The value of 68 Gallium-DOTATATE PET/CT in sinonasal neuroendocrine tumor management: A case series.

BACKGROUND: 68 Gallium-DOTATATE (68 Ga-DOTATATE) is a somatostatin analog used as a PET tracer to successfully identify neuroendocrine tumors (NETs). Due to the rarity of sinonasal NETs, there are few recommendations for 68 Ga-DOTATATE imaging in these patients. METHODS: We discussed the impact of 68 Ga-DOTATATE imaging on the management of six sinonasal NET cases and reviewed existing literature. RESULTS: 68 Ga-DOTATATE PET/CT revealed an unknown primary in one case and identified metastatic disease in a primary sinonasal small cell neuroendocrine carcinoma (SNEC) patient missed on conventional imaging. In two esthesioneuroblastoma (ENB) patients, 68 Ga-DOTATATE detected abnormal radiotracer uptake not present on 18F-FDG PET/CT and identified a patient for treatment with 177 Lu-DOTATATE. CONCLUSIONS: This is the one of the first few reports, and the largest series to our knowledge, demonstrating the utility of 68 Ga-DOTATATE imaging for primary sinonasal SNEC and ENB. Further study is required to determine its role in sinonasal NET management.

Stress response after race and endurance training sessions and competitions in Arabian horses.

Assuring a high level of animal welfare is a critical aspect of contemporary animal husbandry. Equine athletes begin their careers at a very young age when they are still developing and they are both physically and mentally immature. Lack of scientific knowledge of the stress related to horse racing impedes the development of optimal training programs to attain equilibrium between the best sport results and optimal welfare. This study aimed to determine the influence of the intensity and type of physical activity on peripheral blood cortisol concentration. Thirty untrained Arabians, 9 endurance and 21 race horses were enrolled in this longitudinal study. Blood samples were analysed every 3-weeks in 4 training sessions and 2 races in racing horses and monthly after 2 training sessions and 1 competition in endurance horses. Cortisol concentration was measured at rest and 30 min. after physical effort. Racing horses were divided into two groups of the best and the worst performers. Cortisol concentration increased significantly after training and competition, however both in racing and endurance horses the increase was more intensive after competition. In the racing horses, cortisol concentration tended to gradually increase after the subsequent trainings during the racing season, however the starting gate did not appear to exert any impact on cortisol concentration. The best performing race horses appeared to have a lesser increase in cortisol concentration after the race than the worst performing horses, however the cortisol concentration after the race was not significantly different between these two groups of horses. This study suggests that an optimal training program can induce a stress response which is likely not to have any harmful impact on an athlete's welfare. The more intense effort associated with competition events, both in race and endurance horses, results in a greater stress response, indicating that these kinds of events should be limited to assure animal welfare. Finally, better performance horses adapt more readily to physical activity as they experience less increase of serum cortisol concentration after the race.

Virtual Reality as Distraction Analgesia and Anxiolysis for Pediatric Otolaryngology Procedures.

OBJECTIVES/HYPOTHESIS: While virtual reality (VR) has been used as analgesia and anxiolysis for invasive procedures, no literature exists on the use of VR in the pediatric otolaryngology setting. The purpose of this study was to determine the efficacy of VR in reducing pain and anxiety for pediatric otolaryngology patients. STUDY DESIGN: Randomized controlled trial. METHODS: A total of 53 patients aged 7-17 undergoing in-office nasal endoscopies were included. Patients were randomized to receive VR or standard of care. Procedural pain, anxiety, and satisfaction scores were recorded from patients and caregivers. The physician filled out a childhood emotional manifestation scale (CEMS). RESULTS: Patients in VR group reported a significant decrease in pain (0.80 ± 1.06 vs. 2.26 ± 2.38, P = .018) and anxiety (9.50 ± 12.48 vs. 38.48 ± 29.83, P = .0002) and increase in procedural satisfaction (6.40 ± 0.77 vs. 4.74 ± 1.74, P = .0002) compared to patients in control group. CEMS scores were significantly reduced in VR group (5.15 ± 0.46 vs. 9.64 ± 5.66, P = .0001) and caregiver anxiety levels were significantly reduced in VR group (11.50 ± 17.67 vs. 27.39 ± 30.48, P = .041) compared to control group. There were no reported side effects. Procedural time did not significantly differ between groups. CONCLUSIONS: For pediatric otolaryngology patients undergoing in-office nasal endoscopies, VR is a safe and effective form of distraction analgesia and anxiolysis, significantly reducing pain and increasing procedural satisfaction for patients. In addition, VR significantly reduces anxiety for both patients and caregivers without disrupting procedural efficiency and workflow. LEVEL OF EVIDENCE: 2. Laryngoscope, 131:E1714-E1721, 2021.

Identification and validation of two peptide markers for the recognition of Clostridioides difficile MLST-1 and MLST-11 by MALDI-MS.

OBJECTIVES: Clostridioides difficile infection (CDI) has become the main cause of nosocomial infective diarrhoea. To survey and control the spread of different C. difficile strains, there is a need for suitable rapid tests. The aim of this study was to identify peptide/protein markers for the rapid recognition of C. difficile strains by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). METHODS: We analysed 44 well-characterized strains, belonging to eight different multi-locus sequence types (MLST), using ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS. The amino acid sequence of two peptide markers specific for MLST-1 and MLST-11 strains was elucidated by MALDI-TOF-MS/MS. The investigation of 2689 C. difficile genomes allowed the determination of the sensitivity and specificity of these markers. C18-solid-phased extraction was used to enrich the MLST-1 marker. RESULTS: Two peptide markers (m/z 4927.81 and m/z 5001.84) were identified and characterized for MLST-1 and MLST-11 strains, respectively. The MLST-1 marker was found in 786 genomes of which three did not belong to MLST-1. The MLST-11 marker was found in 319 genomes, of which 14 did not belong to MLST-11. Importantly, all MLST-1 and MLST-11 genomes were positive for their respective marker. Furthermore, a peptide marker (m/z 5015.86) specific for MLST-15 was found in 59 genomes. We translated our findings into a fast and simple method that allowed the unambiguous identification of the MLST-1 marker on a MALDI-TOF-MS platform. CONCLUSIONS: MALDI-FTICR MS-based peptide profiling resulted in the identification of peptide markers for C. difficile MLST-1 and MLST-11.

Dermatoglyphic variation among the Limboo of Sikkim, India.

Variations in finger and palmar dermatoglyphic patterns are investigated among the Limboo (18-60 years, 150 males and 150 females), a little known population of Sikkim. The results for Limboo were compared with other North-East Indian populations. The most commonly occurring pattern was loop (males: 64.33%; females: 75.00%) followed by whorl (males: 31.00%; females: 21.33%) and finally arch (males: 4.67%; females: 3.66%). There were no significant differences between sexes in pattern types. The overall values of pattern intensity (P.I.I.), Dankmeijer's (D.I.) and Furuhata's (F.I.) indices were 14.08, 12.60 and 96.06 respectively. The P.I.I. was within the range for East Asian populations of North-East India. The D.I. was similar to those reported for Rajbanshi, Kalita, Rabha and Newar populations, while F.I. was higher than in other populations of Eastern Himalaya and North-East India. The most frequently occurring mainline formulae in all palm prints (left and right combined) were 7.5'.5.- followed by 9.7.5.- and finally 11.9.7.- (p>0.05) and these were similar to the reported values for other North-eastern populations of India. The mean values of total finger ridge count (TFRC) and absolute finger ridge count (AFRC) were greater among males (138.03; s=42.26 and 198.78; s=77.4) than females (137.91; s=44.15 and 194.47; s=86.71). The a-b ridge count was greater among females than males. Sex differences in AFRC and a-b ridge count were both statistically significant (p<0.05). The mean TFRC values were within ranges for populations of North-East India. Cluster analysis based on P.I.I., D.I. and F.I. shows affinity of the Limbo to some of the populations of Assam and North-East India.

The usefulness of the Loewenstein Occupational Therapy Cognition Assessment in evaluating cognitive function in patients with stroke.

OBJECTIVE: We wished to evaluate the usefulness of the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) in early detection of the Vascular Cognitive Impairment, No Dementia (VCIND) in patients with stroke. We also wanted to compare LOTCA with the Mini-Mental State Examination (MMSE). PATIENTS AND METHODS: Thirty patients with stroke and cognitive impairment comprised the cognitive impairment group. Another 30 patients with stroke and no cognitive impairment served as the stroke control group, while 30 healthy individuals served as the normal control group. RESULTS: The age, gender, and education level were comparable among three study groups. All subjects were assessed with both tests. Total LOTCA scores strongly and positively correlated with total MMSE scores in patients with cognitive impairment (r = 0.934, p < 0.001). The correlations were also present between every sub-items of LOTCA and those of MMSE (p < 0.01). In addition, total scores and sub-item scores in LOTCA were significantly lower in the cognitive impairment group compared with both stroke control and normal control groups (p < 0.01), especially, with regard to scores of thinking operations, orientation, and visuomotor organization. The sub-item scores in LOTCA, including thinking operations, visuomotor organization, attention, orientation, and spatial perception were significantly lower in the stroke control group compared with normal control group (p < 0.01), especially in thinking operations and visuomotor organization. There is a good agreement between LOTCA and MMSE. CONCLUSIONS: Compared with MMSE, LOTCA can detect VCIND earlier and more comprehensively, and can, thus, be used clinically for VCIND detection.

Histopathologic changes following neoadjuvant chemotherapy in locally advanced breast cancer.

AIMS: To compare the clinical and pathologic assessment of response to neoadjuvant chemotherapy and describe the various histopathologic changes observed. MATERIALS AND METHODS: We studied a group of 40 patients with locally advanced breast cancer who had their initial workup in the form of clinico-imaging assessment of the size and pretreatment biopsy from the lesion. All the patients received two to six cycles of neoadjuvant chemotherapy, either cyclophosphamide 50 to 60 mg/m 2 IV, doxorubicin 40 to 50 mg/m 2 IV and 5-fluorouracil 500 to 800 mg/m 2 IV (CAF) or cyclophosphamide, epirubicin, and 5-fluorouracil (CEF). Clinical and pathologic assessment of response to chemotherapy was done based on the UICC guidelines. RESULT: Complete clinical response (cCR) was seen in 10% cases (4/40), thirty percent patients had (12/40) partial response and 60% (24/40) had stable disease after neoadjuvant chemotherapy. Pathologic complete response (pCR) with no evidence of viable tumor was observed in 20% patients (8/40). Fifteen patients (37.5%) showed partial response and 42.5% patients (17/40) had a stable disease. No patient progressed during the course of chemotherapy. Changes in the tumor type were observed following chemotherapy, most common being the mucinous change. Histologic changes like dyscohesion, shrinkage of tumor cells, elastosis, collagenization, necrosis, lymphocytic reaction, giant cell response are some of the common observations seen following treatment with neoadjuvant chemotherapy. CONCLUSION: Pathologic assessment of response to neoadjuvant chemotherapy is a better predictor than the clinical response. The chemotherapy drugs can be modified based on the response observed after 1-2 cycles of neoadjuvant, the response being based on both tumor and patient's responsiveness.

Molecular basis for the tissue specificity of ß-catenin oncogenesis.

Wnt-ß-catenin-T-cell factor signaling is causally linked to c-myc-dependent tumorigenesis in mouse and human colon epithelial cells. By contrast, ß-catenin is not similarly associated with oncogenic transformation of other tissues, including T cells. The molecular basis for tissue specificity of ß-catenin-dependent oncogenesis is unknown. Here, we demonstrate that adenomatous polyposis coli mutant APC(Min/+) mice, which have increased expression of ß-catenin in all tissues, develop severe intestinal neoplasia, but fail to develop thymic lymphoma. Whereas ß-catenin-dependent signals elicit a proliferative response from intestinal cells, thymocytes experience oncogene-induced senescence (OIS), growth arrest and apoptosis. We demonstrate that the differential cellular response of thymocytes and intestinal epithelial cells is a direct consequence of the gene expression elicited by ß-catenin expression in each tissue. We find that whereas intestinal cells induce genes that promote proliferation thymocytes induce expression of genes associated with OIS, growth arrest and p53-dependent apoptosis. We correlate gene expression pattern with the role ß-catenin plays in the development of each tissue and suggest that susceptibility of transformation by ß-catenin is intimately related to its function during development. We propose that when oncogenes are used as signaling molecules, safety nets in the form of OIS, growth arrest and apoptosis prevent accidental transformation.

Benign vs malignant soft tissue neoplasms: limitations of magnetic resonance imaging.

AIMS: Various features have been described in the literature to differentiate benign from malignant lesions. The aim of the present study was to study the accuracy of each of these features and that of magnetic resonance imaging (MRI) in diagnosing malignant lesions. MATERIALS AND METHODS: Fifty-five consecutive patients presenting with neoplastic (both benign and malignant) lesions diagnosed clinically and on ultrasound were studied and their MRI features were compared with the findings on surgical exploration and histopathologic examination. RESULTS: There were 32 (58%) benign and 23 (42%) malignant masses. Malignant masses were more common in patients older than 20 years (83%), and these had symptoms of less than 6 months duration (75%), as against benign lesions. The swelling was painful in 8 malignant masses and these were more common in the upper limbs (61%). Various features of malignant lesions were size more than 5 cm in 83%, change in signal intensity from homogenous on T1-weighted images to heterogenous on T2-weighted images in 74%, irregular margins in 74%, and heterogenous contrast enhancement in 91%. The accuracy of these features was 76%, 58%, 78%, and 60%, respectively. Most benign and malignant lesions were intramuscular in location. A significant number (38%) of benign lesions were located in the intermuscular facial plane. Definitive diagnosis was made in 42% of the lesions. CONCLUSIONS: MRI is an excellent modality for evaluating soft tissue neoplasms; however, prediction of a specific diagnosis and differentiation of malignant and benign lesions is not always possible.

Infiltrative ophthalmopathy and primary hypothyroidism: a rare clinical manifestation of a common disease.

The association of infiltrative ophthalmopathy with primary hypothyroidism is uncommon. We describe two such cases manifesting at different times during the course of primary hypothyroidism. The successful outcome of the present cases suggests that the timely addition of levothyroxine treatment alone or in combination with steroids is useful and effective in the management of hypothyroid Graves' ophthalmopathy.

Human milk fortification and gastric emptying in the preterm neonate.

Fortification of expressed breast milk (EBM) is widely recommended for preterm feeding. Fortification of EBM results in increased caloric density and osmolarity, both of which may retard gastric emptying. As gastric emptying is a major determinant of feed tolerance, we investigated the effect of fortification (with Lactodex HMF) of EBM on gastric emptying in preterm neonates. The half gastric emptying time was measured using real time ultrasonography in 25 consecutive preterm neonates first on EBM alone, then on EBM + Lactodex HMF. Each baby served as its own control. The students t-test was used for statistical analysis. The mean gestation age was 34.48 +/- 0.77 weeks. The mean birth weight was 1.92 +/- 0.14 kg. The mean half gastric emptying time at an age of 5.4 +/- 0.86 days on EBM was 24.00 +/- 5.00 min and 24.40 +/- 5.06 min on EBM + human milk fortifier (HMF). The same at 2nd assessment (15.2 +/- 1.79 days), with EBM was 22.80 +/- 4.58 min vs. 23.60 +/- 4.89 min when given EBM + HMF. These differences were not statistically significant. Fortification of EBM with Lactodex HMF does not affect the gastric emptying in preterm neonates and therefore is unlikely to affect feed tolerance in them.

Metabolic failure precedes intracranial pressure rises in traumatic brain injury: a microdialysis study.

BACKGROUND: Cerebral microdialysis (MD) is able to detect markers of tissue damage and cerebral ischaemia and can be used to monitor the biochemical changes subsequent to head injury. In this prospective, observational study we analysed the correlation between microdialysis markers of metabolic impairment and intracranial pressure (ICP) and investigated whether changes in biomarker concentration precede rises in ICP. METHODS: MD and ICP monitoring was carried out in twenty-five patients with severe TBI in Neurointensive care. MD samples were analysed hourly for lactate:pyruvate (LP) ratio, glutamate and glycerol. Abnormal values of microdialysis variables in presence of normal ICP were used to calculate the risk of intracranial hypertension developing within the next 3 h. FINDINGS: An LP ratio >25 and glycerol >100 micromol/L, but not glutamate >12 micromol/L, were associated with significantly higher risk of imminent intracranial hypertension (odds ratio: 9.8, CI 5.8-16.1; 2.2, CI 1.6-3.8; 1.7, CI 0.6-3, respectively). An abnormal LP ratio could predict an ICP rise above normal levels in 89% of cases, whereas glycerol and glutamate had a poorer predictive value. CONCLUSIONS: Changes in the compound concentrations in microdialysate are a useful tool to describe molecular events triggered by TBI. These changes can occur before the onset of intracranial hypertension, suggesting that biochemical impairment can be present before low cerebral perfusion pressure is detectable. This early warning could be exploited to expand the window for therapeutic intervention.

Free phenytoin concentration measurement in brain extracellular fluid: a pilot study.

This article investigates the relationship between brain extracellular fluid free phenytoin concentration and plasma free phenytoin concentration in adults with acute brain injury. Daily cerebral microdialysate free phenytoin concentration was measured in eight adults with acute brain injury and compared with simultaneous measurement of plasma free phenytoin concentration. The group data revealed no significant correlation between microdialysate and plasma free phenytoin concentration (r = 0.34, p = 0.41). However, in two patients, with a sufficient number of samples for intra-individual analysis, there was a significant correlation between microdialysate and plasma free phenytoin concentration (r = 0.92, p < 0.001 and r = 0.88, p < 0.01). In vitro microdialysis relative recovery for phenytoin was 2.1%. In the context of acute brain injury, measurement of free plasma phenytoin concentration may not provide an accurate reflection of regional brain extracellular fluid free phenytoin concentration and may have limitations with respect to achieving reproducible brain extracellular fluid free phenytoin concentrations. This has implications for dosing regimens relying on plasma phenytoin levels.

Extracellular fluid S100B in the injured brain: a future surrogate marker of acute brain injury?

The authors describe the measurement of S100B protein in brain extracellular fluid (ECF) of patients with acute brain injury (traumatic brain injury and subarachnoid haemorrhage) using the technique of microdialysis. To our knowledge, this is the first report of S100B measurement in the human brain. Acute Brain Injury (ABI) is a leading cause of death and disability and the need for a practical and sensitive biochemical marker for monitoring these patients is urgent. The calcium binding astrocyte protein, S100B, may be a candidate for this role. Previous serum studies have shown S100B to be a sensitive predictor of mortality and rise in intracranial pressure in ABI, but it has never before been measured directly within the brain. The ECF reflects the local biochemistry of the brain parenchyma, and the use of intracerebral microdialysis opens up the possibility of studying many novel surrogate markers of injury in the laboratory, in addition to the conventional markers it measures at the bedside (lactate, pyruvate, glucose, and glycerol). In this preliminary report of two cases, the authors demonstrate the quantification of S100B in ECF microdialysate, and investigate whether changes in hourly S100B profile can be related to secondary brain injury. It is shown that extracellular concentrations of S100B change markedly in response to secondary brain injury. Further investigation is required to determine whether extracellular S100B measurement in ABI could assist in patient management.

Axonal pathology in subarachnoid and intracerebral hemorrhage.

Electrically active axons degenerate in the presence of nitric oxide (NO) in vitro. High CSF NO concentrations have been observed in patients with hemorrhagic brain injury such as subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). This study investigated the evidence for axonal injury in SAH and ICH and related this to CSF NO levels. In this study, neurofilament phosphoforms (NfH(SMI34), NfH(SMI35), NfH(SMI38), NfH(SMI310)), surrogate markers for axonal injury, and NO metabolites (nitrate, nitrite = NOx) were measured by ELISA in cerebrospinal fluid (CSF) from patients with SAH and ICH and from a group of controls. Injury severity was classified using the Glasgow Coma Scale, and survival was used as the outcome measure. Compared to the control group, a higher proportion of patients with SAH and ICH had elevated NfH(SMI34) levels from day 0 to day 6 (p < 0.001), elevated NfH(SMI35) levels from day 1 to 6 (p < 0.001), and elevated NfH(SMI310) levels at day 0, 1, 4, and 6 (p < 0.001). The NOx levels were higher in the SAH and ICH patients than in the controls (p < 0.05) and distinguished the non-survivors from the survivors (p < 0.05). No direct correlation was found for NOx with any of the NfH phosphoforms. This study provides evidence for primary and secondary axonal injury in patients with SAH and ICH, with non-survivors also having higher NOx levels. CSF NfH phosphoforms might emerge as a putative surrogate marker for monitoring the development for secondary axonal degeneration in neurocritical care and guiding targeted neuroprotective strategies.

Use of a herbicide or lysine plus threonine for non-antibiotic selection of transgenic chickpea.

A desensitized aspartate kinase (AK) gene has been developed as a non-antibiotic selection marker for use in the production of transgenic chickpea ( Cicer arietinum L.). Transgenic shoots regenerated from embryo explants bombarded with the desensitized AK gene were selected on media containing two amino acids, lysine and threonine (LT). Approximately 15% of the putative transgenic shoots of vars. P-362 and P-1042 survived after 4 weeks of growth on MSB5 medium (MS mineral salts and B5 vitamins) containing 2 microM thidiazuron (TDZ) and 2 mM lysine and 2 m M threonine. These shoots were subsequently grown on MSB5 medium supplemented with 2 micro M TDZ and 5 mM lysine and 5 mM threonine, and nearly 1% continued to grow after 16 weeks of selection. A phosphinothricin (PPT) selection system for Agrobacterium-mediated chickpea transformation was also developed. Three varieties of chickpea, P-362, P-1042 and P-1043, were successfully used for Agrobacterium transformation. Following Agrobacterium infection, 3-8% of the regenerated shoots remained green and continued to grow on MSB5 medium supplemented with 2.5 mg l(-1 )PPT. Increasing the concentrations of PPT to 15 mg l(-1) reduced transgenic shoot production in P-362, P-1042 and P-1043 to 0.7%, 1.2% and 1.1%, respectively. Selected putatively transformed shoots of all three varieties were rooted and grown to maturity. Southern hybridization analysis revealed single as well as multiple integration of genes in selected transgenic lines. The level of AK activity detected in LT-selected plants was higher than that detected in the non-transformed control.

A prospective study of the rate of falls before and after cataract surgery.

BACKGROUND: There has been considerable interest in the development of intervention programmes aimed at reducing the risk of falls. The primary objective was to ascertain whether cataract surgery reduced the risk of falls in elderly patients with age related cataract. METHODS: 97 patients scheduled for cataract surgery were enrolled in this prospective clinical study. The patients were assessed for established risk factors for falls preoperatively and postoperatively. Patients were issued with a diary to record any falls and phoned at 2 monthly intervals during the 6 month preoperative and postoperative periods. RESULTS: Of the 84 patients who completed the study, 31 recorded falls during the preoperative period (37%). This group showed a statistically significant reduction in the number of fallers in the postoperative period (n = 6, p<0.001) CONCLUSION: These results suggest that cataract surgery is an effective intervention to reduce the risk of falls in elderly patients with cataract related visual impairment.