Molecular Basis of Cerebral Vasospasm: What Can We Learn from Transcriptome and Temporal Gene Expression Profiling in Intracranial Aneurysm?

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research.

Endoscopy for T10 nerve sheath tumor.

Minimally invasive surgery (MIS) is increasingly being adopted for spinal intradural tumors. Through the use of conventional microscopy or exoscopy for large lobulated nerve sheath tumors, the posterior root attachment is often visualized only after mobilizing the tumor. Here, the authors describe the utility of angled endoscopy with its panoramic view for a T10 nerve sheath tumor. Gross-total extracapsular excision was achieved utilizing a minimally invasive right paraspinous approach, fenestration, lateral durotomy, sliding delivery of the tumor, sharp dissection of radicular attachments under neuromonitoring, and dural closure with oblique clips. Angled endoscopes help visualize the attachments behind large multilobulated tumors and confirm the totality of excision. The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23214.

Neurogenic myocardial dysfunction post craniopharyngioma resection: A diagnostic dilemma.

Endoscopic transsphenoidal resection of craniopharyngioma is a commonly used technique. Cerebral vasospasm may occur in nearly 10% of cases leading to adverse neurological outcomes. Cardiopulmonary dysfunction may be seen in patients with severe vasospasm. The literature describing the occurrence of neurogenic stunned myocardium following craniopharyngioma resection in pediatric patients is very sparse. Here, we describe such a case managed with a combination of milrinone (to relieve vasospasm and improve cardiac pump function), noradrenaline (to obtain target blood pressure), and vasopressin (to control urine output). This case report proposes the treatment plan of neurogenic stunned myocardium following vasospasm in pediatric patients.

The Call for Neuroendoscopy Cadaveric Workshops in Lower-Middle Income Countries.

OBJECTIVE: This study aims to assess the impact of the workshops organized during Neuroendocon 23 on the perspective and confidence of neurosurgeons toward endoscopy in a lower-middle income country. METHODS: Neuroendocon 23 had cranial and spinal endoscopy cadaveric workshops with 30 delegates each. A pre and postworkshop survey was disseminated among the delegates, and statistical analysis was performed with SPSS (version 26) using P < 0.05. RESULTS: A total of 24 delegates (40%) consented to participate in the study, with only 1 female respondent (4.17%). After the cranial endoscopy workshop, there was an increase in the level of confidence of delegates in cranial endoscopic approaches (P < 0.001). Similarly, after the spine endoscopy workshop, the respondents had increased confidence in managing spine conditions with the endoscopic approach (P = 0.040), to the extent that they preferred the endoscopic over the microsurgical technique (P < 0.001). All respondents (n = 24, 100%) believed that endoscopy should be promoted in lower-middle income countries and integrated into residency curricula. CONCLUSIONS: Cranial and spinal endoscopy cadaveric workshops could be the first step in stimulating the interest of neurosurgeons in endoscopy.

Tractography Navigated Endoscopic En-Bloc Excision of Pediatric Giant Choroid Plexus Tumor.

Giant choroid plexus (CP) tumors in children pose a formidable surgical challenge due to extensive vascularity/blood loss, tumor size impeding early visualization of the pedicle, hydrocephalus/mass effect distorting cerebral localization, considerable prevalence of atypical tumors and carcinoma demanding excision without tumor spillage, and retraction-associated morbidity. However, total resection of CP papilloma has excellent potential for cure. This is probably the first report in the literature of diffusion tensor imaging navigation-guided tumor pedicle targeting, endoscopic devascularization and division of pedicle followed by en bloc delivery in optimally tackling most of these challenges in a 6-year-old girl presenting with a giant lateral ventricular CP tumor. Giant CP tumors pose a formidable challenge. Extensive vascularity can cause life-threatening blood loss in children.1 Large tumor size makes it impractical during microsurgery to achieve early visualization of pedicle.2 Hydrocephalus and mass effect can distort sulcal anatomy, with potentially devastating deficits.3 Still, prevalence of atypical tumors and carcinoma warrants excision without tumor spillage.4 In Video 1, we demonstrate our "10-D" steps of en-bloc excision, exploiting panoramic visualization of endoscope5: 1. Diagnosis, 2. Diffusion tensor imaging guided pedicle targeting, 3. Design position & exposure, 4. Durotomy, 5. Dissection of sulcus, 6. Delineation of pedicle, 7. Devascularization, 8. Division of pedicle, 9. Delivery of tumor, and 10. Dural & skin closure. The conventional superior parietal lobule approach to get the tumor en-bloc would have been from the posterosuperior direction, where the tumor is likely to conceal the pedicle. The trajectory to first get to the pedicle must be from an anterosuperior direction but will violate corticospinal fibers. Hence entry point was chosen in between, just posterior to the post-central sulcus. To accommodate the 'en-bloc' excision avoiding ventricular seedlings, a 5 cm mini-craniotomy was fashioned centered on the entry point planned in the navigation system. Ventricle was entered perpendicular to the sulcus through the roof of the atrium, with least cortical transgression and avoiding injury to laterally placed optic radiation and speech areas.6 A 30-degree, 4-mm endoscope was inserted anterolateral to the tumor and fixed. The wide-angled vision offered by endoscopes enhancing meticulous dissection is the likely cause of better neurological outcomes, as noted in other ventricular lesions.7 Pedicular attachment of the tumor is coagulated thoroughly and cut, ensuring initial sparing of venous drainage. The draining vein is then coagulated and divided. 'En-bloc' excision is also known in other vascular lesions to decrease the risk of bleeding.8 The angled optics & panoramic visualization helps to identify any possible tumor seedlings.9 This is probably the first report of endoscopic en-bloc excision of a giant choroid plexus tumor in literature.

Morphology of intra tumoral cystic vestibular schwannoma and their response to gammaknife radiosurgery.

BACKGROUND: Cystic vestibular schwannoma (CVS) traditionally considered as poor responder to gammaknife radiosurgery (GKRS). Their longterm radiobiological behavior is less known. Here we discuss 38 cases with intra tumoral cyst CVS primarily treated with GKRS. Tumor morphology was assessed to understand their response to GKRS. METHODS: Total 38 patients(21 male and 17 female with median age of 41.7 years) of CVS treated with GKRS were retrospectively analysed. Tumors were divided as predominantly (greater than50% of total tumor volume) cystic or solid. They were subclassified as type 1 (predominantly cystic CVS, single cyst), type 2 (predominantly solid CVS, single cysts), type 3 (multicystic CVS). The entire cyst was incorporated for radiosurgery. The results were compared with volume matched control of 58 solid tumors(SVS). RESULT: The median tumor volume of CVS was 5.8 cc. The median tumor volume reduction was 44.5 % at a median follow-up of 68.5 months (30-110 months). Median tumor volume reduction was 68.5 %, 34.0%, 11.0.%, 30.5% at a median follow up of 52.5months, 66 months, 78.6 months, 96.5 months for type 1 CVS, type 2 CVS, type 3 CVS and SVS respectively. One patient with multicystic CVS showed increased tumor volume and expired after 9 months of surgery.The tumor volume reduction in type 1CVS was statistically significant as compared to type 3 CVS and SVS. However the tumor volume reduction among other groups did not differ significantly. CONCLUSION: Intra tumoral cystic components respond better to gammaknife radiosurgery in CVS. Tumor with single cyst respond better than multicystic vestibular schwannoma.

The Distribution of Lifestyle Risk Factors Among Patients with Stroke in the Indian Setting: Systematic Review and Meta-Analysis.

Background: The burden of stroke is increasing in India, but there is limited understanding of the distribution of reported risk factors in the Indian setting. It is vital to generate robust data on these modifiable risk factors to scale up appropriate strategies for the prevention of cerebrovascular diseases in this setting. Summary: The objective of this study is to estimate the overall proportion of life style risk factors of patients with stroke in the Indian setting. We searched PubMed and Google Scholar and relevant studies published till February 2022 were included. The risk of bias assessment was considered for the study selection criterion in the meta-analysis. The publication bias was evaluated by funnel plots and Egger's test. We identified 61 studies in the systematic review and after quality assessment, 36 studies were included for meta-analysis. Random effect model was used due to the significant inconsistency among the included studies (I2 > 97%). The mean age of the participants was 53.84±9.3 years and patients with stroke were predominantly males (64%). Hypertension (56.69%; 95% CI: - 48.45 - 64.58), obesity (36.61%; 95% CI: - 19.31 - 58.23), dyslipidemia (30.6%; 95% CI: - 22 - 40.81) and diabetes mellitus (23.8%; 95% CI: - 18.79 - 29.83) are the leading intermediate conditions associated with stroke. The Physical inactivity - 29.9% (95% CI: - 22.9 - 37.1), history of tobacco use (28.59 %; 95% CI: - 22.22 - 32.94) and alcohol use (28.15 %; 95% CI: - 20.49 - 37.33) were reported as the behavioral risk factors for stroke in this setting. Key Messages: The current meta-analysis provides robust estimates of the life style related risk-factor of stroke in India based on the observational studies conducted from 1994 to 2019. Estimating the pooled analysis of stroke risk factors is crucial to predict the imposed burden of the illness and ascertain the treatment and prevention strategies for controlling the modifiable risk factors in this setting.

Impulse Control Disorders with Short-term Use of Cabergoline in Macroprolactinomas: A Prospective Study with a Brief Review of Literature.

Impulse control disorders (ICDs) are less-emphasized adverse effects of dopamine agonists. Evidence on prevalence and predictors of ICDs in patients with prolactinomas is limited and confined chiefly to cross-sectional studies. This was a prospective study performed to investigate ICDs in treatment-naïve patients with macroprolactinomas (n = 15) using cabergoline (Group I), compared to consecutive patients of nonfunctioning pituitary macroadenomas (n = 15) (Group II). Clinical, biochemical, radiological parameters and psychiatric comorbidities were evaluated at baseline. ICD was assessed by Minnesota impulsive disorder interview, modified hypersexuality and punding questionnaires, South Oaks gambling scale, kleptomania symptom assessment scale, Barratt impulsive scale (BIS), and internet addiction scores (IAS) at baseline and 12 weeks. Group I had a significantly lower mean age (28.5 vs. 42.2 years) with a female predominance (60%) compared to group II. Median tumor volume was lower in group I (4.92 vs. 14 cm3) despite significantly longer symptom duration (2.13 vs. 0.80 years) than in group II. Serum prolactin decreased by 86% (P = 0.006) and tumor volume decreased by 56% (P = 0.004) at 12 weeks in group I, with a mean weekly cabergoline dose of 0.40 ± 0.13 mg. There was no difference between both groups in hypersexuality, gambling, punding, and kleptomania symptom assessment scale scores at baseline and 12 weeks. Mean BIS showed a more remarkable change in group I (16.2% vs. 8.4%, P = 0.051), and 38.5% of patients transitioned from average to above-average IAS in group I. The current study found no increased risk of ICD with short-term use of cabergoline in patients with macroprolactinomas. The use of age-appropriate scores (such as IAS in younger individuals) may help diagnose subtle alterations in impulsivity.

Giant skull base mass need not be a tumor - a rare presentation of IgG4-related disease.

BACKGROUND: Giant intracranial 'IgG4-related' lesions are uncommon. They may present as pachymeningitis or localized mass. Here we report, probably, the largest IgG4 skull base mass ever to be reported. CASE: A 40-year male presented with headache, diplopia, right-sided sensori-neuronal hearing loss, and left spastic hemiparesis. Magnetic resonance imaging showed a lesion of 8.5 cm extending from the paranasal sinuses to the right petroclival region with uniform contrast enhancement and T2 hypointensity. Endonasal biopsy revealed respiratory epithelium with fibrosis, and lymphoplasmacytic infiltrate having IgG4 positive cells >30/HPF suggestive of 'IgG4-related' disease. Serum IgG4 was within normal levels. With oral prednisolone 60 mg given daily for 6 weeks and then tapered off over 8 weeks, he improved symptomatically. CONCLUSION: Though rare, 'IgG4-related' disease can also present as a giant skull base mass and should be kept as a differential to fungal granulomas and meningiomas. As they improve dramatically with medical management, extensive skull base resection should not be planned before obtaining a tissue biopsy, especially when there is extension into paranasal sinuses and T2 hypointensity.

Feasibility of awake endoscopic third ventriculostomy in selected patients of obstructive hydrocephalus.

BACKGROUND: Endoscopic third ventriculostomy (ETV) is usually performed under general anesthesia (GA) with proper head immobilization. However a few patients with hydrocephalus (HCP) may not be suitable for GA. Once the surgeon is familiar with endoscopic ventricular anatomy and gains adequate surgical experience with the procedure, ETV can be attempted under local anesthesia (LA) in selected patients. Here we discuss our experience of treating 32 patients of HCP with ETV under LA. METHODS: 32 symptomatic HCP patients with in the age range of 13 and 65 years, conscious, alert, cooperative and at high risk for GA owing to deranged liver or renal function, associated co-morbidities, pregnancy were considered for ETV under scalp block. All patients were evaluated for any discomfort during the surgical intervention. RESULT: All procedures were completed under LA. Four patients needed additional sedation prior to the scalp block to alleviate their apprehension. Four patients complained of bilateral orbital pain. In three it coincided with irrigation of fluid lower than body temperature. One patient had pain while touching the dorsum sella and needed analgesic supplement. All of them improved and none required additional CSF diversion within the average follow up of 9.5 months. CONCLUSION: ETV can be performed under local anesthesia in conscious, alert and cooperative patients in experienced hands. Unnecessary stimulation of the painful structures should be avoided and fluid for irrigation should be at body temperature. This ensures patient comfort and safety of the procedure.

Tetraventricular hydrocephalus with aqueductal flow void: an overlooked entity having consistent improvement following endoscopic third ventriculostomy.

BACKGROUND: Tetraventricular Hydrocephalus (TetHCP) is a heterogeneous group of cerebrospinal fluid (CSF) flow disorders having varying success rates with Endoscopic third ventriculostomy (ETV). This is report on the efficacy and rationale of ETV in a specific subset of primary TetHCP with aqueductal CSF flow voids. METHODS: Patients of primary acquired TetHCP presenting with increasing head size and/or headache having aqueductal CSF flow void on sagittal Magnetic Resonance Imaging (MRI) were included in this study. All of them underwent ETV. All patients were evaluated for clinical improvement & MRI at 3 months, and need for any additional procedure, in contrast to those without CSF flow void. The pathophysiology of hyperdynamic CSF circulation and its correlation to ETV was further reviewed. RESULTS: Eleven patients had tetraventricular hydrocephalus and aqueductal flow void, with age ranging from 10 months to 59 years. Two patients who could undergo quantitative flow study confirmed the hyperdynamic flow across the aqueduct. Following ETV, all showed clinical improvement. MRI at 3 months showed CSF flow void across the third ventricular stoma in addition to across the aqueduct. None of these patients required any redo procedures for a mean follow-up of 39.2 months. In contrast, there was 30% failure rate after ETV among 10 patients of tetraventricular hydrocephalus without aqueductal flow void. CONCLUSION: Tetraventricular hydrocephalus with aqueductal CSF flow void may be a unique entity with hyperdynamic CSF circulation and relative resistance at fourth ventricular outlets. ETV is highly efficacious in these patients, resulting in consistent clinico-radiological improvement.

An Integrated Clinical Score to Predict Remission in Cushing's Disease.

Objective: To derive a clinical score from parameters that favor remission of Cushing's disease (CD) after pituitary surgery. Methods: This is an analysis of 11 clinical, hormonal, and post-operative parameters that each favored remission in a cohort of 145 patients with CD treated by trans-sphenoidal surgery (TSS). Each parameter was designated as a categorical variable (presence/absence), and several favorable parameters present for each patient were calculated. From this, a median parameter score (clinical score) of the entire cohort was derived, which was then compared to the event of remission/persistence of CD. Results: The median number of favorable parameters present in the entire cohort was 3 (0-7). The significant count of patients in remission increased with the increasing number of parameters. The receiver-operator characteristic curve showed that the presence of ≥3 parameters was associated with remission in CD with a sensitivity of 84.2% and a specificity of 80%. Patients with a clinical score ≥3 had significantly higher remission rates (88.9%) than those who had persistent disease (27.3%; P = 0.001). Conclusion: A clinical score of ≥3 predicts remission in CD treated by TSS; however, it requires validation in other large cohorts. Rather than assessing individual parameters to predict remission in CD, an integrated clinical score is a better tool for follow-up and patient counseling.

The Quality of Life of Stroke Survivors in the Indian Setting: A Systematic Review and Meta-Analysis.

Background: The significant burden of stroke on the mortality rates of developing countries, including India, is well-documented in the literature. However, robust data regarding the aggregates of evidence on the quality of life (QOL) of stroke survivors is limited. Objective: To gather relevant information for policymakers on the QOL of stroke survivors based on observational studies conducted in the Indian setting. Methods: We searched PubMed, Scopus, and Google Scholar for studies conducted in the Indian setting. The methodological quality of each study was scored, and data were extracted from the published reports. The risk of bias assessment was conducted based on the JBI Critical Appraisal Checklist criteria. The relevant data regarding QOL were analyzed by a random effects model using R software. Results: 16 studies were included in the systematic review in which the majority of the studies recruited study participants in the hospital-based setting with an average duration of 3-6 months following the stroke episode. Our findings suggest that the pooled mean quality of life in the four dimensions of the World Health Organization Quality of Life instrument (WHOQOL-BREF) were ranged from 46.86 to 61.37 and the overall Stroke Specific Quality of Life scale (SS-QOL) mean score was 157.16. There was a significant inconsistency among the included studies as heterogeneity was high (I2 >97%). Conclusion: Assessment of the quality of life among stroke survivors is a crucial step to predict the illness' imposed burden and ascertain the effectiveness of the treatment. The present meta-analysis elucidates the aggregate estimates of quality of life and contributes to the research on the quality of life following a stroke in an Indian context.

Systematic review exploring the effect of therapeutic hypothermia on patients with intracranial hypertension.

Background: Intracranial hypertension is found in patients with various neurological and neurosurgical conditions such as subarachnoid hemorrhage (more than 50% of the patients have intracranial pressure > 20 mmHg at some point during their hospital stay), traumatic brain injury, and stroke. Various modalities are used to control intracranial hypertension, therapeutic hypothermia is one of them. This systematic review aims to assess the efficacy of therapeutic hypothermia in controlling intracranial hypertension in an adult patient. Methods: A systematic review of the literature published between one patient 1990 and 2020 was conducted. Four databases were searched including CINAHL, PubMed, the Cochrane Library, and EMBASE using keywords traumatic brain injury, intracranial pressure, randomized and controlled trials, and the effect of therapeutic hypothermia on intracranial hypertension. Results: All of the studies included in this review were randomized controlled trials. Most of the studies provided their sample demographics. Sample sizes ranged from 14 to 501. Of the 12 studies, five of them were from the United Kingdom, three of them were from China, two from North America, one from India, and one from Japan. Conclusion: Treating intracranial hypertension with therapeutic hypothermia may be beneficial according to a few studies but it is also associated with many adverse effects. Both the groups suffered from adverse events which were higher in the hypothermic group. However, these adverse events can be managed in any health-care setting. To treat the patients with therapeutic hypothermia, one (the managing team) should be competent enough to manage the adverse effects.

Setting up a Neurosurgical Skills Laboratory and Designing Simulation Courses to Augment Resident Training Program.

Background: The surgical skill practice in neurosurgery is being compromised in the recent past owing to the duty time constraint, patient safety concerns, and medico-legal issues. Surgical practice outside the operating room is essential to enhance a resident's operative skills and to gain confidence. Objective: To discuss the experience of establishing an 'in-house neurosurgery skills laboratory' and various training sessions conducted with cadaveric and non-cadaveric simulation modules. Methods: A skills laboratory was set up in the existing resident teaching hall with nine workstations. Each station has been equipped with an operating table, surgeon's chair, basic microscope, endoscope, high-speed drill system, and a suction machine. Vascular anastomosis, high-speed drilling, and basic neuroendoscopy were planned on low-cost non-cadaveric modules. Craniotomy and various surgical approaches were designed on cadaveric modules obtained from the anatomy department. Result: A total of 18 residents in divided groups during their initial three semesters had participated in the non-cadaveric simulation courses. Twenty-six residents had participated and 12 sessions were conducted on the cadaveric modules. Three workshops were conducted and 20 residents and faculty members from five other institutions had participated in the cadaveric hands-on training session. Conclusion: A well-equipped skills laboratory provides an opportunity for the residents to acquire operative expertise in a similar atmosphere to that of the operating theater. A structured program comprising various operative practice sessions should be incorporated into the resident training program.

Acceptance and Preparedness to be COVID Warriors: Self Narratives of Frontline Nurses of a Tertiary Care Center.

AIM: Aim of this study is to gain insight into how frontline nurses accepted and prepared themselves before COVID posting. METHODS: It is a qualitative and phenomenological study design. Eighteen in-depth interviews were conducted with the nurses who provided care to confirmed COVID 19 patients in a tertiary hospital of North India from September to November 2020. The interviews were transcribed and analyzed using Colaizzi's phenomenological method. The consolidated criteria for reporting qualitative research (COREQ) were followed in this study. RESULTS: In this study, the reported experiences were divided into five main themes: (I) Getting ready to be at the frontlines (II) Family and peer support (III) I Can Handle it! (IV) I have to be Strong! (V) Training is key to confidence. The risk of infection, fear of being a source of infection to the family, the worry of staying away from family, uncertainty, and nervousness related to personal protective equipment were the most common thoughts that disturbed the participants. However, taking a good diet, practicing yoga and meditation, having a sense of serving their country and community, faith in God, family support, faith in the organization, and good training helped the participants to prepare for the COVID posting. CONCLUSION: Despite facing various challenges, the nurses showed great strength and resilience. To promote a resilient health system, supportive supervision and adequate administrative support, training and workshops, peer group support, counseling cells, and spiritual support may be considered.

Limited Invasive Protocol: Optimizing Diagnostic Modalities in Corticotropin Mediated Cushing Syndrome.

BACKGROUND: To limit the role of bilateral inferior petrosal sinus sampling (BIPSS) in distinguishing between Cushing disease (CD) and ectopic Cushing syndrome (ECS), recent reports have proposed a noninvasive approach based on a combination of biochemical testing and radiological imaging as an alternative to the conventional invasive strategy (CIS). However, this strategy requires further validation. The current study aimed to evaluate 2 limited invasive protocols (LIP-1 and LIP-2) in limiting the role of BIPSS while maintaining a diagnostic accuracy similar to that of CIS. METHODS: This was a single-center study conducted on individuals with corticotropin-dependent Cushing syndrome. The LIPs were based on performing high-dose dexamethasone suppression (>50% cut-off in first [LIP-1] and >80% in second [LIP-2]) and magnetic resonance imaging of the sella in all individuals and selective use of computed tomography of the chest and abdomen before BIPSS. These LIPs were evaluated for limiting the use of BIPSS, their accuracy, and cost in comparison to CIS. RESULTS: Of the 206 individuals, 114 (97 of CD and 21 of ECS) were eligible for the current study. Using LIP-1, LIP-2, and CIS, BIPSS could have been avoided in 62.3%, 35.9%, and 25.4% of individuals, respectively. The positive predictive value for CD using LIP-1 and LIP-2 was 98.9% and 100%, respectively. The cost per patient evaluated using LIP-1, LIP-2, and CIS was $602.21, $966.81, and $1107.78, respectively. CONCLUSION: LIPs represent an equally accurate, less invasive, and more cost-effective alternative to the CIS for distinguishing between CD and ECS.