A Structured Training for Trans Anal Irrigation in Pediatric Patients Improves Outcomes and Reduce Failures: Results of an Interventional Multicenter Prospective Study.

BACKGROUND: Continence issues due to organic causes including previous colorectal surgery or neurological issues might benefit from Transanal irrigation (TAI) that proved to be highly effective but with a number of limitations including a relatively high discontinuation rates. Our study was aimed at evaluating the efficacy of an advanced protocol tailored to each patient to prevent dropout and increase satisfaction, independence, and quality of life. MATERIALS AND METHODS: This was a prospective, interventional, multicenter, nonrandomized study involving children aged 4-18 years with bowel dysfunction unresponsive to conventional treatments who required TAI. TAI was performed in accordance to the best standards of care with a total irrigation volume that was determined based on low emission X-Ray barium enemas performed at the very beginning of the study. All patients underwent training and assessments of continence, patients' perspectives and quality of life were performed at different timepoints from enrollment (T0) up to 6 months since TAI was introduced (T3). RESULTS: A total of 78 patients were enrolled. Male to female ratio was 1.4:1. Mean age at enrollment was 106.1 ± 42.8 months. Discontinuation was reported by 3 patients (3.8 %). Continence, satisfaction and a number of other outcome measures increased from baseline (T0) to the last visit (T3). In particular, mean Rintala total score increased linearly from 7.8 to 14.8 during the study period (T0 to T3 timepoints). On a multivariate analysis, the only parameter that proved to be inversely associated with continence as well as with other outcome measures was the use of laxatives at enrollment and during the study. CONCLUSIONS: This study has demonstrated the high efficacy of this innovative patient-tailored TAI protocol across all assessed scores. Of note, given the negative impact of laxatives, our findings suggest limiting their use in this patient population to further increase the efficacy of the procedure.

Cochlear implantation in single-sided deafness: a single-center experience of 138 cases.

OBJECTIVES: Assess the outcomes in patients who underwent cochlear implant (CI) for single-sided deafness (SSD). METHODS: All patients affected by SSD who underwent CI at Gruppo Otologico, Piacenza, from October 2012 to May 2022 with at least 6 months of follow-up were selected in the study group. The analysis included subjective and objective measures performed pre-operative and up to 24 months after surgery. Hearing threshold on both sides was evaluated with a weighted four-frequency average (PTA [0.5 kHz + 1 kHz + 2 kHz + 4 kHz]/4) on pure tone audiometry and speech audiometry (Speech Discrimination Score, SDS). The Speech Spatial and Qualities of Hearing scale (SSQ Questionnaire) for binaural hearing benefits and sound localization, the Tinnitus Handicap Inventory Questionnaire (THI) and Dizziness Handicap Inventory Questionnaire (DHI) were used for subjective assessment. RESULTS: Data from 138 patients, 69 males and 69 females, (mean age 49 years, range 17-77 years) underwent CI for SSD were examined. Single-sided hearing deprivation average before undergoing CI surgery was 2.5 years (range 3 months-35 years). There was a significant reduction of THI and DHI scores compared to pre-operative scores alongside a referred improvement in social, physical, and emotional well-being through the SSQ questionnaire. CONCLUSIONS: To the best of our knowledge, this paper descried the largest cohort of SSD who underwent CI in a single institution. According to our findings CI in patients affected by SSD represents a valuable tool for an overall improvement of tinnitus and dizziness but also quality of life, after at least 6 months of follow-up. Further studies are desirable to improve rehabilitation pathways and possibly set new standards of care of this condition.

Holmium Intraductal Laser Lithotripsy of Biliary Stones in Liver Grafts.

BACKGROUND: Biliary stones after liver transplantation (LT) rarely occur but a focus on those complications and their treatment is needed. PATIENTS AND METHODS: In total, 390 adult patients who underwent an LT from July 2004 to July 2014 entered the study. Biliary complications and notably biliary stones after LT were identified. RESULTS: In total, 365 LT were analyzed. Biliary stones were identified in 14 patients (3.8%). Predictive factors for the onset of biliary stones after LT were hepatocellular diseases (P = .038; OR = 9.7) and biliary stenosis (P = .000; OR = 11.9). Treatments consisted of percutaneous transhepatic procedures (4 patients), endoscopic retrograde procedures (9 patients), and in open surgery (1 case); in 2 cases, due to a failure of previous treatments, holmium intraductal laser lithotripsy (HILL) was used: the first patient, a 35-year-old woman developed multiple intrahepatic biliary stones after LT. Percutaneous transhepatic cholangiography (PTC) was ineffective and a HILL was performed, clearing the right common bile duct but leaving residual stones in the left duct. The patient underwent a retransplantation due to recurrent hepatitis C virus infection but died 3 months later because of graft failure. The second patient, a 42-year-old 14 years after retransplantation, developed biliary sludge and stones; after several attempts with PTC and endoscopic retrograde cholangiopancreatography, a HILL was performed. All stones except one big one were treated. The patient is alive and well. CONCLUSIONS: When usual treatments are unsuccessful and biliary stones are large, their fragmentation and treatment could be done with HILL, a promising procedure after LT.

Prognostic evaluation of biofeedback response in patients treated for anorectal malformation.

PURPOSE: Functional bowel outcome in patients with anorectal malformation often is poor. For fecal incontinence resulting from sphincter dysfunction, biofeedback (BFB) training appears to be effective. The aim of study was to investigate the bowel function in incontinent children treated for ARM, using a clinical score, a manometric and pelvic magnetic resonance evaluation, in order to establish predictive parameters of response after BFB. METHODS: 25 children (median age of 6.5 years) with true fecal incontinence were evaluated by clinical score, anorectal manometry and magnetic resonance imaging (MRI). According to these evaluations patients were divided in 4 groups: group 1 (favorables manometry and MRI); group 2 (favorable manometry and unfavorable MRI); group 3 (unfavorable manometry and favorable MRI); group 4 (unfavorables manometry and MRI). All groups started a cycle of BFB and six months after end of BFB, were reevaluated by clinical score and manometry. RESULTS: The overall response to BFB was excellent in 44%, discrete in 40% and poor in 16%; a better response was found in groups 1 and 2 than groups 3 and 4. The differences between groups before BFB proportionally correlated with values after BFB; a correlation with genitourinary and spinal anomalies was found. CONCLUSIONS: Our results showed that BFB is an effective for fecal incontinence when the assessment pretreatment (functional and morphologic) is favorable; the manometry can evaluate the potential sphincterial recovery after BFB with a further prognostic benefit if correlated to morphologic evaluation with MRI.

The lipid theory in the pathogenesis of calcific aortic stenosis.

AIMS: Biologically active phenomena, triggered by atherogenesis and inflammation, lead to aortic valve (AV) calcification. Lipids play an important role in activating the cell signaling leading to AV bone deposition. This review, based on evidence from animal and human studies, mainly focused on the involvement of lipids and atherogenic phenomena in the pathogenesis of calcific aortic stenosis (AS). DATA SYNTHESIS: The role of elevated low density lipoproteins for the risk of both vascular atherosclerosis and AS has been elucidated. Lipid disorders act synergistically with other risk factors to increase prevalence of calcific AS. Atherosclerosis is also involved in the pathogenesis of bone demineralization, a typical hallmark of aging, which is associated with ectopic calcification at vascular and valvular levels. Animal studies have recently contributed to demonstrate that lipids play an important role in AS pathogenesis through the activation of molecular cell signalings, such as Wnt/Lrp5 and RANK/RANKL/Osteprotegerin, which induce the transition of valvular myofibroblasts toward an osteogenic phenotype with consequent valvular bone deposition. Although all these evidence strongly support the lipid theory in AS pathogenesis, lipids lowering therapies failed to demonstrate in controlled trials a significant efficacy to slow AS progression. Encouraging results from animal studies indicate that physical activity may counteract the biological processes inducing AV degeneration. CONCLUSIONS: This review indicates a robust interplay between lipids, inflammation, and calcific AS. This new pathophysiological scenario of such an emerging valvular disease paves the way to the next challenge of cardiovascular research: "prevent and care aortic valve stenosis".

Detection of KI WU and Merkel cell polyomavirus in respiratory tract of cystic fibrosis patients.

In the last few years, many reports have confirmed the presence of WU, KI and Merkel cell (MC) polyomaviruses (PyV) in respiratory samples wordwide, but their pathogenic role in patients with underlying conditions such as cystic fibrosis is still debated. To determine the prevalence of MCPyV, WUPyV and KIPyV, we conducted a 1-year-long microbiological testing of respiratory specimens from 93 patients with cystic fibrosis in Brescia, Italy. We detected PyV DNA in 94 out of 337 analysed specimens. KIPyV was the most common virus detected (12.1%), followed by WUPyV (8.9%) and MCPyV (6.8%). We found an intriguing association between the presence of MCPyV and the concurrent isolation of Pseudomonas aeruginosa, as well as with the patient status, classified as chronically colonized with P. aeruginosa. Our study adds perspective on the prevalence and the potential pathogenic role of PyV infections.

A specific Toll-like receptor profile on T lymphocytes and values of monocytes correlate with bacterial, fungal, and cytomegalovirus infections in the early period of allogeneic stem cell transplantation.

BACKGROUND: Bacterial, fungal, and viral infections often affect non-relapse mortality after allogeneic stem cell transplantation (alloSCT). Recovery from infections depends on a balanced integration between innate and adaptive immune responses. In this complex interplay, a key role is played by Toll-like receptors (TLRs), which are sensors of pathogen-associated molecular patterns. To our knowledge, no previous study deals with both expression and function of all human TLRs together, in relation to infections in the setting of alloSCT. METHODS: We prospectively evaluated 9 TLRs by flow cytometry on T lymphocytes and monocytes of 35 patients in relation to infectious events from day +30 to day +120. Tumor necrois factor-alpha, interleukin-4, interferon-gamma, and monocyte chemoattractant protein-1 induction upon TLR activation was assessed by enzyme-linked immunosorbent assay on cell supernatants. RESULTS: In multivariate Cox regression analysis, levels of TLR-9 expression on T lymphocytes (P = 0.01) and values of natural killer cells (P = 0.01) correlated negatively with bacterial infections, whereas cytomegalovirus (CMV) infection resulted as a positive predictor. We observed a trend for negative correlation between TLR-7 levels on T lymphocytes and fungal infections (P = 0.07). Values of monocytes were negatively associated with CMV infection (P = 0.03), whereas levels of TLR-5 on T lymphocytes were positive predictors (P = 0.01). Age (P = 0.03) and bacterial infections (P = 0.006) negatively influenced overall survival. Monocyte values were positive predictors of survival (P = 0.003). CONCLUSIONS: Bacterial, fungal, and CMV infections were associated with a different expression of some TLRs on T lymphocytes. The protective role of TLR-7 and TLR-9 seemed dominant over other TLRs involved in recognizing fungi and bacteria. We also observed an atypical involvement of TLR-5 in CMV infection. The dominant and atypical role of some TLRs could depend on their pleiotropic functions and the changing inflammatory environment of transplanted patients. A specific TLR profile and an adequate count of monocytes could improve survival, promoting an effective control of infections, and balanced immune responses. If our findings will be confirmed by further studies, these immunological variables could be useful as parameters to predict susceptibility to infections.

Listeria monocytogenes brainstem infection (rhombencephalitis) mimicking ischemic stroke.

The frequency of Listeria monocytogenes (Lm) infection of the central nervous system is increasing. We report a patient recently treated with chemotherapeutic drugs for pulmonary adenocarcinoma who suddenly developed hemiparesis, was initially diagnosed with stroke, and was then found to be affected by Lm rhombencephalitis accompanied by a brain abscess. Lm meningoencephalitis mimicking ischemic stroke is rare but must be considered, especially in specific patients.

Radiofrequency ablation for chronic radiation proctitis: our initial experience with four cases.

BACKGROUND: Chronic radiation proctitis (CRP) occurs up to 20 % of patients after pelvic radiotherapy, with rectal bleeding as the main presenting complaint. Radiofrequency ablation (RFA) has recently been used in the management of Barrett's esophagus, but its efficacy in CRP has to be studied. The aim of this case series was to describe four cases of patients with CRP treated with RFA that demonstrate the efficacy and safety of the technique. METHODS: All the procedures were performed with HALO 90 or HALO 90 Ultra ablation catheter fitted on the distal end of a standard flexible endoscope. For each patient, the severity of symptoms was assessed at baseline and after the last treatment session. RESULTS: At least two sessions of RFA (maximum 4) were necessary, at three-month intervals, to completely control the symptoms. No major complications were observed. CONCLUSIONS: RFA was effective and safe for control bleeding in this case series. Adequately powered randomized controlled trials are needed to establish the safety and efficacy of RFA for CRP.

The immunomodulatory molecule pidotimod induces the expression of the NOD-like receptor NLRP12 and attenuates TLR-induced inflammation.

Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4-carboxylic acid) (PDT) is a synthetic dipeptide with in vitro and in vivo immunomodulatory properties that is largely used for treatment and prevention of infections in paediatric and disease-prone patients. However, the effects of PDT on cellular immune responses are still poorly characterized and there is little information on the mechanism of action of this compound. It has been speculated that PDT action may be exerted through the interaction with a Pattern Recognition Receptor (PRR). Therefore, to gain a further understanding of the immune pathways involved by PDT, we first decided to investigate whether PDT could modify the immune response triggered by TLR ligands. Monocytic cells were exposed to PDT then stimulated with a panel of TLR agonists. Under these experimental conditions, we observed a significant decrease in the synthesis of key proinflammatory mediators in comparison to the production observed in TLR-stimulated cells that were not treated with PDT. Using RT² Profiler PCR Array we have observed that PDT specifically up-regulates the expression of the NOD-like receptor NLRP12 mRNA in the absence of any further costimulation. Increase of NLRP12 in cells treated with PDT was confirmed using specifically designed real-time quantitative PCR and western blotting assays where a clear increase in the amount of NLRP12 protein was detected. Furthermore, in myeloid/monocytic cells we demonstrated that PDT treatment counteracts the NLRP12 reduction induced by TLR agonists. Finally, the results obtained using NLRP12 silenced cells showed that down-regulation of the proinflammatory function occurring in PDT-treated cells upon interaction with TLRs is associated with the increased levels of NLRP12 induced by PDT. To our knowledge this is the first evidence of an immunomodulatory peptide that upregulates NLRP12 and, through this molecule, antagonizes the TLR-induced inflammatory response. These results pave the way for the development of innovative therapeutic approaches aimed at controlling different pathological settings such as tumorigenesis, systemic inflammatory processes and autoimmunity, where NLRP12 plays a crucial role.

The psychological impact of breast and ovarian cancer preventive options in BRCA1 and BRCA2 mutation carriers.

This study was performed to describe the impact of preventive options on the psychological condition of BRCA1/BRCA2 carriers. A sample of 52 cancer-affected (C-A) and 27 cancer-unaffected (C-UN) women were enrolled after gene test disclosure (T0). Psychological evaluations were performed at T0 and 15 months later (T1). The surgical options were more likely to be chosen in C-A women (62%), although a consistent proportion of C-UN women (30%) also opt for these preventive measures. At the baseline, both samples had average anxiety and depression scores below the cut-off value, restrained average cancer worry scores and a risk perception consistent with the risk percentage provided during genetic counselling. The longitudinal results indicated no clinically meaningful variations in the anxiety and depression scores in either of the two samples. Statistically significant reductions in cancer-risk perception emerged in women who chose surgery in both C-A and C-UN women. In BRCA1/BRCA2 mutation carriers, surveillance does not influence their initial psychological condition, whereas prophylactic surgery has a significant impact in reducing the perceived risk and worry about getting sick. C-A and C-UN women have to be considered as two separate populations of BRCA mutation carriers requiring personalized approaches to risk management.

Fetal cystic hygroma: the importance of natural history.

OBJECTIVES: To evaluate the natural history of cystic hygroma (CH) in fetal and neonatal periods to enrich parental counselling. Ultrasonographic characteristics, associated syndromes, chromosomal anomalies, fetal cardiac pathology and life after birth were considered. STUDY DESIGN: From May 1985 to September 2010, 207 pregnancies were seen the authors' centre with suspected vascular-lymphatic fetal malformation: 156 of them had CH. Cases were followed up by telephone interview to determine fetal and neonatal outcomes. Chi-squared test was used for statistical analysis. RESULTS: Among the 156 cases of CH, the condition was septated in 75% of cases, associated with other pathologies in 74%, and retronuchal in 88%. Intrauterine regression was seen in 36% of cases, with complete disappearance in 77%. The karyotype was normal in 55% of cases. Follow-up was completed in 85 cases and revealed 54 spontaneous abortions (63%) and 31 live births (37%). Amongst these, 21 out of 31 children had a favourable outcome (68%). A negative embryo-fetal outcome was significantly associated with CH being associated with other pathologies, such as hydrops, retronuchal position and altered karyotype. Spontaneous regression or resolution of CH was associated with live births. CONCLUSIONS: The management of pregnancies with a diagnosis of fetal CH requires knowledge of natural history of the malformation for appropriate parental counselling.

Adenoma, advanced adenoma and colorectal cancer prevalence in asymptomatic 40- to 49-year-old subjects with a first-degree family history of colorectal cancer.

AIM: First-degree relatives (FDRs) of patients with colorectal cancer (CRC) have an increased CRC risk. Few studies have addressed if adenoma and advanced adenoma risk is increased among individuals, 40-49 years of age, with a family history of CRC. Therefore, the aim of the study was to define the prevalence and location of adenoma, advanced adenoma and CRC, according to age, in asymptomatic individuals with a family history of CRC. METHOD: Retrospective study of asymptomatic FDRs, 40 to ≥70 years of age undergoing first screening colonoscopy over a 3-year period, of CRC patients. RESULTS: Among 464 individuals studied, the prevalence of adenoma and advanced adenoma was 18.1% and 6.4%, respectively. According to age intervals, the prevalences of adenoma and advanced adenoma were 14% and 3.5%, respectively, in subjects 40-49 years of age; 14.4% and 6.3%, respectively, in subjects 50-59 years of age; 27% and 8%, respectively, in subjects 60-69 years of age; and 25% and 14%, respectively, in subjects ≥70 years of age; no significant difference was found among the four groups. No difference in lesion location was found, with similar numbers of preneoplastic lesions being present in the right colon and the left colon. CRC was diagnosed in three (0.64%) subjects, one of whom was in the 40-49 years age group. CONCLUSION: In our population of FDRs of CRC patients, 40-49 years of age, the prevalences of adenoma and advanced adenoma were similar to those observed in older subjects with the same CRC risk. Our data support the current indication to perform screening colonoscopy earlier than 45 years of age in subjects at high CRC risk.

Potential neurodegenerative effect of anabolic androgenic steroid abuse.

Anabolic androgenic steroids (AASs) are synthetic androgen-like compounds which are abused in sport communities despite their side effects. AAS abuse has been coupled with several medical complications, such as sterility, gynecomastia, and increased risk of cardiovascular and hepatic diseases. More recently, it has been observed that non-medical use of these steroids is frequently associated with changes in mood as well as cognitive deficits. Although the nature of this association is still largely unexplored, recent animal studies have shown the neurodegenerative potential of these compounds ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Hence, exposure to AASs may result in a compromised brain, more susceptible, later in life, to the onset or progression of diseases not usually linked to drug abuse, especially neurodegenerative diseases.

Bladder function after spinal anesthesia for cesarean section: an urodynamic evaluation.

BACKGROUND: This study evaluates the effects of spinal anesthesia with hyperbaric bupivacaine plus sufentanil on bladder function in women undergoing cesarean section. SUBJECTS AND METHODS: Thirty caucasian healthy pregnants scheduled for elective Cesarean section under spinal anesthesia performed with hyperbaric bupivacaine plus sufentanil were enrolled. Filling cystometry, proprioceptive bladder sensation during cystometry, rate of spontaneous voiding, post void residual volume, anocutaneous and bulbocavernosus reflex were analyzed at 4, 6 and 8 hours after spinal anesthesia. RESULTS: The proportion of women experiencing first sensation, first desire and strong desire at 4 hours was significantly different from that reported at 6 and 8 hours (p < 0.05 for first sensation and p < 0.01 for first and strong desire). Significant differences were also observed between volumes at which first sensation arose at first measurement (4 hours) and at second and third measurements (p < 0.01). There was a significant difference in rate of spontaneous micturition, with 80% of patients at 8 hours able to spontaneously void versus 40% at 6 hours, (p < 0.01). Moreover, a lower percentage of women had absent and/or light reflexes at 4 hour than at 6 and 8 hours (p < 0.01). CONCLUSIONS: Spinal anesthesia with bupivacaine plus sufentanil causes a clinically significant disturbance on bladder function in women undergoing cesarean section. Even thought recovery of proprioceptive bladder sensation is fast, a full recovery of spontaneous voiding requires a much longer time. A close monitoring of urinary function and of bladder distension is, therefore, advisable.

Sarcoidosis and multiple sclerosis: systemic toxicity associated with the use of interferon-beta therapy.

Sarcoidosis is a multi-systemic inflammatory disease of unknown origin characterized by the presence of noncaseating epitheloid cell granulomas in multiple organs. Diagnosis is made on the basis of a compatible clinical-radiological scenario and the histological demonstration of the typical granulomas in the affected tissues. Interferons are immuno-modulators that have been used in a wide range of diseases, including hepatitis C virus infection, multiple sclerosis, and multiple myeloma and other types of tumours, including leukemia, lymphomas, Kaposi's sarcoma, and melanoma. Interferon-alpha-induced sarcoidosis has been reported repeatedly and there are two reports in the literature of cases of pulmonary sarcoidosis treated with interferon-1b therapy: one for advanced renal cell carcinoma and the other for multiple myeloma. A 35-year-old man on chronic immune-modulant Interferon-1b-based therapy for multiple sclerosis presented to the Neurology Unit with mild dyspnoea, dry cough, and transient pain to right upper abdomen. Lungs, spleen, liver, and almost all lymphnode stations of abdomen and mediastinum were clearly involved on ultrasound examination, chest X-ray, and computed tomography. A transbronchial biopsy showed non-caseating granuloma on histopathologic evaluation of the lungs. To the best of our knowledge, this is the first report of a chronic multisystemic sarcoidosis that was associated with interferon-beta treatment.

Anti-inflammatory effect of 3,4-DHPEA-EDA [2-(3,4 -hydroxyphenyl) ethyl (3S, 4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] on primary human vascular endothelial cells.

Diets in which fat is significantly provided by olive oil and are relatively rich in vegetables, have been associated with a low incidence of cardiovascular diseases, mostly due to the presence of several phenolic compounds which have anti-oxidant and antiinflammatory properties. [1]. In this work, we describe the anti-inflammatory effect of 3,4-DHPEA-EDA in a cell model that we developed to mimic inflammatory injury of endothelium. This was based on the production of the proinflammatory chemokine CCL2, following in vitro stimulation of primary human endothelial cells. Pre-treatment of cells with 3,4-DHPEA-EDA resulted in a dose-dependent inhibition of CCL2 secretion. The effect of 3,4-DHPEA-EDA on CCL2 expression was observed at the transcriptional level. Functional data have shown that 3,4-DHPEA-EDA diminished monocyte adhesion to HUVECs. These results point on the use of 3,4- DHPEA-EDA as a novel drug aimed to prevent or reduce inflammation of endothelium.