Comparative Analysis of Stereotactic Radiation Therapy and Conventional Radiation Therapy in Cancer Pain Control: A Systematic Review and Meta-Analysis.

AIMS: Approximately 55% of patients diagnosed with primary or metastatic cancer endure pain directly attributable to the disease. Consequently, it becomes imperative to address pain management through a comparative analysis of stereotactic radiotherapy (SRT) and conventional radiation therapy (CRT), especially in light of the less efficacious improvement achieved solely through pharmacological interventions. MATERIALS AND METHODS: A systematic exploration was undertaken on PubMed, the Cochrane Library, and Elsevier's ScienceDirect databases to identify studies that compare Stereotactic Radiotherapy to Conventional radiation therapy for pain management in individuals with metastatic bone cancer. The analyses were executed utilizing the random-effects model. RESULTS: A cohort of 1152 participants with metastatic bone cancer was analyzed, demonstrating significantly higher complete pain relief in the Stereotactic Radiotherapy group during both early and late follow-up (RR: 1.61; 95% CI: 1.17, 2.23, p-value: 0.004; I2: 0%). Stereotactic Radiotherapy also showed a non-significant increase in the incidence of partial pain relief (RR: 1.07; 95% CI: 0.85, 1.34, p-value: 0.56; I2: 18%). Furthermore, Stereotactic Radiotherapy was associated with a significantly reduced risk of stationary pain throughout follow-up (RR: 0.61; 95%CI: 0.48, 0.76, p-value: <0.0001; I2: 0. The incidence of progressive pain was non-significantly reduced with Stereotactic Radiotherapy during both early and late follow-up (RR: 0.77; 95% CI: 0.50, 1.17, p-value: 0.22; I2: 0%). Secondary outcomes exhibited a non-significant trend favoring Stereotactic Radiotherapy for dysphagia, esophagitis, pain, and radiodermatitis, while a non-significant increase was observed for nausea, fatigue, and vertebral compression fracture. CONCLUSION: In summary, stereotactic radiation therapy (SRT) has improved in achieving complete pain relief while exhibiting a decreased probability of delivering stationary pain compared to conventional radiation therapy (CRT). Nevertheless, it is crucial in future research to address a noteworthy limitation, specifically, the risk of vertebral compression fracture.

Clinical Trial to Compare Success Rate of Endonasal Dacryocystorhinostomy and External Dacryocystorhinostomy for Treatment of Primary Acquired Nasolacrimal Duct Obstruction.

The purpose of this study is to compare the success rates of endoscopic endonasal dacryocystorhinostomy (EN-DCR) and external DCR (EX-DCR) for the treatment of primary acquired nasolacrimal duct obstruction (PANLDO). Prospective randomized comparative study. Study was conducted for 2 years duration in a teaching hospital with 300 cases of endoscopic and 300 cases of external DCR with a follow-up of minimum 6 months. Data regarding surgical outcome and complications were analyzed and compared using χ2 test. In our study, the overall success rate of DCR for PANLDO was 92.6%, there was difference in terms of anatomical or functional success rate between EN-DCR (93.6%) and EX-DCR (91.6%). The incidence rate of post operative complication in our study was lower in Endonasal DCR (27.33%) as compared to External DCR (48%). Patients who underwent EN-DCR had shorter recovery time, less complications and higher satisfaction due to lack of external incision, although final surgical outcomes were comparable between two groups.

Audit of Molecular Mechanisms of Primary and Secondary Resistance to Various Generations of Tyrosine Kinase Inhibitors in Known Epidermal Growth Factor Receptor-Mutant Non-small Cell Lung Cancer Patients in a Tertiary Centre.

AIMS: Presently, three generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved against oncogene addicted EGFR-mutant non-small cell lung cancer (NSCLC). Patients with actionable EGFR mutations invariably develop resistance. This resistance can be intrinsic (primary) or acquired (secondary). MATERIALS AND METHODS: This was a retrospective study carried out between January 2016 and April 2021 analysing 486 samples of NSCLC for primary and secondary resistance to first- (erlotinib, gefitinb), second- (afatinib) and/or third-generation (osimertinib) TKIs in EGFR-mutant NSCLCs by next generation sequencing (NGS). Tissue NGS was carried out using the Thermofischer Ion Torrent™ Oncomine™ Focus 52 gene assay; liquid biopsy NGS was carried out using the Oncomine Lung Cell-Free Total Nucleic Acid assay. All cases were previously tested for a single EGFR gene with the Therascreen® EGFR RGQ PCR kit. RESULTS: The results were divided into four groups: (i) group 1: primary resistance to first- and/or second-generation TKIs. This group, with 21 cases, showed EGFR exon 20 insertions, dual, complex mutations and variant of unknown significance, de novo MET gene amplification besides other mutations. (ii) Group 2: primary resistance to third-generation TKIs. This group showed two cases, with one showing dual EGFR mutation (L858R and E709A) and EGFR gene amplification. (iii) Group 3: secondary resistance to first- and second-generation TKIs. This group had 27 cases, which were previously reported negative for EGFR T790M by single gene testing. Significant findings were MET gene amplification in four cases, with one also showing MET exon 14 skipping mutation. Three cases showed small cell change and one showed loss of primary mutation. (iv) Group 4: secondary resistance to third-generation TKIs. The latter group was further subgrouped into group 4A: secondary resistance to osimertinib (third-generation TKI) when offered as second-line therapy after first- and second-generation TKIs on detection of T790M mutation. This group had 15 cases. EGFR T790M mutation was lost in 10 (10/15; 67%) cases and was retained in five cases. Patients with T790M loss experienced early resistance (6.9 months versus 12.6 months mean, P = 0.0024) compared with cases that retained T790M. Two cases gained MET amplification as the resistance mechanisms. Other mutations that were found when EGFR T790M was lost were in FGFR3, KRAS, PIK3CA, CTNNB1, BRAF genes. One case had EML4-ALK translocation. Two cases showed driver EGFR deletion 19, retained T790M and C797S mutation in Cis form. Group 4B: secondary resistance to osimertinib (when given as first-line therapy) in EGFR-mutant NSCLC. This group had three cases. The duration of osimertinib treatment ranged from 11 to 17 months. Two patients showed additional C797S mutation along with primary EGFR mutation. CONCLUSION: This study shows the wide spectrum of primary and secondary EGFR resistance mechanisms to first, second and third generation of TKIs and helps us to identify newer therapeutic targets that could carry forward the initial advantage offered by EGFR TKIs.

30-day complication rates and patient-reported outcomes following day case primary lumbar microdiscectomy in a regional NHS spinal centre.

INTRODUCTION: Advances in surgical and anaesthesia technique have reduced length of stay for lumbar discectomy. Current evidence suggests that daycase surgery is associated with improved patient satisfaction, faster recovery, reduced infection rates and financial savings. We present our microdiscectomy daycase protocol, together with 30-day postoperative complication rates and patient reported outcomes in an NHS setting. METHODS AND METHODS: We retrospectively studied all patients that met a locally agreed daycase protocol for lumbar microdiscectomy and were operated upon and discharged on the same calendar day between 1 March 2013 and 31 December 2015. RESULTS: A total of 134 patients underwent primary daycase microdiscectomy (70 males, 64 females). The cohort had a mean age of 41 years (range 16-82 years). Some 96% (n = 129) were single-level procedures, 93% were unilateral (n = 125) and 81% (n = 109) took place at either L4/L5 or L5/S1. All patients were discharged on the same day as admission and operation. Four patients re-presented to hospital within 30 days and three were discharged from the emergency department within four hours following a clinical review. One patient required an inpatient stay for a washout of a superficial postoperative infection. Significant improvements (P < 0.05) were found postoperatively for back pain and leg pain on self-reported visual analogue scores and Oswestry Disability Index. CONCLUSION: In this study, we present a safe and effective protocol for day case lumbar microdiscectomy. Our 30-day postoperative complication rate of under 1% is comparable to that of traditional inpatient primary lumbar microdiscectomy. Patient-reported outcome measures revealed significant improvement in both pain and functional scores.

Ocular Lesions in Red-Tailed Hawks ( Buteo jamaicensis) With Naturally Acquired West Nile Disease.

Ocular lesions are common in red-tailed hawks with West Nile (WN) disease. These lesions consist of pectenitis, choroidal or retinal inflammation, or retinal necrosis, but detailed investigation of the ocular lesions is lacking. Postmortem examination of the eyes of 16 red-tailed hawks with naturally acquired WN disease and 3 red-tailed hawks without WN disease was performed using histopathology, immunohistochemistry for West Nile virus (WNV) antigen, glial fibrillary acid protein, cleaved caspase-3, and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method. Retinal lesions were classified as type I or type II lesions. Type I lesions were characterized by lymphoplasmacytic infiltrates in the subjacent choroid with degeneration limited to the outer retina (type Ia lesion) or with degeneration and necrosis of the outer retina or outer and inner retina (type Ib lesion) while retinal collapse, atrophy, and scarring were hallmarks of type II lesions. Type II retinal lesions were associated with a more pronounced choroiditis. Although not statistically significant, WNV antigen tended to be present in larger quantity in type Ib lesions. Type I lesions are considered acute while type II lesions are chronic. The development of retinal lesions was associated with the presence of an inflammatory infiltrate in the choroid. A breakdown of the blood-retina barrier is suspected to be the main route of infection of the retina. Within the retina, virus appeared to spread via both neuronal and Müller cell processes.

Potential role of periodontal infection in respiratory diseases - a review.

Respiratory diseases are responsible for a significant number of deaths and considerable suffering in humans. Accumulating evidence suggests that oral disorders, particularly periodontal disease, may influence the course of respiratory infections like bacterial pneumonia and chronic obstructive pulmonary disease (COPD). Oral periodontopathic bacteria can be aspirated into the lung causing aspiration pneumonia. The teeth may also serve as a reservoir for respiratory pathogen colonization and subsequent nosocomial pneumonia. The overreaction of the inflammatory process that leads to the destruction of the connective tissue is present in both periodontal disease and emphysema. This overreaction may explain the association between periodontal disease and chronic obstructive pulmonary disease. The mechanisms of infection could be the aspiration into the lung of oral pathogens capable of causing pneumonia, colonization of dental plaque by respiratory pathogens followed by aspiration, or facilitation of colonization of the upper airway by pulmonary pathogens by periodontal pathogens. The present article briefly reviews the epidemiologic evidence & role of periodontopathogens in causing respiratory infections.

Protective effect of nebivolol on reserpine-induced neurobehavioral and biochemical alterations in rats.

Reserpine-induced orofacial dyskinesia is a model that shares some mechanists' aspects with tardive dyskinesia whose pathophysiology has been related to oxidative stress. The present study was aimed to explore neuroprotective effects of nebivolol, an antihypertensive agent, on reserpine-induced neurobehavioral and biochemical alterations in rats. Reserpine (1mg/kg, s.c.) was used to induce neurotoxicity. Administration of reserpine for 3 days every other day significantly increased the vacuous chewing movements (VCMs), tongue protrusions (TPs) and reduced the locomotor activity in rats. Pre-treatment with nebivolol (5 and 10mg/kg, p.o. for 5 days) showed dose dependant decrease in VCMs and TP induced by reserpine. Nebivolol also showed significant improvement in locomotor activity. Reserpine significantly increased lipid peroxidation and reduced the levels of defensive antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) in rat brain. Nebivolol reversed these effects of reserpine on oxidative stress indices; indicating amelioration of oxidative stress in rat brains. The results of the present study indicated that nebivolol has a protective role against reserpine-induced orofacial dyskinesia. Thus, the use of nebivolol as a therapeutic agent for the treatment of tardive dyskinesia may be considered.

Mitochondrial oxygen consumption in permeabilized fibers and its link to colour changes in bovine M. semimembranosus muscle.

Animal and muscle characteristics were recorded for 41 cattle. The oxygen consumption rate (OCR) of M. semimembranosus was measured between 3.0-6.4h post mortem (PM3-6) and after 3 weeks in a vacuum pack at 4°C. Colour change measurements were performed following the 3 weeks using reflectance spectra (400-1,100 nm) and the colour coordinates L, a and b, with the samples being packaged in oxygen permeable film and stored at 4°C for 167 h. Significant individual animal differences in OCR at PM3-6 were found for mitochondrial complexes I and II. OCR of complex I declined with increased temperature and time PM, while residual oxygen-consuming side-reactions (ROX) did not. OCR of stored muscles was dominated by complex II respiration. A three-way regression between samples, colour variables collected upon air exposure and OCR of 3 weeks old fibres revealed a positive relationship between OCR and complex II activity and also between OCR and OCR(ROX). The presence of complex I and ß-oxidation activities increased metmyoglobin formation.

Gonadotropin levels in hypothyroid women of reproductive age group.

OBJECTIVE: To study serum gonadotropin (FSH, LH) levels in cases of subclinical and overt hypothyroid women in reproductive age group. MATERIAL AND METHOD: Female patients of reproductive age group attending thyroid clinic of Acharya Vinoba Bhave Hospital were included in the study. Detail menstrual history was taken, and serum FSH and LH levels were estimated by radio immuno assay method. RESULT: Eighty patients were included in the study, out of whom 46 (57.5%) had subclinical hypothyroidism and 34 (42.5%) had overt hypothyroidism. In subclinical hypothyroidism group the menstrual dysfunction which dominated in our study was oligomenorrhea (28.2%) followed by menorrhagia (17.39%). 39.13% had normal menstruation. In overt hypothyroidism group again it was oligomenorrhoea (23.5%) which was the principal menstrual abnormality followed by menorrhagia (17.64%). The percentage of females with normal menstruation was 47.05%. The levels of serum FSH and LH were significantly low in cases of both subclinical and overt hypothyroid women. They were significantly low when done between day 2 and 5 of the cycle. CONCLUSION: Hypothyroidism decreases levels of serum FSH and serum LH. Subclinical hypothyroidism is one of the major etiological factors of infertility. Autoantibodies against thyroid should be searched for in cases of female patients with infertility.

Characterization of triple reassortant H1N1 influenza A viruses from swine in Ohio.

An H1N1 influenza A virus, A/swine/Ohio/24366/07, was isolated from pigs in an Ohio county fair. Twenty-six people who came in contact with the infected pigs developed respiratory disease and two of these people were laboratory confirmed as H1N1 by the Centers for Disease Control and Prevention (CDC). The A/swine/Ohio/24366/07 virus we isolated from swine was shown at the CDC to have 100% identical genome sequence to the human virus associated with the county fair. This prompted us to characterize three swine and two human origin H1N1 influenza A viruses isolated at different time points in the State of Ohio. The three swine viruses were shown to be triple reassortant viruses harboring genes of human (PB1), swine (HA, NA, NP, M, and NS), and avian (PB2 and PA) lineage viruses. Although viruses evaluated in this study were isolated during a short time interval (3 years), genetic drift was observed within the HA and NA genes, including changes at the receptor binding and antigenic sites of HA1 protein. Nevertheless, all viruses exhibited antigenic similarity as evaluated with hemagglutination inhibition and virus neutralizing tests. Internal genes were similar to other reassortant viruses of various subtypes currently circulating in the United States. Interestingly, two of the swine viruses including the 2007 isolate replicated well in human airway epithelial cells, however, another virus isolated in 2006 showed very little replication.

Structural and magnetic properties of an InGaAs/Fe3Si superlattice in cylindrical geometry.

The structure and magnetic properties of an InGaAs/Fe(3)Si superlattice in a cylindrical geometry are investigated by electron microscopy techniques, x-ray diffraction and magnetometry. To form a radial superlattice, a pseudomorphic InGaAs/Fe(3)Si bilayer has been released from its substrate self-forming into rolled-up microtubes. Oxide-free interfaces as well as areas of crystalline bonding are observed and an overall lattice mismatch between succeeding layers is determined. The cylindrical symmetry of the final radial superlattice shows a significant effect on the magnetization behavior of the rolled-up layers.

Modulation of macrophages by infectious bursal disease virus.

Infectious bursal disease is one of the most important naturally occurring viral diseases of chickens worldwide. The causative agent, infectious bursal disease virus (IBDV), belongs to the family Birnaviridae. This virus causes an acute, highly contagious and immunosuppressive disease in chickens. The virus infects and destroys actively dividing IgM-bearing B cells. Although B cells are the principal targets for IBDV, recent data show that the virus also infects macrophages. IBDV-infected macrophages produce various cytokines and chemokines which may play an important role in the protection and/or pathogenesis of IBDV. In this review, the modulatory effects of IBDV on macrophages will be discussed.

Survival and clinical outcome of SB Charite III disc replacement for back pain.

Between January 1990 and December 2000 we carried out 226 SB Charité III disc replacements for lumbar disc degeneration in 160 patients. They were reviewed at a mean follow-up of 79 months (31 to 161) to determine the clinical and radiological outcome. The clinical results were collected by an independent observer, who was not involved in patient selection, treatment or follow-up, using a combination of outcome measures, including the Oswestry Disability Index. Pain was recorded using a visual analogue score, and the most recent radiographs were reviewed. Survival of the device was analysed by the Kaplan-Meier method and showed a cumulative survival of 35% at 156 months when radiological failure was taken as the endpoint. The mean improvement in the Oswestry disability index scores after disc replacement was 14% (6% to 21%) and the mean improvement in the pain score was 1.6 (0.46 to 2.73), both falling below the clinically significant threshold. Removal of the implant was required in 12 patients, four because of implant failure. These poor results indicate that further use of this implant is not justified.

In vivo activation of chicken macrophages by infectious bursal disease virus.

Infectious bursal disease virus (IBDV) infects and replicates in the dividing B lymphocytes of chickens. In the present study, the in vivo effect of IBDV infection on chicken macrophage populations and macrophage activation were examined. Specific-pathogen-free chickens were exposed to virulent IBDV and splenic macrophages were recovered during the acute phase of the disease. At 3 and 5 days post-infection (dpi), spleens of virus-exposed chickens had fewer macrophages than those of virus-free controls (p < 0.05). Confocal microscopic examination revealed cells that were positive for both KUL01 (macrophage surface marker) and R63 (IBDVVP2), indicating presence of the virus in macrophages. MQ-NCSU cells, an avian macrophage cell line, were susceptible to replication of IBDV. In addition, splenic macrophages were activated and had temporarily increased levels of mRNA transcripts of pro-inflammatory mediators, including IL-1beta, IL-6, IL-18, and iNOS. The robust expression of proinflammatory cytokine transcripts, along with a decrease in macrophage numbers, suggest that IBDV activates and may lead to a reduction of resident macrophages in vivo.

Souter-Strathclyde total elbow arthroplasty in rheumatoid arthritis: medium-term results.

We present the outcome of 47 Souter-Strathclyde replacements of the elbow with a mean follow-up of 82 months (12 to 129). The clinical results were assessed using a condition-specific outcome measure. The mean total score (maximum 100) before the operation was 47.21 and improved to 79.92 (p < 0.001). The mean pain score (maximum 50) improved from 21.41 to 46.70 (p < 0.001) and the mean functional component of the score (maximum 30) from 11.19 to 18.65 (p < 0.001). There was negligible change in the score for the range of movement although a significant improvement in mean flexion from 124 degrees to 136 degrees was noted (p < 0.001). Revision surgery was required in four patients, for dislocation, wound dehiscence and early infection in one, late infection in two and aseptic loosening in one. The cumulative survival was 75% at nine years for all causes of failure and 97% at ten years for aseptic loosening alone. Our study demonstrates the value of the Souter-Strathclyde total elbow arthroplasty in providing relief from pain and functional improvement in rheumatoid patients.

Epley's canalith-repositioning manoeuvre for benign paroxysmal positional vertigo.

The efficacy of the Epley's canalith-repositioning manoeuvre in the treatment of BPPV was assessed in this prospective study of 62 patients. Patients were selected based on symptoms of positional vertigo and positive Dix-Hallpike's positional test. Patients were divided into two groups; first group comprising 34 patients underwent Epley's manoeuvre alone where as the other group comprising 28 patients underwent Epley's manoeuvre along with mastoid oscillator. At the end of 1 month patients were assessed subjectively by visual analogue scale (VAS) and objectively by Dix-Hallpike's positional test. On VAS, 85.7% patients had complete resolution of symptoms of BPPV in both the groups. Objectively 88.2% did not have positional nysfagmus after 1 month in first group whereas in the second group 86% had complete response at the end of 1 month of therapy. Follow up of 6 months could be done in 38 patients, out of which 7 (18.4%) had recurrence of their symptom of vertigo and positive Dix-Hallpike's positional test, whereas one patient continued to have no relief by Epley's manoeuvre. There was no difference in subjective and objective parameters even when CRP was performed using mastoid vibrator.