Evaluation of Meibomian Gland Structure and Function in Patients with Vernal Keratoconjunctivitis Using Non Contact Meibography and Lipid Layer Interferometry.

PURPOSE: This study evaluated the structural and functional impact of vernal keratoconjunctivitis (VKC) on meibomian glands (MGs) using a combination of noncontact meibography and lipid layer interferometry. METHODS: In this observational study 50 patients with moderate persistent or severe VKC and 50 age-matched controls underwent MG imaging and lipid layer thickness (LLT) measurements with Lipiview II. Image J software was used to assess MG loss (meibograde) in both lids. All patients underwent dry eye evaluation comprising tear break-up time (TBUT), ocular surface staining (OSS), Schirmer I scoring, and meiboscoring (expressibility and quality of meibum secreted). RESULTS: Meibograde, OSS score, and meiboscore was higher in cases (2.68 ± 0.96, 0.580 ± 1.07, and 0.56 ± 0.95 respectively) than controls (1.80 ± 0.67, 0.00 ± 0.00, 0.22 ± 0.47 respectively) (p < 0.001, 0.001, 0.025 respectively). LLT and TBUT was lower in cases (54.58 ± 9.43 nm and 4.92 ± 3.09 sec respectively) than controls (70.14 ± 22.50 nm and 12.02 ± 2.73 sec respectively) (both p's = 0.001). Both groups had comparable Schirmer I scores. CONCLUSION: Children with VKC have significant MG dropouts, deterioration in meibum quality and a thinner and less stable tear film. VKC patients are thus prone to a vicious cycle of inflammation attributable both to the allergic component and to deterioration in MG structure and function. Co-management of MG dysfunction warrants as much attention as the allergic component itself.

Responsible Use of Oral Corticosteroids in People with Comorbid Diabetes: An Expert Consensus.

Globally, diabetes mellitus (DM) is a substantial contributor to morbidity and mortality. Comorbidities and intercurrent illnesses in people with diabetes may necessitate the use of steroids. Acute as well as chronic use of steroids contributes substantially to the development of various complications. Despite this, there are no standard guidelines or consensus to provide a unified approach for the rational use of steroids in people with diabetes. Also, there is scant harmonization among clinicians with the use of different steroids in routine practice. To address the inconsistencies in this clinical arena, the consensus working group (CWG) formulated a unified consensus for steroid use in people with diabetes. In people with diabetes, the use of steroids causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA). An increase in weight is directly related to the dose and duration of the steroid therapy. Steroid-related alterations in hyperglycemia, dyslipidemia, and hypertension (HTN) add to the increased risk of cardiovascular (CV) disease. The risk of complications such as infections, osteoporosis, myopathy, acne, cataracts, and glaucoma may increase with the use of steroids. Appropriate and timely monitoring of these complications is necessary for early detection and treatment of such complications. Given the systemic effects of various antihyperglycemic drugs, there is a possibility of aggravating or diminishing the specific complications. Preference to a safer steroid is required matching the steroid dose equivalence and individualizing patient management. In conclusion, short-, intermediate-, or long-term use of steroids in people with diabetes demands their rational use and holistic approach to identify, monitor, and treat the complications induced or aggravated by the steroids.

Role of low-pressure negative pleural suction in patients with thoracic trauma - a randomized controlled trial.

BACKGROUND: Thoracic trauma frequently includes a pneumothorax, hemothorax, or hemopneumothorax, which may necessitate an Intercostal drainage (ICD) for air and fluid evacuation to improve breathing and circulatory function. It is a simple and life-saving procedure; nevertheless, it carries morbidity, even after its removal. Efforts have been made continuously to shorten the duration of ICD, but mostly in non-trauma patients. In this study, we evaluated the impact of negative pleural suction over the duration of ICD. METHODS: This study was a prospective randomized controlled interventional trial conducted at Level 1 Trauma Centre. Thoracic trauma patients with ICD, who met the inclusion criteria (sample size 70) were randomized into two groups, the first group with negative pleural suction up to -20 cm H2O, and the second group as conventional, i.e. ICD connected to underwater seal container only. The primary objective was to compare the duration of ICDs and the secondary objectives were the length of hospital stay and various complications of thoracic trauma. RESULTS: Duration of ICD was measured in median days with minimum & maximum days. For the negative suction group, it was 4 days (2-16 days); for the conventional group, it was also 4 days (2-17 days). There was also no significant difference among both groups in length of hospital stay. CONCLUSION: The beneficial effect of negative pleural suction to ICD could not be demonstrated over the duration of ICD and hospital stay. In both groups, there was no significant difference in complication rates like recurrent pneumothorax, retained hemothorax, persistent air leak, and empyema. LEVEL OF EVIDENCE: Therapeutic Study, Level II TRIAL REGISTRATION: This trial was registered with the Clinical Trial Registry of India (CTRI) with registration no. REF/2020/11/038403.

QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.

BACKGROUND: Pazopanib hydrochloride (PZB) is a protein kinase inhibitor approved by the United States Food and Drug Administration and European agencies for the treatment of renal cell carcinoma and other renal malignancies. However, it exhibits poor aqueous solubility and inconsistent oral drug absorption. In this regard, the current research work entails the development and evaluation of the extrudates of pazopanib hydrochloride by the hot-melt extrusion (HME) technique for solubility enhancement and augmenting oral bioavailability. RESULTS: Solid dispersion of the drug was prepared using polymers such as Kollidon VA64, hydroxypropylmethylcellulose (HPMC), Eudragit EPO, and Affinisol 15LV in a 1:2 ratio by the HME process through a lab-scale 18 mm extruder. Systematic optimization of the formulation variables was carried out with the help of custom screening design (JMP Software by SAS, Version 14.0) to study the impact of polymer type and plasticizer level on the quality of extrudate processability by measuring the torque value, appearance, and disintegration time as the responses. The polymer blends containing Kollidon VA64 and Affinisol 15LV resulted in respective clear transparent extrudates, while Eudragit EPO and HPMC extrudates were found to be opaque white and brownish, respectively. Furthermore, evaluation of the impact of process parameters such as screw rpm and barrel temperature was measured using a definitive screening design on the extrude appearance, torque, disintegration time, and dissolution profile. Based on the statistical outcomes, it can be concluded that barrel temperature has a significant impact on torque, disintegration time, and dissolution at 30 min, while screw speed has an insignificant impact on the response variables. Affinisol extrudates showed less moisture uptake and faster dissolution in comparison to Kollidon VA64 extrudates. Affinisol extrudates were evaluated for polymorphic stability up to a 3-month accelerated condition and found no recrystallization. PZB-Extrudates using the Affinisol polymer (Test formulation A) revealed significantly higher bioavailability (AUC) in comparison to the free Pazopanib drug and marketed formulation.

Fortifying Micronutrient Supplementation in India: Indian Expert consensus.

Micronutrients play a key role in human health, being involved in energy metabolism, immunity, cellular functioning, growth, and development. Deficiencies in micronutrients occur in individuals of all ages due to several factors, including inadequate diets, disease states, and overweight/obesity. Guidelines from the Indian Council of Medical Research (ICMR) National Institute of Nutrition (NIN) Expert Group on Nutrient Requirements for Indians (2023) have specified the Recommended Dietary Allowances (RDA) for macronutrients and micronutrients. In addition, a healthy diet is crucial for overall health and should be the first step toward addressing micronutrient deficiencies. When diet is inadequate, micronutrient supplements can be provided to compensate. An expert panel of Indian doctors was convened to develop a pathway toward micronutrient supplementation among the Indian population. This Consensus Statement recognizes that different populations have varying needs for specific micronutrients, and ensuring adequate intake of such micronutrients can improve health outcomes. The panel provided recommendations for dietary practices and micronutrient supplementation when diet is inadequate. Addressing micronutrient deficiencies at the primary care level can prevent chronic deficiencies and their consequences. This Consensus Statement can serve as a primer for physicians to monitor and address deficiencies and thus help individuals maintain their health.

A Review on Affordable Combinations in Type 2 Diabetes Care: Exploring the Cost-Effective Potential of Glipizide + Metformin and Glimepiride + Metformin + Pioglitazone.

Management of type 2 diabetes mellitus (T2DM) largely relies on medication adherence of individuals with diabetes to achieve optimal glycemic control. The economic burden of diabetes could impede adherence, leading to a reduction in treatment efficacy and increased risk of complications. Furthermore, monotherapy in diabetes is losing traction due to its ineffectiveness in achieving early and sustained optimal glycemic control in a significant proportion of the population. Hence, clinicians prefer combination treatment due to their improved efficacy and safety. Considering these factors, the current review highlights the safety and efficacy of the affordable combination therapies, a dual therapy, glipizide + metformin, and a triple-drug combination of glimepiride + metformin + pioglitazone and its applicability in the management of T2DM among individuals with diabetes in India.

Multimodal Imaging in Mucolipidosis Type IV: Siblings With Novel Genetic Variant.

PURPOSE: Utilization of multimodal imaging techniques to diagnose cases of mucolipidosis type IV (ML-IV) and report a new genetic variant. METHODS: This study is a case report. RESULTS: Case 1 involves a 4-year-old boy with corneal haziness and global developmental delay who showed an increased reflectivity of the corneal epithelium on anterior segment optical coherence tomography (AS-OCT). In addition, neurologic evaluation was suggestive of ML-IV. Further genetics evaluation confirmed ML-IV. Histology of the button revealed a thickened epithelial basement membrane. Case 2, the younger sibling, showed a milder corneal haze with similar changes on AS-OCT prompting us to further evaluate for ML-IV by genetics (positive MCOLN1 gene mutation). Both instances highlighted varied ML-IV presentations, but a persistent feature was hyperreflective epithelium. CONCLUSIONS: Our study emphasizes AS-OCT's role in screening ML-IV and advocates the role of genetic counseling of affected parents. We present 2 South-Asian siblings with ML-IV with a new genetic variant, emphasizing the utility of detailed ophthalmic and neurologic assessments using multimodal imaging.

Benefits of Rib Fixation Utilizing Low-Cost Materials: A Randomized Pilot Trial.

INTRODUCTION: Surgical stabilization of rib fractures (SSRF) using standard rib plating systems has become a norm in developed countries. However, the procedure has not garnered much interest in low-middle-income countries, primarily because of the cost. METHODS: This was a single-center pilot randomized trial. Patients with severe rib fractures were randomized into two groups: SSRF and nonoperative management. SSRF arm patients underwent surgical fixation in addition to the tenets of nonoperative management. Low-cost materials like stainless steel wires and braided polyester sutures were used for fracture fixation. The primary outcome was to assess the duration of hospital stay. RESULTS: Twenty-two patients were randomized, 11 in each arm. Per-protocol analysis showed that the SSRF arm had significantly reduced duration of hospital stay (22.6 ± 19.1 d versus 7.9 ± 5.7 d, P value 0.031), serial pain scores at 48 h and 5 d (median score 5, IQR (3-6) versus median score 7, IQR (6.5-8), P value 0.004 at 48 h and median score 2 IQR (2-3) versus median score 7 IQR (4.5-7) P value 0.0005 at 5 d), significantly reduced need for injectable opioids (9.9 ± 3.8 mg versus 4.4 ± 3.4 mg, P value 0.003) and significantly more ventilator-free days (19.9 ± 8.7 d versus 26.4 ± 3.2 d, P value 0.04). There were no statistically significant differences in the total duration of ICU stay (median number of days 2, IQR 1-4.5 versus median number of days 7, IQR 1-14, P value 0.958), need for tracheostomy (36.4% versus 0%, P value 0.155), and pulmonary and pleural complications. CONCLUSIONS: SSRF with low-cost materials may provide benefits similar to standard rib plating systems and can be used safely in resource-poor settings.

Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

Deep learning reveals lung shape differences on baseline chest CT between mild and severe COVID-19: A multi-site retrospective study.

Severe COVID-19 can lead to extensive lung disease causing lung architectural distortion. In this study we employed machine learning and statistical atlas-based approaches to explore possible changes in lung shape among COVID-19 patients and evaluated whether the extent of these changes was associated with COVID-19 severity. On a large multi-institutional dataset (N = 3443), three different populations were defined; a) healthy (no COVID-19), b) mild COVID-19 (no ventilator required), c) severe COVID-19 (ventilator required), and the presence of lung shape differences between them were explored using baseline chest CT. Significant lung shape differences were observed along mediastinal surfaces of the lungs across all severity of COVID-19 disease. Additionally, differences were seen on basal surfaces of the lung when compared between healthy and severe COVID-19 patients. Finally, an AI model (a 3D residual convolutional network) characterizing these shape differences coupled with lung infiltrates (ground-glass opacities and consolidation regions) was found to be associated with COVID-19 severity.

Perinatal Use and Discontinuation of Disease-Modifying Antirheumatic Drugs: Outcomes of Patients Seen at a Pregnancy and Rheumatic Diseases Clinic.

BACKGROUND: Managing rheumatic disease activity using pregnancy-compatible medications is essential for reducing adverse maternal and fetal outcomes. We characterized medication use and discontinuation before, during, and after pregnancy, among female patients with rheumatic diseases attending a targeted pregnancy and rheumatic diseases clinic. METHODS: We conducted a cross-sectional medical record review of female patients with rheumatic diseases at a Canadian clinic between January 2017 and July 2020. Patients were categorized by pregnancy stage at their latest clinic visit: (1) preconception; (2) pregnant; (3) postpartum. We assessed use of conventional, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs), prednisone, and nonsteroidal anti-inflammatory drugs across 6 perinatal windows: 24 and 12 months preconception, each pregnancy trimester, and 3 months postpartum. We reported adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for medication discontinuation in the first trimester and subsequent disease flare. RESULTS: Of 230 included patients, 85 (37.0%), 12 (5.2%), and 133 (57.8%) were preconception, pregnant, and postpartum, respectively. Approximately half experienced at least 1 disease flare during each pregnancy stage (56.4% preconception, 58.1% during pregnancy, and 53.7% postpartum). Most used at least 1 DMARD throughout the perinatal period (82.6% preconception, 55.6% during pregnancy, and 45.1% postpartum). Overall, 25.5% discontinued at least 1 DMARD in the first trimester. DMARD discontinuation was associated with disease flare during pregnancy (aOR, 1.49; 95% CI, 0.55-4.03; p = 0.87) and postpartum (aOR, 3.09; 95% CI, 0.83-11.47; p = 0.09). CONCLUSIONS: Patients receiving care at a pregnancy and rheumatic disease clinic show perinatal medication use patterns consistent with recent recommendations and clinical guidelines.

Ocular Cicatricial Pemphigoid in Young Patients.

PURPOSE: The purpose of this study is to report ocular cicatricial pemphigoid (OCP) occurring in young patients. Relevant literature is also reviewed. METHODS: Medical records of patients aged 30 years or younger who were treated for OCP between August 2021 and May 2023 at a tertiary care eye institute were reviewed. The most common differential diagnoses of cicatrizing conjunctivitis, such as Stevens-Johnson syndrome sequelae, chemical injury, chronic topical/systemic drug use, autoimmune connective tissue disorders, or allergic eye diseases, were ruled out based on clinical history, examination, and the Cicatrizing Conjunctivitis Score described by Shanbhag et al. The diagnosis of OCP was confirmed by positive direct immunofluorescence of oral mucosal and/or conjunctival biopsy in a majority of the patients. RESULTS: Seven patients fulfilled the criteria for a diagnosis of OCP. The mean age at presentation was 21.86 ± 5.25 years (13-28 years). Some of the patients presented with relatively atypical features for OCP such as corneal immune ring infiltrate and bilateral corneal perforation. Six patients exhibited systemic mucosal lesions, and the direct immunofluorescence yield was 85.71%. All patients required aggressive immunosuppressive treatment. CONCLUSIONS: OCP is classically described as a rare disease that occurs in old age. This case series highlights the importance of a higher index of suspicion for diagnosing OCP at a younger age. Early administration of immunosuppressive agents can potentially control severe ocular surface inflammation and its sequelae.

Ultrasound-guided procedures for postoperative pain management in pediatric patients undergoing abdominal surgeries: A systematic review.

Many ultrasound-guided procedures are available for administering analgesia via peripheral nerve blockade. This systematic review aims to compare different ultrasound-guided procedures to determine which procedure is better suited for pediatric abdominal surgeries. The objective is to understand the efficacy of ultrasound-guided procedures for postoperative pain management in children undergoing abdominal surgeries and to identify which procedure takes less time and is better suited for a particular surgery. A systematic literature search was performed in PubMed, SCOPUS, Central Cochrane Registry of Controlled Trials (The Cochrane Library), and ScienceDirect databases for pediatric abdominal surgeries conducted with ultrasound-guided procedures for administering analgesia. We included studies involving randomized controlled trials (RCTs). Quasi-randomized controlled studies, prospective, retrospective observational studies, case series, case reports, letters, editorials, comments, animal studies, and studies from non-English literature were excluded. We reviewed 13 articles with 910 patients included. Age groups varied from 6 months to 21 years. The most common block used was the transversus abdominis block (47.76%), and the most common surgery performed was hernia and hydrocele (52.10%). Quadratus lumborum block was used in 26.92%, erector spinae block in 8.97%, modified transversus abdominus block and rectus sheath block in 9.62%, and ilioinguinal block in 6.73% of the patients. No complications were reported in any of the studies. Transversus abdominus block is less effective in two of the studies. Each procedure for pediatric postoperative analgesia has specific advantages and limitations, highlighting the complexity of tailoring interventions. Our review focuses on the advancements in ultrasound-guided analgesia for lower abdominal surgeries in pediatric patients while also emphasizing the need for future randomized controlled trials (RCTs) to compare efficacy, standardize practices, and improve patient outcomes.

Xanthogranulomatous Pyelonephritis in a Neonate Masquerading as Renal Mass.

Xanthogranulomatous pyelonephritis (XGP), a variant of chronic obstructive pyelonephritis, is a very rare diagnosis in neonates with three reported cases to date. It is often misdiagnosed in infancy as it mimics the features of renal mass. Herein, we report a case of 20-day-old neonate with XGP presenting as a renal mass.

Risk factors and outcome of antenatally diagnosed congenital diaphragmatic hernia following in-utero transfer in a busy public-sector tertiary care center in North India.

We analyzed the risk factors and outcomes of antenatally diagnosed congenital diaphragmatic hernia (CDH) from a tertiary-care children's hospital following in-utero transfer. A total of 41 antenatally detected cases of CDH were included; 30 were live-born and 11 were still-born. The primary outcome was postnatal survival. The secondary outcome was the probable factor affecting survival. No medical termination of the pregnancy was done. The mean gestational age at diagnosis was 23 weeks. The diagnostic accuracy of antenatal ultrasonography was 40/41 (97.5%). Lung-to-head ratio (LHR) was <1 in 20 cases (survived 2), LHR was >1 in 10 cases (survived 8), and LHR was not recorded in 11 cases (survived 4). Overall survival was 14/41 (34.1%). Survival in fetuses with polyhydramnios was 0% (n=3; survived 0), associated anomalies were 33.3% (n=3; survived 1), and liver herniation was 22.2% (n=9; survived 2). Postnatally, significant risk factors included a low Apgar score, the need for ventilation, and neonatal intensive care unit (NICU) management. Survival in live-born cases was 14/30 (46.6%) and in operated cases was 14/19 (73.6%). We concluded that antenatal ultrasound had a high accuracy rate for detecting CDH. Antenatal risk factors affecting outcomes were low LHR, maternal polyhydramnios, liver herniation, and associated malformations. Postnatal risk factors included a low Apgar score, NICU admission, and a need for ventilation. The overall survival rate, as well as the survival rates for live-borns and those undergoing surgery, were 34.1%, 46.6%, and 73.6%, respectively. This data will guide clinicians in counseling the families of antenatally diagnosed CDH.

Micro-RNAs With Prognostic Significance in Gallbladder Cancer: A Systematic Review and Meta-Analysis.

Gallbladder cancer (GBC) stands out as one of the most widespread malignancies impacting the biliary tract globally. Despite increasing interest, to the best of our knowledge, no meta-analysis has been undertaken to amalgamate the existing data concerning the prognostic significance of micro-RNAs (miRNAs) in GBC in comparison to studies on miRNAs in other cancers. Hence, this systematic review and meta-analysis aimed at determining the prognostic significance of miRNAs in GBC patients. Comprehensive literature searches were conducted across PubMed, Cochrane Library, Ovid, Scopus, and Science Direct databases. Studies that evaluated the association between miRNAs and overall survival in GBC patients were included. Random-effect meta-analysis was employed to pool hazard ratios (HRs) and their 95% confidence intervals (CIs) across studies. A total of 15 studies, encompassing 16 miRs, were included for our analysis. The pooled analysis revealed that a high expression of miR-204, miR-7-2-3p, miR-29c-3p, miR-125b, miR-20a, miR-139-5p, miR-141, miR-92b-3p, miR-335, and miR-372 was significantly associated with poor prognosis and increased risk (HR>1 and the upper bound of the 95% CI>1). Additionally, these miRNAs were associated with the overall survival (HR = 1.56, 95% CI = 0.91-2.20, I2 = 91.82%). Significant heterogeneity was observed and could be attributed to the limited number of studies available on the GBC and significant reliance on quantitative real-time PCR for the detection of miRNAs. In conclusion, specific miRNAs exhibit prognostic significance in GBC, with potential implications for patient stratification and targeted therapeutic interventions. However, due to the heterogeneity among studies, these findings should be interpreted cautiously and validated in larger cohorts.

Measurement and Incorporation of Laryngeal Motion Using cine-MRI on an MR-Linear Accelerator to Generate Radiation Therapy Plans for Early-stage Squamous Cell Cancers of the Glottis.

Purpose: Swallow-related motion of the larynx is most significant in the cranio-caudal directions and of` short duration. Conventional target definition for radical radiation therapy includes coverage of the whole larynx. This study longitudinally examined respiration- and swallow-related laryngeal motions using cine-magnetic resonance imaging. We further analyzed the dosimetry to organs at risk by comparing 3D-conformal radiation therapy (3D-CRT), volumetric modulated arc therapy (VMAT), and intensity modulated radiation therapy (IMRT) techniques. Methods: Fifteen patients with T1-2 N0 glottic squamous cell carcinomas were prospectively recruited for up to 3 cine-MRI scans on the Elekta Unity MR-Linear accelerator, at the beginning, middle, and end of a course of radical radiation therapy. Swallow frequency and motion of the hyoid bone, cricoid and thyroid cartilages, and vocal cords were recorded during swallow and rest. Adapted treatment volumes consisted of gross tumor volume + 0.5-1 cm to a clinical target volume with an additional internal target volume (ITV) for personalized resting-motion. Swallow-related motion was deemed infrequent and was not accounted for in the ITV. We compared radiation therapy plans for 3D-CRT (whole larynx), VMAT (whole larynx), and VMAT and IMRT (ITV for resting motion). Results: Resting- and swallow-related motions were most prominent in the cranio-caudal plane. There were no significant changes in the magnitude of motion over the course of radiation therapy. There was a trend of a progressive reduction in the frequency of swallow. Treatment of partial larynx volumes with intensity modulated methods significantly reduced the dose to carotid arteries, compared with treatment of whole larynx volumes. Robustness analysis demonstrated that when accounting for intrafraction swallow, the total dose delivered to the ITV/planning target volume was maintained at above 95%. Conclusions: Swallow-related motions are infrequent and accounting for resting motion in an ITV is sufficient. VMAT/IMRT techniques that treat more conformal targets can significantly spare critical organs at risk such as the carotid arteries and thyroid gland, potentially reducing the risk of carotid artery stenosis-related complications and other long-term complications.