The role of diffusion tensor imaging in spinal pathology: A review.

Diffusion tensor imaging (DTI) allows for noninvasive, in vivo visualization of white matter fiber tracts in the central nervous system by measuring the diffusion of water molecules. It provides both quantitative and qualitative (i.e., tractography) means to describe a region-of-interest. While protocols for the use of DTI are better established in the brain, the efficacy and potential applications of DTI in spinal cord pathology are less understood. In this review, we examine the current literature regarding the use of DTI in the spinal cord pathology, and in particular its diagnostic and prognostic value in traumatic injury, spinal tumors, cervical myelopathies, amyotrophic lateral sclerosis, and multiple sclerosis. Although structural magnetic resonance imaging (MRI) has long been the gold standard for noninvasive imaging of soft tissues, DTI provides additional tissue characteristics not found in the conventional MRI. We place emphasis on the unique characteristics of DTI, its potential value as an adjunct imaging modality, and its impact on clinical practice.

Nature, timing, and severity of complications from ultrasound-guided percutaneous renal transplant biopsy.

We sought to review our kidney transplant biopsy experience to assess the incidence, type, presenting symptoms, and timing of renal transplant biopsy complications, as well as determine any modifiable risk factors for postbiopsy complications. This is an observational analysis of patients at the University of Wisconsin between January 1, 2000, and December 31, 2009. Patients with an INR ≥1.5 or platelet counts less than 50 000 were not biopsied. An 18-gauge needle was used for biopsy. Over the study period, 3738 biopsies were performed with 66 complications (1.8%). No deaths occurred. A total of 0.7% were mild complications, 0.7% were moderate complications, 0.21% were severe complications, and 0.19% were life-threatening. Most complications occurred within the 4-h postbiopsy period, although serious complications were often delayed: 67% of complications requiring surgical intervention presented greater than 4 h after biopsy. Biopsy within 1 week of transplant had a 311% increased risk of a complication. Postbiopsy reduction in hematocrit and hemoglobin at 4 h was associated with a complication. In conclusion, life-threatening complications after renal allograft biopsy occurred in 0.19% of patients. Most complications occurred within 4 h postprocedure; however, many serious complications occurred with a time delay after initially uneventful monitoring. The only clinically significant laboratory predictor of a complication was a fall in the hematocrit or hemoglobin within 4 h. Patients biopsied within a week of transplant were at the highest risk for a complication and should therefore be most closely monitored.

Macrophage activation syndrome in a patient with systemic onset of the juvenile idiopathic arthritis.

Systemic onset juvenile idiopathic arthritis (sJIA) is defined as arthritis affecting one or more joint usually in the juvenile age group (< 16 years of age) with or preceded by fever of at least 2 weeks duration that is documented to be daily ("quotidian") for at least 3 days which may be associated with evanescent (non-fixed) erythematous rash or generalized lymph node enlargement or hepatomegaly/splenomegaly/both or serositis. Macrophage activation syndrome (MAS) is a life-threatening complication of sJIA marked by sudden onset of non-remitting high fever, profound depression in all three blood cell lines (i.e. leukopenia, anemia, and thrombocytopenia), hepatosplenomegaly, lymphadenopathy, and elevated serum liver enzyme levels. In children with systemic juvenile idiopathic arthritis, the clinical picture may mimic sepsis or an exacerbation of the underlying disease. We report a case of a 16-year-old female patient presenting with high grade fever with joint pains and generalized weakness which proved to be systemic onset juvenile idiopathic arthritis with macrophage activation syndrome after ruling out all other differential diagnoses and responded well to intravenous steroids.

Penumbral cooling in ischemic stroke with intraarterial, intravenous or active conductive head cooling: A thermal modeling study.

In ischemic stroke, selectively cooling the ischemic penumbra might lead to neuroprotection while avoiding systemic complications. Because penumbral tissue has reduced cerebral blood flow and in vivo brain temperature measurement remains challenging, the effect of different methods of therapeutic hypothermia on penumbral temperature are unknown. We used the COMSOL Multiphysics® software to model a range of cases of therapeutic hypothermia in ischemic stroke. Four ischemic stroke models were developed with ischemic core and/or penumbra volumes between 33-300 mL. Four experiments were performed on each model, including no cooling, and intraarterial, intravenous, and active conductive head cooling. The steady-state temperature of the non-ischemic brain, ischemic penumbra, and ischemic core without cooling was 37.3 °C, 37.5-37.8 °C, and 38.9-39.4 °C respectively. Intraarterial, intravenous and active conductive head cooling reduced non-ischemic brain temperature by 4.3 °C, 2.1 °C, and 0.7-0.8 °C respectively. Intraarterial, intravenous and head cooling reduced the temperature of the ischemic penumbra by 3.9-4.3 °C, 1.9-2.1 °C, and 1.2-3.4 °C respectively. Active conductive head cooling was the only method to selectively reduce penumbral temperature. Clinical studies that measure brain temperature in ischemic stroke patients undergoing therapeutic hypothermia are required to validate these hypothesis-generating findings.

Comparison of RECIST and iRECIST criteria in patients with advanced lung cancer treated with nivolumab.

Background: Systemic therapy in lung cancer is mainstay of treatment as most patients present in advanced stages, with rising importance of new immunotherapy agents. Purpose: To compare the RECIST 1.1 and the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECISTs) criteria for response assessment in lung cancer patients on immunotherapy. To find the incidence of pseudoprogression and associated imaging patterns. Material and Methods: Retrospective study in 28 patients treated with immunotherapy for advanced metastatic NSCLC. End points were progression-free survival (PFS) and overall survival (OS). Response assessments were separately tabulated according to RECIST 1.1 and iRECIST and classified into dichotomous groups of responders and nonresponders. Agreement in assessments between RECIST 1.0 and iRECIST examined using Cohen kappa (κ) coefficient with 95% confidence intervals. Kaplan-Meier survival analysis was done for PFS and OS. Differences between RECIST 1.1 and iRECIST for both responder and nonresponder were evaluated by the log rank test, Breslow (Generalized Wilcoxon) test, and Tarone-Ware test. Results: Incidence of pseudoprogression was 7% (2/28). The RECIST1.1 and iRECIST were in disagreement in two patients. The agreement between RECIST and iRECIST was almost perfect. The PFS and the OS are significantly longer in duration for responders in comparison to nonresponders for both RECIST and iRECIST and the difference between two assessment criteria is not significant. Conclusion: Although iRECIST aims to monitor treatment more precisely than conventional response criteria, this must be weighed against how infrequent pseudoprogression is and the cost of this therapy, both financially and in the potential delay in changing to a more effective treatment.

Role of Pathologist in the Era of Image-Guided and EUS-Guided Aspirations: A 10-Year Study at a Single Tertiary Care Oncology Institute in North India.

BACKGROUND: With improved and readily accessible imaging techniques, the shift in fine-needle aspiration cytology (FNAC) from palpation-guided FNA (PGFNA) to image-guided FNA (IGFNA) and endoscopic ultrasound-guided FNA (EUS-FNA) became evident in last few decades. The present study evaluates the impact of IGFNA and EUS-FNA on the practice of cytopathology at our 300-bedded oncology institute. STUDY DESIGN: A 10-year audit of three aspiration modalities PGFNA, IGFNA, and EUS-FNA was done. The number of aspirates, inadequacy rates, new patient registration numbers, and tissue biopsy numbers were compared. RESULTS: A total of 29,610 FNAC were evaluated against a total 141,333 new patient registrations over a period of 10 years. The new cancer patient registration over last 10 years showed a 56% increase, with a comparable increase of 60% in diagnostic biopsies; whereas, the number of FNAC increased by only 6%. This reduction in the number of aspirates was mainly due to fall in the number of PGFNA to 18% of all procedures in the year of 2019 from a high of 44% in 2011. Further, PGFNA showed a reduction by 50% over 3 years. The inadequacy rates of PGFNA increased to 9.1% (in 2019) from 1.6% (in 2012). The IGFNA constituted 46%-60% of procedures, with inadequacy varying from 8.5% to 12.1% over years. The EUS-FNAC gradually increased from 3% to 22% from 2013, and the inadequacy rates were variable overtime showing parallelism with the use of rapid on-site adequacy evaluation (ROSE) by the endoscopist. Inadequacy rates ranged from 7.1% (2013) to 2.6% (2016), 7.7% (2017), and 5.4% (2019). CONCLUSION: The utility of ROSE and diminishing role of pathologist is highlighted in our study. Judicious ROSE improves diagnostic accuracy, decreases the rate of missed diagnosis and the repetition of procedures. The study sheds light on the ever-increasing lacuna in the training of pathologists for blind as well as in image-guided FNAC. Further, it enumerates the factors leading to the underutilization of ROSE, its undisputed advantages, operator variations in procedure, smear preparation, and screening.

Hyperprogression after Immunotherapy: Nivolumab. Analysis of Imaging Findings Associated with Hyperprogression and Tumor Growth Kinetics.

Introduction The increased use of new checkpoint inhibitors in cancer therapy has led to the discovery of new unconventional responses, like pseudoprogression and hyperprogression disease (HPD). The study documents imaging findings of HPD and analyzes the growth kinetics in advanced metastatic cancers patients treated with immunotherapy. Methods We retrospectively reviewed patients treated with anti-PD-1 (anti-progressive disease-1) antibody therapy (nivolumab) between January 2017 and December 2017 at our institute. The patients who exhibited early and rapid progression rates after initiation of immunotherapy were further analyzed for tumor growth kinetics (TGKs) and imaging findings. All prebaseline, baseline, and post nivolumab imaging were retrospectively reviewed to assess the TGKs, time to treatment failure (TTF), and rate of progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results Four patients with HPD had peculiar imaging appearance of unilateral circumferential nodular pleural thickening along with conglomerate pleural masses and effusions. Both primary and secondary sites progressed along with the appearance of new lesions in all these patients. The mean progression-free survival (PFS) was 32 days using Kaplan Meier analysis. Conclusion The unique and recurring imaging pattern of disease progression in patients with HPD as reported in our case series in addition to TGK ratio, and TTF may prove to be of additional help in early identification of this unique and ghastly outcome.

18-FDG PET-CT should be included in preoperative staging of gall bladder cancer.

BACKGROUND: Only few retrospective studies have looked into the ability of PET-CT to diagnose distant metastases in gall bladder cancer (GBC) patients with variable results. This study aims to determine the utility of PET -CT in potentially resectable GBC. METHODS: All GBC patients with resectable disease on CECT chest, abdomen & pelvis were subjected to FDG- PET-CT scan. Incidental GBC was excluded. All additional findings and change in management plan was recorded. RESULTS: Out of 149 patients, 99 (66.4%) were females and the mean age was 56.7 ± 11.0 years,. After PET scan, additional findings were seen in 46/149 (30.9%) patients and it lead to change in management plan in 35 (23.4%) patients due to the presence of distant metastases. Impact of PET scan in changing the stage was higher in patients having node positive disease on CECT (26/96, 27%) as compared to node negative patients (9/53, 16.9%), but this difference was not statistically significant (p = 0.233). After assessment on CECT, 76 patients were planned for NACT in view of locally advanced disease but after PET-CT in these patients, the management plan changed to palliative chemotherapy in 26 (34.2%) cases whereas it changed in only 9 out of 73 (12.3%) patients who were planned for upfront surgery (p = 0.003). CONCLUSION: Our results show that preoperative staging workup for GBC should include PET-CT as it changed the management plan in approximately one-fourth of all resectable GBC patients and in one-third of locally advanced cases.

Role of ADC values in assessing clinical response and identifying residual disease post-chemo radiation in uterine cervix cancer.

OBJECTIVES: To evaluate the role of apparent diffusion coefficient (ADC) values in assessing response after chemo-radiotherapy in cervix cancer and investigate the utility of ADC as a tool to identify residual disease, after the treatment completion. METHODS: A prospective study was done in 100 patients with histopathologically proven cancer of uterine cervix who were classified as either complete response (CR) or residual disease posttreatment. MRI was done pretreatment and after 6 weeks post-treatment with chemo-radiation. 53 patients among the cohort also underwent a fluoro-deoxy glucose positron-emission computed tomography (FDG-PET CT). ADC values, change in ADC values, and metabolic activity obtained from FDG-PET CT were correlated with clinical outcome, and statistical analysis was done to determine the better tool for assessing response evaluation between ADC and PET-CT. RESULTS: Residual lesions have notably lower ADC value than that of posttreatment changes. The mean ADC values of residual tumors: 1.26 ± 0.238 × 10-3 mm2/s and mean ADC values of lesions due to posttreatment changes: 1.540 ± 0.218 × 10-3 mm2/s (statistically significant difference between malignant and posttreatment lesions, P < 0.05). ADC has 67% sensitivity, 83% specificity, 35% positive predictive values (PPV), 95% negative predictive values (NPV), and 81% accuracy in differentiating residual disease from post treatment changes. PPV, NPV, sensitivity, and specificity with PET-CT were 93%, 89%, 98%, and 73%, respectively. PPV, NPV, sensitivity, and specificity of contrast MRI were 16%, 91%, 58%, and 59%, respectively. CONCLUSION: Diffusion imaging differentiates residual cervix malignancies from post treatment changes based on ADC values and can be a promising and evocative biomarker. Complimentary use of ADC and PET/CT may increase diagnostic confidence.

Value of diffusion MR imaging in differentiation of recurrent head and neck malignancies from post treatment changes.

PURPOSE: Role of diffusion-weighted (DW) MR imaging in differentiating residual or recurrent neck malignancies from postoperative/post-radiation changes with histopathological correlation and comparison with PET-CT. METHODS AND MATERIALS: Prospective observational study for a period of 1 year in 62 post-radiation/post-operative patients suspected to have residual/recurrent tumors of neck with lesion diameter more than 5 mm measured on MRI. RESULTS: Mean ADC for recurrent/residual tumors: 1.008 ±â€¯0.220 × 10-3 mm2/s - significantly lower than mean ADC value for post-treatment changes of 1.69 ±â€¯0.40 × 10-3 mm2/s (p < 0.0001). The overall diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the qualitative assessment for the use of DWI in differentiating tumors recurrence from post-treatment changes were 96.6%, 96% and 83.3%, respectively. Upon quantitative analysis of the DW imaging data, a threshold ADC value of 1.3 × 10-3 mm2/s used for differentiating between post-treatment changes and recurrent cancers showed the highest combined sensitivity of 94%, specificity of 83.3%, accuracy of 93.6%, positive predictive value of 95.9%, and negative predictive value of 83.3%. CONCLUSION: DW MRI is a promising non-invasive MRI technique used to differentiate recurrent/residual head and neck malignancies from posttreatment changes based on ADC values. DWI offers advantage as it has a short scanning time and can be safely added to standard MRI protocol with minimum patient discomfort. Complementary use of DWI and PET/CT imaging may increase diagnostic confidence for differentiating recurrent disease from radiation therapy-induced changes after 6-12 months in posttreatment cases.

Diffusion Tensor Imaging in a Large Longitudinal Series of Patients With Cervical Spondylotic Myelopathy Correlated With Long-Term Functional Outcome.

BACKGROUND: Fractional anisotropy (FA) of the high cervical cord correlates with upper limb function in acute cervical cord injury. We investigated the correlation between preoperative FA at the level of maximal compression and functional recovery in a group of patients after decompressive surgery for cervical spondylotic myelopathy (CSM). OBJECTIVE: To determine the usefulness of FA as a biomarker for severity of CSM and as a prognostic biomarker for improvement after surgery. METHODS: Patients received diffusion tensor imaging (DTI) scans preoperatively. FA values of the whole cord cross-section at the level of maximal compression and upper cervical cord (C1-2) were calculated. Functional status was measured using the modified Japanese Orthopedic Association (mJOA) scale preoperatively and at follow-up up to 2 yr. Regression analysis between FA and mJOA was performed. DTI at C4-7 was obtained in controls. RESULTS: Forty-four CSM patients enrolled prior to decompression were compared with 24 controls. FA at the level of maximal compression correlated positively with preoperative mJOA score. Preoperative FA correlated inversely with recovery throughout the postoperative period. This was statistically significant at 12 mo postoperation and nearly so at 6 and 24 mo. Patients with preoperative FA <0.55 had a statistically significant difference in outcome compared to FA >0.55. CONCLUSION: In the largest longitudinal study of this kind, FA promises a valid biomarker for severity of CSM and postoperative improvement. FA is an objective measure of function and could provide a basis for prognosis. FA is particularly useful if preoperative values are less than 0.55.

Role of Coma Acidosis Malaria Score in Patients with Severe Malaria among Indian Population: a Tertiary Care Center Experience.

OBJECTIVE: Malaria is a prime public health threat in developing countries like India. There is an unmet need of a simplified methodology for the purpose of triage and provision of intensive care to the severely infected patients in these areas. MATERIALS AND METHODS: We did a prospective study in patients (n=60) admitted with severe malaria in a single tertiary care center in the state of Haryana, India. We assessed the role of coma acidosis malaria (CAM) score in these patients when predicting mortality and morbidity events. Stepwise logistic regression analysis was applied to identify patients requiring intensive care based on the CAM score, and the prediction value of the scoring system was assessed among these patients. RESULTS: Cerebral malaria (measured using the Glasgow coma scale) and acidosis (base deficit) were the major determinants of the CAM score. Serum bicarbonate levels and respiratory rates were assessed as the proxy markers of the base deficit as it is not always available. Morbidity increased steadily as the CAM scores increased. Sensitivity and negative predictive value of 100% depicted that the scoring system was able to identify patients who needed intensive care and accurately exclude the patients who could be conservatively managed in the ward. Positive predictive values of 73.9%, 68%, and 80.9% indicated that CAM, bicarbonate-based CAM (BCAM), and respiratory rate-based CAM (RCAM) scores, respectively, could precisely predict the morbidity and mortality events among patients with CAM scores ≥2. CONCLUSION: CAM scores have precise predictive values in assessing patients with severe malaria. The scoring system helps in accurate and systemic triage of patients, irrespective of species, and directs the treating physicians toward vigilant treatment and emergency care.

Diffusion Tensor Imaging Correlates with Short-Term Myelopathy Outcome in Patients with Cervical Spondylotic Myelopathy.

OBJECTIVE: To determine if spinal cord diffusion tensor imaging indexes correlate with short-term clinical outcome in patients undergoing elective cervical spine surgery for cervical spondylotic myelopathy (CSM). METHODS: A prospective consecutive cohort study was performed in patients undergoing elective cervical spine surgery for CSM. After obtaining informed consent, patients with CSM underwent preoperative T2-weighted magnetic resonance imaging and diffusion tensor imaging of the cervical spine. Fractional anisotropy (FA) values at the level of maximum cord compression and at the noncompressed C1-2 level were calculated on axial images. We recorded the modified Japanese Orthopaedic Association (mJOA) scale, Neck Disability Index, and Short Form-36 physical functioning subscale scores for all patients preoperatively and 3 months postoperatively. Statistical analysis was performed to identify correlations between FA and clinical outcome scores. RESULTS: The study included 27 patients (mean age 54.5 years ± 1.9, 12 men). The mean postoperative changes in mJOA scale, Neck Disability Index, and Short Form-36 physical functioning subscale scores were 0.9 ± 0.3, -6.0 ± 1.9, and 3.4 ± 1.9. The mean FA at the level of maximum compression was significantly lower than the mean FA at the C1-2 level (0.5 vs. 0.55, P = 0.01). FA was significantly correlated with change in mJOA scale score (Pearson r = -0.42, P = 0.02). FA was significantly correlated with the preoperative mJOA scale score (Pearson r = 0.65, P < 0.001). CONCLUSIONS: Preoperative FA at the level of maximum cord compression significantly correlates with the 3-month change in mJOA scale score among patients with CSM. FA was also significantly associated with preoperative mJOA scale score and is a potential biomarker for spinal cord dysfunction in CSM.

A study of the pathological outcome of positron emission tomography-computed tomography 2-(18F)-fluro-2-deoxy-D-glucose avid lesion: A 5 years retrospective study.

INTRODUCTION: Positron emission tomography-computed tomography (PET-CT) has been commonly used for staging and follow-up in cancer patients. The present study compares radiological and pathological outcomes at all the sites. The benign nonphysiological uptake reduces the specificity of the modality due to high false positive (FP) rate although sensitivity for malignant lesions may be high. AIMS AND OBJECTIVES: To study the sensitivity, specificity, positive and negative predictive value (PPV and NPV) of PET-CT in the detection of malignant lesions for all sites using pathological and final clinical outcome. MATERIALS AND METHODS: A retrospective study of 195 cases of PET-CT detected lesions subjected to pathological diagnosis in the form of fine-needle aspiration cytology (FNAC) and/or Tru-cut biopsies were performed on patients with proven or suspected malignancy over a period of 1-year (2009) with a 5 years follow-up. During the same period, 2900 PET-CT imaging studies were performed, of which 195 were suspected to be malignant or benign. Of these, 193 patients were subjected for tissue diagnosis for confirmation. FNAC smears and Tru-cut biopsy were prepared and examined as per standard protocols. RESULTS: Of 195 aspirates in 183 aspirates, a conclusive tissue diagnosis was rendered. The follow-up was available in 79 cases of suspicious PET avid lesions for a period of 1-5 years. The PET-CT correlation with the tissue diagnosis and clinical outcome showed the sensitivity of 97.7% and an overall accuracy of 83% for malignant lesions. However, due to a large number of FP (n = 28) the specificity was only 43% and FP rates were 57%. PPV and NPV for malignant lesions was 82.4% and 87.5%, respectively. CONCLUSION: PET-CT is a sensitive investigation for detection of malignant lesions in treated and newly diagnosed cases of malignancy.

Effects of Hospital-Based Physical Therapy on Hospital Discharge Outcomes among Hospitalized Older Adults with Community-Acquired Pneumonia and Declining Physical Function.

To examine whether hospital-based physical therapy is associated with functional changes and early hospital readmission among hospitalized older adults with community-acquired pneumonia and declining physical function. Study design was a retrospective observation study. Participants were community-dwelling older adults admitted to medicine floor for community-acquired pneumonia (n = 1,058). Their physical function using Katz activities of daily living (ADL) Index declined between hospital admission and 48 hours since hospital admission (Katz ADL Index 6→5). The intervention group was those receiving physical therapy for ≥ 0.5 hour/day. Outcomes were Katz ADL Index at hospital discharge and all-cause 30-day hospital readmission rate. The intervention and control groups did not differ in the Katz ADL Index at hospital discharge (p = 0.11). All-cause 30-day hospital readmission rate was lower in the intervention than in control groups (OR = 0.65, p = 0.02). Hospital-based physical therapy has the benefits toward reducing 30-day hospital readmission rate of acutely ill older adults with community-acquired pneumonia and declining physical function.

Survival outcome and neurotoxicity in patients of high-grade gliomas treated with conformal radiation and temozolamide.

BACKGROUND: To study the survival outcome and neurotoxicity grades in patients of high-grade glioma (HGG) treated with conformal radiation and temozolamide. MATERIALS AND METHODS: Forty-six patients of HGG received conformal post operative radiation and temozolamide in the period 2003 to 2007. Twenty seven patients had near total resection, 17 had subtotal resection and 2 had biopsy only. 33 patients (71.7%) were treated with IMRT and 13 (28.3%) received 3DCRT (conformal radiation). Median dose delivered to PTV2 was 61.58 Gy and PTV1 was 54.3 Gy. Neurotoxicity was assessed with sequential MRI and cognitive disturbance was evaluated and grading was done according to CTCAE version 2.0 and 3.0 respectively. RESULTS: At a median follow-up of 12 months, median progression free and overall survival was 9 months and 15 months respectively. At 6 months, MRI neurotoxicity of grade 1, 2, and 3 was seen in 34.3, 11.4 and 2.9% patients. At 24 months, 35.3 and 29.4% patients had grade 1 and 2 neurotoxicity respectively. Cognitive disturbance was grade 0, 1, 2 and 3 in 55, 34.4, 6.8 and 3.4% patients at 6 months and grade 0 and grade 1 in 51.1 and 42.8% patients respectively at 24 months. CONCLUSION: Conformal Radiation yields low grades of MRI assessed neurotoxicity and cognitive disturbance in patients of HGG with no adverse impact on local control and survival.