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.

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.

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.

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.

Thyroid cancer in suppressed contralateral lobe of patients with hot thyroid nodule.

We studied 60 patients with thyrotoxicosis due to single toxic nodule. At surgery in 3 patients (5%) a papillary carcinoma has been detected in the contralateral suppressed lobe. Thyroid function tests and thyroid scan confirmed thyrotoxicosis. Thyroid stimulating hormone (TSH) was undetectable in all patients. It is common opinion that differentiated thyroid tumour growth is TSH dependent. On the basis of our study two hypotheses are possible: (1) the development of thyroid carcinoma precedes the adenoma and suppressed TSH levels inhibit tumour growth; (2) suppressed TSH levels do not protect patients from the occurrence of cancer. In the evaluation of hot thyroid nodule we suggest careful ultrasonographic control in order to look for nodules outside the adenoma. A complete surgical examination of the whole thyroid gland is required and intraoperative biopsies are advocated in abnormal areas.

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.

AFP, CEA, CA 19-9 and TPA in hepatocellular carcinoma.

The present study is based on the assay of four markers (AFP, CEA, TPA, Ca 19-9) using IRMA methods in 36 normal subjects, 44 cirrhosis and 66 HCC patients. Parametric and non parametric tests were used to test differences and correlations. ROC curves and discriminant functions were also elaborated. Normal 95% "cut-off" was determined by the "boostrap" method yielding: CEA 3.4 ng/ml; Ca 19-9 55 U/ml; TPA 58U/l and AFP 5.2 ng/ml. In HCC patients the values of the four markers were, on average, significantly different from those of normal subjects. However, only AFP and TPA exhibited high diagnostic accuracy (90%) for detection of the tumor. Higher than normal mean values for all markers were, also observed in cirrhotic patients. Only AFP yielded effective discrimination between HCC and cirrhosis. The positive prediction for the presence of the tumor on cirrhotic ground was 95% for AFP values higher than 18.5 ng/ml, with a 78% negative predictive value with a 6 ng/ml threshold. Association of AFP with TPA showed only a marginal diagnostic improvement. Results were not improved at all by combining CEA and Ca 19-9 with AFP and/or TPA. In conclusion, AFP is and remains the best marker for HCC and the only one effective in discriminating of HCC from cirrhosis. TPA may be considered a valid alternative if cirrhosis is not present. CEA and Ca19-9 are of no use.

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.

[Morphological and functional study of the liver using scintigraphy with 99m-Tc-HIDA before and after major resection for echinococcosis]. / Studio morfologico e funzionale del fegato mediante scintigrafia con 99m-Tc HIDA prima e dopo resezioni maggiori per echinococcosi.

Personal experience in the monitoring of liver function and morphology after resection using hepatobiliary HIDA 99mTc scintigraphy is reported. This investigation provides useful functional and morphological data. In three patients subjected to right hepatectomy for echinococcosis the examination performed preoperatively and 25 and 90 days after surgery revealed functional normalisation of the residual liver and biliary excretion. On the basis of this experience and data from the literature the value of the technique is confirmed and it is suggested that it might be usefully adopted in the study of other liver conditions such as neoplasms, traumas as well as in the monitoring of transplanted livers.

A contribution to knowledge of the compartments and the fascial and septal formations of the popliteal fossa in the human fetus and the adult.

A contribution to knowledge of the compartments and the fascial and septal formations of the popliteal fossa in the human fetus and the adult. A study was made in human fetuses from the 3rd month onwards, newborn and the adult of the fascial and septal formations and the compartments of the popliteal fossa. Observations of serial sections of the knee of human fetuses, of macroscopic preparations of the knee of newborns and of ultrasound images of the popliteal fossa in adults showed that: the fascial formation covering the popliteal fossa consists of the popliteal fascia and the superficial fascia. The bud of the popliteal fascia is observable in the 3-month fetus as a layer of thin fibrillar connective tissue which is thicker in the tracts between the muscle buds. At birth the popliteal fascia is clearly a separate anatomical entity of continuous laminar structure which is thicker in the tracts between the muscles and thinner where it covers them. The superficial fascia becomes evident in fetuses at a later stage (6th month) in the form of a thin lamina in the frontal plane which at birth is well defined and observable as a thin continuous line deep below the subcutaneous layer. The septal formation consists of four septa: two in the sagittal plane (lateral and medial) and two in the frontal plane (lateral and medial). The bud of these septa appears in 4-month fetuses after the appearance of the popliteal fascia. They branch off from the thicker connective areas between the muscles buds as connective prolongations which later assume a laminar aspect and eventually become compact and form septa. In at-term fetuses and newborns these septal formations are clearly recognizable as antomical entities, which branch off from the deep surface of the thicker tracts of the popliteal fascia and are inserted into the femur. The relationships and connections with the muscular groups are also clearly visible. The organization and demarcation of the compartments, which is already delineated in the 6-month fetus, seems to be completed at birth, considering the presence of the superficial fascia, the popliteal fascia and the septa. It is possible to distinguish a superficial compartment between the popliteal and the superficial fascia an a deep compartment between the frontal septa, the skeletal plane and the popliteal fascia. This deep compartment is clearly subdivided by the two sagittal septa into three sectors (medial, intermediate and lateral). The medial and lateral sectors contain muscles, while the intermediate compartment contains the vasculonervous bundle and the popliteal adipose body.

[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.

[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.

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.