Nevin Manimala

Mult Scler Relat Disord. 2021 Sep 28;56:103286. doi: 10.1016/j.msard.2021.103286. Online ahead of print.

ABSTRACT

BACKGROUND: Despite better characterization of the spectrum of MOG-IgG-associated disorders (MOGAD) in children, the role of infection in its pathophysiology remains unclear. The goal of this study was to evaluate if public health measures put in place to prevent the spread of SARS-CoV-2 in March 2020 in Ontario (Canada) have been associated with a change in the incidence of MOGAD and other neuroinflammatory disorders in children.

METHODOLOGY: We reviewed a single-centre cohort of children referred for a suspicion of neuroinflammatory disorder between January 2015 and March 2021. Age, date, sex, diagnosis, MOG-IgG antibodies status and detected pathogens at presentation were identified. Comparative statistical analysis was performed based on diagnosis between years and seasons using Pearson’s Chi-squared test or Fisher’s exact test for categorical variables and using ANOVA or Kruskal-Wallis test for continuous variables, as appropriate. We compared the post-lockdown period (March 17th, 2020, to March 31st, 2021) to previous calendar years (2015 to 2019) alone and to previous calendar years and the pre-lockdown 2020 period (January 1st, 2020, to March 16th, 2020). A p-value of < 0.05 was considered significant. Post-hoc pairwise comparisons between the post-lockdown period and previous years were performed on significant results. A false discovery rate adjustment with an adjusted p-value (q-value) < 0.05 was computed. We hypothesized that the number of new MOGAD would be significantly lower in the post-lockdown period compared to previous years due to decreased regional pathogen transmission.

RESULTS: Among 491 referred cases, we identified 415 new cases of neuroinflammatory disorder between January 2015 and March 2021. The number of new neuroinflammatory disorder diagnoses did not change between years. We noted significantly fewer new MOGAD diagnoses in 2020 compared to previous years, with no MOGAD patients presenting in 2020 after the spring lockdown (q=0.0009). In addition, there were significantly fewer parainfectious neuroinflammatory cases (q=0.04) and pathogen detected (q=0.04) in the post-lockdown period. The number of new multiple sclerosis (MS) and aquaporin-4 neuromyelitis optica spectrum disorders (AQP4-NMOSD) cases remained stable despite the lockdown (q=0.185 and 0.693 respectively).

INTERPRETATION: Enhanced population-based infection control strategies may have a role in modulating the incidence of MOGAD and parainfectious neuroinflammatory disorders, but not MS or AQP4-NMOSD.

PMID:34627003 | DOI:10.1016/j.msard.2021.103286

Mult Scler Relat Disord. 2021 Sep 28;56:103280. doi: 10.1016/j.msard.2021.103280. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to investigate serum glial fibrillary acidic protein (GFAP) and serum neurofilament light chain (NfL) levels as potential discriminative biomarkers between benign relapsing-remitting multiple sclerosis (BRRMS) and aggressive relapsing-remitting MS (ARRMS).

METHODS: Serum GFAP and NfL levels were analyzed in patients with BRRMS (n = 34), ARRMS (n = 29), and healthy controls (n = 14) by using Single Molecule Array (Simoa). Patients with ARRMS had been treated with highly effective disease-modifying treatments (DMT) (fingolimod or natalizumab).

RESULTS: Serum GFAP levels in both BRRMS (median 210.19 pg/ml, IQR 163.69-287.19) and in ARRMS (median 188.60 pg/ml, IQR39.23-244.93) were significantly higher (p = 0.035 and p = 0.034, respectively) compared to healthy controls (median 117.93 pg/ml, IQR 60.28-183.83). Serum GFAP levels did not differ between BRRMS and ARRMS. There were no statistical differences in NfL levels between BRRMS, ARRMS and healthy controls. GFAP level was significantly higher (p = 0.04) in BRRMS without DMT (median 216.04 pg/ml, IQR 188.60-274.79) than in those BRRMS patients who had used DMT (median 196.26 pg/ml, IQR 133.33-325.54).

CONCLUSIONS: We found elevated levels of serum GFAP in both BRRMS and ARRMS compared to healthy controls, reflecting astrocytic activation. Serum NfL did not differ between BRRMS and ARRMS, probably due to the stable inflammatory phase of the disease and effective DMT use in ARRMS. Single serum NfL and GFAP measurements cannot separate a patient with BRRMS from effectively treated ARRMS after a long history of the disease, thus consecutive samples are needed in the follow-up.

PMID:34627002 | DOI:10.1016/j.msard.2021.103280

Ann Diagn Pathol. 2021 Oct 4;55:151837. doi: 10.1016/j.anndiagpath.2021.151837. Online ahead of print.

ABSTRACT

Bronchiolar adenomas (BAs)/ciliated muco-nodular papillary tumors (CMPTs), are small, peripheral lung nodules arising predominantly in the elderly that follow a benign course. They can be mistaken for adenocarcinomas on frozen section. Immunohistochemistry (IHC) for basal cell markers highlights the continuous layer of basal cells underlying the tumor cells in BAs. BAs are further subdivided into proximal-type and distal type. Six BAs were retrieved from the pathology archives. The cases were classified based on morphology into proximal and distal BAs. The clinical and radiological features were reviewed. Immunohistochemistry and special stains were performed. The most common radiological picture of BA/CMPT was of a solid nodule with SUV_max < 3 as seen in 60% cases. 40% cases showed cavitation on CT. On histological examination, four cases were morphologically classified as proximal BAs and two as distal BAs. In proximal BAs, TTF1 was focally positive only in the basal cells in three of four. The mucin stained acidic. In distal BAs, TTF1 was diffusely positive in both basal and luminal cells. There was scant intracellular neutral mucin. Both the distal BAs had concomitant neuroendocrine tumors in the same lobe. Though the number of cases evaluated in this study is too low to be statistically significant, this study provides additional evidence to the concept of BA classification based on site specific histology and supplementary immunohistochemistry and reiterates the radiological features that may help distinguish it from malignant lesions.

PMID:34626934 | DOI:10.1016/j.anndiagpath.2021.151837

J Clin Anesth. 2021 Oct 6;75:110527. doi: 10.1016/j.jclinane.2021.110527. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE: To investigate efficacy and safety of liposomal bupivacaine (LB) transversus abdominis plane (TAP) block with or without intrathecal morphine (ITM) compared with ITM alone for postsurgical analgesia after cesarean delivery (CD).

DESIGN: Multicenter, open-label, randomized trial (NCT03853694).

SETTING: Operating room.

PATIENTS: Women with term pregnancy of 37 to 42 weeks scheduled for elective CD under spinal anesthesia.

INTERVENTION: Patients were randomized 1:1:1 to LB 266 mg TAP block alone (LB group), ITM 50 μg followed by LB 266 mg TAP block (LB + ITM group), or ITM 150 μg alone (ITM group). All groups received the same postsurgical multimodal analgesic regimen.

MEASUREMENTS: The LB and LB + ITM groups were compared with the ITM group for all efficacy outcomes. Postsurgical opioid consumption in morphine milligram equivalents (MMEs) through 72 h was compared by assessing noninferiority before testing superiority. Postsurgical pruritus severity was assessed on an 11-point numerical rating scale.

MAIN RESULTS: Between March 4, 2019, and January 10, 2020, 153 patients (LB, n = 52; LB + ITM, n = 48; ITM, n = 53) were enrolled. Baseline characteristics were comparable across groups. The LB group had statistically noninferior postsurgical opioid consumption through 72 h compared with the ITM group (least squares mean [LSM], 19.2 vs 16.4 MMEs; LSM treatment ratio, 1.17 [95% confidence interval (CI), 0.74-1.86]; noninferiority P < 0.0034) as did the LB + ITM group (LSM, 14.6 vs 16.4 MMEs; LSM treatment ratio, 0.89 [95% CI, 0.55-1.44]; noninferiority P < 0.0001). The LB and LB + ITM groups had significantly reduced pruritus severity scores through 12, 24, 48, and 72 h compared with the ITM group (P ≤ 0.0121). Adverse events occurred in 58%, 85%, and 81% of the LB, LB + ITM, and ITM groups, respectively.

CONCLUSIONS: LB TAP block with or without ITM resulted in statistically noninferior postsurgical opioid consumption through 72 h, reduced pruritus, and favorable safety compared with ITM in women undergoing CD.

PMID:34626927 | DOI:10.1016/j.jclinane.2021.110527

ESMO Open. 2021 Oct 6;6(5):100277. doi: 10.1016/j.esmoop.2021.100277. Online ahead of print.

ABSTRACT

BACKGROUND: Oral mucositis (OM) is an unpleasant adverse event in patients receiving chemotherapy. A prospective feasibility study showed that elemental diet (ED), an oral supplement that does not require digestion, may prevent OM. Based on this, we established a central review system for oral cavity assessment by dental oncology specialists blinded to background data. We used this system to elucidate the preventive effect of an ED against OM in patients with esophageal cancer receiving docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy.

PATIENTS AND METHODS: In this phase III, multicenter, parallel-group, controlled trial, patients consuming a normal diet orally were randomly assigned (1 : 1) to receive two cycles of DCF with (group A) or without (group B) an ED (Elental® 160 g/day). We assessed the incidence of grade ≥2 OM evaluated by two reviewers, changes in body weight, prealbumin, C-reactive protein, and DCF completion rate based on ED compliance.

RESULTS: Of the 117 patients randomly assigned to treatment, four failed to start treatment and were excluded from the primary analysis; thus, groups A and B comprised 55 and 58 patients, respectively. There were no significant differences in background characteristics. Grade ≥2 OM was observed in eight (15%) and 20 (34%) patients in groups A and B, respectively (P = 0.0141). Changes in body weight and prealbumin during the two DCF cycles were significantly higher in group A than B (P = 0.0022 and 0.0203, respectively). During the first cycle, changes in C-reactive protein were significantly lower in group A than B (P = 0.0338). In group A (receiving ED), the DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (P = 0.0046).

CONCLUSIONS: The study findings demonstrate that an ED can prevent OM in patients with esophageal cancer receiving chemotherapy.

PMID:34626918 | DOI:10.1016/j.esmoop.2021.100277

Cancer Epidemiol. 2021 Oct 6;75:102017. doi: 10.1016/j.canep.2021.102017. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic cancer (PC) is ranked as the seventh leading cause of cancer deaths worldwide. The current study was conducted to explore the correlation between the use of opium and its derivatives (opium) and PC in Iran.

METHODS: In this case-control study which was conducted in Kerman province, south east part of Iran; 176 patients with PC, and 352 healthy individuals as the control group were matched in terms of age, sex, and place of residence. A structured questionnaire including questions of opium usage, alcohol usage, cigarette smoking, and diet was used to collect the data. The relation between the use of opium and PC was adjusted for tobacco smoking, education, daily intake of fruit, vegetables, red meat, and hydrogenated fats and analyzed using the conditional logistic regression.

RESULTS: There was a positive relationship between the opium use and the increased risk of PC (Adjusted Odds Ratio (AOR) = 4.33, 95 % CI: 2.09-8.95), which was even stronger than its association with cigarette smoking (AOR = 1.67, 95 % CI: 0.86-3.24), although their difference was not statistically significant. A significant dose-response relation was detected between the use of opium; as the relation was stronger in heavy users (AOR low users = 4.93, 95 % CI: 1.79-13.54 and AOR heavy users = 5.10, 95 % CI: 2.10-12.35). Moreover, PC was higher among participants starting the use of opium at a younger age than those who started opium at an older age (AOR = 8.03, 95 % CI: 3.19-20.23).

CONCLUSION: This study demonstrated that opium use is associated with a high and strong risk of PC as an independent risk factor. Further studies should be done to reduce the use of opium in Iran and other world countries.

PMID:34626910 | DOI:10.1016/j.canep.2021.102017

Phys Ther Sport. 2021 Sep 27;52:217-223. doi: 10.1016/j.ptsp.2021.09.009. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this pilot study was to examine the preliminary feasibility and efficacy of in vivo exposure therapy (IVET) to decrease injury-related fear in females with history of ACLR.

DESIGN: Pilot Study.

SETTING: Sports Medicine Research Laboratory.

PARTICIPANTS: 12 female participants with history of ACLR (≥ 1 year post-operative) were randomized into a 5-week IVET group (n = 6) or 5-week sham physical activity (PA) monitoring group (n = 6).

MAIN OUTCOME MEASURES: The independent variables were Group and Time. The dependent variables were the Photographic Series of Sports Activities for ACLR (PHOSA-ACLR) and the Tampa Scale of Kinesiophobia-11 (TSK-11) scores. A Group x Time repeated measures two-way analysis of variance was completed for the PHOSA-ACLR and the TSK-11. Partial η² effect sizes were used to examine clinically meaningful differences.

RESULTS: High retention and adherence rates were observed in the intervention group. The PHOSA-ACLR exhibited a significant main effect for Time (F_1,10 = 9.92, p = 0.01, partial η² = 0.50), but not for Group. No statistically significant or clinically meaningful differences were observed for the TSK-11.

CONCLUSION: Both groups exhibited decreased injury-related fear for specific functional tasks. Future research should further examine the efficacy of IVET and PA monitoring to decrease injury-related fear in patients after ACLR.

PMID:34626890 | DOI:10.1016/j.ptsp.2021.09.009

Neuroimage Clin. 2021 Oct 5;32:102842. doi: 10.1016/j.nicl.2021.102842. Online ahead of print.

ABSTRACT

BACKGROUND: Frontotemporal dementia (FTD) is a common cause of young onset dementia, and whilst there are currently no treatments, there are several promising candidates in development and early phase trials. Comprehensive investigations of neuroimaging markers of disease progression across the full spectrum of FTD disorders are lacking and urgently needed to facilitate these trials.

OBJECTIVE: To investigate the comparative performance of multiple automated segmentation and registration pipelines used to quantify longitudinal whole-brain atrophy across the clinical, genetic and pathological subgroups of FTD, in order to inform upcoming trials about suitable neuroimaging-based endpoints.

METHODS: Seventeen fully automated techniques for extracting whole-brain atrophy measures were applied and directly compared in a cohort of 226 participants who had undergone longitudinal structural 3D T1-weighted imaging. Clinical diagnoses were behavioural variant FTD (n = 56) and primary progressive aphasia (PPA, n = 104), comprising semantic variant PPA (n = 38), non-fluent variant PPA (n = 42), logopenic variant PPA (n = 18), and PPA-not otherwise specified (n = 6). 49 of these patients had either a known pathogenic mutation or postmortem confirmation of their underlying pathology. 66 healthy controls were included for comparison. Sample size estimates to detect a 30% reduction in atrophy (80% power; 0.05 significance) were computed to explore the relative feasibility of these brain measures as surrogate markers of disease progression and their ability to detect putative disease-modifying treatment effects.

RESULTS: Multiple automated techniques showed great promise, detecting significantly increased rates of whole-brain atrophy (p<0.001) and requiring sample sizes of substantially less than 100 patients per treatment arm. Across the different FTD subgroups, direct measures of volume change consistently outperformed their indirect counterparts, irrespective of the initial segmentation quality. Significant differences in performance were found between both techniques and patient subgroups, highlighting the importance of informed biomarker choice based on the patient population of interest.

CONCLUSION: This work expands current knowledge and builds on the limited longitudinal investigations currently available in FTD, as well as providing valuable information about the potential of fully automated neuroimaging biomarkers for sporadic and genetic FTD trials.

PMID:34626889 | DOI:10.1016/j.nicl.2021.102842

Knee. 2021 Oct 6;33:169-175. doi: 10.1016/j.knee.2021.09.007. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the ultimate failure load and stiffness of two patellar fixation techniques for medial patellofemoral ligament (MPFL) reconstruction: (1) quadriceps tendon fixation (QT), (2) single tunnel (STG) patella fixation with gracilis autograft.

METHODS: A total of 16 fresh-frozen cadaveric knees (eight matched pairs) were randomized into two groups (QT vs. STG). The MPFL reconstructions were subjected to cyclic loading for 10 cycles to 30 N and then tested to failure at a constant displacement rate of 15 mm/min using a materials-testing machine (MTS 810 Universal Testing System). Failure mode, ultimate failure load and stiffness were recorded for each cadaveric specimen.

RESULTS: There was no significant difference in mean ultimate failure load among groups (P = 0.35). The STG group failed at a mean ultimate load of 190.04 N [standard deviation (SD) 23.18] and the QT group failed at 206.24 N (SD 37.99). The STG group had a mean stiffness of 21.38 N/mm (SD 1.44). This was not significantly higher than the mean stiffness value achieved for the QT group at 20.36 N/mm (SD 1.3) (P = 0.19). In the QT group all reconstructions failed due to tendon rupture at the patella attachment. The reason for failure in the STG group was the graft-suture connection.

CONCLUSIONS: This cadaver study showed no statistically significant difference in biomechanical performance of the evaluated patella fixation techniques, in terms of maximum load to failure and stiffness. Both techniques are reliable in terms of biomechanical properties and could offer additional surgical solutions.

PMID:34626887 | DOI:10.1016/j.knee.2021.09.007

Int J Clin Pract. 2021 Oct 9:e14970. doi: 10.1111/ijcp.14970. Online ahead of print.

ABSTRACT

BACKGROUND: COVID 19 was first observed in December 2019 and has affected the world entire. Effective laboratory markers and prognostic indicators are needed to predict the clinical progression of the disease.

AIMS: The purpose of this study was to investigate IL6, IL8/CXCL8, and IP10/CXCL10, and biochemical parameters associated with SARS, MERS, and SARS-CoV-2 infections and their significance on prognosis in healthy volunteers and mild-moderate and severe COVID 19 patients.

METHODS: Healthy volunteers (n=30), and patients with mild-moderate (n=30) and severe (n=30) COVID-19 patients were included in the study. IL-6, IL-8 and IP-10 levels and biochemical parameters were assessed among the groups and their correlations with each other were subjected to statistical analysis.

RESULTS: Blood serum IL-6, IL-8 and IP-10 levels were the highest in the severe patient group (p=0.001), and also higher in the mild-moderate group as compared to the healthy volunteers (p=0.001). Statistically significant positive correlations were identified between serum IL-8 and IL-6 levels (p=0.001 r=0.660), between serum IP-10 and IL-6 (p=0.001 r =0.599) and between serum IP-10 and IL-8 (p=0.001 r=0.729).

CONCLUSIONS: A statistically significant difference was found in WBC, NE%, NE, LY%, LY, HB, BUN, total protein, albumin, D-dimer, sedimentation differed significantly between the groups. Biomarkers of potential significance in terms of the severity of COVID 19 disease were examined, and high IL-6, IL-8, IP-10, CRP, PCT, and LY parameters values emerged as associated with the severity of the disease.

PMID:34626520 | DOI:10.1111/ijcp.14970