial role in adapting the metabolic functions during stress and critical illness. Patients who are critically ill may have profound changes in thyroid hormone metabolism. Non-thyroidal Illness Syndrome (NTIS) is one among them, in which there is marked abnormality seen in the thyroid hormone levels. Hence this study is to understand the alterations of the thyroid function tests (TFTs) encountered in critically ill patients admitted in medical intensive care unit (MICU) without primary thyroid disease and to correlate with the severity of Acute Physiology and Chronic Health Evaluation (APACHE III) scoring.

METHODS: The study was conducted on 100 critically ill patients with no previous thyroid disorders, admitted in MICU in the Department of General Medicine in a tertiary care hospital between September 2017 and August 2019 who fulfilled the inclusion and exclusion criteria.

RESULTS: Out of 100 critically ill patients the abnormal thyroid function prevalence was seen in 78% patients. The most common abnormality seen in our study was low total triiodothyronine (TT3) (61%) followed by low free triiodothyronine (FT3) (36%), low total thyroxine (TT4) (29%), high thyroid-stimulating hormone (TSH) (18%), and low free thyroxine (FT4) (12%). Low TT3, TT4, and FT3 values had a significant correlation with increasing critical severity score of APACHE III with a p value which was statistically significant (p<0.05).

CONCLUSIONS: With increase in severity of critical illness assessed by APACHE III, TFT, that is, TT3, TT4, and FT3 levels were decreasing, suggestive of increasing non-thyroidal illness in critically ill patients.

PMID:35833393 | DOI:10.5005/japi-11001-0047

J Assoc Physicians India. 2022 Jul;70(7):11-12. doi: 10.5005/japi-11001-0045.

ABSTRACT

BACKGROUND: Vitamin D plays an important role in bone and modulates mineral metabolism and immune function with probable link to several chronic and infectious conditions. In vivo studies have revealed that vitamin D deficiency reduces insulin secretion capacity of the islet beta cells in pancreas. Several studies have shown a correlation between vitamin D levels and insulin resistance, nonetheless, extensive studies showing the relationship between the two are lacking especially among southern Indian population. So the present study was aimed at evaluating the relationship between vitamin D and insulin resistance by using homeostatic model assessment-insulin resistance (HOMA-IR).

MATERIALS AND METHODS: In a cross-sectional study, 184 people among which 92 were diabetic and 92 were nondiabetic were recruited at RL Jalappa Hospital, Kolar in the Department of Medicine between May 2018 and April 2019. Fasting serum insulin (I0), fasting plasma glucose (G0), hemoglobin A1c (HbA1C), renal function test, liver function test (LFT), lipid profile, and vitamin D levels were estimated. IBM SPSS version 22 was used for statistical analysis.

RESULTS: The prevalence of vitamin D deficiency in our study was (72) 78.2% among diabetic cases and (59) 64.1% among the nondiabetic controls, with the diabetic cases showing lower levels of vitamin D than the controls, however, it was not statistically significant. There was no significant difference in homeostatic model assessment-beta-cell function (HOMA-B) and HOMA-IR between vitamin D deficient and nondeficient groups among cases and controls.

CONCLUSION: Vitamin D deficiency is prevalent in both type II diabetes mellitus (T2DM) as well as nondiabetic. Furthermore, there is no association between vitamin D deficiency and insulin resistance or beta-cell function.

PMID:35833392 | DOI:10.5005/japi-11001-0045

Foot Ankle Spec. 2022 Jul 14:19386400221107004. doi: 10.1177/19386400221107004. Online ahead of print.

ABSTRACT

Background: In orthopaedic surgery departments, foot and ankle fellowship directors are tasked to create a robust clinical curriculum for trainees, while division chiefs manage the division’s delivery of patient care. The primary aim of this study was to describe characteristics of foot and ankle surgery fellowship directors and division chiefs in an effort to recognize trends or disparities in leadership traits. Methods: The American Orthopaedic Foot and Ankle Society (AOFAS) fellowship directory for 2021 to 2022 was reviewed for AOFAS-recognized fellowship programs in the United States. Between March 2021 and June 2021, 48 fellowship directors and 23 publicly recognized division chiefs were administered an electronic survey to collect demographic, educational, and professional data. Univariate and bivariate statistical analyses were performed. Results: A total of 42 of the 48 (87.5%) fellowship directors and 18 of the 23 (78.3%) division chiefs responded to the questionnaire. Of the 48 fellowship directors, 45 (93.8%) were male, 43 (89.6%) identified as Caucasian, their average age at leadership appointment was 42.6 ± 7.5 (range, 32-70) years, and the average time between fellowship graduation and leadership appointment was 9.9 ± 7.8 (range, 0-36) years. Of the 23 chiefs, 22 (95.7%) were male, 20 (87.0%) identified as Caucasians, their average age at leadership appointment was 41.7 ± 7.8 (range, 32-53) years, and the average time between fellowship graduation and leadership appointment was 9.8 ± 6.8 (range, 2-21) years. The average H-index for the chiefs was greater than that of the fellowship directors (18.4 vs 13.4, P = .0373) when controlling for years of training>. Conclusion: The majority of current leaders identify as middle-age Caucasian males, demonstrate high research productivity, and have attended a select number of the same residency and fellowship training programs. By demonstrating the lack of diversity within foot and ankle surgery leadership, this study serves as a call to action for making inclusivity a priority.Levels of Evidence: Level IV: Cross-sectional study.

PMID:35833388 | DOI:10.1177/19386400221107004

Psychol Med. 2022 Jul 14:1-10. doi: 10.1017/S0033291722002069. Online ahead of print.

ABSTRACT

BACKGROUND: This confirmatory study aimed to examine whether we can foresee recurrence of depressive symptoms using personalized modeling of rises in restlessness.

METHODS: Participants were formerly depressed patients (N = 41) in remission who (gradually) discontinued antidepressants. Participants completed five smartphone-based Ecological Momentary Assessments (EMA) a day, for a period of 4 months, yielding a total of 21 180 observations. Statistical Process Control by means of Exponentially Weighted Moving Average (EWMA) control charts was used to detect rises in the EMA item ‘I feel restless’, for each individual separately.

RESULTS: An increase in restlessness was detected in 68.3% of the participants with recurring depressive symptoms, and in 26.3% of those who stayed in remission (Fisher’s exact test p = 0.01, sensitivity was 68.3%, specificity was 73.7%). In the participants with a recurrence and an increase in restlessness, this increase could be detected in the prodromal phase of depression in 93.3% of the cases and at least a month before the onset of the core symptoms of depression in 66.7% of the cases.

CONCLUSIONS: Restlessness is a common prodromal symptom of depression. The sensitivity and specificity of the EWMA charts was at least as good as prognostic models based on cross-sectional patient characteristics. An advantage of the current idiographic method is that the EWMA charts provide real-time personalized insight in a within-person increase in early signs of depression, which is key to alert the right patient at the right time.

PMID:35833374 | DOI:10.1017/S0033291722002069

Cancer Med. 2022 Jul 14. doi: 10.1002/cam4.5023. Online ahead of print.

ABSTRACT

PURPOSE: Infertility is a critical late toxicity that impacts adolescent and young adult (AYA, ages 15-39 years) cancer survivors. International oncology societies recommend discussing fertility preservation (FP) for all AYA patients, regardless of stage or prognosis. We aim to understand Canadian medical oncologists’ perceptions, attitudes, and knowledge toward FP and pregnancy in patients with cancer, including advanced stages and high risk for recurrence.

METHODS: An anonymous electronic survey utilizing hypothetical scenarios was sent to medical oncologists in the province of Ontario, Canada. Descriptive statistics were used to summarize all data. Logistic regression models were constructed to identify factors that predicted FP discussions and referrals.

RESULTS: The survey was received by 91 medical oncologists, and the response rate was 44%. Fifty-eight percent of respondents offer FP for all patients. Physicians are more likely to refer patients for FP before curative intent therapy than before palliative chemotherapy (95% vs. 39.5%, p < 0.001). Most respondents (86%) are comfortable discussing FP; however, only 31% self-reported feeling up-to-date on knowledge of current FP methods. Female physicians were more likely to report up-to-date knowledge and confidence discussing FP with patients. Forty percent of respondents identified that concerns about the welfare of the resulting offspring should not be a cause for denying patients assistance in reproduction.

CONCLUSION: There is a significant difference in physician attitude toward offering FP based on the cancer stage. Increased awareness of standard of care guidelines and resources for difficult situations may improve the frequency of discussions about FP in motivated cancer patients.

PMID:35833372 | DOI:10.1002/cam4.5023

Psychol Med. 2022 Jul 14:1-11. doi: 10.1017/S0033291722001490. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with bipolar disorder (BD) show reduced fractional anisotropy (FA) compared to patients with major depressive disorder (MDD). Little is known about whether these differences are mood state-independent or influenced by acute symptom severity. Therefore, the aim of this study was (1) to replicate abnormalities in white matter microstructure in BD v. MDD and (2) to investigate whether these vary across depressed, euthymic, and manic mood.

METHODS: In this cross-sectional diffusion tensor imaging study, n = 136 patients with BD were compared to age- and sex-matched MDD patients and healthy controls (HC) (n = 136 each). Differences in FA were investigated using tract-based spatial statistics. Using interaction models, the influence of acute symptom severity and mood state on the differences between patient groups were tested.

RESULTS: Analyses revealed a main effect of diagnosis on FA across all three groups (p_tfce-FWE = 0.003). BD patients showed reduced FA compared to both MDD (p_tfce-FWE = 0.005) and HC (p_tfce-FWE < 0.001) in large bilateral clusters. These consisted of several white matter tracts previously described in the literature, including commissural, association, and projection tracts. There were no significant interaction effects between diagnosis and symptom severity or mood state (all p_tfce-FWE > 0.704).

CONCLUSIONS: Results indicated that the difference between BD and MDD was independent of depressive and manic symptom severity and mood state. Disruptions in white matter microstructure in BD might be a trait effect of the disorder. The potential of FA values to be used as a biomarker to differentiate BD from MDD should be further addressed in future studies using longitudinal designs.

PMID:35833369 | DOI:10.1017/S0033291722001490

J Cosmet Dermatol. 2022 Jul 14. doi: 10.1111/jocd.15241. Online ahead of print.

ABSTRACT

BACKGROUND: A new Hyaluronic acid (HA) formulation was developed based on high molecular weight (MW) compounds used on the surface of the skin while using peptides to stimulate the high MW HA production by fibroblasts and keratinocytes from within the skin layers. Detailed science has been submitted to this journal in a previous publication. This multicenter study aims to validate the science by demonstrating the safety and efficacy of the product in the clinical realm.

OBJECTIVES: This study evaluated the efficacy and safety of a topical HA serum in facial skin.

METHODS: An open label clinical study was undertaken over 4 months from November 2021 – March 2022. Participants applied the topical serum twice daily and were provided a gentle cleanser and an SPF 30+ to use in the morning. Follow-up visits were conducted at weeks 2, 4, and 8. At every visit, participants were measured for hydration post 15 minutes of cleansing the skin and post 15 minutes of product application for cumulative skin hydration sensor measurements. Additional procedures included; participant assessments and satisfaction, investigator assessments, biopsies and photography.

RESULTS: At each follow-up visit there was an increase in the hydration measurements compared to baseline, both in immediate scores and cumulative long-term scores. At weeks 4 and 8 there was a statistically significant increase in hydration compared to baseline and the prior visit. Participants assessments progressively increased over 2, 4- and 8-week intervals with significantly favorable ratings in all measured parameters. Similarly, investigator assessment grades were statistically significant (p<.0001) for decreased fine lines/wrinkling, crepiness, texture, erythema, and dryness, and increased (p<.0001) for moisture/hydration. Histology revealed increased CD44 staining in 6 of the 7 participants biopsied, denoting increased HA stimulation. In all of the participant biopsies, H&E staining demonstrated improvement in solar elastosis. Photography revealed remarkable improvement in erythema, tone and texture.

CONCLUSIONS: Study results demonstrated that the formulation produced significant improvements in immediate and long-term hydration effects on the skin as measured by the skin hydration sensor, ‘wearifi’ technology, comparison of pre and post biopsies, and participant and investigator assessments. This high MW HA formulation produced excellent clinical improvement in skin health and hydration.

PMID:35833366 | DOI:10.1111/jocd.15241