Surgical management of complex ileocolonic Crohn's disease: a survey of IBD colorectal surgeons to assess variability in operative strategy.

INTRODUCTION: To explore the reported variability in the surgical management of ileocolonic Crohn' s disease and identify areas of standard practice, we present this study which aims to assess how different colorectal surgeons with a subspecialty interest in inflammatory bowel disease (IBD) surgery may act in different clinical scenarios of ileocolonic Crohn's disease. METHODS: Anonymous videos demonstrating the small bowel walkthrough and anonymised patients' clinical data, imaging and pathological findings were distributed to the surgeons using an electronic tool. Surgeons answered on operative strategy, bowel resections, management of small bowel mesentery, type of anastomosis and use of stomas. RESULTS: Eight small bowel walkthrough videos were registered and 12 assessors completed the survey with a questionnaire completion rate of 87.5%. There was 87.7% agreement in the need to perform an ileocolonic resection. However, the agreement for the need to perform associated surgical procedures such as strictureplasties or further bowel resections was only 57.4%. When an anastomosis was fashioned, the side to side configuration was the most commonly used. The preferred management of the mesentery was dissection close to the bowel. CONCLUSIONS: The decision on the main procedure to be performed had a high agreement amongst the different assessors, but the treatment of multifocal disease was highly controversial, with low agreement on the need for associated procedures to treat internal fistulae and the use of strictureplasties. At the same time, there was significant heterogeneity in the decision on when to anastomose and when to fashion an ileostomy.

Video-laparoscopic assessment of the small bowel in Crohn's disease: a comparative study to evaluate surgeons' inter-observer variability.

BACKGROUND: Assessment of the entire small bowel is advocated during Crohn's disease (CD) surgery, as intraoperative detection of new lesions may lead to change in the planned procedure. The aim of this study was to evaluate the inter-observer variability in the assessment of extent and severity of CD at the small bowel laparoscopic "walkthrough". METHODS: A survey on laparoscopic assessment of the small bowel in patients with CD, including items adapted from the MREnterography or ultrasound in Crohn's disease (METRIC) study and from the classification of severity of mesenteric disease was developed by an invited committee of colorectal surgeons. Anonymous laparoscopic videos demonstrating the small bowel "walkthrough" in ileocolonic resection for primary and recurrent CD were distributed to the committee members together with the anonymous survey. The primary outcome was the rate of inter-observer variability on assessment of strictures, dilatations, complications and severity of mesenteric inflammation. RESULTS: 12 assessors completed the survey on 8 small bowel walkthrough videos. The evaluation of the small bowel thickening and of the mesenteric fat wrapping were the most reliable assessments with an overall agreement of 87.1% (k = 0.31; 95% CI - 0.22, 0.84) and 82.7% (k = 0.35; 95% CI - 0.04, 0.73), respectively. The presence of strictures and pre-stenotic dilatation demonstrated agreement of 75.2% (k = 0.06: 95% CI - 0.33, 0.45) and 71.2% (k = 0.33; 95% CI 0.15, 0.51), respectively. Evaluation of fistulae had an overall agreement of 75.3%, while there was a significant variation in the evaluation of mild, moderate and severe mesenteric disease with overall agreement ranging from 33.3 to 100%. CONCLUSION: Laparoscopic assessment of the small bowel thickening and of the presence of mesenteric fat wrapping is reliable for the intraoperative evaluation of CD with high inter-rater agreement. There is significant heterogeneity in the assessment of the severity of the mesenteric disease involvement.

Efficacy of cefiderocol- vs colistin-containing regimen for treatment of bacteraemic ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19.

INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. METHODS: This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. RESULTS: During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. CONCLUSIONS: This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

[Assessment of congenital malformation risk in the progeny of the military and civilian personnel of the Salto di Quirra military base: preliminary results]. / Valutazione del rischio di malformazioni congenite nella progenie del personale militare e civile del Poligono Interforze del salto di Quirra: risultati preliminari.

INTRODUCTION: We evaluated the congenital malformation rate in the progeny of the personnel of the Salto di Quirra military base in Sardinia. METHODS: During 2011, we gathered questionnaire information on the reproductive history of 389 employees, more then 99% of those eligible for routine health surveillance. RESULTS: the observed congenital malformation rate (20.1 x 10(-3), 95% CI 6.3 - 33.8) was lower than that reported by the Italian Registries of Congenital Malformations, and it did not vary by exposure to radiofrequency, elf electromagnetic fields, and solvents, and by jobs associated with alleged exposure to nanoparticles or alpha radiation. CONCLUSIONS: Our findings suggest that the documented or alleged occupational exposures among the PISQ workforce did not increase the congenital malformation rate in the progeny.

Oestrogen and progesterone receptor binding capacity and oestrogen receptor alpha expression (ERalpha mRNA) along the cervix of cycling ewes.

The aim of the present work was to study the oestrogen receptor (ER) and progesterone receptor (PR) binding capacity and the oestrogen receptor alpha (ERalpha) mRNA concentration in cranial and caudal cervix during the ovine oestrous cycle. Cervical samples of synchronised Corriedale ewes were obtained on Day 1 (n=7), 6 (n=6) or 13 (n=7) after oestrus detection (Day 0). The ER and PR binding capacity by ligand-binding assay and the ERalpha mRNA concentration by solution hybridisation in both cranial and caudal zones of the cervix were determined. The ER and PR binding capacity were higher (P<0.005) on Day 1 than on Days 6 and 13 in both cranial and caudal zones. The ERalpha mRNA concentrations were higher (P<0.0001) on Day 1 than on Days 6 and 13 only in the caudal zone. The PR binding capacity and ERalpha mRNA concentration were higher (P<0.005) in the caudal than in the cranial zone on Day 1. The ER and PR expression in the ovine cervix varied during the oestrous cycle in agreement with the known upregulation exerted by oestrogen and downregulation exerted by progesterone. Differences in ER and PR expression along the longitudinal axis of the ovine cervix were found, reflecting histological and functional differences between the cranial and caudal zones.

[The MMPI-2 test in the evaluation of the mobbing syndrome]. / Il test MMPI-2 nella valutazione della sindrome da mobbing.

MMPI-2 test is widely used in psychodiagnostic evaluation as well as in the evaluation of psychic pathologies related to psychosocial adversative events in working activities. A more efficacious use of MMPI-2 test in the working context can be achieved by the individuation of indexes able to facilitate the evaluation of mobbing syndrome. This work is based on the analysis of 150 cases (39.7% women and 60.7% men, 30 to 60 years of age), evaluated through an accurate examination of working history and a series of clinic conversations, followed by psychodiagnostic evaluation. The average of T-scores on the clinical scale, the content scale, the PK addition scale and the validation scale were calculated from tests. Pathologic high T-scores on the scales Hs, D. Hy e Pa were found in subjects having positive mobbing anamnesis. These results strongly indicate the presence of clinical specificities in workers exposed to working harassments, and that these specificities can be efficaciously evidenced by the MMPI-2 test.

Transport, mechanical and global migration data of multilayer copolyamide nanocomposite films with different layouts.

Transport, mechanical and global migration data concern multilayer food packaging films with different layouts, all incorporating a layered silicate/polyamide nanocomposite as oxygen barrier layer, and a low-density polyethylene (LDPE) as moisture resistant layer in direct contact with food. The data are related to "Tuning of co-extrusion processing conditions and film layout to optimize the performances of PA/PE multilayer nanocomposite films for food packaging" by Garofalo et al. (2017) [1]. Nanocomposite multilayer films, with different relative layer thicknesses and clay types, were produced using a laboratory scale co-extrusion blown-film equipment and were analyzed in terms of transport to oxygen and water vapor, mechanical properties and overall migration. The results have shown that all the multilayer hybrid films, based on the copolyamide layer filled with Cloisite 30B, displayed the most significant oxygen barrier improvements and the best mechanical properties compared to the unfilled films. No significant alteration of the overall migration values was observed, as expectable [2], [3], [4]. The performance improvement was more relevant in the case of the film with the thinner nanocomposite layer.

Cognition and behavior in children with benign epilepsy with centrotemporal spikes (BECTS).

Characteristics of cognitive deficits in benign childhood epilepsy with centrotemporal spikes (BECTS) remain unclear. The authors screened 200 BECTS children presenting for a clinical trial, finding relative weaknesses in fine motor control, visual learning, and attention in the presence of overall normal intellect, with simple partial seizures associated with more difficulty. Parental concerns for psychosomatic and learning problems were noted. Monitoring select cognitive and behavioral features in BECTS appears appropriate.

Corpus luteum life span and pituitary oestrogen and progesterone receptors in cyclic and gonadotrophin-releasing hormone-treated anoestrous ewes.

The present study investigated the pituitary oestrogen (ER) and progesterone (PR) receptor concentrations in ewes during the oestrous cycle in the breeding season (n = 19), and in anoestrous ewes treated with gonadotrophin-releasing hormone (GnRH) (n = 11) and anoestrous ewes treated with progesterone + GnRH (n = 11). The pituitary ER and PR concentrations at the expected time of ovulation and in the early and late luteal phases were measured by binding assay. The pattern of pituitary ER and PR concentrations in the progesterone + GnRH-treated ewes resembled the pattern found during the normal oestrous cycle, with ER and PR concentrations decreasing from the time of ovulation to the early luteal phase. In contrast, in ewes treated with GnRH alone, ER and PR concentrations increased in the early luteal phase, which may increase the inhibitory effects of steroid hormones on luteinising hormone secretion, ultimately leading to the development of subnormal luteal phases.

Experimentally induced subnormal or normal luteal phases in sheep: reproductive hormone profiles and uterine sex steroid receptor expression.

This study investigated if ewes expected to have subnormal luteal phases (SNLP) present a different pattern of uterine oestrogen receptor (ER) and progesterone receptor (PR) expression at the expected time of premature luteolysis. The concentrations of uterine ER, PR and ERalpha mRNA, and the steroid ovarian hormone were determined in anoestrous ewes treated with either gonadotrophin-releasing hormone (GnRH) to develop a SNLP (n = 16), or progesterone + GnRH to develop a normal luteal phase (NLP; n = 16). The ER, PR and ERalpha mRNA concentrations were measured using binding and solution hybridisation assays, while the hormone level concentration was measured by radioimmunoassay. In all ewes, a luteinising hormone- and follicle-stimulating hormone-synchronised surge was found. The SNLP group had lower preovulatory oestradiol levels than the NLP group. On Day 5, the SNLP group had lower progesterone levels, and higher uterine ER, PR and ERalpha mRNA concentrations than the NLP group. While in the SNLP group the receptor expression increased from Days 1 to 5, in the NLP group the receptor expression decreased. The results suggest that the induction of steroid receptor expression in the uterus and the hormonal environment found in the experimental SNLP group at the expected time of premature luteolysis may be involved in the mechanisms causing SNLP.

Differential estradiol effects on estrogen and progesterone receptors expression in the oviduct and cervix of immature ewes.

In order to study the effect of estradiol-17beta (E2) on estrogen (E) and progesterone (P) receptors expression in oviduct and cervix of lambs, their respective transcripts (ERalpha mRNA and PR mRNA) were determined by solution hybridization and the receptor proteins (ER and PR) by binding assays after E2 treatments. Lambs (n=4 in each group) were not treated or treated with one, two or three i.m. injections of E2 (1 microg/kg) at 24 h of interval. Tissues were obtained 12 or 24 h after the last E2 injection. Estradiol treatments increased ERalpha mRNA and PR mRNA concentrations in an organ-dependent manner: transitory in the oviduct while maintained in the cervix. The E2 effect on the oviductal and cervical ER and PR concentrations were biphasic, with an initial reduction of receptors content that was followed by restoration. The ER restoration in oviduct was earlier than in the cervix. In summary, this study shows that E2 treatments may exert an inductive effect in ERalpha mRNA and PR mRNA levels and a biphasic effect in ER and PR concentrations in oviduct and cervix of immature ewe. These E2 effects varied in timing and strength depending on the organ of the reproductive tract.

Collagen and matrix metalloproteinase-2 and -9 in the ewe cervix during the estrous cycle.

The cervical collagen remodeling during the estrous cycle of the ewe was examined. The collagen concentration determined by a hydroxyproline assay and the area occupied by collagen fibers (%C), determined by van Gieson staining, were assessed in the cranial and caudal cervix of Corriedale ewes on Days 1 (n = 6), 6 (n = 5), or 13 (n = 6) after estrous detection (defined as Day 0). In addition, the gelatinase activity by in situ and SDS-PAGE gelatin zymographies and matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9, respectively) expression by immunohistochemistry were determined. The collagen concentration and %C were lowest on Day 1 of the estrous cycle (P < 0.04), when MMP-2 activity was highest (P < 0.006) and the ratio of activated to latent MMP-2 trend to be highest (P = 0.0819). The MMP-2 activity was detected in 73% of the homogenized cervical samples, and its expression was mainly detected in active fibroblasts. By contrast, the MMP-9 activity was detected in 9% of the samples, and its scarce expression was associated with plasmocytes, macrophages, and lymphocytes. Matrix metalloproteinase-2 expression was maximal on Day 1 in the cranial cervix and on Day 13 in the caudal cervix and was lower in the cranial than in the caudal cervix (P < 0.0001). This time-dependent increase in MMP-2 expression that differed between the cranial and caudal cervix may reflect their different physiological roles. The decrease in the collagen content and increase in fibroblast MMP-2 activity in sheep cervix on Day 1 of the estrous cycle suggests that cervical dilation at estrus is due to the occurrence of collagen fiber degradation modulated by changes in periovulatory hormone levels.

Spinal cord schistosomiasis: a pediatric case mimicking intrinsic cord neoplasm.

We present the clinical, myelographic, MRI, and histologic data on a 7-year-old girl with confirmed Schistosoma mansoni infection of the spinal cord. MRI of the granulomatous spinal lesion revealed extensive enlargement of the cord in the T11-12 area, with some intramedullary swelling extending to T-5 through T-7. The clinical manifestations of spinal schistosomiasis can be diverse, and there should be a high index of suspicion for all patients from endemic areas.

A double-blind trial of gabapentin monotherapy for newly diagnosed partial seizures. International Gabapentin Monotherapy Study Group 945-77.

BACKGROUND: Gabapentin is widely approved as add-on therapy for epilepsy treatment for partial seizures with and without secondary generalization. To investigate the efficacy of gabapentin administered as monotherapy in patients with newly diagnosed partial epilepsy, a randomized double-blind trial was performed. METHODS: Eligible patients were randomized to receive one of three masked doses of gabapentin (300, 900, or 1,800 mg/day) or open-label carbamazepine (600 mg/day) and kept daily seizure diaries throughout the study. After titration, patients entered a 24-week evaluation phase. Patients were required to exit the study if they experienced an exit event, defined as a total of three simple or complex partial seizures, one generalized tonic-clonic (GTC) seizure, or status epilepticus. Patients could be withdrawn for lack of efficacy, adverse events, or noncompliance. Kaplan-Meier statistics were used to estimate the probability that patients would continue in the study without having an exit event. RESULTS: Time to exit event was longer for patients on 900 mg/day (n = 72) or 1,800 mg/day (n = 74) of gabapentin than for patients receiving 300 mg/day (n = 72; p = 0.0395 and 0.0175, respectively). The most clinically relevant measure of retention on treatment (exit event plus adverse event withdrawal rate) was similar for carbamazepine (n = 74) and 1,800 mg/day gabapentin (54% versus 57%) but was lower (better) for 900 mg/day gabapentin (44%). No unexpected new adverse events emerged with gabapentin monotherapy. CONCLUSIONS: Gabapentin at 900 or 1,800 mg/day is effective and safe as monotherapy for patients with newly diagnosed partial epilepsy.

Gabapentin monotherapy: I. An 8-day, double-blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 88/89.

We evaluated the efficacy and safety of gabapentin administered as monotherapy in an 8-day, randomized, double-blind, dose-controlled, parallel-group, multicenter study comparing dosages of 300 and 3,600 mg/d gabapentin in 82 hospitalized patients whose antiepileptic medications had been discontinued for seizure monitoring. Seizures under study were complex partial seizures with or without secondary generalization. Patients exited the study if they experienced a protocol-defined exit event indicating lack of efficacy. Time to exit was significantly longer (p = 0.0001) and completion rate was significantly higher (53% versus 17%; p = 0.002) for patients receiving 3,600 mg/d gabapentin. Gabapentin was well tolerated by patients in both dosage groups, and no patients exited the study due to adverse events, despite rapid initiation of full dose within 24 hours. These results demonstrate that gabapentin has anticonvulsant activity and is well tolerated when administered as monotherapy in patients with refractory partial seizures.

Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 82/83.

This study evaluated gabapentin monotherapy in 275 patients with medically refractory complex partial or secondarily generalized seizures who were taking one or two antiepileptic drugs (AEDs). Following an 8-week baseline, patients received randomized dosages of gabapentin (600, 1,200, or 2,400 mg/d) during a 26-week double-blind phase comprising 2 weeks gabapentin add-on therapy, an 8-week AED taper, and a 16-week gabapentin monotherapy period. Patients exited the study if they experienced a protocol-defined exit event. Results of outcome measures, including time to exit, completion rate, and mean time on monotherapy, showed no significant differences among dosage groups. Possible reasons for this lack of a dose-response relationship include withdrawal seizures and the limited range of gabapentin dosages studied. Overall, 20% of patients completed the study. Completion rates were higher among patients who had discontinued one AED (23%) than two AEDs (14%), and higher among patients who were not withdrawn from carbamazepine (27%) than among those who were (16%).

Epidermal growth factor and transforming growth factor alpha mRNA expression in human breast cancer biopsies; analysis in relation to estradiol, progesterone and EGF receptor content.

Among the peptide growth factors active in breast glandular cell proliferation epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are thought to play a major role in tumour development. They operate through binding to and activation of a common membrane receptor, defined as EGF-R. Their production is modulated by hormones and local growth factors. After it was shown by previous investigation in this laboratory that EGF-R could be detected in 90% of the tumours, but was masked by endogenous ligand in 36% of them, the question was raised as to the level of the ligand's expression in tumour tissue biopsies. Therefore, we investigated the expression of EGF and TGF alpha mRNA in 146 breast cancer biopsies by slot blot analysis using specific 32P-labelled probes. The data were correlated with sex steroids and EGF receptor content. Our results showed that EGF and TGF alpha coexisted in all tumour samples, and that their level of mRNA expression was similar in half of the tumours. Northern blot and polymerase chain reaction (PCR) analysis validated these findings. A significant direct correlation was found between the level of TGF alpha/EGF mRNA expression and the ER/progesterone receptor (PGR) content. TGF alpha and EGF mRNA levels were significantly higher in ER+ (P = 0.0015 and P = 0.0001, respectively) and in PGR+ tumours (P < 0.005 and P = 0.0001) than in their negative counterparts. Moreover, TGF alpha mRNA expression negatively correlated with the number of EGF-R binding sites measured by the standard method (P = 0.02), and it was significantly related to the number of sites occupied by endogenous ligand. In conclusion, it was shown that TGF alpha and EGF mRNA were coexpressed in all the tumour biopsies tested and that their level was higher in the hormone receptor positive than in negative samples. The correlation between the presence of ER/PGR sites, high level of TGF alpha/EGF mRNA and EGF-R occupancy by endogenous ligand is in favour of ER mediated control of TGF alpha and EGF production.

Influence of the estrous cycle on the action of oxytocin on rat ovarian contractility in vivo.

This investigation was designed to determine the influence of the estrous cycle on the response of ovarian smooth muscle to oxytocin. Muscular activity in vivo was studied by recording intraovarian pressure. Intra-aortic injections of oxytocin were given to the rats at all stages of the estrous cycle. The effect of oxytocin was evaluated by the number of responding ovaries and the magnitude of the responses. According to these parameters, a greater response was observed during proestrus, compared with the other cycle stages. The significance of these results id discussed.