Determination of the Frequency of Celiac Disease in Patients Presenting With Chronic Diarrhea.

INTRODUCTION: Celiac disease (CD) is a chronic inflammatory disorder affecting mainly the digestive system and accounts for more than 50% of adult cases presenting to the gastrointestinal clinic with chronic diarrhea. Therefore, in our study, we aimed to determine the prevalence of CD in patients presenting with chronic diarrhea at the gastroenterology outpatient department of Jinnah Hospital, Lahore. METHODS: This cross-sectional study was conducted from December 9, 2021, to June 8, 2022, and included 140 patients aged 18 to 50 years with chronic diarrhea. Exclusion criteria were lack of informed consent and history of abdominal trauma or surgery. Data collected included age, gender, family history of CD, and clinical symptoms. Diagnostic measures involved serum tissue transglutaminase antibody IgA and IgG levels, endoscopy, and duodenal biopsy. Statistical analysis was performed using SPSS version 23 (IBM Corp, Armonk, NY), with a p-value of ≤0.05 considered significant. RESULTS: Among the 140 patients, 80 (57.14%) were males, with a mean age of 21 ± 4.35 years. Common symptoms included weight loss (73.5%), abdominal pain (20.7%), and stunted growth (5.7%). A family history of CD was reported in 14.29% of patients. Endoscopy findings included fissuring of the duodenal mucosa (77.9%), decreased height of duodenal folds (15.7%), and nodularity (6.4%). Histopathological examination revealed Marsh III b (65%), Marsh III c (21.4%), and Marsh III a (9.3%). CD was diagnosed in 23.57% of patients. Significant associations were found between CD and female gender, family history of CD, weight loss, stunted growth, and Marsh III c histopathology. CONCLUSION: CD was diagnosed in 23.57% of patients with chronic diarrhea. It was more prevalent in females and those with a family history of CD. These findings emphasize the need for considering CD in the differential diagnosis of chronic diarrhea to ensure early detection and management.

Using Neurocognitive Phenotypes to Inform Interventions for Adult Survivors of Childhood Cancer.

BACKGROUND: Neurocognitive impairments are sequelae of childhood cancer treatment, however little guidance is given to clinicians on common phenotypes of impairment, or modifiable risk factors that could lead to personalized interventions in survivorship. METHODS: Standardized clinical testing of neurocognitive function was conducted in 2,958 (74.1%) eligible survivors, who were ≥5 years post-diagnosis and >18 years old, and 477 community controls. Impairment was examined across 20 measures and phenotypes were determined by latent class analysis. Multinomial logistic regression was used to estimate risk for phenotype, predicted by cancer diagnosis and treatment exposures, chronic health conditions, and lifestyle, adjusted for sex and age. Associations between phenotypes and social attainment were examined. RESULTS: Five neurocognitive phenotypes were identified in survivors (global impairment 3.7%, impaired attention 5.0%, memory impairment 7.2%, processing speed/executive function impairment 9.3%, no impairment 74.8%). Risk of global impairment was associated with severe chronic health condition burden (odds ratio [OR]=20.17, 95% confidence interval [95%CI] 11.41-35.63) including cerebrovascular disease (OR = 14.5, 95%CI = 5.47-38.44) and cerebrovascular accident (OR = 14.7, 95%CI = 7.50-26.40). Modifiable risk factors, like quitting smoking reduced risk for global impairment (OR = 0.21, 95%CI 0.06-0.66). Low physical activity increased risk for global impairment (OR = 4.54, 95%CI 2.86-7.21), attention impairment (OR 2.01, 95%CI 1.41-2.87), processing speed/executive function impairment (OR 1.90, 95%CI 1.46-2.48), and memory impairment (OR 2.09, 95%CI 1.54-2.82). CONCLUSIONS: Results support the clinical utility of neurocognitive phenotyping to develop risk profiles and personalized clinical interventions, such as preventing cerebrovascular disease in anthracycline treated survivors by preventing hypercholesterolemia, smoking, and sedentary lifestyle, to reduce the risk for global impairment.

Cerebellar Mutism Syndrome and Dentato-Thalamo-Cortical Tract Disruption in Diffusion Tractography Following Surgery for Medulloblastoma.

Background Cerebellar mutism syndrome (CMS), a complication following medulloblastoma surgery, has been linked to dentato-thalamo-cortical tract (DTCT) injury; the association of the degree of DTCT injury with severity of CMS-related symptoms has not been investigated. Purpose To investigate the association between severity of CMS-related symptoms and degree and patterns of DTCT injury with use of diffusion tensor imaging (DTI), and if laterality of injury influences neurologic symptoms. Materials and Methods This retrospective case-control study used prospectively collected clinical and DTI data on patients with medulloblastoma enrolled in a clinical trial (between July 2016 and February 2020) and healthy controls (between April and November 2017), matched with the age range of the participants with medulloblastoma. CMS was divided into types 1 (CMS1) and 2 (CMS2). Multivariable logistic regression was used to investigate the relationship between CMS likelihood and DTCT injury. Results Overall, 82 participants with medulloblastoma (mean age, 11.0 years ± 5.2 [SD]; 53 male) and 35 healthy controls (mean age, 18.0 years ± 3.06; 18 female) were included. In participants with medulloblastoma, DTCT was absent bilaterally (AB), absent on the right side (AR), absent on the left side (AL), or present bilaterally (PB), while it was PB in all healthy controls. Odds of having CMS were associated with higher degree of DTCT damage (AB, odds ratio = 272.7 [95% CI: 269.68, 275.75; P < .001]; AR, odds ratio = 14.40 [95% CI: 2.84, 101.48; P < .001]; and AL, odds ratio = 8.55 [95% CI: 1.15, 74.14; P < .001). Left (coefficient = -0.07, χ2 = 12.4, P < .001) and right (coefficient = -0.15, χ2 = 33.82, P < .001) DTCT volumes were negatively associated with the odds of CMS. More participants with medulloblastoma with AB showed CMS1; unilateral DTCT absence prevailed in CMS2. Lower DTCT volumes correlated with more severe ataxia. Unilateral DTCT injury caused ipsilateral dysmetria; AB caused symmetric dysmetria. PB indicated better neurologic outcome. Conclusion The severity of CMS-associated mutism, ataxia, and dysmetria was associated with DTCT damage severity. DTCT damage patterns differed between CMS1 and CMS2. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Dorigatti Soldatelli and Ertl-Wagner in this issue.

Secondary cerebro-cerebellar and intracerebellar dysfunction in cerebellar mutism syndrome.

BACKGROUND: Cerebellar mutism syndrome (CMS) is characterized by deficits of speech, movement, and affect that can occur following tumor removal from the posterior fossa. The role of cerebrocerebellar tract injuries in the etiology of CMS remains unclear, with recent studies suggesting that cerebrocerebellar dysfunction may be related to chronic, rather than transient, symptomatology. METHODS: We measured functional connectivity between the cerebellar cortex and functional nodes throughout the brain using fMRI acquired after tumor removal but prior to adjuvant therapy in a cohort of 70 patients diagnosed with medulloblastoma. Surgical lesions were mapped to the infratentorial anatomy, and connectivity with cerebral cortex was tested for statistical dependence on extent of cerebellar outflow pathway injury. RESULTS: CMS diagnosis was associated with an increase in connectivity between the right cerebellar and left cerebral hemisphere, maximally between cerebellum and ventromedial prefrontal cortex (VM-PFC). Connectivity dependence on cerebellar outflow was significant for some speech nodes but not for VM-PFC, suggesting altered input to the cerebellum. Connectivity between posterior regions of cerebellar cortex and ipsilateral dentate nuclei was abnormal in CMS participants, maximally within the right cerebellar hemisphere. CONCLUSIONS: The functional abnormalities we identified are notably upstream of where causal surgical injury is thought to occur, indicating a secondary phenomenon. The VM-PFC is involved in several functions that may be relevant to the symptomatology of CMS, including emotional control and motor learning. We hypothesize that these abnormalities may reflect maladaptive learning within the cerebellum consequent to disordered motor and limbic function by the periaqueductal grey and other critical midbrain targets.

Exploring the Relationship of Comorbidities, Smoking Status, HRCT Findings With COVID-19 Disease Severity and Outcomes.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a serious illness that can affect multiple organs including the lungs. The COVID-mortality risk is attributed to the quick transmission of the virus, the severity of disease, and preclinical risk factors, such as the presence of comorbidities. High-resolution computed tomography (HRCT) can predict disease severity in COVID-19 patients. METHODOLOGY: This was a retrospective cohort study in which data were obtained from COVID centers at tertiary care hospitals in Azad Jammu and Kashmir. Details of clinical characteristics and HRCT findings along with details of smoking and comorbid history were obtained. RESULTS: Fever at hospital admission, HRCT findings, and having a partner predicted disease severity showed a significant p-value of <0.05. Old age and living in a combined household were associated with severe outcomes (p<0.05). Symptoms of shortness of breath (SOB) on hospital admission could predict the need for ICU admission in COVID-19 patients. CONCLUSION: HRCT has a good predictive value for disease severity in patients with COVID-19, and old age is a risk factor. Although, limited associations were established in the analysis, in this study hyperlipidemia and hypertension significantly affected the course of disease. Further studies should be done to explore the relationship.

Application of the Rotterdam postoperative cerebellar mutism syndrome prediction model in patients undergoing surgery for medulloblastoma in a single institution.

OBJECTIVE: Postoperative cerebellar mutism syndrome (CMS) develops in up to 40% of children with medulloblastoma. The Rotterdam model (RM) has been reported to predict a 66% risk of CMS in patients with a score of ≥ 100. The aim of this study was to retrospectively apply the RM to an independent cohort of patients with newly diagnosed medulloblastoma and study the applicability of the RM in predicting postoperative CMS. METHODS: Participants had to have their first tumor resection at the authors' institution and be enrolled in the SJMB12 protocol (NCT01878617). All participants underwent structured serial neurological evaluations before and then periodically after completing radiation therapy. Imaging was reviewed by the study neurologist who was blinded to CMS status when reviewing the scans and retrospectively applied RM score to each participant. RESULTS: Forty participants were included (14 females and 26 males). Four (10%) patients had CMS. The median age at tumor resection was 11.7 years (range 3.5-17.8 years). Tumor location was midline in 30 (75%), right lateral in 6 (15%), and left lateral in 4 (10%). The median Evans index was 0.3 (range 0.2-0.4), and 34 (85%) patients had an Evans index ≥ 0.3. Five participants required a ventricular shunt. The median tumor volume was 51.97 cm3 (range 20.13-180.58 cm3). Gross-total resection was achieved in 35 (87.5%) patients, near-total resection in 4 (10%), and subtotal in 1. The median RM score was 90 (range 25-145). Eighteen participants had an RM score of ≥ 100, and of these 16.7% (n = 3) had CMS. Of the 22 patients with an RM score < 100, 1 child developed CMS (4.5%, CI 0.1%-22.8%); 3 of the 18 patients with an RM score ≥ 100 developed CMS (16.7%, CI 3.6%-41.4%). The observed rate of CMS in the cohort of children with an RM score ≥ 100 was significantly lower than the observed rate in the original RM cohort (66.7%, CI 51%-80.0%, p < 0.001). A greater risk of CMS in patients with an RM score ≥ 100 could not be confirmed (p = 0.31). CONCLUSIONS: At the authors' institution, the incidence of CMS in patients who had an RM ≥ 100 was significantly lower than the RM cohort. These findings raise questions regarding generalizability of RM; however, fewer cases of CMS and a relatively small cohort limit this conclusion.

Neurocognitive impairment associated with chronic morbidity in long-term survivors of Hodgkin Lymphoma.

Thoracic radiation is associated with significant cardiopulmonary morbidities in survivors of long-term Hodgkin lymphoma and may affect neurocognitive outcomes. Survivors (N = 204; 52.5% female; mean [standard deviation] age, 36.6 [8.01] years) treated with thoracic radiation and age-, sex-, and race/ethnicity-matched community controls (N = 205; 51.7% female; age, 36.7 [9.17] years) completed standardized neurocognitive testing, echocardiography, pulmonary function tests, and vascular studies during the same visit. Treatments were abstracted from medical records. Cardiac (ie, left ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), vascular (ie, large and small artery elasticity [SAE]), pulmonary (ie, diffusing capacity of the lungs for carbon monoxide [DLCO] and forced expiratory volume [FEV1]), and chronic health conditions were evaluated for associations with age-adjusted neurocognitive performance using multivariable linear regression. Compared with controls, survivors had lower performance (P < 0.05) in visuomotor (0.11 vs 0.41), visual processing speed (0.25 vs 0.64), short-term recall (-0.24 vs 0.12), and flexibility (-0.04 vs 0.28). Survivors had lower pulmonary (FEV1, DLCOcorr), cardiac (LVEF, GLS), and vascular function (SAE) than controls (all P < 0.001). FEV1 was associated with visuomotor (P = .008) and visual processing speed (P = .05), and flexibility (P = .05). GLS was associated with short-term recall (P = .03). SAE was associated with flexibility (P = .007). Neurocognitive outcomes were also associated with moderate-to-severe neurologic chronic conditions (P < .05). Findings suggest a link between subclinical cardiopulmonary and vascular findings, neurologic morbidity, and neurocognitive impairments. Prevention of health morbidity may benefit neurocognitive outcomes.

Changes in m6A RNA methylation of goat lung following PPRV infection.

Peste des petits ruminants (PPR) is an acute, highly contagious viral disease of goats and sheep, caused by the Peste des petits ruminants virus (PPRV). Earlier studies suggest the involvement of diverse regulatory mechanisms in PPRV infection. Methylation at N6 of Adenosine called m6A is a type RNA modification that influences various physiological and pathological phenomena. As the lung tissue represents the primary target organ of PPRV, the present study explored the m6A changes and their functional significance in PPRV disease pathogenesis. m6A-seq analysis revealed 1289 m6A peaks to be significantly altered in PPRV infected lung in comparison to normal lung, out of which 975 m6A peaks were hypomethylated and 314 peaks were hypermethylated. Importantly, hypomethylated genes were enriched in Interleukin-4 and Interleukin-13 signaling and various processes associated with extracellular matrix organization. Further, of the 843 differentially m6A-containing cellular transcripts, 282 transcripts were also found to be differentially expressed. Functional analysis revealed that these 282 transcripts are significantly enriched in signaling by Interleukins, extracellular matrix organization, cytokine signaling in the immune system, signaling by receptor tyrosine kinases, and Toll-like Receptor Cascades. We also found m6A reader HNRNPC and the core component of methyltransferase complex METTL14 to be highly upregulated than the m6A readers - HNRNPA2B1 and YTHDF1 at the transcriptome level. These findings suggest that alteration in the m6A landscape following PPRV is implicated in diverse processes including Interleukin signaling.

Cerebellar mutism is linked to midbrain volatility and desynchronization from speech cortices.

Cerebellar mutism syndrome is a disorder of speech, movement and affect that can occur after tumour removal from the posterior fossa. Projections from the fastigial nuclei to the periaqueductal grey area were recently implicated in its pathogenesis, but the functional consequences of damaging these projections remain poorly understood. Here, we examine functional MRI data from patients treated for medulloblastoma to identify functional changes in key brain areas that comprise the motor system for speech, which occur along the timeline of acute speech impairment in cerebellar mutism syndrome. One hundred and twenty-four participants, all with medulloblastoma, contributed to the study: 45 with cerebellar mutism syndrome, 11 patients with severe postoperative deficits other than mutism, and 68 without either (asymptomatic). We first performed a data-driven parcellation to spatially define functional nodes relevant to the cohort that align with brain regions critical for the motor control of speech. We then estimated functional connectivity between these nodes during the initial postoperative imaging sessions to identify functional deficits associated with the acute phase of the disorder. We further analysed how functional connectivity changed over time within a subset of participants that had suitable imaging acquired over the course of recovery. Signal dispersion was also measured in the periaqueductal grey area and red nuclei to estimate activity in midbrain regions considered key targets of the cerebellum with suspected involvement in cerebellar mutism pathogenesis. We found evidence of periaqueductal grey dysfunction in the acute phase of the disorder, with abnormal volatility and desynchronization with neocortical language nodes. Functional connectivity with periaqueductal grey was restored in imaging sessions that occurred after speech recovery and was further shown to be increased with left dorsolateral prefrontal cortex. The amygdalae were also broadly hyperconnected with neocortical nodes in the acute phase. Stable connectivity differences between groups were broadly present throughout the cerebrum, and one of the most substantial differences-between Broca's area and the supplementary motor area-was found to be inversely related to cerebellar outflow pathway damage in the mutism group. These results reveal systemic changes in the speech motor system of patients with mutism, centred on limbic areas tasked with the control of phonation. These findings provide further support for the hypothesis that periaqueductal grey dysfunction (following cerebellar surgical injury) contributes to the transient postoperative non-verbal episode commonly observed in cerebellar mutism syndrome but highlights a potential role of intact cerebellocortical projections in chronic features of the disorder.

Association of neutrophil-to-lymphocyte ratio with clinical, pathological, radiological, laboratory features and disease outcomes of invasive breast cancer patients: A retrospective observational cohort study.

Inflammatory conditions play part in the progression of malignancies, and markers signifying growth of these factors can indicate prognosis. Neutrophil-to-lymphocyte (NLR) is used as a marker of subclinical inflammation that may become an integral part of workup to indicate prognosis and associated pathology. This study aims to explore the association of NLR ratio with clinical characteristics, radiological assessment and staging, histopathology, and disease outcomes of breast cancer. A retrospective cohort study was conducted in a tertiary care center to include breast cancer patients that were diagnosed between January 2001 and December 2020. Data including tumor size, lymph nodes, metastasis, histological grading, ER/PR/HER2-neu status, molecular subtypes, clinical staging); nodal findings (sentinel and axillary); pathology from frozen section; and disease outcomes were assessed. Multivariable regression and Kaplan-Meier survival curves were employed to indicate the association of NLR with breast cancer features and disease-free survival. A total of 2050 patients had a median age of 50 years, median NLR levels of 2.14, most common pathology ductal followed by lobular, and most common site of metastasis being lungs followed by bones. Disease-free rate was 7.6%, and a recurrence rate of 1.8%, while 1.6% deaths were reported. NLR was found associated with age, treatment outcomes, tumor size, lymph nodes, metastasis and clinical staging. Other positive correlations were with Ki67 proliferation index, molecular subtypes, and tumor size on frozen section (at transverse and craniocaudal dimensions). Negative correlations were seen with estrogen and progesterone receptors. However, NLR was not found predictable of disease-free survival (P = .160). Significant predictors of disease-free survival were histological grading, ER, PR status, molecular subtype, and Ki67 proliferation index. NLR being a readily available marker has shown novel findings in its association with tumor staging, disease outcomes and characteristics of breast malignancy.

Comparative study of wound infection between elective and emergency abdominal surgeries: a retrospective cohort study.

The objective of this study was to determine the frequency of wound infection among patients with abdominal surgeries and to compare the surgical site infection following elective versus emergency abdominal surgeries in a tertiary care hospital. Subjects and methods: All patients who fulfilled the inclusion criteria in the Department of General Surgery were included in the study. After taking informed written consent history was taken, clinical examination and patients were divided into two groups: group A (elective abdominal surgery) and group B (emergency abdominal surgery), patients in both groups were compared for the outcome that is surgical site infection. Result: A total of 140 patients who underwent abdominal surgery were included. Wound infection in abdominal surgeries was noted in 26 patients (18.6%), in group A wound infection was noted in 7 (5%), while in group B wound infection was seen in 19 (13.6%). Conclusion: The rate of wound infection in patients with abdominal surgeries was not low among the study population and the rate of wound infection was higher in emergency abdominal surgeries as compared with elective abdominal surgeries.

Proton therapy and limited surgery for paediatric and adolescent patients with craniopharyngioma (RT2CR): a single-arm, phase 2 study.

BACKGROUND: Compared with photon therapy, proton therapy reduces exposure of normal brain tissue in patients with craniopharyngioma, which might reduce cognitive deficits associated with radiotherapy. Because there are known physical differences between the two methods of radiotherapy, we aimed to estimate progression-free survival and overall survival distributions for paediatric and adolescent patients with craniopharyngioma treated with limited surgery and proton therapy, while monitoring for excessive CNS toxicity. METHODS: In this single-arm, phase 2 study, patients with craniopharyngioma at St Jude Children's Research Hospital (Memphis TN, USA) and University of Florida Health Proton Therapy Institute (Jacksonville, FL, USA) were recruited. Patients were eligible if they were aged 0-21 years at the time of enrolment and had not been treated with previous radiotherapeutic or intracystic therapies. Eligible patients were treated using passively scattered proton beams, 54 Gy (relative biological effect), and a 0·5 cm clinical target volume margin. Surgical treatment was individualised before proton therapy and included no surgery, single procedures with catheter and Ommaya reservoir placement through a burr hole or craniotomy, endoscopic resection, trans-sphenoidal resection, craniotomy, or multiple procedure types. After completing treatment, patients were evaluated clinically and by neuroimaging for tumour progression and evidence of necrosis, vasculopathy, permanent neurological deficits, vision loss, and endocrinopathy. Neurocognitive tests were administered at baseline and once a year for 5 years. Outcomes were compared with a historical cohort treated with surgery and photon therapy. The coprimary endpoints were progression-free survival and overall survival. Progression was defined as an increase in tumour dimensions on successive imaging evaluations more than 2 years after treatment. Survival and safety were also assessed in all patients who received photon therapy and limited surgery. This study is registered with ClinicalTrials.gov, NCT01419067. FINDINGS: Between Aug 22, 2011, and Jan 19, 2016, 94 patients were enrolled and treated with surgery and proton therapy, of whom 49 (52%) were female, 45 (48%) were male, 62 (66%) were White, 16 (17%) were Black, two (2%) were Asian, and 14 (15%) were other races, and median age was 9·39 years (IQR 6·39-13·38) at the time of radiotherapy. As of data cutoff (Feb 2, 2022), median follow-up was 7·52 years (IQR 6·28-8·53) for patients who did not have progression and 7·62 years (IQR 6·48-8·54) for the full cohort of 94 patients. 3-year progression-free survival was 96·8% (95% CI 90·4-99·0; p=0·89), with progression occurring in three of 94 patients. No deaths occurred at 3 years, such that overall survival was 100%. At 5 years, necrosis had occurred in two (2%) of 94 patients, severe vasculopathy in four (4%), and permanent neurological conditions in three (3%); decline in vision from normal to abnormal occurred in four (7%) of 54 patients with normal vision at baseline. The most common grade 3-4 adverse events were headache (six [6%] of 94 patients), seizure (five [5%]), and vascular disorders (six [6%]). No deaths occurred as of data cutoff. INTERPRETATION: Proton therapy did not improve survival outcomes in paediatric and adolescent patients with craniopharyngioma compared with a historical cohort, and severe complication rates were similar. However, cognitive outcomes with proton therapy were improved over photon therapy. Children and adolescents treated for craniopharyngioma using limited surgery and post-operative proton therapy have a high rate of tumour control and low rate of severe complications. The outcomes achieved with this treatment represent a new benchmark to which other regimens can be compared. FUNDING: American Lebanese Syrian Associated Charities, American Cancer Society, the US National Cancer Institute, and Research to Prevent Blindness.

Fastigial nuclei surgical damage and focal midbrain disruption implicate PAG survival circuits in cerebellar mutism syndrome.

BACKGROUND: Pediatric postoperative cerebellar mutism syndrome (CMS) is a rare but well-known complication of medulloblastoma (Mb) resection with devastating effects on expressive language, mobility, cognition, and emotional regulation that diminishes quality of life for many Mb survivors. The specific anatomical and neuronal basis of CMS remains obscure. We address this issue by identifying patterns of surgical damage and secondary axonal degeneration in Mb survivors with CMS. METHODS: Children with Mb deemed high risk for CMS based on intraventricular location of the tumor had T1 images analyzed for location(s) of surgical damage using a specially developed algorithm. We used three complementary methods of spatial analysis to identify surgical damage linked to CMS diagnosis. Magnetization transfer ratio (MTR) images were analyzed for evidence of demyelination in anatomic regions downstream of the cerebellum, indicating neuronal dysfunction. RESULTS: Spatial analyses highlighted damage to the fastigial nuclei and their associated cerebellar cortices as the strongest predictors of CMS. CMS-related MTR decrease was greatest in the ventral periaqueductal gray (PAG) area and highly consistent in the left red nucleus. CONCLUSION: Our evidence points to disruption of output from the fastigial nuclei as a likely causal trigger for CMS. We propose that core CMS symptoms result from a disruption in the triggering of survival behaviors regulated by the PAG, including the gating of vocalization and volitional movement. The fastigial nuclei provide the densest output to the PAG from the cerebellum, thus sparing these structures may provide a greater likelihood of CMS prevention.

Disseminated hydatid cyst disease; a rare presentation in a tertiary care hospital of Azad Jammu Kashmir.

Cystic Echinococcosis (CE) is one of the many neglected animal-based diseases also called zoonotic, it has been highlighted by the World Health Organization. It is a human and animal health issue in numerous endemic regions around the globe. CE is caused by the tapeworm Echinococcus granulosus. We will discuss a case of a 36 years old female from a rural area who presented to the emergency department with abdominal distension, fever, and shortness of breath. History revealed that she reared sheep in her village so ELISA for anti-Echinococcus antibodies shows positive titers, and CT scan revealed type IIA and III hydatid cysts in the lungs, chest, liver, spleen, abdomen, and pelvis. An extensive exploratory laparotomy was performed and an effort was made to remove all cysts from the liver, pelvis, spleen, and abdomen. The patient remained in a vegetative state post-operatively on ventilator support. She passed away five days post-surgery. As per author's knowledge, there has not been a similar case reported as yet.

Human Astrovirus VA1 Encephalitis in Pediatric Patients With Cancer: Report of 2 Cases and Review of the Literature.

Novel human astroviruses (HAstVs) have recently been implicated as rare causes of fatal encephalitis in immunocompromised patients, for which there is no proven treatment. We report 2 cases from our institution in which HAstV-VA1 was detected in the cerebrospinal fluid by metagenomic next-generation sequencing after the initial evaluation revealed no etiology.

Limited surgery and conformal photon radiation therapy for pediatric craniopharyngioma: long-term results from the RT1 protocol.

BACKGROUND: Our aim was to estimate long-term disease control and complications after conformal radiation therapy (CRT) in children and adolescents with craniopharyngioma. MATERIALS AND METHODS: Pediatric patients with craniopharyngioma (n = 101) were enrolled on or treated according to a phase II single institutional protocol from 1998. Surgery was individualized, and CRT (54Gy) was administered using a 1.0 cm or 0.5 cm clinical target volume margin. Patients were followed for 10 years by serial MR imaging and MR angiography and a battery of tests to measure the effects of treatment. RESULTS: Twenty patients had tumor progression. Twelve patients who had tumor progression died due to tumor (n = 6) or complications related to tumor or treatment (n = 6). With a median follow-up of 14.94 years for survivors, the 10 year estimates (±SE) of progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) were 78.84% ± 4.10%, 77.12% ± 4.19%, and 96.02% ± 1.95%, respectively. OS, EFS, and PFS were significantly associated with race, shunt status, and tumor volume. The 10 year cumulative incidence (±SE) of the secondary tumor (1.99% ± 1.40%), secondary malignant tumor (1.0% ± 1.0%), necrosis (1.98% ± 1.39%), vasculopathy (8.47% ± 2.90%), and permanent neurologic deficits (8.28% ± 3.37%) were estimated by competing risk analysis. Three patients required revascularization surgery. Salvage therapy was successful in 13 patients using surgery and radiosurgery. CONCLUSIONS: Limited surgery and CRT using photons results in excellent tumor control. Tumor control and the incidence and severity of complications are associated with host, tumor, and treatment factors.

Phenolic Contents, Organic Acids, and the Antioxidant and Bio Activity of Wild Medicinal Berberis Plants- as Sustainable Sources of Functional Food.

Wild fruits have increasingly been investigated as part of recent searches for food products with a high antioxidant activity. In this study, wild edible berberis Berberis vulgaris collected from three different provinces (Jilin, Heilongjiang, and Liaoning) were investigated for their phenolic contents, organic acid contents, mineral contents, antioxidant activity as well as their antimicrobial potential against a range of common food borne pathogens. In addition, a physiochemical and mineral analysis of the fruits was also performed. The methanol extracts of berberis fruit collected from Jilin province were highly active against all the studied food borne bacterial pathogens, i.e., S. aureus and L. monocytogenes, E. coli, P. fluorescens, V. parahaemolyticus, and A. caviae while the berberis extracts from Heilongjiang and Liaoning showed activity only against Gram-negative bacteria. The phenolic content and antioxidant activity were determined by the HPLC separation method and ß-carotene bleaching methods, respectively. Four organic acids such as malic acid, citric acid, tartaric acid, and succinic acid were identified while a variety of phenolic compounds were detected among which catechin, chlorogenic acid, and gallic acid were found to be the predominant phenolic compounds in all three of berberis fruit samples. The berberis fruit from Jilin was found to be superior to the Heilongjiang and Liaoning fruit regarding desired physiochemical analysis; however, there were no significant differences in the mineral contents among the three samples. Overall, the berberis fruit from Jilin was ranked as the best in term of the nutritional, physiochemical, antimicrobial, and antioxidant properties. This study confirms the various useful characteristics and features of berberis at a molecular level that can be used as a sustainable source for their potential nutritional applications for making functional foods in different food industries.

The posterior fossa syndrome questionnaire: using science to inform practice.

INTRODUCTION: Up to 34% of patients with medulloblastoma develop posterior fossa syndrome (PFS) following brain tumor resection and have increased risk of long-term neurocognitive impairments. Lack of agreement in conceptualization and diagnosis of PFS calls for improvements in diagnostic methods. The current study aimed to describe psychometric properties of a new posterior fossa syndrome questionnaire (PFSQ). METHODS: The PFSQ was informed by prior research and developed by a multidisciplinary team with subject matter expertise. Participants (N = 164; 63.4% Male; 78.7% White; Mage at diagnosis = 10.38 years, SD = 5.09, range 3-31 years) included patients with newly diagnosed medulloblastoma enrolled in the SJMB12 clinical trial. Forty-four patients (26.8%) were classified as having PFS based on attending physician's post-surgical yes/no report. A PFSQ was completed by a neurologist within 2 weeks of coming to St. Jude Children's Research Hospital for adjuvant treatment, irrespective of suspicion for PFS. RESULTS: PFSQ items ataxia (100.00%), dysmetria (95.45%), and speech/language changes (79.55%) were most sensitive. However, ataxia (26.50%) and dysmetria (46.61%) demonstrated low specificity. Speech/language changes (81.36%), mutism (95.76%), orofacial apraxia (98.29%) and irritability (96.61%) had high specificity. A principal component analysis found four components: (1) speech/language changes, (2) apraxias (including mutism), (3) motor/oromotor, and (4) emotional lability. CONCLUSIONS: The PFSQ is a dimensional diagnostic approach that can be used to improve diagnostic consistency across clinical and research groups to help accelerate understanding of PFS etiology, identify surgical correlates of risk, predict long-term impairments, and develop targeted interventions. Additional measure validation, including correlation with symptom resolution, is required.

Ocular Neuromyotonia in Children and Adolescents Following Radiation Treatment of Pediatric Brain Tumors.

PURPOSE: To report five cases of ocular neuromyotonia in children and adolescents following radiation therapy for a variety of pediatric brain tumors. Notably, three cases occurred in children younger than 11 years. METHODS: Case series of five patients with ocular neuromyotonia following proton beam therapy or conventional radiation. RESULTS: Five cases of ocular neuromyotonia were identified following radiation treatment of various pediatric brain tumors. Onset ranged from 5 to 142 months after radiation treatment. The abducens nerve/lateral rectus muscle was affected in three patients, and the trochlear nerve/superior oblique muscle was affected in two patients. Ages at symptom presentation were 4 years (intermittent head tilt), 9 years (intermittent blurry vision and head tilt), 10 years (intermittent blurry vision progressing to intermittent diplopia), 15 years (intermittent diplopia), and 17 years (intermittent diplopia). One patient improved with gabapentin. Two patients experienced spontaneous resolution. One patient died due to meta-static disease, and one patient has planned follow-up. CONCLUSIONS: Ocular neuromyotonia occurs most commonly following radiation to the brain and skull base. Clinicians need to be aware that ocular neuromyotonia presents differently in children (who may not report diplopia) than in adults or adolescents (who typically report diplopia). Two children in this series never reported diplopia, only intermittent head tilt and blurry vision. Ocular neuromyotonia requires a high index of suspicion to diagnose, especially in children. Membrane stabilizers can be used effectively, but observation may be a valid option in children because spontaneous resolution was seen. [J Pediatr Ophthalmol Strabismus. 2022;59(5):338-343.].

Pre- and Posttherapy Risk Factors for Vasculopathy in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Radiation Therapy.

PURPOSE: Vasculopathy (VAS) is a significant complication associated with radiation therapy in patients treated for brain tumors. We studied the type, location, severity, timing, and resolution of VAS in children with craniopharyngioma treated with proton radiation therapy (PRT) and evaluated predictors of stenosis (STN) using a novel patient and imaging-based modeling approach. METHODS AND MATERIALS: Children with craniopharyngioma (n = 94) were treated with 54 Gy relative biological effectiveness PRT in a clinical trial, NCT01419067. We evaluated VAS type, location, severity, and resolution. VAS events were segmented and related to their location, operative corridor, PRT dose, and vascular territory to facilitate mixed effect logistic regression modeling of spatial predictors of STN events. RESULTS: Forty-five (47.9%) patients had 111 instances of confirmed VAS (pre-PRT n = 37, 33.3%). The median time to post-PRT VAS was 3.41 years (95% confidence interval, 1.86-6.11). STN events were observed post-PRT in 23.4% (n = 22) of patients. Post-PRT VAS was detected by cerebral angiogram in 9.6% (n = 9), severe in 4.3% (n = 4), and compensated on perfusion in 2.1% (n = 2). Revascularization was required for 5 (5.3%) patients. Postsurgical, pre-PRT VAS, and PRT dose to unperturbed vessels were predictive of STN. The effect of PRT on STN was negligible within the surgical corridor. CONCLUSIONS: VAS often precedes PRT and was the strongest predictor of post-PRT STN. The adverse effect of PRT on STN was only apparent in unperturbed vasculature beyond the operative corridor.