Does Heparin Affect 99mTc-MAA In Vitro Stability?

INTRODUCTION: Pulmonary embolism (PE) can be diagnosed by perfusion lung scintigraphy using human albumin macroaggregates labelled 99mTc (99mTc-MAA). When PE is suspected, subcutaneous Low Molecular Weight Heparin (LMWH) should be administered even before the results of the PE diagnostic flowchart. In our study, we aimed to evaluate a possible interaction (in vitro interference) between 99mTc-MAA and LMWH. METHODS: The reconstitution of MAA kit was performed according to the manufacturer's instruction. After labelling, we carried out the following preparations: a standard dose of 99mTc-MAA alone, as control; 99mTc-MAA and enoxaparin at different ratios. According to the manufacturer's instruction, the radiochemical purity was performed and evaluated immediately (T0), after 15 and 30 minutes after incubation (T15 and T30). RESULTS: We compared the radiochemical purity of 99mTc-MAA with: (i) radiochemical purity of 99mTc-MAA and enoxaparin (11 ratio), (ii) radiochemical purity of 99mTc-MAA and enoxaparin (0.5 ratio), and (iii) radiochemical purity of 99mTc-MAA and enoxaparin (ratio 2). No significant differences were found between all the measured parameters at each time point for each ratio. We also tested the stability of 99mTc-MAA in physiological conditions (at 37°C in PBS): the initial radiochemical purity of 99mTc-MAA was 99.78%. The values of 99mTc-MAA radiochemical purity were high in all conditions of possible interaction with LMWH, with values ranging from 98.00% at T0 to 95% at T30. CONCLUSION: We found no statistically significant change in the in vitro stability of 99mTc-MAA in the presence of enoxaparin, excluding a possible direct interference. Future studies will be needed to check the 99mTc-MAA stability under physiological conditions.

Oropharyngoesophageal Scintigraphy in a Case of Complex Swallowing Disorders After a Major Oral Surgery.

ABSTRACT: A 75-year-old woman had an occasional finding of a left tonsil mass for dysphagia, which resulted a high-grade squamous carcinoma. Therefore, the patient was sent to have a left pharyngectomy. After the pharyngectomy, the patient reported persistent swallowing disorders and nasal reflux. Consequently, she had an oropharyngoesophageal scintigraphy, demonstrating irregular oral and pharyngeal swallowing phases and confirming reflux episodes into the rhinopharynx and into the oropharynx. In line with these findings, the patient was send to rehabilitation; the abnormal functional mechanisms, previously identified by the scintigraphy, allowed to guide the speech therapy, with a progressive clinical improvement.

Clinical characteristics of metabolic associated fatty liver disease (MAFLD) in subjects with myotonic dystrophy type 1 (DM1).

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated with insulin resistance, and its association with metabolically associated fatty liver disease (MAFLD) has never been explored in prospective studies. The aim of this study was to assess the clinical features of MAFLD in DM1 patients. METHODS: We investigated the prevalence and the diagnostic features of MAFLD in a cohort of 29 outpatient fully characterized DM1 patients; afterward, we compared the selected cohort of DM1-MAFLD individuals with a propensity-matched cohort of non-DM1-MAFLD RESULTS: 13/29 (44.83%) DM1 patients received a clinical diagnosis of MAFLD. Compared to DM1 patients with normal liver, DM1-MAFLD individuals showed a higher male prevalence (p = 0.008), BMI (p = 0.014), HOMA score (p = 0.012), and GGT levels (p = 0.050). The statistical comparison showed that the DM1-MAFLD group had a more severe MAFLD according to the FIB4 score than non-DM1-MAFLD patients. This association of a more severe form of liver disease with DM1 remained significant after logistic regression analysis (OR: 6.12, 95% CI 1.44- 26.55).

Impact of Tracheal Tube on Swallowing in Post-Operative Head and Neck Cancer Patients: Scintigraphic Analysis.

Dysphagia is common in tracheostomized patients who underwent head and neck surgery for cancer treatment. The objective of this study was to evaluate, by means of oropharyngoesophageal scintigraphy (OPES), the impact of an occluded tracheal tube (TT) on swallowing in patients treated for head and neck cancer before hospital discharge, to provide further information to the benefit of out-patient care management. From October 2018 to November 2019, we enrolled 19 tracheostomized patients (6 females and 13 males; mean age 61 years) who underwent primary surgical resection of head and neck tumor and swallowing rehabilitation during hospitalization. All subjects underwent a double-standard OPES, one with occluded tracheal tube and the other without TT, with their tracheal stoma being closed directly by a plaster. For each study, we assessed and compared the following quantitative parameters: oral transit time (OTTsec), pharyngeal transit time (PTTsec), esophageal transit time (ETTsec), oral retention index (ORI%), pharyngeal retention index (PRI%), esophageal retention index (ERI%), and aspiration percentage (AP%). The mean values of OTT, PTT, ORI%, PRI%, and ERI% were abnormal during OPES both with TT and without TT and did not statistically differ between the two tests (p > 0.05). Aspiration was detected in 4 cases out of 19 (21.05%) cases during OPES with TT and in 4/19 (21.05%) cases without TT who showed a mean AP% of 11.4% and 11.5% respectively (p > 0.05). Patients with abnormal AP% (> 0%) during OPES with TT showed aspiration signs without TT. Our study showed that the mere presence of a closed tracheal tube does not impact significantly the oropharyngeal transit of bolus during swallowing. This result suggests the possibility to maintain a small-diameter occluded tracheal tube in place for the postsurgical management of head and neck cancer patients.

High Prevalence and Gender-Related Differences of Gastrointestinal Manifestations in a Cohort of DM1 Patients: A Perspective, Cross-Sectional Study.

Myotonic dystrophy type 1 (DM1, MIM #160900), the most common muscular dystrophy among adults, is a multisystem disorder, which affects, besides the skeletal muscle, several other tissues and/or organs, including the gastrointestinal apparatus, with manifestations that frequently affect the quality of life of DM1 patients. So far, only few, mainly retrospective studies evaluated this specific topic in DM1, so we performed a perspective study, enrolling 61 DM1 patients who underwent an extensive diagnostic protocol, including administration of the Gastrointestinal Symptom Rating Scale (GSRS), a validated patient-reported questionnaire about GI symptoms, laboratory tests, liver US scan, and an intestinal permeability assay, in order to characterize frequency and assess correlations regarding specific gastrointestinal manifestations with demographic or other DM1-related features. Our results in our DM1 cohort confirm the high frequency of various gastrointestinal manifestations, with the most frequent being constipation (45.9%). γGT levels were pathologically increased in 65% of DM1 patients and GPT in 29.82%; liver ultrasound studies showed steatosis in 34.4% of patients. Significantly, 91.22% of DM1 patients showed signs of altered intestinal permeability at the specific assay. We documented a gender-related prevalence and severity of gastrointestinal manifestations in DM1 females compared to DM1 males, while males showed higher serum GPT and γGT levels than females. Correlation studies documented a direct correlation between severity of muscle weakness estimated by MIRS score and γGT and alkaline phosphatase levels, suggesting their potential use as biomarkers of muscle disease severity in DM1.

Effect of liver transplantation on intestinal permeability and correlation with infection episodes.

BACKGROUND: Liver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections. METHODS: LT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA). RESULTS: The median 51Cr-EDTA excretion was found to be higher in 35 LT recipients as compared with that in the healthy controls [4.77% (2.79-6.03) vs. 2.07% (1.57-2.42), p<0.0001], and comparable to that in the cirrhotic patients [3.69% (2.34-6.57), p = 0.445]. 51Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections [infection/no infection: 4.97% (3.14-7.03) vs 4.62% (2.79-5.82), p = 0.938]. CONCLUSION: LT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted.

Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation.

The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis. The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis. In this mutual relationship, the liver acts as a second firewall towards potentially harmful substances translocated from the gut, and is, in turn, is implicated in the regulation of the barrier. Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage. In particular, in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment, diet and gut dysbiosis as the primary pathogenic trigger. In advanced liver disease, intestinal permeability is enhanced by portal hypertension. The clinical consequence is an increased bacterial translocation that further worsens liver damage. Furthermore, this pathogenic mechanism is implicated in most of liver cirrhosis complications, such as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, and hepatocellular carcinoma. After liver transplantation, the decrease in portal pressure should determine beneficial effects on the gut-liver axis, although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking. How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area, which deserves further attention.

Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease.

BACKGROUND: In non-alcoholic fatty liver disease (NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis. We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD. AIM: To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet. METHODS: The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing (51Cr-EDTA). RESULTS: Twenty Caucasian patients, 90% male, median age 43 years, body mass index (BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight (-5.3 ± 4.1 kg, P = 0.003), mean waist circumference (-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase (ALT) -28.3 ± 11.9 IU/L, P = 0.0001; aspartate aminotransferase (AST) -6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after 16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline (mean percentage retention of 51Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet. CONCLUSION: Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.

Bile Collection Detected With BrIDA Scintigraphy in a Patient With Hepatocellular Carcinoma.

A 47-year-old man, with a history of anabolic steroid abuse, developed hepatic adenomatosis and multifocal hepatocellular carcinoma. He underwent ultrasound and CT follow-up, showing multiple solid and fluid hepatic lesions. Consequently, hospitalization was required because of high fever (up to 39°C), weakness, and anorexia. An abdominal CT scan revealed an enlargement of one of the intrahepatic fluid collections. Biochemical and microbiological analyses of a fluid sample showed bilirubin and bile acids as well as Streptococcus cristatus and Enterobacter cloacae. Thus, the patient underwent Tc-trimethylbromo-iminodiacetic acid scintigraphy, demonstrating bile collection in the lesion with a flow from a bile duct.

Irritable Bowel Syndrome and Nickel Allergy: What Is the Role of the Low Nickel Diet?

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain or discomfort accompanied by abnormal bowel movements. In sensitized subjects, ingested nickel (Ni) may induce gastrointestinal symptoms similar to IBS, in addition to typical systemic cutaneous lesions (systemic nickel allergy syndrome [SNAS]). A low nickel diet could improve the systemic manifestations. We evaluated prevalence of nickel allergy in IBS and effects of low Ni diet on (1) gastrointestinal symptoms control, (2) intestinal barrier function, (3) quality of life, and (4) psychological status of patients with IBS and Ni-sensitized patients. METHODS: Twenty consecutive patients affected by IBS and suspected SNAS underwent intestinal permeability tests. Gastrointestinal symptoms were evaluated using the visual analogue scale before and after 3 months low Ni diet. Subjects with increased intestinal permeability at baseline repeated nuclear examination after the diet. RESULTS: The most frequent profile was diarrhea-predominant IBS (8/20). The low Ni diet induced a significant and constant improvement of gastrointestinal symptoms and an equally significant improvement of visual analogue scale. Mean urinary output of 5¹Chromium ethylene-diamine-tetra-acetate (5¹Cr-EDTA) was 5.91%/24 hr (± 2.08), significantly different from the control group (2.20%/24 hr ± 0.60, P < 0.0001). CONCLUSION: This pilot study shows that low Ni diet improves gastrointestinal symptoms in patients with IBS and SNAS.

Evaluation of swallowing function after supracricoid laryngectomy as a primary or salvage procedure.

The primary functional issues following conservative therapy for advanced laryngeal cancer concern swallowing. Here, we evaluated the recovery of swallowing after supracricoid partial laryngectomy (SCL) in patients with primary or recurrent laryngeal cancer. We evaluated the swallowing recovery in 27 SCL patients through oropharyngoesophageal scintigraphy, and we evaluated their quality of life using EORTC questionnaires. Four patients underwent total laryngectomy during follow-up. Patients who retained their larynges were able to feed without nutritional support and without tracheostoma. The only significantly different parameter between the primary and salvage cases was the time elapsed to the removal of nasogastric/PEG tubes, which was longer in salvage cases. SCL has been demonstrated as a valuable option for primary and recurrent laryngeal cancer patients. The present data demonstrate good functional results, particularly in terms of swallowing after previous treatments and in primary settings. The combination of oropharyngoesophageal scintigraphy and questionnaires appears to be an adequate, standardizable approach to assessing swallowing function after SCL.

Prevalence and clinical correlates of sleep disordered breathing in myotonic dystrophy types 1 and 2.

PURPOSE: Myotonic dystrophy types 1 (DM1) and 2 (DM2) are the most common muscular dystrophies in adulthood. A high prevalence of excessive daytime sleepiness (EDS) and sleep disordered breathing was documented in DM1; however, there are limited data available regarding DM2. Goals of the study were: (1) to evaluate the prevalence of sleep apnea in a large cohort of patients (71 DM1 and 14 DM2) and (2) to analyze correlations among such disorders and clinical features of myotonic dystrophies. METHODS: All patients underwent clinical examination, subjective sleep evaluation, and home based cardiorespiratory monitoring, and most of them performed pulmonary function tests and oropharyngeal-oesophageal scintigraphy (OPES). RESULTS: Almost 45% of patients reported poor sleep quality; only 20% of them referred EDS. Sleep studies documented sleep apnea, mostly obstructive, in 69% DM1 patients and 43% DM2 patients; overall, 28% of cases needed non-invasive ventilation. Neither age, gender, illness duration, body mass index, muscle involvement, OPES respiratory function indexes, nor n(CTG) in leukocytes were predictive of sleep apnea in DM1 patients. Conversely, in DM1 the central apnea-hypopnea index is correlated with the oral transit time estimated by OPES, whereas in DM2 apnea indexes are correlated with pulmonary function parameters. CONCLUSIONS: Sleep apnea is highly prevalent in both forms of myotonic dystrophies. In DM1, no clinical parameters appear to be predictive, while age appears to influence the severity of the obstructive variant; in DM2, the severity of sleep apnea is correlated with the degree of respiratory muscle involvement. Considering the harmful consequences of sleep apnea on cardiorespiratory function, our findings suggest including PSG in the follow-up of myotonic dystrophies.

Long-term treatment of severe SAPHO syndrome with adalimumab: case report and a review of the literature.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome defines an association of inflammatory cutaneous disorders with osteoarticular manifestations and represents a clinical and therapeutic challenge. We report a case of severe SAPHO syndrome with acne conglobata and a diffuse involvement of the anterior chest wall and sacroiliac joints that required treatment with isotretinoin and adalimumab, a new fully human anti-tumor necrosis factor (TNF)-α monoclonal antibody. Combination treatment determined a complete clinical remission of cutaneous and osteoarticular manifestations after 48 weeks. Despite maintenance of clinical remission, follow-up imaging studies after 24 months of adalimumab monotherapy revealed osteoarticular disease progression, with features of inflammatory osteitis. TNFα antagonists have been used as third-line therapy for SAPHO syndrome in single case reports or case series, but these lack consistent long-term follow-up. SAPHO syndrome can present an intermittent-favorable course in the majority of cases as well as a chronic-progressive course, the latter requiring aggressive combination treatment with TNFα antagonists and conventional systemic agents.

Surgical prophylaxis of pouchitis in ulcerative colitis.

Ileal pouch-anal anastomosis (IPAA) is now the procedure of choice for most patients requiring proctocolectomy for ulcerative colitis. The J-shaped pouch, usually 15-20 cm in length, is easiest to construct and has functional outcomes identical to those of the more complex designs. IPAA is a complex procedure, and complications occur frequently. Despite the significant improvements this surgical advance has made on the quality of life in these patients, inflammation of the surgically created ileal pouch or pouchitis remains a major late postoperative complication that can often overshadow the benefits of this otherwise curative operation. Several inflammatory and noninflammatory complications can occur after IPAA. Pouchitis is the most common, occurring in ≈50% of patients. Whereas acute pouchitis can be treated rapidly and successfully in the majority of patients, refractory and chronic pouchitis remain therapeutic challenges to patients and physicians. The problem is believed to be caused by stasis of feces in the pouch with overgrowth of aerobic and anaerobic organisms. The size of the pouch has a significant influence on the incidence of pouchitis: a smaller pouch usually empties better than a larger pouch and so may be less susceptible to pouchitis.

Intestinal permeability in cirrhotic patients with and without spontaneous bacterial peritonitis: is the ring closed?

OBJECTIVES: Impaired intestinal permeability (IP) may have a role in the pathogenesis of ascites and in spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis (LC). The aim of this study was to assess IP in LC patients with respect to healthy controls. METHODS: IP was evaluated by the (51)Cr-ethylenediaminetetraacetic acid ((51)Cr-EDTA) permeability test in 52 LC patients and in 48 sex- and age-matched controls. The presence of (51)Cr-EDTA was also evaluated in ascitic fluid after therapeutic paracentesis in all LC patients with ascites. RESULTS: An altered IP was found in 45% of LC patients compared with 4% of controls (P<0.00001). IP impairment was significantly associated with Child-Pugh status (75% of Child C patients vs. 39% of Child B and 22% of Child A patients), with the presence of ascites (60% in ascitic patients vs. 31% in nonascitic patients), and with a history of SBP (100% of patients with SBP vs. 50% of those without SBP). (51)Cr-EDTA was present in all ascitic samples obtained from patients with SBP compared with 22% of patients without SBP. CONCLUSIONS: IP derangement was a common finding in LC, especially in patients with more advanced disease (presence of ascites and history of SBP). The presence of (51)Cr-EDTA in ascites in patients with SBP suggests an altered permeability of splancnic vessels and/or peritoneal membranes. Further studies are required to assess (51)Cr-EDTA urine and ascite cutoffs to set up SBP preventive strategies.

Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease.

UNLABELLED: The role played by the gut in nonalcoholic fatty liver disease (NAFLD) is still a matter of debate, although animal and human studies suggest that gut-derived endotoxin may be important. We investigated intestinal permeability in patients with NAFLD and evaluated the correlations between this phenomenon and the stage of the disease, the integrity of tight junctions within the small intestine, and prevalence of small intestinal bacterial overgrowth (SIBO). We examined 35 consecutive patients with biopsy-proven NAFLD, 27 with untreated celiac disease (as a model of intestinal hyperpermeability) and 24 healthy volunteers. We assessed the presence of SIBO by glucose breath testing (GBT), intestinal permeability by means of urinary excretion of (51)Cr-ethylene diamine tetraacetate ((51)Cr-EDTA) test, and the integrity of tight junctions within the gut by immunohistochemical analysis of zona occludens-1 (ZO-1) expression in duodenal biopsy specimens. Patients with NAFLD had significantly increased gut permeability (compared with healthy subjects; P < 0.001) and a higher prevalence of SIBO, although both were lower than in the untreated celiac patients. In patients with NAFLD, both gut permeability and the prevalence of SIBO correlated with the severity of steatosis but not with presence of NASH. CONCLUSIONS: Our results provide the first evidence that NAFLD in humans is associated with increased gut permeability and that this abnormality is related to the increased prevalence of SIBO in these patients. The increased permeability appears to be caused by disruption of intercellular tight junctions in the intestine, and it may play an important role in the pathogenesis of hepatic fat deposition.

Imaging of peritoneal carcinomatosis with FDG PET-CT: diagnostic patterns, case examples and pitfalls.

Early diagnosis of peritoneal spread in malignant disease is essential to prevent unnecessary laparotomies and to select the patients in whom complete cytoreduction is feasible. Although anatomic imaging is the mainstay for evaluating peritoneal seeding, small neoplastic implants can be difficult to detect with CT and MR imaging. FDG PET-CT has the potential to improve detection of peritoneal metastases as lesion conspicuity is high at PET due to low background activity and fused PET-CT offers the combined benefits of anatomic and functional imaging. Correlation of uptake modalities with the pathogenesis of intraperitoneal spread of malignancies, provides a rational system of analysis and is essential to define disease. Distinct patterns appear to predict the presence of either nodular or diffuse peritoneal pathology. Main pitfalls are related to normal physiologic activity in bowel loops and blood vessels or focal retained activity in ureters and urinary bladder. PET-CT is most suitable in patients with high tumor markers and negative or uncertain conventional imaging data and in selecting patients for complete cytoreduction. FDG PET-CT adds to conventional imaging in the detection and staging of peritoneal carcinomatosis and is a useful diagnostic tool in monitoring response to therapy and in long term follow-up.