Optimized antiangiogenic reprogramming of the tumor microenvironment potentiates CD40 immunotherapy.

Cancer immunotherapies are increasingly combined with targeted therapies to improve therapeutic outcomes. We show that combination of agonistic anti-CD40 with antiangiogenic antibodies targeting 2 proangiogenic factors, vascular endothelial growth factor A (VEGFA) and angiopoietin 2 (Ang2/ANGPT2), induces pleiotropic immune mechanisms that facilitate tumor rejection in several tumor models. On the one hand, VEGFA/Ang2 blockade induced regression of the tumor microvasculature while decreasing the proportion of nonperfused vessels and reducing leakiness of the remaining vessels. On the other hand, both anti-VEGFA/Ang2 and anti-CD40 independently promoted proinflammatory macrophage skewing and increased dendritic cell activation in the tumor microenvironment, which were further amplified upon combination of the 2 treatments. Finally, combined therapy provoked brisk infiltration and intratumoral redistribution of cytotoxic CD8+ T cells in the tumors, which was mainly driven by Ang2 blockade. Overall, these nonredundant synergistic mechanisms endowed T cells with improved effector functions that were conducive to more efficient tumor control, underscoring the therapeutic potential of antiangiogenic immunotherapy in cancer.

Bone defect classifications in revision total knee arthroplasty, their reliability and utility: a systematic review.

BACKGROUND: There are various classification systems described in the literature for managing bone defects in revision knee arthroplasty (RTKA). We analysed the reliability and usefulness of these classification systems. QUESTIONS/PURPOSES: (1) To review and critique the various classification systems proposed for bone loss in RTKA. (2) Among all the proposed classifications which one is the most commonly used by surgeons to report their results. (3) What is the reliability of various bone defect classification systems for RTKA. In this review, we have assessed the studies validating those classifications with a detailed description of the limitations and the proposed modifications. METHODS: This systematic review was conducted following PRISMA guidelines. Pubmed/Medline, CINAHL, EMBASE, Scopus, Cochrane databases and Web of Science databases were searched using multiple search terms and MeSH terms where possible. Studies meeting inclusion criteria were assessed for statistical parameters of reliability of a classification system. RESULTS: We found 16 classification systems for bone defects in RTKA. Six studies were found evaluating a classification system with reporting their reliability parameters. Fifty-four studies were found which classified bone loss using AORI classification in their series. AORI classification is most commonly reported for classifying bone defects. Type T2B and F2B are the most common bone defects in RTKA. The average kappa value for AORI classification for femoral bone loss was 0.38 (0.27-0.50) and 0.76 (0.63-1) for tibial bone loss assessment. CONCLUSION: None of the available classification systems is reliably established in determining the bone loss and treatment plans in RTKA. Among all, AORI classification is the most widely used system in clinical practice. The reliability of AORI Classification is fair for femoral bone loss and substantial for tibial bone loss.

The Duhem-Quine problem for equiprobable conjuncts.

In this paper, we distinguish Quine's thesis of holism from the related Duhem-Quine problem. We discuss the construal of holism which claims that the effect of falsification is felt on a conjunction of hypotheses. The Duhem-Quine problem claims that there is no principled way of knowing how falsification affects individual conjuncts. This latter claim relies on holism and an additional commitment to the hypothetico-deductive model of theory confirmation such that it need not arise in non-deductive accounts. While existing personalist Bayesian treatments of the problem make this point by assuming values of priors for the conjuncts, we arrive at the same conclusion without invoking such assumptions. Our discussion focuses on the falsification of equiprobable conjuncts and highlights the role played by their alternatives in ascertaining their relative disconfirmation. The equiprobability of conjuncts is discussed alongside a historical case study.

The multi-receptor inhibitor axitinib reverses tumor-induced immunosuppression and potentiates treatment with immune-modulatory antibodies in preclinical murine models.

Cancer immunotherapies have significantly improved the prognosis of cancer patients. Despite the clinical success of targeting inhibitory checkpoint receptors, including PD-1 and/or CTLA-4 on T cells, only a minority of patients derive benefit from these therapies. New strategies to improve cancer immunotherapy are therefore needed. Combination therapy of checkpoint inhibitors with targeted agents has promisingly shown to increase the efficacy of immunotherapy. Here, we analyzed the immunomodulatory effects of the multi-receptor tyrosine kinase inhibitor axitinib and its efficacy in combination with immunotherapies. In different syngeneic murine tumor models, axitinib showed therapeutic efficacy that was not only mediated by VEGF-VEGFR inhibition, but also through the induction of anti-cancer immunity. Mechanistically, a significant reduction of immune-suppressive cells, including a decrease of tumor-promoting mast cells and tumor-associated macrophages was observed upon axitinib treatment. Inhibition of mast cells by axitinib as well as their experimental depletion led to reduced tumor growth. Of note, treatment with axitinib led to an improved T cell response, while the latter was pivotal for the therapeutic efficacy. Combination with immune checkpoint inhibitors anti-PD-1 and anti-TIM-3 and/or agonistic engagement of the activating receptor CD137 resulted in a synergistic therapeutic efficacy. This demonstrates non-redundant immune activation induced by axitinib via modulation of myeloid and mast cells. These findings provide important mechanistic insights into axitinib-mediated anti-cancer immunity and provide rationale for clinical combinations of axitinib with different immunotherapeutic modalities.

Development of a Pediatric Cardiac Mechanical Support Program.

The development of a pediatric cardiac support program is a complex, multidisciplinary project. This study describes the University of Iowa Congenital Heart Program's experience from its inception to the present. In, we examine those specific factors that have led to substantial improvements in the program, additionally identifying where further gains can be made. We retrospectively reviewed all pediatric patients who received mechanical cardiac support at the University of Iowa from the inception of the program in 1991. In total, 29 patients received mechanical support between December 1991 and December 2015 and are included in the study. Twelve patients received continuous flow devices and 17 patients received pulsatile flow devices. Median age at implant was 12.8 years (range 0.1-18.2 years). Median weight at implant was 40.5 kg (3.2-123.4 kg). Factors examined included: operating room (OR) time, intensive care unit and hospital length of stay, intubation days, blood product usage, pre- and post-operative bilirubin, creatinine, natriuretic peptide B (NPPB), and device implanted. Categorical and continuous variables were compared using Chi-squared and Wilcoxon rank-sum tests, respectively. Of the 29 patients who received mechanical support, 17 (58.6%) were discharged home, 11 (37.9%) died during their hospitalization, and 1 (3.5%) remains hospitalized. Median length of ventricular assist device support was 59.5 days (range 1-653 days). Between December 1991 and December 2011, in-hospital mortality was 64.3%. Following this period, significant changes were made to patient management with in-hospital mortality decreasing to 13.3% between February 2013 and December 2015. Comparison between deceased and living patients revealed several significant factors including: median number of packed red blood cells transfused, 8 versus 4 units (P = 0.048), median OR time, 396 versus 299 min (P = 0.003), and device implanted. During the early stages of the mechanical support program, higher than expected mortality rates prompted changes in the management of pediatric cardiac patients, specifically, the development of a dedicated management team. These changes significantly improved outcomes and we suggest can be used as a model for similar cardiac support programs, especially in smaller volume programs.

Acromioclavicular joint septic arthritis in an immunocompetent child: A case report.

Septic arthritis of acromioclavicular (AC) joint is a rare entity. It is generally seen in patients who are immunocompromised. Only 15 cases have been reported till now, with only one case series of 6 patients. We report a case of septic arthritis of AC joint in an immunocompetent child. A 9 years old girl presented with history of pain in left shoulder for 4 days associated with fever. No history suggestive of any immunocompromised state was complained. On local examination, a swelling of around 3 cm in diameter was found over left AC joint region with raised local temperature, tenderness on palpation and positive response in fluctuation test. Total leukocyte count was 18.7 × 109/L with 80% of neutrophils. Erythrocyte sedimentation rate (ESR) was 28 mm/1 h. C-reactive protein (CRP) was 12 mg/L. X-ray showed enlarged left AC joint space. Ultrasound revealed hypoechoic collection in the AC joint and the surrounding area. The aspirate was thick and purulent in nature, revealing Gram positive cocci at staining. Arthrotomy and thorough lavage of AC joint was done. Culture of the aspirate showed Methicillin Resistant Staphylococcus Aureus (MRSA) after 48 hours that was sensitive to amikacin, gentamicin, erythromycin and teicoplanin. Patient was symptom-free at 2 months of follow-up with no signs of osteomyelitis on the radiographs. Thus this is the first case of AC joint septic arthritis in healthy individual. Being proximal to the shoulder joint, AC joint septic arthritis can be confused with the shoulder joint septic arthritis. Thus, high index of suspicion is required for accurate diagnosis.

PEGylation of lysine residues reduces the pro-migratory activity of IGF-I.

BACKGROUND: The insulin-like growth factor (IGF) system is composed of ligands and receptors which regulate cell proliferation, survival, differentiation and migration. Some of these functions involve regulation by the extracellular milieu, including binding proteins and other extracellular matrix proteins. However, the functions and exact nature of these interactions remain incomplete. METHODS: IGF-I variants PEGylated at lysines K27, K65 and K68, were assessed for binding to IGFBPs using BIAcore, and for phosphorylation of the IGF-IR. Furthermore, functional consequences of PEGylation were investigated using cell viability and migration assays. In addition, downstream signaling pathways were analyzed using phospho-AKT and phospho-ERK1/2 assays. RESULTS: IGF-I PEGylated at lysines 27 (PEG-K27), 65 (PEG-K65) or 68 (PEG-K68) was employed. Receptor phosphorylation was similarly reduced 2-fold with PEG-K65 and PEG-K68 in 3T3 fibroblasts and MCF-7 breast cancer cells, whereas PEG-K27 showed a more than 10- and 3-fold lower activation for 3T3 and MCF-7 cells, respectively. In addition, all PEG-IGF-I variants had a 10-fold reduced association rate to IGF binding proteins (IGFBPs). Functionally, all PEG variants lost their ability to induce cell migration in the presence of IGFBP-3/vitronectin (VN) complexes, whereas cell viability was fully preserved. Analysis of downstream signaling revealed that AKT was preferentially affected upon treatment with PEG-IGF-I variants whereas MAPK signaling was unaffected by PEGylation. CONCLUSION: PEGylation of IGF-I has an impact on cell migration but not on cell viability. GENERAL SIGNIFICANCE: PEG-IGF-I may differentially modulate IGF-I mediated functions that are dependent on receptor interaction as well as key extracellular proteins such as VN and IGFBPs.

Differential subcellular and extracellular localisations of proteins required for insulin-like growth factor- and extracellular matrix-induced signalling events in breast cancer progression.

BACKGROUND: Cancer metastasis is the main contributor to breast cancer fatalities as women with the metastatic disease have poorer survival outcomes than women with localised breast cancers. There is an urgent need to develop appropriate prognostic methods to stratify patients based on the propensities of their cancers to metastasise. The insulin-like growth factor (IGF)-I: IGF binding protein (IGFBP):vitronectin complexes have been shown to stimulate changes in gene expression favouring increased breast cancer cell survival and a migratory phenotype. We therefore investigated the prognostic potential of these IGF- and extracellular matrix (ECM) interaction-induced proteins in the early identification of breast cancers with a propensity to metastasise using patient-derived tissue microarrays. METHODS: Semiquantitative immunohistochemistry analyses were performed to compare the extracellular and subcellular distribution of IGF- and ECM-induced signalling proteins among matched normal, primary cancer and metastatic cancer formalin-fixed paraffin-embedded breast tissue samples. RESULTS: The IGF- and ECM-induced signalling proteins were differentially expressed between subcellular and extracellular localisations. Vitronectin and IGFBP-5 immunoreactivity was lower while ß1 integrin immunoreactivity was higher in the stroma surrounding metastatic cancer tissues, as compared to normal breast and primary cancer stromal tissues. Similarly, immunoreactive stratifin was found to be increased in the stroma of primary as well as metastatic breast tissues. Immunoreactive fibronectin and ß1 integrin was found to be highly expressed at the leading edge of tumours. Based on the immunoreactivity it was apparent that the cell signalling proteins AKT1 and ERK1/2 shuffled from the nucleus to the cytoplasm with tumour progression. CONCLUSION: This is the first in-depth, compartmentalised analysis of the distribution of IGF- and ECM-induced signalling proteins in metastatic breast cancers. This study has provided insights into the changing pattern of cellular localisation and expression of IGF- and ECM-induced signalling proteins in different stages of breast cancer. The differential distribution of these biomarkers could provide important prognostic and predictive indicators that may assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy.

Double level Chance-type fractures of spine in ankylosing spondylitis.

Chance fractures are usually associated with seat belt injuries. Mechanism is always related to flexion-distraction at vertebral level. Double level Chance-type fractures have rarely been reported in published literature. We presented such a fracture at D10 and L3 level in a 38-year-old patient with ankylosing spondylitis. Management was done with posterior decompression and short segment fixation separately.

Real-time object-removal tampering localization in surveillance videos by employing YOLO-V8.

Videos are considered as most trustworthy means of communication in the present digital era. The advancement in multimedia technology has made video content sharing and manipulation very easy. Hence, the video authenticity is a challenging task for the research community. Video forensics refer to uncovering the forgery traces. The detection of spatiotemporal object-removal forgery in surveillance videos is crucial for judicial forensics, as the presence of objects in the video has significant information as legal evidence. The author proposes a passive max-median averaging motion residual algorithm for revealing the forgery traces, successfully giving visible object-removal traces followed by a deep learning approach, YOLO-V8, for forged region localization. YOLO-V8 is the latest deep learning model, which has a wide scope for real-time application. The proposed method utilizes YOLO-V8 for object-removal forgery in surveillance videos. The network is trained on the SYSU-OBJFORG dataset for object-removal forged region localization in videos. The fine-tuned YOLO-V8 successfully classifies and localizes the object-removal tampered region with an F1-score of 0.99 and a precision of 0.99. The observed high confidence score of the bounding box around the forged region makes the model reliable. This fine-tuned YOLO-V8 would be a better choice in real-time applications as it solves the complex object-based forgery detection in videos. The performance of the proposed system is far better than the existing deep learning approach.

A Rare Case of Sporadic Hemiplegic Migraine Mimicking Stroke: A Diagnostic Challenge Solved by Comprehensive History Taking.

Migraine, a common affliction, manifests as debilitating headaches often accompanied by auras. However, hemiplegic migraine presents an unusual symptomatology, inducing unilateral paralysis during attacks. This condition, occurring in two forms, familial and sporadic, merits attention due to its rarity. To raise awareness of this ailment, we recount the case of a 33-year-old woman. This instance serves as a poignant reminder of the potential severity and complexity of hemiplegic migraines. By shedding light on this less-understood variant, we aim to enhance recognition and understanding within medical communities and among the general public. Additionally, emphasizing the importance of thorough history taking in identifying characteristic features, such as the presence of auras or unilateral paralysis preceding headaches, is paramount. Understanding these nuances aids in accurate diagnosis and formulation of tailored management strategies. It's imperative to recognize the distinct characteristics of hemiplegic migraines to ensure timely and appropriate management for affected individuals, offering them relief and improving their quality of life.

Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with Combined SOS1 and MEK Inhibition for Improved Immunotherapy Response.

KRAS inhibitors have demonstrated exciting preclinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KrasG12D, p53-mutant, murine pancreatic ductal adenocarcinoma-derived cell lines (KPCY) to leverage immune-oncology combination strategies for long-term tumor efficacy. Our findings show that SOS1 and MEK inhibitors (SOS1i+MEKi) suppressed tumor growth in syngeneic models and increased intratumoral CD8+ T cells without durable responses. Single-cell RNA sequencing revealed an increase in inflammatory cancer-associated fibroblasts (iCAF), M2 macrophages, and a decreased dendritic cell (DC) quality that ultimately resulted in a highly immunosuppressive microenvironment driven by IL6+ iCAFs. Agonist CD40 treatment was effective to revert macrophage polarization and overcome the lack of mature antigen-presenting DCs after SOS1i+MEKi therapy. Treatment increased the overall survival of KPCY tumor-bearing mice. The addition of checkpoint blockade to SOS1i+MEKi combination resulted in tumor-free mice with established immune memory. Our data suggest that KRAS inhibition affects myeloid cell maturation and highlights the need for combining KRAS cancer-targeted therapy with myeloid activation to enhance and prolong antitumor effects. SIGNIFICANCE: Combination of SOS1 and MEK inhibitors increase T cell infiltration while blunting pro-immune myeloid cell maturation and highlights the need for combining KRAS cancer-targeted therapy with myeloid activation to enhance and prolong anti-tumor effects.

Vitronectin--master controller or micromanager?

The concept that the mammalian glycoprotein vitronectin acts as a biological 'glue' and key controller of mammalian tissue repair and remodelling activity is emerging from nearly 50 years of experimental in vitro and in vivo data. Unexpectedly, the vitronectin-knockout (VN-KO) mouse was found to be viable and to have largely normal phenotype. However, diligent observation revealed that the VN-KO animal exhibits delayed coagulation and poor wound healing. This is interpreted to indicate that VN occupies a role in the earliest events of thrombogenesis and tissue repair. VN is the foundation upon which the thrombus grows in an organised structure. In addition to sealing the wound, the thrombus also serves to protect the underlying tissue from oxidation, is a reservoir of mitogens and tissue repair mediators, and provides a provisional scaffold for the repairing tissue. In the absence of VN (e.g., VN-KO animal), this cascade is disrupted before it begins. A wide variety of biologically active species associate with VN. Although initial studies were focused on mitogens, other classes of bioactives (e.g., glycosaminoglycans and metalloproteinases) are now also known to specifically interact with VN. Although some interactions are transient, others are long-lived and often result in multi-protein complexes. Multi-protein complexes provide several advantages: prolonging molecular interactions, sustaining local concentrations, facilitating co-stimulation of cell surface receptors and thereby enhancing cellular/biological responses. We contend that these, or equivalent, multi-protein complexes facilitate VN polyfunctionality in vivo. It is also likely that many of the species demonstrated to associate with VN in vitro, also associate with VN in vivo in similar multi-protein complexes. Thus, the predominant biological function of VN is that of a master controller of the extracellular environment; informing, and possibly instructing cells 'where' to behave, 'when' to behave and 'how' to behave (i.e., appropriately for the current circumstance).

Missed posterior shoulder dislocation with malunited proximal humerus fracture.

Posterior dislocation of the shoulder may be missed or neglected at initial presentation especially in developing countries. We present a case of 40-year-old Indian man who had 3-month missed posterior dislocation of the right shoulder along with malunited fracture of the anatomical neck of the humerus. Open reduction and stabilization with modified McLaughlin procedure was performed. Rotational osteotomy of proximal humerus had to be performed as supplementary procedure to keep the humeral head stable in glenoid cavity during functional range of movements. The patient had excellent result of the shoulder at 3 years follow-up.

Penicillin-resistant gonorrheal endocarditis presenting with large annular abscess and aortic valve destruction.

Disseminated gonorrheal infections with cardiac involvement are rare, with fewer than 100 cases reported. The increasing prevalence of gonococcal infections and increasing antibiotic resistance represent a concerning challenge to public health. Here we report a case of antibiotic-resistant gonococcal endocarditis presenting with cardiogenic shock and discuss principles of diagnosis and treatment.

Is Masquelet Technique A Successful Viable Treatment In Reconstructing Large Tumor Bone Gaps in Adolescent and Adult?

Objectives: The reconstruction of large bony defect caused by tumor resection can be managed by different technique like bone graft, Masquelet technique, mega-prosthesis etc. Literature lacks studies discussing Masquelet technique in tumor cases especially pertaining to infected tumor in adults. We aimed to determine 1) How often and how fast is the bone healing achieved after resection greater than 10 cm bone in tumour patient's using Masquelet technique?, 2) Whether Masquelet technique can achieve optimum outcomes in adult infected cases too? Methods: We reviewed 154 patients of benign & malignant tumour managed by us between 2013 and 2019. Patients belonging to all the age group with infected tumor/diaphysial tumor/periarticular tumor, where single stage surgery or mega-prosthesis is not a viable option and were treated with Masquelet technique for reconstructing a bone defect of at least 10 cm were included in our study. We evaluated outcomes of eight patients for four parameters i.e. bony union, healing index, number of re-do surgeries required and limb length discrepancy. Results: Mean age of our study group was 20.25 years and patients followed for mean duration of 3.36 years. Mean bone loss after tumor resection was 13.1 cm (range = 11.5 cm to 15 cm). There was no sign of recurrence of tumor in any patient at the time of last follow up. Average time required to achieve bony union was 23.25 months (mean healing index of 1.67 months/cm). All but one patient achieved bony union. Mean limb length discrepancy seen was 1.44cm. Infected cases showed low healing index with higher percentage of re-do surgeries. Conclusion: Induced membrane technique is quick, safe and reliable alternative method of reconstruction to mega-prosthesis in cases with all age group where risk of failure of mega-prosthesis is high, either due to infection or shorter expected lifespan of prosthesis. However, obtaining union can be a difficult preposition in infected tumor cases and multiple surgeries may be required to get the desired result even after two stages. However, a comparative study with large sample size is required to further validate our results.

Evaluation of vertebral shortening and interbody fusion with short segment pedicle screw fixation for unstable thoracolumbar fractures.

Background: Various operative procedures have been described for the treatment of traumatic paraplegia caused by unstable thoracolumbar fractures. We prospectively evaluated interbody fusion (IBF) with SS-PSF in these cases with regard to clinico-radiological outcome with the objectives: (1) Does IBF and short segment pedicle screw fixation (SS-PSF) prevent progression of kyphotic angle after surgery? (2) Can this procedure be safely performed in the setting of acute trauma?. Methods: Sixteen patients suffering from traumatic paraplegia caused by acute unstable thoracolumbar fractures were enrolled prospectively and underwent IBF with SS-PSF. They were evaluated for magnitude of shortening in spine, progression of kyphotic angle, and neurological improvement by American spinal injury association scale (ASIA). Results: Out of total sixteen, 14 patients were ASIA grade A and 2 were grade C, at the time of presentation. Thirteen out of these 14 remained grade A and one improved to B. Both the patients who had grade C involvement at the time of presentation improved to grade D at one-year follow-up. The mean blood loss was 750 ml (range; 650 ml-1150 ml). Mean kyphotic angle decreased from 20.6° (range; 13° to 37°) preoperatively to 6.2° (range; 3° to 10°) at postoperative day 2 (p = 0.002). Its mean value after 6 months was 6.5° (range; 3° to 11°). The procedure resulted in mean spinal column shortening of 18 mm (range; 16 mm-22 mm) in the spinal column. All the patients achieved bony union by a mean duration of 3.9 months (range; 3 months-6 months). Conclusions: IBF with SS-PSF has the shortest possible instrumented construct for thoracolumbar junction fusion done by posterior approach. The interbody fusion for unstable thoracolumbar junction fractures prevents the progression of kyphotic angle post-operatively. Level of evidence: Level 4.

Concomitant Ipsilateral Intracapsular and Extracapsular Femoral Neck Fractures in Young Individuals: A Report of 3 Cases.

CASES: Concomitant ipsilateral intracapsular and extracapsular fractures of the femoral neck, also termed "segmental fracture neck femur," are rare injuries, especially in physiologically young patients. We present 3 such cases that successfully underwent operative fixation with an extramedullary implant. CONCLUSION: Good clinical outcomes may be obtained after osteosynthesis with extramedullary fixation devices in concomitant ipsilateral intracapsular and extracapsular fractures of the femoral neck in young patients (<60 years). They should be followed for a long duration to look for avascular necrosis.

Accuracy of Patient-Specific, 3D-Printed Laminofacetal Based Trajectory-Guide for Pedicle Screw Placement in Subaxial Cervical and Thoracic Spine.

Background: Conventional methods of pedicle-screw placement have higher breach rates due to variations in pedicle trajectories. Objective: We studied the accuracy of patient-specific, three-dimensional (3D)-printed laminofacetal-based trajectory guide for pedicle-screw placement in the subaxial-cervical and thoracic spine. Materials and Methods: We enrolled 23 consecutive patients who underwent subaxial cervical and thoracic pedicle-screw instrumentation. They were divided into two groups: group A (cases without spinal deformity) and group B (cases with pre-existing spinal deformity). Patient-specific, 3D-printed laminofacetal-based trajectory guide for each instrumented level was designed. The accuracy of screw placement was assessed on postoperative computed tomography (CT) using the Gertzbein-Robbins grading. Results: A total of 194 pedicle screws (114 cervical and 80 thoracics) were placed using trajectory guides, of which 102 belonged to group B (34 cervical and 68 thoracics). Out of a total of 194 pedicle screws, 193 had clinically acceptable placement (grade A: 187; grade B: 6; and grade C: 1). In the cervical spine, 110 pedicle screws out of a total of 114 had grade A placement (grade B: 4). In the thoracic spine, 77 pedicle screws out of a total of 80 had grade A placement (grade B: 2; grade C: 1). Out of a total of 92 pedicle screws in group A, 90 had grade A placement, and the rest 2 had grade B breach. Similarly, 97 out of a total of 102 pedicle screws in group B were placed accurately, 4 had grade B and another had a grade C breach. Conclusions: Patient-specific, 3D-printed laminofacetal-based trajectory guide may help in accurate placement of subaxial cervical and thoracic pedicle screws. It may help reduce surgical time, blood loss, and radiation exposure.