Nevin Manimala

Curr Microbiol. 2022 Jul 14;79(9):256. doi: 10.1007/s00284-022-02943-0.

ABSTRACT

Acinetobacter baumannii is a significant nosocomial pathogen, with its biofilm forming capacity playing an important role in its pathogenicity. The fast and reliable detection of the biofilm formation and measurement of antibiofilm activity of various molecules are critical for combating A. baumannii infections. In this study, we aimed to detect biofilm formation by real time cell analyses (RTCA) method in clinical A. baumannii isolates and to investigate antibiofilm activities of tigecycline (TGC), N-acetylcysteine (NAC), and acetylsalicylic acid (ASA). The effect of the tested drugs on expressions of biofilm-related genes bap and csuE in clinical A. baumannii strains was also analyzed by real time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Biofilm forming capacities for strong and weak biofilm producer A. baumannii strains were detected within 10 h by RTCA method (P < 0.05). We also observed that sub-minimum inhibitory concentrations of NAC + TGC and ASA + TGC combinations could significantly reduce biofilm formation and expression of biofilm-related genes in A. baumanii strains. No statistically significant activity of the tested drugs was detected against mature biofilms of the bacterial strains with the RTCA method. These results suggest that reproducible results on biofilm production capacity of A. baumannii strains and antibiofilm activities of various compounds can be obtained in a short time using RTCA method. Therefore, RTCA method seems to be a beneficial technique for biofilm detection and can help in combating A. baumannii infections by giving health providers the opportunity of implementing antibiofilm treatment strategies in a timely manner.

PMID:35834022 | DOI:10.1007/s00284-022-02943-0

Int J Implant Dent. 2022 Jul 14;8(1):30. doi: 10.1186/s40729-022-00429-z.

ABSTRACT

BACKGROUND: The present study was based on the null hypothesis that there is no difference in clinicoradiographic parameters and whole salivary alpha amylase (AA) and mucin-4 levels before and after non-surgical mechanical debridement (NSMD) of patients with peri-implant mucositis (PM). The aim was to assess whole salivary AA and mucin-4 levels before and after treatment of PM.

METHODS: Patients with PM (Group-1) and individuals without peri-implant diseases (Group-2) were included. Demographic data was collected and peri-implant modified plaque and bleeding indices (mPI and mBI, respectively), probing depth (PD) and crestal bone loss were measured at baseline. Levels of AA and mucin-4 were assessed in unstimulated whole saliva samples. All patients underwent full-mouth non-surgical periodontal therapy (NSPT) and NSMD; and clinical parameters and salivary biomarkers were re-assessed after 3 months. Level of significance was set at P < 0.01.

RESULTS: Twenty-six and 32 individuals were included in groups 1 and 2, respectively. None of the participants had periodontitis. At baseline clinical periodontal parameters (PI [P < 0.001], GI [P < 0.001], clinical AL [P < 0.001] and PD [P < 0.001]) were significantly high in Group-1 than Group-2. At 3-month follow-up, there was a statistically significant reduction in clinical periodontal and peri-implant parameters (PI [P < 0.01], GI [P < 0.01], and PD [P < 0.01]) in Group-1 compared with their baseline values. At baseline, salivary AA levels were significantly high in Group-1 than Group-2 (P < 0.01). At 3-month follow-up, there was no significant difference in whole salivary AA levels among patients in groups 1 and 2.

CONCLUSIONS: The AA and mucin-4 levels are potential biomarkers for evaluation of peri-implant diseases including PM. Mechanical instrumentation continues to be the most predictable treatment option for the management of peri-implant diseases.

PMID:35834021 | DOI:10.1186/s40729-022-00429-z

Eur Arch Otorhinolaryngol. 2022 Jul 14. doi: 10.1007/s00405-022-07532-2. Online ahead of print.

ABSTRACT

PURPOSE: Studies have assessed the trauma and change in hearing function from the use of otological drills on the ossicular chain, but not the effects of partial laser ablation of the incus. A study of the effectiveness of a novel middle-ear microphone for a cochlear implant, which required an incus recess for the microphone balltip, provided an opportunity to compare methods and inform a feasibility study of the microphone with patients.

METHODS: We used laser Doppler vibrometry with an insert earphone and probe microphone in 23 ears from 14 fresh-frozen cadavers to measure the equivalent noise level at the tympanic membrane that would have led to the same stapes velocity as the creation of the incus recess.

RESULTS: Drilling on the incus with a diamond burr created peak noise levels equivalent to 125.1-155.0 dB SPL at the tympanic membrane, whilst using the laser generated equivalent noise levels barely above the baseline level. The change in middle ear transfer function following drilling showed greater variability at high frequencies, but the change was not statistically significant in the three frequency bands tested.

CONCLUSIONS: Whilst drilling resulted in substantially higher equivalent noise, we considered that the recess created by laser ablation was more likely to lead to movement of the microphone balltip, and therefore decrease performance or result in malfunction over time. For patients with greatly reduced residual hearing, the greater consistency from drilling the incus recess may outweigh the potential benefits of hearing preservation with laser ablation.

PMID:35834014 | DOI:10.1007/s00405-022-07532-2

Hepatol Commun. 2022 Jul 14. doi: 10.1002/hep4.2032. Online ahead of print.

ABSTRACT

In nonalcoholic fatty liver disease (NAFLD) the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 variant is a contributor. In mice, the Pnpla3 148M variant accumulates on lipid droplets and probably leads to sequestration of a lipase cofactor leading to impaired mobilization of triglycerides. To advance our understanding of the localization and abundance of PNPLA3 protein in humans, we used liver biopsies from patients with NAFLD to investigate the link to NAFLD and the PNPLA3 148M genotype. We experimentally qualified an antibody against human PNPLA3. Hepatic PNPLA3 protein fractional area and localization were determined by immunohistochemistry in biopsies from a well-characterized NAFLD cohort of 67 patients. Potential differences in hepatic PNPLA3 protein levels among patients related to degree of steatosis, lobular inflammation, ballooning, and fibrosis, and PNPLA3 I148M gene variants were assessed. Immunohistochemistry staining in biopsies from patients with NAFLD showed that hepatic PNPLA3 protein was predominantly localized to the membranes of small and large lipid droplets in hepatocytes. PNPLA3 protein levels correlated strongly with steatosis grade (p = 0.000027) and were also significantly higher in patients with lobular inflammation (p = 0.009), ballooning (p = 0.022), and significant fibrosis (stage 2-4, p = 0.014). In addition, PNPLA3 levels were higher in PNPLA3 rs738409 148M (CG, GG) risk allele carriers compared to 148I (CC) nonrisk allele carriers (p = 0.0029). Conclusion: PNPLA3 protein levels were associated with increased hepatic lipid content and disease severity in patients with NAFLD and were higher in PNPLA3 rs738409 (148M) risk allele carriers. Our hypothesis that increased hepatic levels of PNPLA3 may be part of the pathophysiological mechanism of NAFLD is supported.

PMID:35833455 | DOI:10.1002/hep4.2032

J Neurotrauma. 2022 Jul 14. doi: 10.1089/neu.2022.0139. Online ahead of print.

ABSTRACT

Agitation is common during post-traumatic amnesia (PTA) following traumatic brain injury (TBI) and is associated with risk of harm to patients and caregivers. Antipsychotics are frequently used to manage agitation in early TBI recovery despite limited evidence to support their efficacy, safety and impact upon patient outcomes. The sedating and cognitive side-effects of these agents are theorised to exacerbate confusion during PTA, leading to prolonged PTA duration and increased agitation. This study, conducted in a subacute inpatient rehabilitation setting, describes the results of a double-blind, randomized, placebo-controlled trial investigating the efficacy of olanzapine for agitation management during PTA, analysed as an n-of-1 series. Group comparisons were additionally conducted, examining level of agitation, number of agitated days, agitation at discharge, duration and depth of PTA, length of hospitalisation, cognitive outcome, adverse events and rescue medication use. Eleven agitated participants in PTA (mean age = 39.82 years, SD = 20.06; mean time post injury = 46.09 days, SD = 32.75) received oral olanzapine (n = 5) or placebo (n = 6) for the duration of PTA, beginning at a dose of 5mg/day and titrated every three to four days to a maximum dose of 20mg/day. All participants received recommended environmental management for agitation. A significant decrease in agitation with moderate to very large effect (Tau-U effect size = .37-.86) was observed for three of five participants receiving olanzapine, while no significant reduction in agitation over the PTA period was observed for any participant receiving placebo. Effective olanzapine dose ranged from 5-20mg. Response to treatment was characterised by lower level of agitation and response to treatment within 3 days. In group analyses, participants receiving olanzapine demonstrated poorer orientation and memory during PTA with large effect size (olanzapine M = 9.32, SD = 0.69; placebo M = 10.68, SD = 0.30; p = .009, d = -2.16), and a trend toward longer PTA duration with large effect size (olanzapine M = 71.96 days, SD = 20.31; placebo M = 47.50 days, SD = 11.27; p = .072, d = 1.26). No further group comparisons were statistically significant. These results suggest that olanzapine can be effective in reducing agitation during PTA, but not universally so. Importantly, administration of olanzapine during PTA may lead to increased patient confusion, possibly prolonging PTA. When utilising olanzapine, physicians must therefore balance the possible advantages of agitation management with the possibility that the patient may never respond to the medication and may experience increased confusion, longer PTA and potentially poorer outcomes. Further high-quality research is required to support these findings, and the efficacy and outcomes associated with the use of any pharmacological agent for the management of agitation during the PTA period.

PMID:35833454 | DOI:10.1089/neu.2022.0139

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 &lt; 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 &lt; 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&lt;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