Does Magnetic Resonance Imaging Predict Neurological Deficit in Patients with Traumatic Lower Lumbar Fractures?

Study Design: A retrospective cohort study. Purpose: This study aimed to understand the role of magnetic resonance imaging (MRI) in predicting neurological deficits in traumatic lower lumbar fractures (LLFs; L3-L5). Overview of Literature: Despite studies on the radiological risk factors for neurological deficits in thoracolumbar fractures, very few have focused on LLFs. Moreover, the potential utility of MRI in LLFs has not been evaluated. Methods: In total, 108 patients who underwent surgery for traumatic LLFs between January 2010 and January 2020 were reviewed to obtain their demographic details, injury level, and neurology status at the time of presentation (American Spinal Injury Association [ASIA] grade). Preoperative computed tomography scans were used to measure parameters such as anterior vertebral body height, posterior vertebral body height, loss of vertebral body height, local kyphosis, retropulsion of fracture fragment, interpedicular distance, canal compromise, sagittal transverse ratio, and presence of vertical lamina fracture. MRI was used to measure the canal encroachment ratio (CER), cross-sectional area of the thecal sac (CSAT), and presence of an epidural hematoma. Results: Of the 108 patients, 9 (8.3%) had ASIA A, 4 (3.7%) had ASIA B, 17 (15.7%) had ASIA C, 21 (19.4%) had ASIA D, and 57 (52.9%) had ASIA E neurology upon admission. The Thoracolumbar Injury Classification and Severity score (p =0.000), CER (p =0.050), and CSAT (p =0.019) were found to be independently associated with neurological deficits on the multivariate analysis. The receiver operating characteristic curves showed that only CER (area under the curve [AUC], 0.926; 95% confidence interval [CI], 0.860-0.968) and CSAT (AUC, 0.963; 95% CI, 0.908-0.990) had good discriminatory ability, with the optimal cutoff of 50% and 65.3 mm2, respectively. Conclusions: Based on the results, the optimal cutoff values of CER >50% and CSAT >65.3 mm2 can predict the incidence of neurological deficits in LLFs.

Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers.

The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Oncogenic EGFR has been successfully targeted by tyrosine kinase inhibitors, but acquired drug resistance eventually overcomes the efficacy of these treatments. Attempts to surmount this therapeutic challenge are hindered by a poor understanding of how and why cancer mutations specifically amplify ligand-independent EGFR auto-phosphorylation signals to enhance cell survival and how this amplification is related to ligand-dependent cell proliferation. Here we show that drug-resistant EGFR mutations manipulate the assembly of ligand-free, kinase-active oligomers to promote and stabilize the assembly of oligomer-obligate active dimer sub-units and circumvent the need for ligand binding. We reveal the structure and assembly mechanisms of these ligand-free, kinase-active oligomers, uncovering oncogenic functions for hitherto orphan transmembrane and kinase interfaces, and for the ectodomain tethered conformation of EGFR. Importantly, we find that the active dimer sub-units within ligand-free oligomers are the high affinity binding sites competent to bind physiological ligand concentrations and thus drive tumor growth, revealing a link with tumor proliferation. Our findings provide a framework for future drug discovery directed at tackling oncogenic EGFR mutations by disabling oligomer-assembling interactions.

Body mass index's effect on CRSwNP extends to pathological endotype and recurrence.

BACKGROUND: Elevated body mass index (BMI) has been recognized as an important contributor to corticosteroid insensitivity in chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to delineate the effects of elevated BMI on immunological endotype and recurrence in CRSwNP individuals. METHODOLOGY: A total of 325 patients with CRSwNP undergoing FESS were recruited and stratified by BMI. H&E staining was employed for histological evaluation. Characteristics of inflammatory patterns were identified by immunohistochemical staining. The predictive factors for recurrence were determined and evaluated by multivariable logistic regression analysis and the receiver operating characteristic (ROC) curves across all subjects and by weight group. RESULTS: In all patients with CRSwNP, 26.15% subjects were classified as overweight/obese group across BMI categories and exhibited a higher symptom burden. The upregulated eosinophil/neutrophil-dominant cellular endotype and amplified type 2/ type 3 coexisting inflammation was present in overweight/obese compared to underweight/normal weight controls. Additionally, a higher recurrent proportion was shown in overweight/obese patients than that in underweight/normal weight cohorts. Multivariable logistic regression analysis identified BMI as an independent predictor for recurrence. The predictive capacity of each conventional parameter (tissue eosinophil and CLCs count, and blood eosinophil percentage) alone or in combination was poor in overweight/obese subjects. CONCLUSIONS: Overweight/obese CRSwNP stands for a unique phenotype and endotype. Conventional parameters predicting recurrence are compromised in overweight/obese CRSwNP, and there is an urgent need for novel biomarkers that predict recurrence for these patients.

Congenital Stenosis of the Spine-A Cross-Sectional Study of 1019 Whole-Spine Computed Tomography Scans to Determine Prevalence and Association Among Multilevel, Tandem, and Triple Region Stenosis.

BACKGOUND: Patients with congenital stenosis of the spine (CSS) present with clinical symptoms at an early age and fewer degenerative hypertrophic changes than the more common degenerative cohort. Literature is lacking in the true prevalence of CSS affecting the 3 segments of the spine in isolation, as well as in tandem in the Indian subcontinent. METHODS: Anteroposterior spinal canal diameter in axial plane computed tomography at the midvertebral level was measured in asymptomatic patients with whole-spine computed tomography. Spinal canal stenosis was defined as a diameter of <12 mm for the cervical region, <12 mm for the thoracic region, and <13 mm for the lumbar region. Single-level and multilevel stenosis, as well as tandem and triple-region stenosis, were evaluated. RESULTS: The results show the prevalence of CSS as 16.6%, 11.5%, and 20.1% involving the cervical, thoracic, and lumbar spine, respectively. Single-level stenosis affected 90.6%, 94%, and 79.8% of the patients with cervical, thoracic, and lumbar CSS, respectively. Tandem stenosis affected 10.4% of the population (n = 104), with cervicolumbar stenosis being the most prevalent (n = 51, 5%). The presence of CSS in any one segment of the spine was significantly associated with the presence of stenosis at one of the other segments (P < 0.05). Triple-region stenosis was seen in 0.3% (n = 3) patients. CONCLUSIONS: The prevalence of cervical, thoracic, lumbar and tandem stenosis from our study is established at 16.6%, 11.5%, 20.1%, and 10.4%. Additionally, our study demonstrates the association between stenosis of the different regions of the spine.

Vancomycin Flushing Syndrome After the Use of Vancomycin-Impregnated Bone Graft During Spine Surgery: A Case Report.

CASE: Intrawound vancomycin in spine surgery is a common clinical practice. We report a case of a 14-year-old adolescent girl undergoing surgery for scoliosis correction who developed features of vancomycin flushing syndrome after the use of vancomycin-impregnated bone graft. After resuscitation, she was extubated and had an uneventful postoperative recovery. At 1-year follow-up, she is back to her routine without any sequelae of the intraoperative event. CONCLUSION: The use of intrawound vancomycin can result in life-threatening reactions. With the increase in its use, the anesthetist and the surgeon must be aware of such complications.

Outcomes of Laparoscopic Optimal Interval Cytoreduction Surgery (LOICS) in Patients with Advanced Ovarian Cancers Having Low Burden Disease.

Laparoscopy has been increasingly utilised for cytoreduction surgery in patients with early ovarian cancers. The present study tries to assess the feasibility of laparoscopic interval cytoreduction surgery (LOICS) in patients with advanced ovarian cancer (AOC) having low burden residual disease. A retrospective study of was done of AOC's who underwent LOICS between 2010 and 2014. Epithelial ovarian cancer patients who underwent interval cytoreduction surgery were included and analysed for short-term and long-term outcomes. In all, 36 patients with stage III ovarian cancers were included in the analysis. Twenty-two (61.1%) were grade 3 and 14 (38.8%) were grade 2, and no patient had grade 1 tumour. Stage wise majority were stage IIIC (94.4%) followed by 2 (5.5%) in stage IIIA. There was 1 postoperative complication (2.5%) and no intraoperative complications. Median time to discharge and to start chemotherapy was 5 days and 23 days respectively. After a median follow-up of 60 months, 3 patients (8.3%) were lost to follow-up and the remaining 33 patients were analysed for survival outcomes. The overall survival (OS) and recurrence-free survival (RFS) were 58.3% and 36.1% respectively. The median RFS and OS were 24 months and 51 months, respectively. Most recurrences involved the peritoneum (82.6%), and 5 patients (21.7%) had nodal recurrence alone. Laparoscopic optimal interval cytoreduction is feasible in patients with advanced ovarian cancers provided the disease burden permits optimal surgery, especially in centres with expertise in complex laparoscopic procedures.

Biological Stabilisation vs Mechanical Fixation: Do We Always Require Instrumentation in Anterior Decompression Surgeries for Thoracolumbar Spinal Tuberculosis?

Study Design: A retrospective cohort study. Purpose: To compare the outcomes of anterior decompression with bone grafting alone and anterior decompression with bone grafting and fixation. Methods: 93 patients with minimum 2 year follow-up were included in the study. 50 patients had undergone anterior decompression with bone grafting without instrumentation (group 1) and 43 patients with instrumentation (group 2). Both groups were compared using their demographic data, vertebral level of involvement, neurological recovery and progression of kyphotic deformity. Results: Demographic data and pre-operative parameters were comparable in both groups. The mean (SD) of pre-operative kyphotic angle (in degrees) in group 1 was 29° (8.47°) and in group 2 was 29.81° (9.51°). The mean loss of correction at follow-up was 9.6° for group 1 compared to 3.4° for group 2. The mean loss of correction in patients of group 1 involving upper thoracic spine was 5.6°. There was no significant difference between the two groups across different age groups. Conclusion: Use of anterior instrumentation for decompression surgeries in cases of tubercular spine have shown significantly better results compared to strut grafting alone with respect to restricting the progression of kyphotic deformity at follow-up. Instrumentation may be avoided in patients older than 60 years of age and those involving the upper thoracic spine, more so if both of these co-exist. However, further studies are needed to make our patient selection more rational, so as to avoid the failures and complications of this morbid procedure. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-023-00827-4.

Floating Thoracic Spine Due to Noncontiguous Fracture-Dislocations of the Thoracolumbar Spine.

The thoracolumbar spine is the most commonly afflicted area in vertebral column injuries. Here we bring up a case of a 20-year-old male who presented to our emergency department with a history of a high-velocity road traffic accident with noncontiguous two-level fracture-dislocations of the thoracolumbar spine with blunt trauma to the chest. The patient was managed with posterior reduction and instrumented postero-lateral fusion. Such an injury pattern has been reported only rarely in the literature. This report expects to highlight the unusual fracture pattern of a common injury and the challenges of managing such severe injuries intra-operatively and in the post-operative period.

Thigh Pain and Peri-Implant Fractures with the Use of Short Cephalo-medullary Nails: A Retrospective Study of 122 Patients.

Introduction: To assess the incidence and causes of persistent thigh pain and peri-implant fractures after union in patients of intertrochanteric fractures treated with short cephalo-medullary nails. Materials and methods: A retrospective observational study conducted at a Level 1 Trauma centre. A total of 122 patients of intertrochanteric fractures who were operated using short cephalo-medullary nails (170mm and 200mm lengths) between January 2018 to June 2019 were included in the study. Main outcomes measured were the incidence of thigh pain and peri-implant fractures. Results: Out of the 122 patients with a mean follow-up of 14.1 month, 12 patients had persistent thigh pain. Six patients had the helical blade protruding from the lateral cortex, two of them had distal tip of nail abutting on the anterior cortex and four cases had prominent proximal segment of nail which may explain the cause of their pain. Five of these patients had a combination of these findings. Two patients had pain for which no other obvious cause was found. There were no cases of peri-implant fractures in our study. Conclusion: Thigh pain associated with the use of short cephalon-medullary nails is often unrelated to nail length and can be prevented by using proper surgical technique. There seems to be no association between the use of short nails and peri-implant fractures.

Detection and visualization of human tears using alternate light sources for forensic purposes.

The current scientific techniques for locating body fluids focus on quick and effective methodologies for easy and reliable identification. Efficient detection and identification of body fluids play a vital role in establishing the 'corpus delecti' of a crime. Non-destructive techniques such as the use of Alternate Light Sources (ALS) have been exploited for crime scene searches over large areas and detection of body fluids such as blood, semen, vaginal secretions, and saliva on a range of substrates. Tears are rarely found but can be considered as potential body fluid evidence due to their unique biochemical and molecular properties. Tears are secreted in response to physical or emotional stimuli. Due to the small volume of secretions, they are often overlooked in the crime scene. Tears may be found on surfaces such as clothing, bedding, tissue, handkerchief, or balaclava. The use of ALS to locate tears on tissue paper and fabric surfaces was tested which were not apparent to the naked eye. Tears stains were successfully detected on surfaces of forensic interest with varying sample ages up to three months with a broad excitation spectrum between 254 nm and 410 nm. Dried stains on tissue paper and fabric substrates were better detected with sharp margins, clear stain pattern visibility, and fluorescence intensity in comparison with moist and fresh stains. Tears stains can hence be detected with the use of ALS and suitable filter combinations under normal conditions and do not require any specific settings to locate them. These findings are suggestive for easy and quick identification of tears on large surfaces and as a presumptive test for forensic casework evidence examination.

Joint preservation surgery in grade 2 and 3 giant cell tumors of bone around the knee.

OBJECTIVE: To evaluate the clinical and functional outcomes of joint preservation surgery in high-grade giant cell tumors (GCT) around the knee joint. METHODS: A retrospective review of 25 patients of high-grade GCT (Campanacci grade 2 and 3) involving proximal tibia or distal femur managed by extended curettage, bone grafting, and stabilization with knee spanning external fixator between 2016 and 2018 was done. The radiographic outcomes, functional outcomes (Musculoskeletal Tumor Society [MSTS] score for lower limb), and complications including donor site morbidity were evaluated. RESULTS: The mean age of the patient population was 24.04 years with an average follow-up period of 30.24 months. Fourteen patients had involvement of distal femur, and 11 involved proximal tibia. There were 16 cases of grade 2 lesions and 9 cases of grade 3 lesions. Twenty-four out of the 25 patients had radiological consolidation of graft, while one patient had graft subsidence. Twenty-two out of 25 patients had full extension and knee flexion more than 100 degrees. The mean MSTS score was 25.2. Three patients had an MSTS score under 20. All three patients had an extension lag with a restricted range of motion. CONCLUSION: Joint preservation surgery, when done in line with the basic principles of tumor surgery, gives good radiographic and functional outcomes even in grade 2 and 3 giant cell tumors of bone around the knee and should be attempted before replacement surgeries.

Forensic DNA profiling of tears stains from commonly encountered substrates.

The detection and recovery of body fluid evidence to reconstruct the involvement of people in a crime is an essential step in forensic investigation. The presence of tears is extremely rare but widely misunderstood because of its nature of secretion and low volumes found. They may be secreted in cases of sexual crimes, kidnaping, and violence among many other emotionally disturbing scenarios. It is suggestive that tears are an excellent source of epithelial cells for DNA to establish identity. They are deposited on tissue paper or handkerchief and lesser common substrates include bedding, face mask, and balaclava. Trace or touch DNA can also be retrieved from used contact lenses. Since tears can be secreted due to an emotional response, they can attract forensic analysis for identification. DNA profiling from these substrates is promising in the absence of other commonly found body fluids such as blood or saliva. The current study was done to explore the use of fresh and aged tear samples for forensic DNA analysis from three different substrates i.e., tissue paper, cotton fabric, and contact lenses. STR profiles were successfully obtained from all sample types (n = 60) with 100% allele recovery. The analysis provided consistent evidence that DNA extracted using this methodology was helpful to get reliable DNA profiles for forensics comparable with that from blood or saliva for personal identification.

Fluorescence-guided cancer surgery-A new paradigm.

Fluorescence-guided surgery is an emerging and promising operative adjunct to assist the surgeon in various aspects of oncosurgery, ranging from assessing perfusion, identification, and characterization of tumors and peritoneal metastases, mapping of lymph nodes/leaks, and assistance for fluorescence-guided surgery (FGS). This study aims to provide an overview of principles, currently available dyes, platforms, and surgical applications and summarizes the available literature on the utility of FGS with a focus on abdomino-thoracic malignancies.

Laparoscopic Repair of Acute Post-Esophagectomy Diaphragmatic Herniation Following Minimal Access Esophagectomy.

This study's objective was to assess the presentation, incidence, operative approach, and outcomes of acute symptomatic post-esophagectomy diaphragmatic hernia (PEDH), following minimal access esophagectomy (MAE) for esophageal and gastro-esophageal junctional cancer. Between January 2010 and December 2020, all consecutive patients undergoing esophagectomy were retrospectively analyzed. Acute symptomatic PEDH occurred in 4 patients out of 680 consecutive patients undergoing esophagectomy (0.58%) and 636 MAE (0.63%). All patients were men, with a median age of 56.5 years, and underwent minimal access transhiatal resection. The presentation was varied; 2 had restlessness, agitation, and tachycardia; one acute respiratory distress; and the last was asymptomatic but had reduced air entry over left hemithorax with unexplained hypoxia. All had transverse colon herniation into the left hemithorax. Herniated viscera were reduced with closure of hiatal defect, 3 underwent laparoscopic repair, and one needed laparotomy. Meshplasty or bowel resection was not required. The median hospital stay was 9 days with no perioperative mortality. The major complications (Clavien-Dindo grade ≥ IIIa) occurred in 2 patients. One patient was lost to follow-up, 2 died of disease after a year and 15 months post-procedure, and one is doing well at 10 months without any relapse of hernia. Acute symptomatic PEDH is a rare complication after transhiatal esophagectomy and mainly occurs in the left hemithorax. The incidence appears to be less than 1% after MAE. Laparoscopic repair is feasible in most cases. We recommend routine assessment of hiatus and tightening of hiatus to snuggly accommodate the gastric conduit.

Cooperation and Interplay between EGFR Signalling and Extracellular Vesicle Biogenesis in Cancer.

Epidermal growth factor receptor (EGFR) takes centre stage in carcinogenesis throughout its entire cellular trafficking odyssey. When loaded in extracellular vesicles (EVs), EGFR is one of the key proteins involved in the transfer of information between parental cancer and bystander cells in the tumour microenvironment. To hijack EVs, EGFR needs to play multiple signalling roles in the life cycle of EVs. The receptor is involved in the biogenesis of specific EV subpopulations, it signals as an active cargo, and it can influence the uptake of EVs by recipient cells. EGFR regulates its own inclusion in EVs through feedback loops during disease progression and in response to challenges such as hypoxia, epithelial-to-mesenchymal transition and drugs. Here, we highlight how the spatiotemporal rules that regulate EGFR intracellular function intersect with and influence different EV biogenesis pathways and discuss key regulatory features and interactions of this interplay. We also elaborate on outstanding questions relating to EGFR-driven EV biogenesis and available methods to explore them. This mechanistic understanding will be key to unravelling the functional consequences of direct anti-EGFR targeted and indirect EGFR-impacting cancer therapies on the secretion of pro-tumoural EVs and on their effects on drug resistance and microenvironment subversion.