Spatial analysis of food and water-borne diseases in Ahmedabad, India: Implications for urban public health planning.

Spatial analysis of infectious diseases can play an important role in mapping the spread of diseases and can support policy making at local level. Moreover, identification of disease clusters based on local geography and landscape forms the basis for disease control and prevention. Therefore, this study aimed to examine the spatial-temporal variations, hotspot areas, and potential risk factors of infectious diseases (including Viral Hepatitis, Typhoid and Diarrhea) in Ahmedabad city of India. We used Moran's I and Local Indicators of Spatial Association (LISA) mapping to detect spatial clustering of diseases. Spatial and temporal regression analysis was used to identify the association between disease incidence and spatial risk factors. The Moran's I statistics identified presence of positive spatial autocorrelation within the considered diseases, with Moran's I from 0.09 for typhoid to 0.21 for diarrhea (p < 0.001). This indicates a clustering of affected wards for each disease, suggesting that cases were not randomly distributed across the city. LISA mapping demonstrated the clustering of hotspots in central regions of the city, especially towards the east of the river Sabarmati, highlighting key geographical areas with elevated disease risk. The spatial clusters of infectious diseases were consistently associated with slum population density and illiteracy. Furthermore, temporal analysis suggested illiteracy rates could increase risk of viral hepatitis by 13 % (95 % Confidence Interval (CI): 1.01-1.26) and of diarrhea by 18 % (95 % CI: 1.07-1.31). Significant inverse association was also seen between viral hepatitis incidence and the distance of wards from rivers. Conclusively, the study highlight the impact of socio-economic gradients, such as slum population density (indicative of poverty) and illiteracy, on the localized transmission of water and foodborne infections. The evident social stratification between impoverished and affluent households emerges as a notable contributing factor and a potential source of differences in the dynamics of infectious diseases in Ahmedabad.

El Niño Southern Oscillation, monsoon anomaly, and childhood diarrheal disease morbidity in Nepal.

Climate change is adversely impacting the burden of diarrheal diseases. Despite significant reduction in global prevalence, diarrheal disease remains a leading cause of morbidity and mortality among young children in low- and middle-income countries. Previous studies have shown that diarrheal disease is associated with meteorological conditions but the role of large-scale climate phenomena such as El Niño-Southern Oscillation (ENSO) and monsoon anomaly is less understood. We obtained 13 years (2002-2014) of diarrheal disease data from Nepal and investigated how the disease rate is associated with phases of ENSO (El Niño, La Niña, vs. ENSO neutral) monsoon rainfall anomaly (below normal, above normal, vs. normal), and changes in timing of monsoon onset, and withdrawal (early, late, vs. normal). Monsoon season was associated with a 21% increase in diarrheal disease rates (Incident Rate Ratios [IRR]: 1.21; 95% CI: 1.16-1.27). El Niño was associated with an 8% reduction in risk while the La Niña was associated with a 32% increase in under-5 diarrheal disease rates. Likewise, higher-than-normal monsoon rainfall was associated with increased rates of diarrheal disease, with considerably higher rates observed in the mountain region (IRR 1.51, 95% CI: 1.19-1.92). Our findings suggest that under-5 diarrheal disease burden in Nepal is significantly influenced by ENSO and changes in seasonal monsoon dynamics. Since both ENSO phases and monsoon can be predicted with considerably longer lead time compared to weather, our findings will pave the way for the development of more effective early warning systems for climate sensitive infectious diseases.

Increased Incidence of Thrombotic Complications With Non-small Cell Lung Cancer Necessitates Consideration of Prophylactic Anticoagulation in Young Individuals.

Venous thromboembolism (VTE) is a common complication in cancer patients and is associated with increased morbidity and mortality. Lung cancer is commonly associated with VTE including pulmonary embolism. We did a retrospective analysis from the 2013 Healthcare Cost and Utilization Project data to determine the role of age as a factor in the development of VTE in this patient group. Patients were selected using the International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes for metastatic lung cancer and VTE. The patients were stratified by age, sex, race/ethnicity, and site of VTE. There was a total of 16,577 VTE events detected out of a total of 182,863 cases of metastatic lung cancer, representing 9% of the total cases. In patients under 65 years of age, there were 356.82 more cases of pulmonary embolism per 100,000 individuals compared to those older than 65 years (p<0.0001). The same age group also showed 374.83 more upper extremity VTE, 286.94 more non-pulmonary thoracic VTE, and 263.97 more abdominal VTE events per 100,000 individuals (p<0.0001). In conclusion, we found that patients under the age of 65 years had a significantly higher incidence of VTE, pulmonary embolism, upper extremity VTE as well as abdominal and non-pulmonary VTE.

Nodal recurrences after stereotactic body radiotherapy for early stage non-small-cell lung cancer.

Lobectomy is considered the standard of care for early stage non-small-cell lung cancer. However, for those patients who remain unfit to undergo surgery due to advanced age, poor performance status, comorbidities, poor pulmonary reserve or a combination of these are now treated with stereotactic body radiation therapy (SBRT). Due to its noninvasive nature, lower cost, lower toxicity, reduced recovery time and equivalent efficacy, even medically operable patients are attracted to the option of SBRT despite the lack of level I evidence. Thus, studying the incidence and patterns of recurrence after SBRT help in understanding the magnitude of the problem, risk factors associated with the different patterns of recurrence, and aid in devising strategies to prevent them in future. Nodal recurrences are not uncommon after SBRT and can potentially lead to further seeding for distant metastases and ultimately poor survival. This review is aimed at reviewing the published data on the incidence of nodal recurrences after SBRT and compare it to surgery, identify potential risk factors for recurrence, salvage treatment options and prevention strategies.

Role of extreme weather events and El Niño Southern Oscillation on incidence of Enteric Fever in Ahmedabad and Surat, Gujarat, India.

INTRODUCTION: Enteric Fever (EF) affects over 14.5 million people every year globally, with India accounting for the largest share of this burden. The water-borne nature of the disease makes it prone to be influenced as much by unsanitary living conditions as by climatic factors. The detection and quantification of the climatic effect can lead to improved public health measures which would in turn reduce this burden. METHODOLOGY: We obtained a list of monthly Widal positive EF cases from 1995 to 2017 from Ahmedabad and Surat Municipalities. We obtained population data, daily weather data, and Oceanic Niño Index values from appropriate sources. We quantified the association between extreme weather events, phases of El Niño Southern Oscillations (ENSO) and incidence of EF. RESULTS: Both cities showed a seasonal pattern of EF, with cases peaking in early monsoon. Risk of EF was affected equally in both cities by the monsoon season -- Ahmedabad (35%) and Surat (34%). Extreme precipitation was associated with 5% increase in EF in Ahmedabad but not in Surat. Similarly, phases of ENSO had opposite effects on EF across the two cities. In Ahmedabad, strong El Niño months were associated with 64% increase in EF risk while strong La Niña months with a 41% reduction in risk. In Surat, strong El Niño was associated with 25% reduction in risk while moderate La Niña with 21% increase in risk. CONCLUSIONS: Our results show that the risk of EF incidence in Gujarat is highly variable, even between the two cities only 260 kms apart. In addition to improvements in water supply and sewage systems, preventive public health measures should incorporate variability in risk across season and phases of ENSO. Further studies are needed to characterize nationwide heterogeneity in climate-mediated risk, and to identify most vulnerable populations that can benefit through early warning systems.

Perceptions of quality of care during birth at private Chiranjeevi facilities in Gujarat: lessons for Universal Health Coverage.

The Indian national health policy encourages partnerships with private providers as a means to achieve universal health coverage. One of these was the Chiranjeevi Yojana (CY), a partnership since 2006 with private obstetricians to increase access to institutional births in the state of Gujarat. More than a million births have occurred under this programme. We studied women's perceptions of quality of care in the private CY facilities, conducting 30 narrative interviews between June 2012 and April 2013 with mothers who had birthed in 10 CY facilities within the last month. The commonly agreed upon characteristics of a "good (sari) delivery" were: giving birth vaginally, to a male child, with the shortest period of pain, and preferably free of charge. But all this mattered only after the primary outcome of being "saved" was satisfied. Women ensured this by choosing a competent provider, a "good doctor". They wanted a quick delivery by manipulating "heat" (intensifying contractions) through oxytocics. There were instances of inadequate clinical care for serious morbidities although the few women who experienced poor quality of care still expressed satisfaction with their overall care. Mothers' experiences during birth are more accurate indicators of the quality of care received by them, than the satisfaction they report at discharge. Improving health literacy of communities regarding the common causes of severe maternal morbidity and mortality must be addressed urgently. It is essential that cashless CY services be ensured to achieve the goal of 100% institutional births.

Determinants of Breastfeeding Practices and Its Association With Infant Anthropometry: Results From a Prospective Cohort Study in South India.

Introduction: Despite national efforts for promoting exclusive breastfeeding (EBF) during the first 6 months of the infants' life, breastfeeding rates are low in India. Evidence on the interference of supplementary food on optimal nourishment and growth of the infant has also been well-established. Our study was undertaken to assess the effect of breastfeeding practices on infant anthropometry and determine the various factors affecting breastfeeding practices. Methods: A prospective cohort study - Maternal antecedents of adiposity and studying the transgenerational role of hyperglycemia and insulin (MAASTHI) was conducted at a tertiary care public hospital in Bengaluru, South India. From the consenting women, data such as obstetric history, infant feeding practices, anthropometry of mother and child, the psychosocial status of the women using the Edinburgh Postnatal Depression Scale (EPDS), was collected at baseline and subsequent follow-up: post-delivery and 14 weeks after birth. In this study, we analyzed data collected from April 2016 to April 2018, with descriptive statistics presented in mean and standard deviation, and logistic regression adjusting for confounders. Results: Among the 240 women enrolled in the study, 33% (n= 80) were using supplementary food for their infants at 14 weeks of infants age. Infants who received supplementary feeding at age 14 weeks had nearly 2.5 times higher odds of being wasted (OR: 2.449, p-value: 0.002) as compared to exclusively breastfed infants. Conclusion: Infants between 14 to 16 weeks of age who received supplementary feeding were at risk of wasting as compared to exclusively breastfed infants. Despite strong evidence in support of the benefits of exclusive breastfeeding, awareness in urban women in India is low. Increased focus on promoting exclusive breastfeeding is necessary to ensure proper nutritional intake and healthy growth of infants.

Image quality in abdominal CT using an iodine contrast reduction algorithm employing patient size and weight and low kV CT technique.

BACKGROUND: Low tube potential-high tube current computed tomography (CT) imaging allows reduction in iodine-based contrast dose and may extend the benefit of routine contrast-enhanced CT exams to patients at risk of nephrotoxicity. PURPOSE: To determine the ability of an iodine contrast reduction algorithm to maintain diagnostic image quality for contrast-enhanced abdominal CT. MATERIAL AND METHODS: CT exams with iodine contrast reduction were prescribed for patients at risk for renal dysfunction. The iodine contrast reduction algorithm combines weight-based contrast volume reduction with patient width-based low tube potential selection and bolus-tracking. Control exams with routine iodine dose were selected based on weight, width, and scan protocol. Three radiologists evaluated image quality and diagnostic confidence using a 4-point scale (<2 acceptable). Another radiologist assessed contrast reduction indications and measured portal vein and liver contrast-to-noise ratios. RESULTS: Forty-six contrast reduction algorithm and control exams were compared (mean creatinine 1.6 vs. 1.2 mg/dL, P ≤ 0.0001). Thirty-nine contrast reduction patients had an eGFR <60 mL/min/1.73m2 and 15 had single or transplanted kidney. Mean iodine contrast dose was lower in the contrast reduction group (20.9 vs. 39.4 g/mL, P < 0.0001). Diagnostic confidence was rated as acceptable in 95% (131/138) of contrast reduction and 100% of control exams (1.18-1.28 vs. 1.02-1.13, respectively; P > 0.06). Liver attenuation and contrast-to-noise ratio (CNR) were similar (P = 0.08), but portal vein attenuation and CNR were lower with contrast-reduction (mean 176 vs. 198 HU, P = 0.02; 13 vs. 16, P = 0.0002). CONCLUSION: This size-based contrast reduction algorithm using low kV and bolus tracking reduced iodine contrast dose by 50%, while achieving acceptable image quality in 95% of exams.

Antimicrobial Resistance Surveillance in Typhoidal Salmonella in Ahmedabad in an Era of Global Antimicrobial Resistance Surveillance Systems.

INTRODUCTION: India possibly carries the highest burden of antimicrobial resistant typhoidal salmonellae in the world. We report on the health-care ecosystem that produces data on antimicrobial resistance (AMR) testing and the resistance patterns of typhoidal Salmonella isolates in the city of Ahmedabad. MATERIALS AND METHODS: Through municipality records and internet searches, we identified 1696 private and 83 public laboratories in the city; 4 medical colleges, 4 health-care institution attached laboratories, and 4 corporate laboratories (CLs) were performing culture and antibiotic sensitivity testing (AST), but only 2 medical colleges and 1 CL shared their data with us. There was considerable variation in culturing and sensitivity testing methodology across laboratories. RESULTS: Out of 51,260 blood cultures, Salmonella isolates were detected in only 146 (0.28%). AST was conducted on 124 isolates, of which 67 (54%) were found resistant. Multidrug resistance was absent. Concurrent resistance to more than one antibiotic was very high, 88%, among the 67 resistant isolates. Ciprofloxacin resistance varied widely between the private and public sector laboratories. Notably, isolates from the private sector laboratory showed complete resistance to azithromycin. CONCLUSIONS: High resistance to ciprofloxacin and azithromycin observed in Ahmedabad may be due to the increased use of these two antibiotics in the public and private sectors, respectively. The need of the hour is to identify a representative sample of laboratories from both the public and the private sectors and encourage them to participate in the national AMR surveillance network.

Procedure-Related Pain During Image-Guided Percutaneous Biopsies: A Retrospective Study of Prevalence and Predictive Factors.

OBJECTIVE. The purpose of this study was to evaluate the prevalence and severity of pain reported during image-guided percutaneous biopsies and to identify factors associated with increased reported pain. MATERIALS AND METHODS. In this retrospective study, a database of adult patients who underwent CT- or ultrasound-guided percutaneous core needle biopsy between July 22, 2013, and February 1, 2018, was reviewed. Data collected included patient age and sex, biopsy site, biopsy type (lesion or parenchymal), needle gauge, number of passes, use of sedation, and whether it was the patient's first recorded biopsy. The maximum procedure-related pain reported on a 0-10 numeric rating scale was recorded. Multivariable logistic regression with generalized estimating equations was used to assess the association between covariates and patient-reported pain. RESULTS. A total of 13,344 biopsy procedures were performed in 10,474 patients. Patients reported no pain (0 of 10 scale) during 9765 (73.2%) procedures. Female sex, younger age at biopsy, undergoing IV sedation, and larger needle diameter were all associated with increases in patient-reported pain. Biopsies of renal allografts were the least likely to be painful, followed by hepatic allografts. CONCLUSION. Patients typically report mild or no pain from image-guided biopsy performed by radiologists. Younger patients and women report greater pain. This information can assist preprocedural counseling and reassurance of patients and may help them predict procedure-related patient needs.

Comparison of two small bowel distending agents for enterography in pediatric small bowel imaging.

OBJECTIVE: To evaluate the ability of pediatric patients with known or suspected inflammatory bowel disease to ingest a new oral distending agent at CT or MR enterography (CTE/MRE), and to determine the impact on small bowel (SB) distension and diagnostic confidence. MATERIALS AND METHODS: The study design is that of retrospective review of pediatric patients who underwent CTE or MRE from January 2014 to June 2016. Patients ingested low-concentration barium suspension or flavored beverage containing sorbitol and mannitol. The need for nasogastric tube (NGT) administration, amount ingested, emesis, distal extent of contrast, SB distension, terminal ileum (TI) transverse dimension, and diagnostic confidence in TI disease were assessed. Three radiologists each blindly reviewed a subset of the studies. RESULTS: Of the total 591 scans in 504 patients, 316 scans used low-concentration barium suspension and 275 scans flavored beverage. Nearly all consumed the entire amount (97% vs. 96%). Low-concentration barium suspension exams required NGT more often (7% [23/316] vs. 1% [3/275]; p < 0.0003), and tended to have more emesis (3% [9/316] vs. 1% [3/275]; p = 0.13). Diagnostic confidence score was nearly identical (p = 0.94). Qualitative and quantitative analyses showed no difference in SB distension, except for distension of mid-ileum (flavored beverage > low-concentration barium suspension; p = 0.02). Flavored beverage exams demonstrated a slight increase in distal extent of luminal distension (p = 0.02). CONCLUSIONS: A new flavored beverage distends small bowel as well as low-concentration barium suspension, with decreased requirement for NGT insertion and improved distal extent of luminal distension, and without any decrease in diagnostic confidence in the presence or the absence of TI disease.

Mucinous appendiceal neoplasms: classification, imaging, and HIPEC.

Recent advances, specifically cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), offer advantages compared to the traditional therapeutic approach of systemic chemotherapy in the treatment of peritoneal carcinomatosis from mucinous appendiceal neoplasms (MAN). This review provides an up-to-date, comprehensive summary of the histologic classification of MAN, reviews common imaging findings of mucoceles and pseudomyxoma peritonei, and describes the radiologist's role in the multidisciplinary care team in quantifying disease and in helping select patients for definitive surgery.

A Rare Case of Metastasis to the Thyroid Gland from Renal Clear Cell Carcinoma 11 Years after Nephrectomy and Concurrent Primary Esophageal Carcinoma.

Renal cell carcinoma is known to cause metastasis to unusual sites, which can be both synchronous or metachronous. Thyroid gland is a rare site for metastasis, but when it occurs, renal cell carcinoma is the most common primary neoplasm. We report the case of a 81-year-old female patient who had a significant medical history of right clear cell renal carcinoma with adrenal metastasis. She underwent right radical nephrectomy and adrenalectomy followed by radiofrequency ablation of left adrenal metastasis and systemic chemotherapy with sunitinib. Eleven years later, she presented with dysphagia and was found to have distal esophageal adenocarcinoma. On imaging, there was incidental detection of a left renal mass lesion and a right thyroid nodule, which on histopathology and immunohistochemistry were confirmed to be clear cell carcinoma of renal origin.

Primary Small Intestinal Angiosarcoma: Epidemiology, Diagnosis and Treatment.

Angiosarcoma is an aggressive mesenchymal sarcoma of endothelial cell origin with high mortality. Its occurrence in the small intestine is exceedingly low. In addition to the rarity of small intestine angiosarcoma, the nonspecific early clinical symptoms obscure the suspicion of such tumors and thereby delay the diagnosis. In a hope to improve the knowledge of this rare but fatal neoplasm, we report one case of angiosarcoma of duodenum and jejunum in a 73-year-old man. Furthermore, we summarize and analyze the common clinical features, tumor markers, treatment, and survival of previous reported cases of this malignancy. Small bowel angiosarcoma occurs more often in men than women (1.6:1). The median age at diagnosis is 68.5 years. The overall median survival time is 150 days; the median survival time in female (300 days) is longer than that of male patients (120 days). Von Willebrand factor (vWF), CD31, CD34, vimentin, and Ulex europaeus agglutinin 1 appear to be the most useful markers for the diagnosis. The majority of the patients underwent surgical resection alone or surgery with subsequent chemotherapy. The patients treated with surgery plus chemotherapy survive longer than those underwent surgical resection only (median 420 days, n = 7 vs. 96.5 days, n = 26, respectively; P = 0.0275). Further studies of more cases are needed for a better understanding of this rare entity, as well as the development of effective strategies for prevention, early diagnosis, and treatment.

Reproducible imaging features of biologically aggressive gastrointestinal stromal tumors of the small bowel.

PURPOSE: To identify reproducible CT imaging features of small bowel gastrointestinal stromal tumors (GIST) that are associated with biologic aggressiveness. METHODS: Patients with histologically proven small bowel GISTs and CT enterography or abdominopelvic CT were included. Biologic aggressiveness was established based on initial histologic grading (very low risk to malignant), with "malignant" assigned if recurrence or metastases developed subsequently. CT exams were independently evaluated by three gastrointestinal radiologists for tumor size, growth pattern, enhancement, tumor borders, necrosis, calcification, ulceration, multiplicity, internal air or enteric contrast, nodal metastasis, liver metastasis, peritoneal metastasis, ascites, and draining vein size. Inter-observer variability and imaging features associated with high-grade and malignant small bowel GISTs were determined. RESULTS: Of 78 patients with small bowel GISTs, 10/78 (13%) were high grade and 18/78 (23%) were malignant. There was moderate to substantial inter-observer agreement (Kappa > 0.4) for all findings except tumor border, ulceration, and nodal metastases. Tumor size, irregular or invasive tumor border, necrosis, liver metastasis, ascites, and iso-enhancement were associated with high-grade/malignant small bowel GISTs (p < 0.04). Internal air or enteric contrast and peritoneal metastases additionally predicted malignant behavior (p < 0.03). When imaging features predicting malignant small bowel GISTs were absent and size was ≤ 3 cm, 0% (0/16), 5% (1/19), and 5% (1/17) of patients had high grade, and 0% (0/16, 0/19, and 0/17) had malignant tumors for the three readers, respectively. CONCLUSION: Multiple, reproducibly identified, small bowel GIST imaging features suggest biologic aggressiveness. The absence of these imaging features may identify small tumors that can be followed in asymptomatic or high-risk patients.

Characteristics of private partners in Chiranjeevi Yojana, a public-private-partnership to promote institutional births in Gujarat, India - Lessons for universal health coverage.

BACKGROUND: The Chiranjeevi Yojana (CY) is a Public-Private-Partnership between the state and private obstetricians in Gujarat, India, since 2007. The state pays for institutional births of the most vulnerable households (below-poverty-line and tribal) in private hospitals. An innovative remuneration package has been designed to disincentivise unnecessary cesareans. This study examines characteristics of private facilities which participated in the program. METHODS: We conducted a cross-sectional survey of all facilities which had conducted any births between June 2012 and April 2013 in three districts. We identified 111 private and 47 public facilities. Ninety of the 111 private facilities did caesarean sections in the last three months and were eligible to participate in the CY program. Of these, 40 (44%) participated in the CY program. We conducted descriptive and bivariate analyses followed by a Poisson regression model to estimate prevalence ratios of facility characteristics that predicted participation. RESULTS: We found that facilities participating in the CY program had a significantly higher likelihood of being general facilities (PR 1.9, 95% CI 1.3-2.9), or conducting lower proportion of cesarean births (PR 2.1, 95% CI 1.2-3.5) or having obstetricians new in private practice (PR 1.9, 95% CI 1.2-3.1) or being less expensive (PR 1.8, 95% CI 1.1-3.0). But none of these factors retained significance in a multi variable model. CONCLUSION: Private obstetricians who participate in the CY program tend to be new to private practice, provide general services, conduct fewer caesareans and are also less expensive. This is advantageous to the PPP and widens the target beneficiary groups that can be serviced by the PPP. The state should design remuneration packages with the aim of attracting relatively new obstetricians to set up practices in more remote areas. It is possible that the CY remuneration package design is effective in keeping caesarean rates in check, and needs to be studied further.

Occult myeloproliferative neoplasms: not so occult any more.

Non-cirrhotic, non-malignant portal vein thrombosis (PVT) is commonly secondary to inherited or acquired prothrombotic states. However, even after extensive workup, 25% of patients with PVT have no apparent prothrombotic aetiology identified (idiopathic PVT). Inherited conditions include factor V Leiden, PT mutation and protein C/S/AT deficiency. Acquired conditions include APS, PNH and BCR-ABL 1-negative myeloproliferative neoplasms (MPN). BCR-ABL-1 negative MPNs are the most frequent underlying prothrombotic risk factor for PVT (15%-30%). However, peripheral blood counts often remain within normal ranges in these patients with MPN because of portal hypertension sequel. Despite suggestive features of MPN in bone marrow, these patients lack adequate diagnostic criteria and are classified as occult MPN. The discovery of recurrent molecular abnormalities such as CALR gene exon 9 mutation presented a crucial advance in the diagnosis of occult MPNs. In our patient, the diagnosis of MPN was made on this basis, despite lack of peripheral evidence of MPN.

Blocking the PD-1/PD-L1 pathway in glioma: a potential new treatment strategy.

Gliomas are the most common type of primary brain tumor in adults. High-grade neoplasms are associated with poor prognoses, whereas low-grade neoplasms are associated with 5-year overall survival rates of approximately 85%. Despite considerable progress in treatment modalities, the outcomes remain dismal. As is the case with many other tumors, gliomas express or secrete several immunosuppressive molecules that regulate immune cell function. Programmed death-ligand 1 (PD-L1) is a coinhibitory ligand that is predominantly expressed by tumor cells. The binding of PD-L1 to its receptor PD-1 has been demonstrated to induce an immune escape mechanism and to play a critical role in tumor initiation and development. Encouraging results following the blockade of the PD-1/PD-L1 pathway have validated PD-L1 or PD-1 as a target for cancer immunotherapy. Studies have reported that the PD-1/PD-L1 pathway plays a key role in glioma progression and in the efficacy of immunotherapies. Thus, progress in research into PD-L1 will enable us to develop a more effective and individualized immunotherapeutic strategy for gliomas. In this paper, we review PD-L1 expression, PD-L1-mediated immunosuppressive mechanisms, and the clinical applications of PD-1/PD-L1 inhibitors in gliomas. Potential treatment strategies and the challenges that may occur during the clinical development of these agents for gliomas are also reviewed.

Utility of coronal contrast-enhanced fat-suppressed FLAIR in the evaluation of optic neuropathy and atrophy.

BACKGROUND AND PURPOSE: Evaluating chronic sequelae of optic neuritis, such as optic neuropathy with or without optic nerve atrophy, can be challenging on whole brain MRI. This study evaluated the utility of dedicated coronal contrast-enhanced fat-suppressed FLAIR (CE-FS-FLAIR) MR imaging to detect optic neuropathy and optic nerve atrophy. MATERIALS AND METHODS: Over 4.5 years, a 3 mm coronal CE-FS-FLAIR sequence at 1.5T was added to the routine brain MRIs of 124 consecutive patients, 102 of whom had suspected or known demyelinating disease. Retrospective record reviews confirmed that 28 of these 102 had documented onset of optic neuritis >4 weeks prior to the brain MRI. These 28 were compared to the other 22 ("controls") of the 124 patients who lacked a history of demyelinating disease or visual symptoms. Using coronal CE-FS-FLAIR, two neuroradiologists separately graded each optic nerve (n = 50 patients, 100 total nerves) as either negative, equivocal, or positive for optic neuropathy or atrophy. The scoring was later repeated. RESULTS: The mean time from acute optic neuritis onset to MRI was 4.1 ± 4.6 years (range 34 days-17.4 years). Per individual nerve grading, the range of sensitivity, specificity, and accuracy of coronal CE-FS-FLAIR in detecting optic neuropathy was 71.4-77.1%, 93.8-95.4%, and 85.5-89.0%, respectively, with strong interobserver (k = 0.667 - 0.678, p < 0.0001), and intraobserver (k = 0.706 - 0.763, p < 0.0001) agreement. For optic atrophy, interobserver agreement was moderate (k = 0.437 - 0.484, p < 0.0001), while intraobserver agreement was moderate-strong (k = 0.491 - 0.596, p < 0.0001). CONCLUSION: Coronal CE-FS-FLAIR is quite specific in detecting optic neuropathy years after the onset of acute optic neuritis, but is less useful in detecting optic nerve atrophy.