Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Simultaneous X-Ray and Infrared Observations of Sagittarius A*'s Variability.

Emission from Saggitarius A* is highly variable at both X-ray and infrared (IR) wavelengths. Observations over the last ~20 yr have revealed X-ray flares that rise above a quiescent thermal background about once per day, while faint X-ray flares from Sgr A* are undetectable below the constant thermal emission. In contrast, the IR emission of Sgr A* is observed to be continuously variable. Recently, simultaneous observations have indicated a rise in IR flux density around the same time as every distinct X-ray flare, while the opposite is not always true (peaks in the IR emission may not be coincident with an X-ray flare). Characterizing the behavior of these simultaneous X-ray/IR events and measuring any time lag between them can constrain models of Sgr A*'s accretion flow and the flare emission mechanism. Using 100+ hours of data from a coordinated campaign between the Spitzer Space Telescope and the Chandra X-ray Observatory, we present results of the longest simultaneous IR and X-ray observations of Sgr A* taken to date. The cross-correlation between the IR and X-ray light curves in this unprecedented data set, which includes four modest X-ray/IR flares, indicates that flaring in the X-ray may lead the IR by approximately 10-20 min with 68% confidence. However, the 99.7% confidence interval on the time-lag also includes zero, i.e., the flaring remains statistically consistent with simultaneity. Long-duration and simultaneous multi-wavelength observations of additional bright flares will improve our ability to constrain the flare timing characteristics and emission mechanisms, and must be a priority for Galactic Center observing campaigns.

The changing faces of eosinophilic esophagitis: the impact of consensus guidelines at the University of South Florida.

BACKGROUND AND AIMS: Prior to the consensus guideline conference in 2007, eosinophilic esophagitis (EoE) was uncommon dominated by the fibrostenotic phenotype, but over the past decade has become a common cause of dysphagia with more inflammatory phenotypes diagnosed. We assessed the impact of guideline definitions on the characteristics of EoE phenotypes over the past 26 years at our institution. METHODS: We reviewed the electronic health record of 75 consecutive patients meeting guideline definition EoE from 1/1988 to 5/2014. We separated groups based on 5-year intervals of diagnosis and phenotype. For continuous data, results were summarized as mean difference and standard deviation with 95 % confidence intervals. RESULTS: Five groups based on 5-year intervals of diagnosis were identified: group 1-1988-1993 (n = 7), group 2-1994-1999 (n = 7), group 3-2000-2005 (n = 4), group 4-2006-2011 (n = 35), and group 5-2012-2014 (n = 22). Prior to 2000, all patients were diagnosed with fibrostenotic EoE. After the initial 2007 guideline conference, inflammatory EoE has predominated with only one-third diagnosed with fibrostenotic EoE. Prior to 2011, only two were diagnosed with PPI-REE. In the last 3 years, 8 out of 22 patients (32 %) had PPI-REE. Overall, 8 out of 10 (80 %) PPI-REE were the inflammatory phenotype. When comparing pre- (n = 18) and post (n = 57)-consensus definitions, there was a significant difference between age of diagnosis (30.710.2 vs. 41.3 ± 14.3; p = 0.001), age of symptom onset (18.4 +/15.2 vs. 32.4 ± 15.5), and initial esophageal diameter (10.5 ± 2.7 vs. 14.3 ± 4.2; p < 0.0001), respectively. CONCLUSIONS: Fibrostenotic EoE has steadily decreased, and inflammatory EoE is now the most recognized form. Across our 26-year experience, there was a decrease in delay in diagnosis and severity of esophageal stricture. The pivotal change occurred around 2007 corresponding to the first EoE guideline emphasizing the impact and importance of early detection of disease.

Outcomes of primary lymphoma of the ocular adnexa (orbital lymphoma) treated with radiotherapy.

AIMS: Low-grade ocular adnexal lymphoma is a rare disease and often treated with local radiotherapy to varying doses. Most previously reported studies have a very heterogeneous patient population and treatments. We report the outcomes from a 10 year cohort of patients at our institution treated with primary radiation therapy. MATERIALS AND METHODS: We analysed a retrospective case series of patients with stage IE low-grade ocular adnexal lymphoma including a review of case notes, histological reports and radiotherapy charts. We assessed local and distant tumour control and relapse rates in addition to toxicity. Disease-free survival was estimated using the Kaplan-Meier method. RESULTS: In total, 81 patients and 85 orbits were treated with primary radiotherapy to a median dose of 30 Gy in 15 fractions over 3 weeks. Seventy-nine per cent were treated with standard MV external beam radiotherapy to the whole orbit and 21% with a lens-sparing technique. The median follow-up was 4.4 years (range 0.2-10.4). Local control rates were 100%, with 5% of patients experiencing disease relapse elsewhere. No patients died from lymphoma. Cumulative acute toxicity rates were 51% (mainly erythema and conjunctivitis) and late toxicity rates were 8% (mainly cataract). The lens-sparing technique was associated with a significant reduction in cataract rate (P = 0.013) and an increase in acute toxicity (P < 0.001). CONCLUSIONS: This study has shown excellent local control rates and acceptable toxicity from the treatment of stage IE low-grade ocular adnexal lymphoma with localised radiotherapy to a median dose of 30 Gy in 15 fractions over 3 weeks.

The natural history of steroid-naïve eosinophilic esophagitis in adults treated with endoscopic dilation and proton pump inhibitor therapy over a mean duration of nearly 14 years.

BACKGROUND: Despite the vast focus of research in eosinophilic esophagitis (EoE), the natural history of untreated EoE remains undefined. Current expert consensus panels are calling for natural history studies to define long-term risks, adverse events, and progression of the disease. OBJECTIVE: To address the natural course and long-term adverse events of EoE. DESIGN: Retrospective, single-center study. SETTING: Tertiary-care center. A cohort of patients from the year 1988 initially diagnosed as having congenital esophageal stenosis who were later reclassified as having EoE. PATIENTS: Ninety-five patients, with 13 meeting entrance criteria for idiopathic EoE with follow-up >5 years. INTERVENTIONS: Anti-acids and esophageal dilation. MAIN OUTCOME MEASUREMENTS: Clinical response, adverse events, long-term clinical outcomes, and progression of disease. RESULTS: Thirteen patients (mean age at diagnosis 30.3 years, 10 male) were evaluated over a 13.6-year mean follow-up (range 5-24 years). All patients experienced daily dysphagia, with 12 presenting with food impactions. Patients were treated with esophageal dilation (64% Maloney, 34% Savary, 2.5% through-the-scope balloon) and daily anti-acids. Patients were initially treated with an average of 3.2 dilations over the first year (range 1-6) to achieve a luminal size of 15.8 mm (range 14-18 mm). They were maintained successfully with dilations every 2 years, on average, based on symptoms. Two patients not adhering to recommended dilation schedules experienced repeat impactions. One adverse event from a mucosal tear required hospitalization (1 of 157, 0.6%). Seven of 13 had Barrett's esophagus, average length 2.4 cm (range 1-4 cm), 3 on initial EGD and 4 identified over a mean duration of 9.4 years. No patient developed dysplasia or malignancy. LIMITATIONS: Retrospective, small sample. CONCLUSION: The course of EoE over a 13.6-year mean duration, although persistent, appears benign and not associated with cancer risk. A program of regular esophageal dilations based on symptom recurrence appears to be a safe, long-term treatment.

Eosinophilic esophagitis: a paradigm shift for pathology.

BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly recognized disease only reported in the adult literature since 1993. Our facility has the opportunity to evaluate steroid-naive EoE patients since 1988, allowing us to describe the evolution of the histologic diagnosis of EoE. METHODS: This retrospective study analyzed 95 patient charts with initial diagnosis of congenital esophageal stenosis/EoE from 1988 to 2012. Patients had dysphagia and met endoscopic criteria consistent with current EoE histologic criteria while on chronic proton-pump inhibitor therapy. Histologic slides were obtained for only 10 patients because of limited slide availability; and the slides were reviewed by a single pathologist. EoE is defined as ≥1 biopsy specimens demonstrating >15 eosinophils/HPF. RESULTS: Following review of histologic analysis reports, pathologists in our 2 academic hospitals began recognizing EoE as separate disease entity starting in 2007, coincidental with first EoE guidelines. After 2007, there was a clear surge in histologic diagnosis of EoE. Slides from 10 patients from 1988 to 2012 were reviewed. Of 35 biopsy sets, 19 were previously interpreted as reflux esophagitis (RE) or acute/chronic inflammation, 3 as RE with eosinophils, 2 as normal, and 11 as EoE. Reevaluation revealed EoE in 79% specimens with RE/inflammation and 100% with RE and eosinophils; remaining specimens had confirmed original diagnosis. All 10 patients had at least one set of slides meeting current EoE histologic criteria. CONCLUSIONS: EoE as a disease has been present for at least 2 to 3 decades. This is the first report of a clearly demarcated time point reflecting a paradigm shift in the histologic diagnosis of EoE as a distinct entity resulting from a seminal consensus report.

Use of thromboelastography to assess the combined role of pregnancy and obesity on coagulation: a prospective study.

BACKGROUND: Thromboelastography (TEG®) is a point of care monitor of whole blood coagulation and has previously demonstrated hypercoagulability in both pregnant and obese populations. However, the individual and combined contribution of pregnancy and obesity on coagulation status has not been defined. We carried out a study to assess the effect of both pregnancy and body mass index (BMI) on blood coagulation using laboratory tests of coagulation and thromboelastography. METHODS: This was a prospective study of 96 women divided into four equal groups; non-pregnant lean (NPL) BMI <25kg/m(2), pregnant lean (PL) BMI <25kg/m(2), non-pregnant obese (NPO) BMI >35kg/m(2) and pregnant obese (PO) BMI >35kg/m(2). Women were of either >36weeks of gestation presenting for elective caesarean delivery; non-pregnant women with BMI >35kg/m(2) presenting for bariatric surgery; or non-pregnant volunteers with BMI <25kg/m(2). Eligible women were then allocated to a group based on BMI and pregnancy status. TEG® analysis, full blood count and coagulation profiles were performed on all patients. The main outcome measures were TEG® profile (including r time, k time, α angle, maximum amplitude and coagulation index), platelet count, activated partial thromboplastin time, prothrombin time, and fibrinogen levels. RESULTS: The coagulation index was significantly higher in the obese patient groups compared with the lean groups (NPL -4.5 vs. NPO 1.9, P<0.001; PL -4.3 vs. PO 2.5, P<0.001). However, comparisons between the pregnant and non-pregnant groups when matched for BMI demonstrated no significant difference in coagulation. CONCLUSIONS: The combined effect of pregnancy and obesity on coagulation has not previously been investigated. Thromboelastographic comparison of pregnant and non-pregnant females separated into low or high BMI cohorts in the current study suggests that obesity correlates more with a hypercoagulable state than with pregnancy, particularly in pregnant patients at the extremes of low and high body weight.

Endoscopic lumen restoration for obstructive aphagia: outcomes of a 25-year experience.

BACKGROUND: After chemoradiation therapy for head/neck cancer, some patients develop strictures that progress to complete pharyngoesophageal occlusion. Total lumen occlusion is less often due to other conditions. Enteral access (enterostomy tube) and good nutritional status tend to minimize the significance of dysphagia and therefore may mask recognition of impending complete lumen occlusion. OBJECTIVE: Review outcomes of a 25-year experience with endoscopic lumen restoration (ELR) in 30 patients. DESIGN: Retrospective, case review study. SETTING: Two tertiary-care referral centers. PATIENTS: This study involved 30 consecutive patients referred for obstructive aphagia due to complete lumen occlusion, primarily after chemoradiation therapy for head/neck cancer. INTERVENTION: Antegrade and retrograde endoscopy with tri-plane fluoroscopy for penetrating the occluded segment, serial retrograde and antegrade dilations, plus swallowing rehabilitation therapy. MAIN OUTCOME MEASUREMENTS: Restoration of lumen patency, swallowing function, and removal of enteral feeding tube. RESULTS: ELR was successful in 30 patients in 31 of 33 attempts (93%). Return to soft to regular diet was achieved in 15 of 30 patients (50%), and fluids to pureed food with partial percutaneous endoscopic gastrostomy nutrition was achieved in 5 of 30 patients (17%). Ten of 30 patients (33%) were considered unsafe for oral feeding because of oropharyngeal neuromotor deficits. Complications occurred in 5 of 30 patients (17%), with no prolonged sequelae, deaths, or surgery, but two stents were placed for anastomotic fistulas. The median duration of follow-up was 22.75 months. LIMITATIONS: Retrospective, case review study. CONCLUSION: ELR by using tri-plane fluoroscopic guidance with antegrade and retrograde endoscopy and serial dilations allows lumen restoration and swallowing to some degree in a majority of patients. Engagement of a core team of specialists can provide optimal restoration of swallowing function.

Use of thromboelastography to guide thromboprophylaxis after caesarean section.

BACKGROUND: Thromboprophylaxis is commonly required following caesarean section. However the effect of thromboprophylactic dosages of subcutaneous heparin on coagulation is unknown because conventional laboratory tests are largely unaffected. The aim of this study was to determine if thromboelastography could detect and quantify the effect of unfractionated heparin on coagulation profile when given at the time of surgery. METHODS: Nineteen women undergoing elective caesarean section were recruited. Blood samples collected before and after administration of subcutaneous unfractionated heparin 7500 IU underwent thromboelastography using both plain and heparinase cuvettes. Anti-factor Xa levels were also measured. RESULTS: There was a significant difference in R times between plain and heparinase samples (-10.6%, P=0.0072) indicating that thromboelastography could detect an effect of unfractionated heparin. Compared to baseline there were significant decreases of R times in plain (-20.4%, P=0.033) and heparinase (-28.8%, P=0.0001) samples despite the administration of unfractionated heparin. Anti-factor Xa levels were virtually undetectable (mean 0.01 U/mL). CONCLUSION: Thromboelastography was able to detect and quantify the effect of unfractionated heparin on blood coagulability, an effect not detected by conventional laboratory tests. Thromboelastography demonstrated a pro-coagulant effect of surgery that was only partially mitigated by the use of unfractionated heparin. In this study, at a dose of 7500 IU subcutaneous unfractionated heparin appears to have little anticoagulant effect.

Estimation of blood haemoglobin concentration using the HemoCue during caesarean section: the effect of sampling site.

BACKGROUND: Haemoglobin concentration measured using the HemoCue is accurate for capillary and venous/arterial blood, provided the recommended sampling method is strictly observed. Analysis of blood, particularly of capillary samples, using the HemoCue is useful during caesarean section. The toe might be preferred to the thumb since it is numb during neuraxial anaesthesia, but whether sampling at either site is accurate in this situation, given the cardiovascular effects of anaesthesia and pregnancy, is not known. We aimed to compare haemoglobin values measured in venous and capillary samples (toe and thumb) during caesarean section under neuraxial anaesthesia. METHOD: Fifty healthy women having caesarean section under spinal or combined spinal-epidural anaesthesia were included. At the end of surgery, the great toe and thumb (non-i.v. fluid side) were lanced as recommended for a HemoCue reading. A venous blood sample (non-i.v. fluid side) was also taken and sent for formal laboratory measurement and tested with the HemoCue. Bland-Altman analysis was applied to the haemoglobin values. RESULTS: Bias (mean difference) and precision +/- 2 SD were respectively 0.2 +/-1.6 for laboratory vs. toe, 0.1 +/-1.8 for laboratory vs. thumb, and 0.2 +/-1.6 laboratory vs. venous. CONCLUSION: Our results suggest that in terms of accuracy, the two sites are equally suitable for use during caesarean section under neuraxial anaesthesia.

The normal anatomy around the oesophagogastric junction: an endoscopic view.

Where the oesophagus ends and the stomach begins has been a bone of contention for decades between the histologist, physiologist, gastroenterologist, radiologist and surgeon. The oesophagogastric junction (OGJ) is an important anatomical region because of its essential functions in relation to swallowing and as a site of structural defects, inflammation, metaplasia and neoplasia. The location of the diaphragmatic hiatus in relation to the distal oesophagus, the level of the squamocolumnar mucosal junction (SCJ), the location of the distal margin of the mucosal palisade veins and the proximal margin of the gastric mucosal folds are features that permit an accurate endoscopic diagnosis of hiatal hernia and reflux sequelae, including even a minimal extent for Barrett's oesophagus. The physiological OGJ region can be considered to be between the rosette of the lower oesophageal sphincter (LOS) and the angle of His. The most reliable benchmarks for the precise mural OGJ that can be identified during endoscopy are the levels of the cephalad margins of the linear gastric mucosal folds, viewed with the lumen deflated as much as possible, that are juxtaposed to the level of the caudad extent of the oesophageal mucosal palisade veins.

Esophagography predicts favorable outcomes after laparoscopic Nissen fundoplication for patients with esophageal dysmotility.

BACKGROUND: We undertook this study to determine if clearance of a food bolus at preoperative esophagography predicts acceptable outcomes after laparoscopic Nissen fundoplication for patients with manometrically abnormal esophageal motility. STUDY DESIGN: Patients with gastroesophageal reflux disease (GERD) or symptomatic hiatal hernia with evidence of esophageal dysmotility by stationary manometry underwent videoesophagography to document the ability of their esophagus to clear food boluses of varying consistencies. Sixty-six patients were identified who had manometric dysmotility yet were able to clear a food bolus at esophagography, and subsequently underwent laparoscopic Nissen fundoplication. These patients were compared with 100 randomly selected patients with normal motility who underwent laparoscopic Nissen fundoplication. Symptom reduction and satisfaction were assessed through followup. Patients with normal motility were compared with those with manometrically moderate and severe dysmotility. RESULTS: Preoperative patient demographic data, symptoms, and symptom scores were similar among patients with normal motility and moderate or severe dysmotility. After fundoplication, symptom reduction was notable for all patients regardless of preoperative motility (p < 0.01, paired Student's t-test). There was no notable difference in postoperative symptom scores (p = NS, Kruskal-Wallis ANOVA) or in patient satisfaction (p = NS, chi-square analysis) among patients stratified by esophageal motility. CONCLUSIONS: Patients with esophageal dysmotility documented by manometry who are able to clear a food bolus at contrast esophagography, have functional results after laparoscopic Nissen fundoplication similar to patients with normal motility. Preoperative esophagography predicts successful outcomes after laparoscopic Nissen fundoplication for patients with manometric esophageal dysmotility.

Sialorrhea: a review of a vexing, often unrecognized sign of oropharyngeal and esophageal disease.

Saliva is produced by the major salivary glands (parotid, submandibular, and sublingual), as well as several smaller glands. Salivary flow can be altered by multiple entities. There is much written regarding xerostomia ("dry mouth"), the condition related to inhibited or decreased salivary flow. This condition is widely recognized in certain systemic diseases, particularly Sjögren syndrome, diabetes mellitus, after anticholinergic, antihistamine, and decongestant medications, as well as states of enhanced sympathetic drive, such as anxiety or emotional disturbances and various other psychosocial conditions. On the other hand, sialorrhea or ptyalism, the condition of increased salivary flow, is rarely discussed in the clinical literature. Sialorrhea can occur with various neurologic disorders, infections, the secretory phase of the menstrual cycle, heavy metal poisoning, Wilson disease, Angelman syndrome, as well as a relatively unknown condition called idiopathic paroxysmal sialorrhea. Normal salivation may be altered by drugs (such as clozapine, risperidone, nitrazepam, lithium, and bethanecol) that have a cholinergic effect that induces sialorrhea. This report focuses on sialorrhea as it relates to disorders of the oropharynx and esophagus. The patient typically recognizes a problem with excessive "foamy mucus" but does not understand its origin. Infections and obstruction are the most common oropharyngeal causes. Increased salivary flow occurs as a typically subtle manifestation of gastroesophageal reflux disease. This occurrence is referred to as water brash. Idiopathic achalasia and megaesophagus due to the parasite Trypanosoma cruzi are regularly associated with sialorrhea. Esophageal obstruction (foreign body, cancer, or stricture formation), infection, and nasogastric intubation are the more common conditions associated with the symptomatic sequelae of sialorrhea. Sialorrhea-related respiratory and pulmonary complications are greatest in those with a diminished sensation of salivary flow and hypopharyngeal retention. Extremes of age, the chronically debilitated, or those in chronic care facilities, especially associated with cerebrovascular accidents and esophageal cancer, typically comprise this population. For the patient with an intact awareness of saliva, sialorrhea can present with significant social stigmas. Occult drooling or regular oral evacuation into a tissue or "spit cup" is socially incapacitating. This report provides a review of the physiology, pathogenesis, clinical manifestations, and therapeutic options for sialorrhea. Physicians and other healthcare professionals should recognize the importance of sialorrhea as a possible indicator or complication of a variety of disease states of the oropharynx and esophagus as well as its impact on the patient's physical and social quality of life.

Early results of laparoscopic Heller myotomy do not necessarily predict long-term outcome.

BACKGROUND: We sought to evaluate how patients' symptoms evolve after laparoscopic Heller myotomy. METHODS: Before and after laparoscopic Heller myotomy, 88 patients graded dysphagia and heartburn on a Likert scale (0 = none; 5 = severe). Patients graded outcomes as excellent, good, fair, or poor. Outcomes were compared in the same patients at 1 and 3 years of follow-up. RESULTS: At early follow-up (10.6 +/- 7.8 months) significant reductions were noted in dysphagia (11% versus 100%), dysphagia scores (0.6 +/- 1.1 versus 4.7 +/- 0.7), heartburn (31% versus 72%), and heartburn scores (1.2 +/- 1.6 versus 2.7 +/- 1.9). By late follow-up (37.6 months +/- 18.0) these values increased (47%, 1.9 +/- 1.7, 48%, 1.8 +/- 1.5, respectively) but remained significantly reduced compared with before operation. Excellent/good outcomes at early and late follow-up were 89% and 85%, respectively (P = not significant). CONCLUSIONS: Laparoscopic Heller myotomy is highly effective at palliating the symptoms of achalasia. With time, symptoms may recur owing to esophageal dysmotility, mandating continued surveillance.