Category: Nevin Manimala

Eur Arch Otorhinolaryngol. 2023 Mar 7. doi: 10.1007/s00405-023-07896-z. Online ahead of print.

ABSTRACT

PURPOSE: Disturbance of cochlear microcirculation is discussed as final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a possible factor for a critical reduction of cochlear blood flow that might lead to sudden sensorineural hearing loss (SSHL). The aim was to determine the efficacy and safety of drug-induced defibrinogenation by ancrod for SSHL.

METHODS: Double-blind, randomized, placebo-controlled, multicenter, parallel group, phase II (proof-of-concept) study (planned enrollment: 99 patients). Patients received an infusion of ancrod or placebo (day 1) followed by subcutaneous administrations (day 2, 4, 6). Primary outcome was the change in pure tone audiogram air conduction average until day 8.

RESULTS: The study was terminated early due to slow recruiting (31 enrolled patients: 22 ancrod, 9 placebo). A significant improvement of hearing loss was registered in both groups (ancrod: – 14.3 dB ± 20.4 dB, – 39.9% ± 50.4%; placebo: – 22.3 dB ± 13.7 dB, – 59.1% ± 38.0%). A statistically significant group-difference was not detected (p = 0.374). Placebo response of 33.3% complete and 85.7% at least partial recovery was observed. Plasma fibrinogen levels were reduced significantly by ancrod (baseline: 325.2 mg/dL, day 2: 107.2 mg/dL). Ancrod was tolerated well, no adverse drug reaction was of severe intensity, no serious adverse events occurred.

CONCLUSION: Ancrod reduced fibrinogen levels that support its mechanism of action. The safety profile can be rated positively. Since the planned number of patients could not be enrolled, no efficacy conclusion can be drawn. The high rate of placebo response challenges clinical trials for SSHL and needs to be considered in future investigations. Trial registrations This study was registered in the EU Clinical Trials Register, EudraCT-No. 2012-000066-37 at 2012-07-02.

PMID:36881166 | DOI:10.1007/s00405-023-07896-z

Clin Oral Investig. 2023 Mar 7. doi: 10.1007/s00784-023-04906-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the correlation between oral health status in terms of present teeth, implants, removable prostheses, and polypharmacy and/or multimorbidity in three Swiss nursing homes with affiliated or integrated dental care.

METHODS: A cross-sectional study was conducted in three Swiss geriatric nursing homes with integrated dental care. Dental information consisted of the number of teeth, root remnants, implants, and presence of removable dental prostheses. Furthermore, the medical history was assessed in terms of diagnosed medical conditions and prescribed medication. Age, dental status, polypharmacy, and multimorbidity were compared and correlated using t-tests and Pearson correlation coefficients.

RESULTS: One hundred eighty patients with a mean age of 85.5 ± 7.4 years were included of which a portion of 62% presented with multimorbidity and 92% with polypharmacy. The mean number of remaining teeth and remnant roots were 14.1 ± 9.9 and 1.0 ± 3.1, respectively. Edentulous individuals comprised 14%, and over 75% of the population did not have implants. Over 50% of the included patients wore removable dental prostheses. A negative correlation with statistical significance (p = 0.001) between age and tooth loss (r = – 0.27) was observed. Finally, there was a non-statistically correlation between a higher number of remnant roots and specific medications linked to salivary dysfunction; specifically antihypertensive medication and central nervous system stimulants.

CONCLUSION: The presence of a poor oral health status was associated with polypharmacy and multimorbidity among the study population.

CLINICAL RELEVANCE: Identifying elderly patients in need of oral healthcare in nursing homes is a challenge. In Switzerland, the collaboration of dentists and nursing staff is still improvable, but is urgently needed due to the demographic changes and raising treatment demand of the oldest portion of the population.

PMID:36881159 | DOI:10.1007/s00784-023-04906-6

J Neurol. 2023 Mar 7. doi: 10.1007/s00415-023-11636-y. Online ahead of print.

ABSTRACT

BACKGROUND: Performing cognitive-motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown.

OBJECTIVE: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level.

METHODS: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5-5.5, ≥ 6). Spearman correlations were conducted between the DTC_motor with clinical measures. Adjusted significance level was 0.01.

RESULTS: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTC_motor of 15.8% and DTC_cognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTC_motor different from zero (p’s < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTC_cognitive did not differ from zero for any of the groups (p ≥ 0.039).

CONCLUSION: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups.

PMID:36881147 | DOI:10.1007/s00415-023-11636-y

Cancer Immunol Immunother. 2023 Mar 7. doi: 10.1007/s00262-023-03400-y. Online ahead of print.

ABSTRACT

AIM: We have previously reported that polyfunctional T cell responses can be induced to the cancer testis antigen NY-ESO-1 in melanoma patients injected with mature autologous monocyte-derived dendritic cells (DCs) loaded with long NY-ESO-1-derived peptides together with α-galactosylceramide (α-GalCer), an agonist for type 1 Natural Killer T (NKT) cells.

OBJECTIVE: To assess whether inclusion of α-GalCer in autologous NY-ESO-1 long peptide-pulsed DC vaccines (DCV + α-GalCer) improves T cell responses when compared to peptide-pulsed DC vaccines without α-GalCer (DCV).

DESIGN, SETTING AND PARTICIPANTS: Single-centre blinded randomised controlled trial in patients ≥ 18 years old with histologically confirmed, fully resected stage II-IV malignant cutaneous melanoma, conducted between July 2015 and June 2018 at the Wellington Blood and Cancer Centre of the Capital and Coast District Health Board.

INTERVENTIONS: Stage I. Patients were randomised to two cycles of DCV or DCV + α-GalCer (intravenous dose of 10 × 10⁶ cells, interval of 28 days). Stage II. Patients assigned to DCV + α-GalCer were randomised to two further cycles of DCV + α-GalCer or observation, while patients initially assigned to DCV crossed over to two cycles of DCV + α-GalCer.

OUTCOME MEASURES: Primary: Area under the curve (AUC) of mean NY-ESO-1-specific T cell count detected by ex vivo IFN-γ ELISpot in pre- and post-treatment blood samples, compared between treatment arms at Stage I. Secondary: Proportion of responders in each arm at Stage I; NKT cell count in each arm at Stage I; serum cytokine levels at Stage I; adverse events Stage I; T cell count for DCV + α-GalCer versus observation at Stage II, T cell count before versus after cross-over.

RESULTS: Thirty-eight patients gave written informed consent; 5 were excluded before randomisation due to progressive disease or incomplete leukapheresis, 17 were assigned to DCV, and 16 to DCV + α-GalCer. The vaccines were well tolerated and associated with increases in mean total T cell count, predominantly CD4⁺ T cells, but the difference between the treatment arms was not statistically significant (difference – 6.85, 95% confidence interval, – 21.65 to 7.92; P = 0.36). No significant improvements in T cell response were associated with DCV + α-GalCer with increased dosing, or in the cross-over. However, the NKT cell response to α-GalCer-loaded vaccines was limited compared to previous studies, with mean circulating NKT cell levels not significantly increased in the DCV + α-GalCer arm and no significant differences in cytokine response between the treatment arms.

CONCLUSIONS: A high population coverage of NY-ESO-1-specific T cell responses was achieved with a good safety profile, but we failed to demonstrate that loading with α-GalCer provided an additional advantage to the T cell response with this cellular vaccine design.

CLINICAL TRIAL REGISTRATION: ACTRN12612001101875. Funded by the Health Research Council of New Zealand.

PMID:36881133 | DOI:10.1007/s00262-023-03400-y

Abdom Radiol (NY). 2023 Mar 7. doi: 10.1007/s00261-023-03853-w. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to assess the utility of dual reader interpretation of prostate MRI in the evaluation/detection of prostate cancer, using the PI-RADS v2.1 scoring system.

METHODS: We performed a retrospective study to assess the utility of dual reader interpretation for prostate MRI. All MRI cases compiled for analysis were accompanied with prostate biopsy pathology reports that included Gleason scores to correlate to the MRI PI-RADS v2.1 score, tissue findings and location of pathology within the prostate gland. To assess for dual reader utility, two fellowship trained abdominal imagers (each with > 5 years of experience) provided independent and concurrent PI-RADS v2.1 scores on all included MRI examinations, which were then compared to the biopsy proven Gleason scores.

RESULTS: After application of inclusion criteria, 131 cases were used for analysis. The mean age of the cohort was 63.6 years. Sensitivity, specificity and positive/negative predictive values were calculated for each reader and concurrent scores. Reader 1 demonstrated 71.43% sensitivity, 85.39% specificity, 69.77% PPV and 86.36% NPV. Reader 2 demonstrated 83.33% sensitivity, 78.65% specificity, 64.81% PPV and 90.91% NPV. Concurrent reads demonstrated 78.57% sensitivity, 80.9% specificity, 66% PPV and 88.89% NPV. There was no statistically significant difference between the individual readers or concurrent reads (p = 0.79).

CONCLUSION: Our results highlight that dual reader interpretation in prostate MRI is not needed to detect clinically relevant tumor and that radiologists with experience and training in prostate MRI interpretation establish acceptable sensitivity and specificity marks on PI-RADS v2.1 assessment.

PMID:36881131 | DOI:10.1007/s00261-023-03853-w

J Orofac Orthop. 2023 Mar 7. doi: 10.1007/s00056-023-00456-4. Online ahead of print.

ABSTRACT

PURPOSE: The purposes of this study were to compare and evaluate the surface texture of different restorative computer-aided design and computer-aided manufacturing (CAD/CAM) materials before bonding and after debonding of metal orthodontic brackets.

MATERIALS AND METHODS: A total of 60 rectangular ceramic test specimens (n = 20 in each group) were prepared using feldspathic ceramic blocks (FLD; served as control), hybrid ceramic blocks (HC), and lithium disilicate ceramic blocks (LDC). Surface roughness (Ra) analysis was conducted using a profilometer before bonding the metal brackets. After the debonding and polishing procedures, a second surface roughness analysis was conducted on each specimen. The shear bond strength (SBS) test was applied to each specimen using a universal test machine for debonding the metal brackets. The debonded specimens were examined under a stereomicroscope and scored using a 4-step adhesive remnant index (ARI). The Ra and SBS values and the ARI scores were saved, and the data were analyzed statistically at a significance level of 0.05. One specimen from each group was examined under atomic force microscopy to visualize surface roughness. Furthermore, one specimen from each group was additionally prepared for scanning electron microscopy analysis.

RESULTS: Statistically significant differences in SBS measurements were observed between all three groups. The highest SBS values were obtained from the FLD group, the lowest from the LDC group. The HC group showed significantly (P = 0.001) lower Ra values than the LDC and FLD groups after debonding and polishing. No significant differences were observed in the ARI scores between the groups.

CONCLUSIONS: Hybrid ceramics could be a suitable alternative for fixed restorations in adult patients receiving subsequent treatments with fixed orthodontic appliances.

PMID:36881111 | DOI:10.1007/s00056-023-00456-4

J Intellect Disabil Res. 2023 Mar 7. doi: 10.1111/jir.13023. Online ahead of print.

ABSTRACT

BACKGROUND: There is evidence that psychotropic medications are overprescribed and overused to manage behaviours of concern for people with intellectual disabilities. Disability support workers and support staff lack education and training on the administration and safety of psychotropic medication use. This study aimed to test the applicability and preliminary efficacy of SPECTROM, an education programme developed in the UK, in an Australian context.

METHODS: The training comprises two parts: Module 1 encompasses psychotropic medications, their use and side effects. Module 2 focuses on non-pharmacological interventions for supporting people with behaviours of concern. Thirty-three participants attended the training course and completed pre-training and post-training surveys on the Psychotropic Knowledge Questionnaire and Management of Aggression and Violence Attitude Scale-Revised at four time points: pre-training, 2 weeks, 3 months and 5 months post-training.

RESULTS: Psychotropic Knowledge Questionnaire scores showed statistically significant post-training improvement at all post-training time points (P < 0.05). Management of Aggression and Violence Attitude Scale-Revised scores were high at pre-training and did not change significantly at any of the post-training survey time points. A 2-week post-training feedback questionnaire reported 80% agreement that the training programme was appropriate, useful and valid. Only 36% of participants completed questionnaires at all time points.

CONCLUSIONS: SPECTROM training increased staff knowledge of psychotropic medications, yet loss of participants was high. Further refinement of the applicability of the training for the Australian context and evaluation of the feasibility of implementation, clinical and cost-effectiveness of the programme are required.

PMID:36880447 | DOI:10.1111/jir.13023

Int J Dermatol. 2023 Mar 7. doi: 10.1111/ijd.16619. Online ahead of print.

ABSTRACT

BACKGROUND: Dating back to the mid-1500s, maggot debridement therapy (MDT) has been a viable treatment modality for chronic wounds. In early 2004, the sterile larvae of Lucilia sericata received FDA approval for medical marketing for neuropathic, venous, and pressure ulcers, traumatic or surgical wounds, and nonhealing wounds that have not responded to standard care. However, it currently remains an under-utilized therapy. The proven efficacy of MDT begs the question if this treatment modality should be considered as a first-line option for all or a subset of chronic lower extremity ulcers.

OBJECTIVE: This article aims to address the history, production, and evidence of MDT and discuss future considerations for maggot therapy in the healthcare field.

METHODS: A literature search using the PubMed database was conducted using keywords, such as wound debridement, maggot therapy, diabetic ulcers, venous ulcers, among others.

RESULTS: MDT reduced short-term morbidity in non-ambulatory patients with neuroischemic diabetic ulcers and comorbidity with peripheral vascular disease. Larval therapy was associated with statistically significant bioburden reductions against both Staphylococcus aureus and Pseudomonas aeruginosa. Faster time to debridement was achieved when chronic venous or mixed venous and arterial ulcers were treated with maggot therapy versus hydrogels.

CONCLUSIONS: The literature supports the use of MDT in decreasing the significant costs of treating chronic lower extremity ulcers, with emphasis on those of diabetic origin. Additional studies with global standards for reporting outcomes are necessary to substantiate our results.

PMID:36880424 | DOI:10.1111/ijd.16619

New Phytol. 2023 Mar 7. doi: 10.1111/nph.18859. Online ahead of print.

ABSTRACT

The black nectar produced by Melianthus flowers is thought to serve as a visual attractant to bird pollinators, but the chemical identity and synthesis of the black pigment are unknown. A combination of analytical biochemistry, transcriptomics, proteomics, and enzyme assays was used to identify the pigment that gives Melianthus nectar its black color and how it is synthesized. Visual modeling of pollinators was also used to infer a potential function of the black coloration. High concentrations of ellagic acid and iron give the nectar its dark black color, which can be recapitulated through synthetic solutions containing only ellagic acid and iron(III). The nectar also contains a peroxidase that oxidizes gallic acid to form ellagic acid. In vitro reactions containing the nectar peroxidase, gallic acid, hydrogen peroxide, and iron(III) fully recreate the black color of the nectar. Visual modeling indicates that the black color is highly conspicuous to avian pollinators within the context of the flower. Melianthus nectar contains a natural analog of iron-gall ink, which humans have used since at least medieval times. This pigment is derived from an ellagic acid-Fe complex synthesized in the nectar and is likely involved in the attraction of passerine pollinators endemic to southern Africa.

PMID:36880409 | DOI:10.1111/nph.18859

Asia Pac J Clin Oncol. 2023 Mar 7. doi: 10.1111/ajco.13949. Online ahead of print.

ABSTRACT

AIM: Peritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective.

METHOD: A prospective database of 294 patients with advanced appendiceal primary tumors undergoing CRS ± HIPEC between June 2009 and December 2020 was reviewed. Baseline characteristics and long-term outcomes were compared between patients with adenocarcinoma who received neoadjuvant chemotherapy or upfront surgery.

RESULTS: Eighty-six (29%) patients were histologically diagnosed with an appendiceal cancer. These included intestinal-type adenocarcinoma (11.6%), mucinous adenocarcinoma (43%), and goblet cell adenocarcinoma (GCA) or signet ring cell adenocarcinoma (SRCA) (45.4%). Twenty-five (29%) of these underwent NAC, of which eight (32%) exhibited some degree of radiological response. There was no statistical difference in OS at 3 years between the NAC and upfront surgery groups (47.3% vs. 75.8%, p = 0.372). Appendiceal histology subtypes, particularly GCA and SRCA (p = 0.039) and peritoneal carcinomatosis index >10 (p = 0.009), were factors independently associated with worse OS.

CONCLUSION: Administration of NAC did not appear to prolong OS in the operative management of disseminated appendiceal adenocarcinomas. GCA and SRCA subtypes display a more aggressive biological phenotype.

PMID:36880398 | DOI:10.1111/ajco.13949