Correction to: Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation?

Following publication of the original article [1], the authors reported updated affiliations for five of the authors. The updated affiliations are shown below and reflected in the affiliation list of this Correction.

Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation?

BACKGROUND: Recurrent pregnancy loss (RPL) occurs in 3-5% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation. METHODS: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent 51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20 healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1ß and IL-18 by ELISA, respectively. RESULTS: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS (P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial expression of Nalp-3, caspase-1 and IL-1ß was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001, respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women. CONCLUSIONS: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers, potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis. Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and pregnancy outcome.

Pharyngocutaneous fistula onset after total laryngectomy: scintigraphic analysis.

Pharyngocutaneous fistula is the most common non-fatal complication following total laryngectomy. To start oral feeding and exclude the presence of a pharyngocutaneous fistula, a subjective test and instrumental assessments using videofluoroscopy, have been described. The aim of this study was to evaluate the effectiveness of oral-pharyngo-oesophageal scintigraphy as an objective and non-invasive tool to establish presence, site and dimensions of the fistula. Observations were performed on 3 male patients, mean age 65 years, who underwent total laryngectomy and mono or bilateral neck dissection after failure of radiotherapy in 2 cases and of conservative laryngeal surgery in the third case, complicated by post-operative pharyngocutaneous fistula. Oral-pharyngo-oesophageal scintigraphy dynamic study with sequential images were obtained during the swallowing phases. In case 1, the test showed a wide pharyngocutaneous fistula the internal orifice of which was at the level of the base of the tongue: on the scintigraphic images, the radiomarked water bolus, from the fistulous orifice, descended along the stoma walls and only a small part reached the oesophagus. In the other two patients, the pharyngocutaneous fistula was small and the internal fistulous orifice was detected in the lower part of T-suture line. In conclusion, scintigraphy offered the possibility to precisely identify presence of pharyngocutaneous fistula and location of its internal orifice and to monitor its spontaneous closure. Therefore, important information could be obtained regarding the suture line status and the possibility of deciding whether to remove the nasogastric tube or to leave it in place. Finally, these data showed that oral-pharyngo-oesophageal scintigraphy could be performed in the early post-operative period to optimize starting safe oral feeding.

Meckel's diverticulum findings on Tc-99m red blood cell scintigraphy in a bleeding leukemic patient confirmed by Tc-99m pertechnetate scintigraphy.

A 25-year-old Caucasian woman with a medical history of acute promyelocytic leukemia presented to the emergency department with massive gastrointestinal bleeding. A bone marrow biopsy excluded hemorrhagic leukemia. Esophagogastroduodenoscopy, colonoscopy, emergency abdominal angiography, abdominal CT scan, and wireless capsule endoscopy were performed but no source of bleeding could be detected. Tc-99m RBC scintigraphy was consistent with a small bowel bleeding focus. The persistent and focal images in the right abdomen were suggestive of Tc-99m RBC trapping in the lumen of a Meckel diverticulum (MD). In accordance with this suspicion, successive Tc-99m pertechnetate scintigraphy was performed after 3 days, consistent with the diagnostic hypothesis. Due to the persisting severe bleeding (with a drop in baseline hemoglobin from 10.4 to 7.1 g/dL), despite 8 units of blood transfusion, emergency surgery was performed. Through a minilaparotomy a segmental small bowel resection, including Meckel diverticulum, was performed. The postoperative course was uneventful.

Evaluation of the clinical and histological effectiveness of isotretinoin in the therapy of oral leukoplakia: ten years of experience: is management still up to date and effective?

Various studies have evaluated the therapeutic effectiveness of vitamin A derivatives in the treatment of oral leukoplakia (OL). Not all the studies have shown concordant results. The aim of our study, which has a 10-year follow-up, was to test the effectiveness of topical therapy based on 0.18% isotretinoin by comparing it with that most frequently used, i.e., at 0.05% concentration. Forty patients with an established diagnosis of OL were involved in the study. The patients were randomly divided into two groups and the drug was administered topically at 0.05% and 0.18% concentrations. The drug was applied twice a day for 3 consecutive months; then it was suspended for 1 month, and the biopsy sample was repeated for the histological follow-up. The higher concentration of the drug, according to the same protocol, was administered to patients who did not benefit from the lower concentration. The results showed a significant reduction in lesions (85%), with no documented topical or systemic adverse reactions at 0.18% concentration. A significant reduction of the aggressiveness of the disease and the disappearance of dysplastic phenomena were observed histologically. The proposed therapeutic protocol was effective toward highly active oral leukoplakia with dysplastic phenomena, and therefore at higher risk of malignant progression.

Effect of botulinum toxin antral injection on gastric emptying and weight reduction in obese patients: a pilot study.

BACKGROUND: A potential approach to the treatment of morbid obesity is reduction of gastric emptying to achieve satiety. Botulinum toxin A (Btx-A) is a long-acting inhibitor of acetylcholine-mediated peristalsis, which is mainly responsible for gastric motility. AIM: To investigate whether botulinum toxin A, injected in the antrum of obese patients, delays gastric emptying. METHODS: In a double_blind study, 18 healthy obese subjects (body mass index >30) were randomized into three groups (BTX133, BTX200 and Saline); they received Btx-A133U, Btx-A200U, or saline under endoscopic control. Gastric emptying was tested by scintigraphy before and 10 days after treatment. Body weight variations and appetite sensation were recorded after 5 weeks. RESULTS: Fourteen patients completed the study. The botulinum toxin A-treated groups showed weight reduction, which was not statistically significant. The effects on gastric emptying were variable. Most of the botulinum toxin A treated patients reported a reduced appetite. CONCLUSION: This pilot clinical trial suggests potential activity of botulinum toxin A for the manipulation of appetite.

Topical capsaicin application and axon reflex vasodilatation of the tongue: neurogenic involvement in burning mouth syndrome.

The aim of this study was to evaluate the effects of topical capsaicin application on human lingual mucosa and to assess if neurogenic inflammation might have a role in the pathogenesis of lingual diseases. Thirty patients (16 males and 14 females; mean age: 41.46 +/- 11.8 years; range: 23-60) were examined in our laboratory. The neurogenic inflammation was experimentally induced in the lingual mucosa close to 1) the left margin of the tongue and 2) the right margin of the tongue after ipsilateral nerve trunk anesthesia. The characteristics of lingual microcirculation were observed using computerized videocapillaroscopic techniques. The vasodilatation was observed close to the left margin of the tongue, and an important correlation was observed between capsaicin application and capillary tortuosity. No significant modifications in vascular diameter and tortuosity were observed after capsaicin application close to the right margin of the tongue. The results of the present study are of interest, in particular, in regard to recent studies pointing to neurogenic involvement in oral diseases such as burning mouth syndrome.

Composite of low contraction and rapid polymerization. A study of marginal infiltration.

The aim of this work consists in a comparative biomorphological analysis of the properties of infiltration and of adhesion to dental tissues of two different composits (Tetric Ceram and Inten-S) with different modalities of of application of halogen light. The results have given evidence that there was found to be no significant difference between the two groups examined.

Comparative biomorphologic analysis about three dentinal adhesives of last generations.

The aim of this work consists in a comparative biomorphological analysis of the properties of infiltration and of adhesion to dental tissues of three among the more used enamel dentinal adhesives of the last generation known with the commercial name of Syntac, Excite and Prompt. The results have given evidence that Syntac has got short adhesion, Excite has got good capacity of infiltration and moderate adhesion, Prompt seems to possess a capacity of infiltration equal to Excite's one, but a better adhesion besides an easier modality of use.

[Validity of schintigraphy in the study of neurogenic dysphagia]. / Validità della metodica scintigrafica nello studio della disfagia neurogena.

The purpose of the present study was to verify the validity and potential application of oropharyngealesophageal scintigraphy in the analysis of neurogenic dysphagia. Scintigraphy was used on 36 patients divided into 2 groups: Group 1 (control) comprised 17 healthy volunteers; Group 2 included 19 patients suffering from various neurological and neuromuscular pathologies (myasthenia gravis, Parkinson's disease, polymyositis, stroke, paralysis of the last cranial nerves). In group 1 scintigraphy provided normal results both for mode of swallowing and transit, and for the values of the various parameters studied. On the other hand, scintigraphy showed that in group 2 all oral, pharyngeal and esophageal phases of swallowing were altered vs the controls with a statistically significant increase in the average values for the oral transit time (OTT) (1.45 sec., p = 0.0005), pharyngeal transit time (OTT) (3.23 sec., p = 0.044), esophageal transit time (ETT) e19.87 sec., p = 0.005) as well as in the corresponding bolus retention indexes ORU (12.95%, p = 0.0003), FIR (15.05%, p = 0.0003) and ERI (28.63%, p = 0.002). Moreover, the quality and means of swallowing also proved altered while tracheobronchial aspiration was only seen in 6 of the 19 patients (maximum value: 90%, average value; 7.66%) with a marked prevalence in the stroke subgroup (4/8). In light of these results and considering the low dose of radiation (0.00043 Gy), the lack of invasiveness and excellent tolerability, scintigraphy has confirmed its clinical validity in the functional, objective and quali-quantitative study of deglutition, even in patients suffering from neurogenic dysphagia.

Immunohistochemical localization of atrial natriuretic factor (ANF) in the excretory system of the rabbit parotid gland.

The immunohistochemical localization of atrial natriuretic factor (ANF) in the rabbit parotid gland was performed using an antibody against rabbit ANF and avidin-biotin or streptoavidin as detector. Results showed positivity in cuboidal and columnar cells of intralobular ducts and in basal cells of extralobular and main excretory duct. These data support the hypothesis that ANF produced by intralobular ducts could act through a paracrine mechanism; ANF produced by extralobular and main ducts may play a role in the regulation of salivary composition.

Scintigraphic assessment of swallowing after horizontal supraglottic laryngectomy.

OBJECTIVE: Oral-pharyngo-esophageal scintigraphy (OPES) proved to be able to demonstrate the pharyngeal residue of the radioactive bolus after deglutition and the presence and amount of tracheobronchial aspiration, and to calculate exactly the transit time of the various swallowing phases. The aim of this study was to evaluate the real objective effectiveness of OPES in order to assess the degree of swallowing recovery after horizontal supraglottic laryngectomy (HSL). METHODS: Nineteen patients entered the study, and 17 healthy subjects were included as control group (group 1). Nineteen patients in whom HSL had been performed at least 1 year before underwent OPES. They were divided into two groups: 13 patients (group 2) in whom the tracheal cannula had been removed and swallowing, phonatory, and respiratory functions were satisfactory and 6 patients (group 3) in whom the tracheostomy tube was still in situ for aspiration of liquids and scarring of the laryngeal vestibule. RESULTS: Our results showed that in the patients who underwent HSL, all scintigraphic semiquantitative parameters and particularly aspiration percentage values and Pharyngeal Ritention Index (PRI) at 10 and 60 seconds were able to pinpoint some residual "subclinical" alteration and/or minimal surgical sequelae frequently observed after this kind of functional surgery, even though a substantially satisfactory recovery was achieved clinically (group 2 versus group 1). In addition, aspiration amounts in group 3 were markedly higher than those in group 2 (p < .0002), and mean PRI values at 10 and 60 seconds were significantly different (p < .0001) from normal mean control values (group 1). CONCLUSION: Oral-pharyngo-esophageal scintigraphy may be regarded as a noninvasive, well-tolerated technique, with a radiation body burden within satisfactory limits of radioprotection. It appeared to be also sensitive in assessing the swallowing recovery after HSL.

Is there still a role for functional radionuclide study of the liver?

Clinical applications of radionuclide methods for the study of liver hemodynamics and hepatocyte function are examined. In particular, as for hemodynamic studies, perfusion assessment with radiocolloids, 99mTc-IDA scintigraphy or 99mTc-labeled red blood cells, is underlined; they allow characterization of the different cellular component of space-occupying liver processes. The use of hepatic perfusion index (HPI) is reconsidered both as prognostic parameter in cirrhotic patients and as predictor of liver metastasis from colorectal cancer. The diagnostic role of recent procedures, as those based on endorectal radiopharmaceuticals in the evaluation of portosystemic shunts in cirrhosis, is analyzed. Studies of hepatocyte function of practical concern are essentially devoted to the "excretory function" and "asialoglycoprotein metabolism". In the first case, a major role is played by IDA halogenated derivatives and functional parameters drawn from them by mathematico-statistical evaluations of radiohepatogram (simple or applied to compartmental models). For metabolic studies, at present an artificial glycoprotein, 99mTc-galactosylneoglycoalbumin (99mTc-NGA) that binds with hepatocellular receptors is used. Information on the rate of blood plasma clearance and liver uptake, receptor density (altered in some pathologic conditions) and plasmic hepatic flow, is supplied.

Vitamin B12 and folic acid plasma levels after ileocecal and ileal neobladder reconstruction.

OBJECTIVES: To compare the plasma levels of vitamin B12 and folic acid following resection of ileocecal or ileal segments used for orthotopic bladder substitution. METHODS: Hemoglobin, hematocrit, and plasma levels of vitamin B12 and folic acid were measured in 34 patients with ileocecourethrostomy (ICUS) and in 16 patients with ileal reservoir (IR), with a mean follow-up of 59.8 +/- 41.9 months. The results were compared with regard to both the type of operation and the length of time since surgery. RESULTS: The level of folic acid was normal in all patients. The mean level of vitamin B12 in the ICUS group was 413.67 +/- 160.45 ng/mL compared to 257.63 +/- 121.36 for the IR group. This difference was statistically significant. In the IR group, 18.75% of the patients had a level of vitamin B12 below normal. CONCLUSIONS: There is a tendency for vitamin B12 levels to fall in patients in whom the ileum is used. Resection of the ileocecal segment including the junction does not alter the level of vitamin B12.

[An oropharyngeal-esophageal scintigraphic study of deglutition]. / Studio della deglutizione con scintigrafia oro-faringo-esofagea.

The aim of the present work was to evaluate whether oro-pharyngeal-esophageal scintigraphy could be used in the dynamic study of the various phases of deglutition and to determine whether it could be applied in otorhinolaryngological practice along with videofluoroscopy and videoendoscopy. The patients were divided into four different groups according to clinical features and the scintigraphic data were analyzed on this basis. Emphasis is placed on the ease of this technique, its tolerability and the low level of radiation. It is pointed out that scintigraphy is quite useful in determinating the exact percentage of the bolus inhaled into the trachealbronchial branch and in measuring the transit time of the various phases of deglutition in detail. In patients affected by upper airway-digestive tract neoplasms it is, therefore, possible to make a semiquantitative evaluation of the results of surgery. Moreover, with this method the results of any rehabilitation can be measured as well as the onset of compensation mechanisms.

Comparison between TRH-stimulated TSH and basal TSH measurement by a commercial immunoradiometric assay in the management of thyroid disease.

In order to assess the current diagnostic role of the TRH test following the introduction of more sensitive "second generation" TSH assays, we studied a series of 259 outpatients, 237 women and 22 men, mean age 44.7 years (range 12-82), 91 of whom (35%) with untreated simple goiter, 133 (51%) with simple nodular goiter on steady state I-thyroxine treatment, 18 (7%) with overt or subclinical hyperthyroidism and 17 (7%) with overt or subclinical hypothyroidism, compared to a control group of 26 euthyroid healthy subjects. Serum TSH was measured by a commercial immunoradiometric assay (clinical sensitivity 0.1 microU/ml). TSH response to TRH was evaluated 30 minutes after giving 200 micrograms TRH i.v. bolus, the results being analyzed both as absolute increase (delta-TSH=stimulated TSH minus basal TSH) and as relative increase (R-TSH stimulated TSH/basal TSH). Using cut-off values of 0.3-3.2 microU/ml, basal TSH measurement was able to detect hypothyroidism (specificity = 100%) and to exclude hyperthyroidism (sensivity = 96.9%), but failed to accurately prove hyperthyroidism (specificity = 93.4%) and, above all, to exclude hypothyroidism (sensitivity = 35.3%) in our ambulatory patients. The delta-TSH values showed a basal TSH dependent linear increase (r = + 0.87, p < 0.001) both including only patients (n = 139) with basal TSH level in the euthyroidism range and including all patients (n = 223) having TSH responsive to TRH. All the patients with detectable basal TSH level displayed detectable TSH response to TRH, as did 19 (= 23.5%) of 81 patients with undetectable (< 0.1 microU/ml) basal value. In particular: a) for subnormal but detectable basal TSH ranging between 0.1 and 0.2 microU/ml, TSH was always hyporesponsive (delta-TSH < or = 2.5 microU/ml), while between 0.2 and 0.3 microU/ml TSH was hyporesponsive in 72.2% and normoresponsive (delta-TSH > 2.5 and < or = 11.9 microU/ml) in the remaining 27.8%; b) for basal TSH values within the normal range (0.3-3.2 microU/ml). TSH was hyporesponsive in 13.7%, normoresponsive in 74.8% and hyperresponsive in 11.5%; c) for high basal TSH values TSH was always hyperresponsive. The analysis of R TSH showed relatively constant values in the range of euthyroidism and hypothyroidism (m +/- SD: 7.4 +/- 2.3 and 7.7 +/- 3.1, respectively), and a marked differentiation of hyperthyroid patients whose R-TSH values were significantly lower (4.2 +/- 3.4) but had a wide individual variability. Linear regression analysis of basal or stimulated TSH and circulating thyroid hormones showed a close negative relationship, being highly significant between delta-TSH and T4 (r = 0.57, p < 0.001) and delta-TSH and FT4 (r = 0.46, p < 0.001). In conclusion, after the introduction of current second generation TSH immunoradiometric assay, the diagnostic role of the TRH test is greatly limited but not to be excluded: it can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism and in the precise evaluation of the degree of TSH suppression in patients with a subnormal basal TSH, either for endogenous thyrotoxicosis or I.-thyroxine treatment.

Radiolabeled somatostatin analog scintigraphy in medullary thyroid carcinoma and carcinoid tumor.

The aim of this study was to evaluate the effectiveness of a recently developed radiolabelled somatostatin analog (111In-pentetreotide) for the detection and localization of both medullary thyroid carcinoma (MTC) and carcinoid tumors, and to compare the results obtained with the results of 99mTc(V)-DMSA, and radioiodinated MIBG imaging. 111In-pentetreotide scintigraphy was performed in 9 patients with MTC and in 9 patients with carcinoid tumor. Whole body and SPECT studies were performed at 4 and 24 hours post-injection. SMS scintigraphy gave a positive result in 5 out of 7 patients with proven MTC lesions, and in 7 out of 9 patients with known lesions of carcinoid tumor. It gave a negative result in 2 MTC patients with high levels of calcitonin but with no evidence of disease at conventional diagnostic modalities. The scintigraphic results were comparable with those obtained with 99mTc(V)-DMSA in MTC and were superior to those of radioiodinated MIBG in both MTC and carcinoid tumors. When compared with the modifications of calcitonin levels brought about by the acute administration of octreotide ("Octeotride test"), these correlated well in 8 out of 9 patients studied.