Cerebral cortical thickness and gyrification changes in first-episode psychoses and multi-episode schizophrenia.

Cortical thickness (CT) and local gyrification index (LGI) in psychotic disorders may show modifications that relate to clinical course. This observational study aimed to analyse such variables in patients with schizophrenia, compared to healthy controls (HCs). We compared CT and LGI of 18 patients with first-episode psychosis with that of 21 with multi-episode schizophrenia and 16 HCs. CT corrected for false-positive cases (Family-Wise Error Rate) showed a reduction in the multi-episode group compared to HCs in left temporal and parietal, and right temporal, parietal, occipital, and hippocampal cortices. Family-wise corrected LGI was increased in the left inferior and middle frontal cortices, and in the right fusiform gyrus, cingulate, lingual, and parahippocampal gyri in first onset patients compared to HCs. Increased LGI was absent from later stages of psychosis, suggesting that specific CT and LGI alterations may underlie different stages of illness.

Metabarcoding analysis of gut microbiota of healthy individuals reveals impact of probiotic and maltodextrin consumption.

In a previously published double-blind, placebo-controlled study, we showed that probiotics intake exerted a positive effect on sleep quality and a general improvement across time in different aspects of the profile of mood state, like sadness, anger, and fatigue in 33 healthy individuals. The present work investigates the impact of the probiotic product, constituted of Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01 (all former members of Lactobacillus genus), and Bifidobacterium longum 04, on the gut microbiota composition of the same cohort through a metabarcoding analysis. Both the placebo and probiotic treatments had a significant impact on the microbiota composition. Statistical analysis showed that the microbiota of the individuals could be clustered into three groups, or bacteriotypes, at the baseline, and, inherently, bacterial compositions were linked to different responses to probiotic and placebo intakes. Interestingly, L. rhamnosus and L. fermentum were retrieved in the probiotic-treated cohort, while a bifidogenic effect of maltodextrin, used as placebo, was observed. The present study shed light on the importance of defining bacteriotypes to assess the impact of interventions on the gut microbiota and allowed to reveal microbial components which could be related to positive effects (i.e. sleep quality improvement) to be verified in further studies.

Single-Scaffold Genome Sequence of Probiotic Strain Bifidobacterium breve BR03 (DSM 16604), Obtained by Combining Hybrid Sequencing and Optical Mapping.

Bifidobacterium breve BR03 (DSM 16604) is known for its health-promoting activity. We present a single-scaffold genome obtained by using a hybrid approach combining long- and short-read sequencing techniques integrated by an optical map. This approach could be set as an industry standard for probiotic strain characterization.

Neural functional correlates of emotional processing in patients with first-episode psychoses: an activation likelihood estimation (ALE) meta-analysis.

BACKGROUND: Early emotional recognition impairment characterises rst-episode psychoses (FEP) and remains stable thereafter. Patients with FEP consistently show brain activation changes during emotional processing in functional neuroimaging studies. AIM AND METHODS: To identify and compare cerebral activation correlates of FEP patients and healthy controls (HCs) during emotional task performances, we performed an Activation Likelihood Estimation (ALE) meta-analysis of peer-reviewed functional magnetic resonance imaging (fMRI) studies. RESULTS: Five studies included 71 patients with FEP and 75 HCs. Within-group analyses showed that HCs activated during emotional task performance the bilateral inferior parietal lobule (BAs 39 and 40), left inferior frontal gyrus (BAs 9 and 47), right amygdala, left middle frontal gyrus (BA 9), right cingulate gyrus (BA 32), and right middle temporal gyrus (BA 21). FEP activations correlating with emotional tasks included the right cuneus (BA 17) and right angular gyrus (BA 39). CONCLUSIONS: During emotional task performance, FEP patients fail to activate an extensive brain network comprising emotional processing-related areas, including both cortical and subcortical areas.

Prediction of acute pancreatitis risk based on PIP score in children with cystic fibrosis.

BACKGROUND: Currently no tools to predict risk of acute (AP) and recurrent pancreatitis (ARP) in children with cystic fibrosis (CF) are available. We assessed the prevalence of AP/ARP and tested the potential role of Pancreatic Insufficiency Prevalence (PIP) score in a cohort of children with CF. METHODS: We identified two groups of children, on the basis of presence/absence of AP/ARP, who were compared for age at diagnosis, clinical features, genotypes and sweat chloride level. PIP score was calculated for each patient. RESULTS: 10/167 (5.9%) experienced at least one episode of AP during follow up; 10/10 were pancreatic sufficient (PS). Patients with AP/ARP showed a PIP score ≤0.25 more frequently (6/10) than patients without AP/ARP. The odds ratio (95% CI) of developing pancreatitis was 4.54 (1.22-16.92) for patients with PIP <0.25 when compared with those who have a PIP score >0.25 (p 0.0151). PIP score was correlated with sweat chloride test (p < 0.01). CONCLUSION: PIP score, PS status and normal/borderline sweat chloride levels could be applied to predict pancreatitis development in children with CF. ARP could lead to pancreatic insufficiency.

Brand new SPINK1 and CFTR mutations in a child with acute recurrent pancreatitis: a case report.

We report a case of a 2,5 years old female, referred to our center for pancreatitis. Medical investigation revealed history of acute recurrent pancreatitis (ARP) since 1 year of age. Family history was negative for pancreatitis. Abdominal ultrasonography and magnetic resonance excluded both biliary tract stenosis and anatomic abnormalities. Calcium metabolic disorders, viral and bacterial infections were ruled out. Molecular sequencing of CFTR revealed heterozygosis for the mutation S1235R, a CFTR-related disorders associated mutation. Fecal elastase-1 (E1) was 529 µg/gr feces (normal value 200-500 µg/gr feces). No mutation of PRSS1 gene was detected but heterozygosity for p.Lys41Asn (c.123G>C), a new mutation of SPINK1 gene, was revealed. We speculate that the association of both SPINK1 and CFTR gene mutations may be responsible of ARP in our patient. Further studies need to better elucidate the role of genetic factors in ARP, as well as the influence of environmental factors.

Phase II study on lapatinib in advanced EGFR-positive chordoma.

BACKGROUND: To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients. PATIENTS AND METHODS: From December 2009 to January 2012, 18 advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phospho-arrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) ≥ 6 months). RESULTS: All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12) months, with a 22% CBR. CONCLUSIONS: This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29.

Functional neuroimaging in obsessive-compulsive disorder.

BACKGROUND AND AIM: Obsessive-compulsive disorder (OCD) is a severe, highly prevalent and chronically disabling psychiatric disorder that usually emerges during childhood or adolescence. This paper aims to review the literature on functional neuroimaging in OCD, analysing the reported dysfunctional connectivity in the corticostriatothalamocortical circuitry. METHOD: This study included papers published in peer-reviewed journals dealing with functional imaging in OCD. RESULTS: Striatal dysfunction, mainly of the caudate nucleus, leads to inefficient thalamic gating, resulting in hyperactivity within the orbitofrontal cortex (intrusive thoughts) and the anterior cingulate cortex (non-specific anxiety). Compulsions consist of ritualistic behaviours performed to recruit the inefficient striatum and neutralise unwanted thoughts and anxiety. Functional neuroimaging findings are discussed against the background of specific cognitive impairments, mainly regarding visuospatial processing, executive functioning and motor speed. Cognitive deficits are partial and specific, matching imaging data. CONCLUSIONS: Several studies have targeted brain regions hypothesised to be involved in the pathogenesis of OCD, showing the existence of dysfunctional connectivity in the corticostriatothalamocortical circuitry. Improvements in spatial resolution of neuroimaging techniques may contribute to a better understanding of the neurocircuitry of OCD and other anxiety disorders.

Duloxetine versus venlafaxine in the treatment of unipolar and bipolar depression.

OBJECTIVES: Both duloxetine and venlafaxine are efficacious in treating patients with Major Depressive Disorder (MDD), even though the advantages in treatment patients with bipolar disorder is unclear. This study aimed to evaluate the efficacy of duloxetine vs venlafaxine in the acute treatment of unipolar and bipolar depression. MATERIALS AND METHODS: The study was a non randomized controlled trial. The participants were 62 consecutive outpatients (41 men; 21 women) affected by unipolar and bipolar depression treated either with duloxetine and venlafaxine. RESULTS: More patients treated with duloxetine had a positive response to treatment and remission both for depression (HAMD17 response: 90.3% vs 0.0%; p < .001; HAM-D17 remission: 48.4% vs 0.0%; p < .001), and anxiety (HAM-A response: 90.3% vs 6.5%; p < .001; HAM-A remission: 71.0% vs 6.5%; p < .001) than controls. Patients treated with duloxetine were also more likely to show a decrease in HAM-D17 suicidality (100% vs 45.2%; p less than .001) and an increase in the quality of life (SF-36 percentage of improvement: 6.35 [SD=9.66 vs -2.58 [9.98]; p less than .001) than controls. CONCLUSIONS: Duloxetine is more effective in reducing anxiety and suicidal ideation. Both treatments were safe and tolerated, and both may be successfully used in unipolar and bipolar depression.

ProvenCare: quality improvement model for designing highly reliable care in cardiac surgery.

OBJECTIVE: To test whether an integrated delivery system could, through the application of process redesign methodology and reliability science, implement multiple evidence-based medical practices across the continuum of care for a specific surgical intervention and deliver these practices consistently. METHODS: The programme-ProvenCare--had three components: establishing best practices for elective coronary artery bypass graft (CABG) patients; assembling a multidisciplinary team to "hardwire" these best practices into everyday workflow; and implementing the programme with real-time data collection, feedback and focused redesign to reach high reliability. Surgeons reviewed all class I and IIa 2004 ACC/AHA guidelines for CABG surgery and translated them into 19 clinically applicable recommendations. A frontline multidisciplinary team "hardwired" these, resulting in 40 measurable process elements. Feedback of gaps in care was given and the process redesigned as needed. Clinical outcome data on consecutive elective CABG patients seen in the 12 months pre-intervention were then compared with a post-intervention group. RESULTS: Initially, 59% of patients received all 40 elements. At 3 months, compliance reached 100%, fell transiently to 86% and then reached 100% again, and was sustained for the remainder of the study. The overall trend in reliability was significant (p = 0.001). 30-day clinical outcomes showed improved trends in 8/9 measured areas (eg, patient readmissions to ICU decreased from 2.9% to 0.9% and blood products usage decreased from 23.4% to 16.2%). Operative mortality decreased to zero, but only likelihood of discharge was significant (p = 0.033). Frequency and length of readmissions fell, as did mean hospital charges. CONCLUSION: Frontline medical care providers, led by process design specialists, can successfully redesign episodic processes to consistently deliver evidence-based medicine, which may improve patient outcomes and reduce resource use.

[Predicting risk of suicide in bipolar and unipolar depression: correlation between temperament and personality]. / Prädiktion des Suizidrisikos bei bipolar und unipolar depressiven Patienten: Wechselwirkung von Temperament und Persönlichkeit.

OBJECTIVE: The aim of this study was to evaluate the roles of personality and affective temperament traits in the prediction of suicide risk in mood disorders. METHODS: The participants were 147 psychiatric inpatients with bipolar disorders I and II and major depressive disorder. Patients undertook the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego self-rating questionnaire, the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), and the Beck Hopelessness Scale. RESULTS: Sixty-four subjects were diagnosed with increased suicidal risk based on the Mini International Neuropsychiatric Interview (MINI). Logistic regression analysis resulted in two models predictive of MINI-based suicidal risk: irritable temperament and the MMPI-2 scale. Multiple regression analysis further indicated that higher hyperthymic values are protective against hopelessness, while MINI-based suicidal intent is a predictor of hopelessness. CONCLUSIONS: Personality and affective temperament traits may have a role in the prediction of suicide.

Development of an objective score to quantify the pediatric cystometrogram.

PURPOSE: We developed a reliable tool for quantitative assessment of the pediatric cystometrogram. MATERIALS AND METHODS: Scores for expected capacity (EV), compliance (EV20), activity and sensation were developed according to established formulas for norms. Ordinal scores were derived by calculating observed over expected findings. Based on the derived percents scores of 1 to 5 were assigned. For EV--0 to 5 the formula used was EV = (age + 2) x 30 and for EV20--0 to 5 the formula used was EV20 = 17 x age + 55. Activity was determined as the volume of the first, total number and magnitude of involuntary contractions, each scored 0 to 5 and divided by 3. Sensation was scored as 0 to 3 according to volume at first sensation. A total of 87 blinded cystometrograms in 49 patients were independently scored twice by 3 pediatric urologists. The resultant 522 total and 2,088 component scores were assessed for reliability. RESULTS: Intrarater reliability was strong with 80% of total scores (208 of 261) within +/- 1 point from initial to subsequent retest. Reliability component scores were stronger with 94% (983 of 1,044) within +/- 1 point from test to retest. Spearman's rank correlations for total score was 0.82 to 0.98, indicating a strong relationship between test and retest. Interrater reliability of components was strong with 89% of scores (1,851 of 2,088) between urologists within +/- 1 point. Correlation coefficients for total scores were 0.80 to 0.96, indicating a high degree of consistency between urologist assessments (p <0.05). CONCLUSIONS: This score appears to reliably quantify the pediatric cystometrogram. Its application may be useful for the objective assessment of detrusor behavior before and after intervention. Further applications should allow refinement of this tool.

Use of the mobilized sinus with total urogenital mobilization.

PURPOSE: The surgical treatment of urogenital sinus anomalies has undergone significant advances in recent years. Total urogenital mobilization, which mobilizes the urogenital sinus, vagina and urethra en bloc toward the perineum, represents one of these advances. MATERIALS AND METHODS: We have improved our results with total urogenital mobilization by incorporating the mobilized urogenital sinus tissue into the repair rather than discarding it, as described originally. We have found this a readily available, easily manipulated and well vascularized flap that is a significant aid to reconstruction. RESULTS: We present our 3 favored means of using the mobilized sinus tissue to create a mucosa lined vestibule, a posterior vaginal wall flap and an anterior vaginal wall flap. CONCLUSIONS: We believe that our techniques result in a further advancement in the cosmetic and surgical outcomes in these patients, and are beneficial in the reconstructive surgery armamentarium.

Total continence reconstruction: a comparison to staged reconstruction of neuropathic bowel and bladder.

PURPOSE: Surgical treatment for neuropathic bowel and bladder has become an essential tool in maximizing the quality of life in patients with myelomeningocele. We present our results comparing results in patients who underwent total continence reconstruction of the urinary and gastrointestinal tracts to patients who underwent a separate or single operation. MATERIALS AND METHODS: We performed a retrospective chart review of all patients with myelomeningocele at our institution who underwent reconstruction with a cutaneous catheterizable urinary channel or Malone antegrade continence enema. We compared outcomes with regard to surgical revisions of the channel between patients who underwent the construction of each simultaneously, that is total continence reconstruction, to outcomes in those with a single channel or who underwent reconstruction at 2 or more operations. RESULTS: Most of our patients underwent genitourinary and gastrointestinal reconstruction, and few desired surgical intervention for only a single system. We were unable to find any differences in the continence rate or stomal complications. However, patients who underwent staged reconstruction usually had significant secondary reasons for repeat surgery. CONCLUSIONS: Surgical success for urinary and fecal continence can be safely and effectively achieved through single or multiple procedures. However, because of shared pathophysiology, we believe that most patients benefit from intervention in the gastrointestinal and the genitourinary tract. Therefore, a major advantage of total continence reconstruction is avoidance of the morbidity of a second major surgical procedure.

What is the need for additional bladder surgery after bladder augmentation in childhood?

PURPOSE: Bladder augmentation has revolutionized the care of children with a neuropathic bladder but it remains a major surgical procedure. However, the need for subsequent bladder surgery has not been well defined in a large series with long-term followup. MATERIALS AND METHODS: We retrospectively reviewed the records of the first 500 bladder augmentations performed from 1978 to 2003 at our institution. Charts were reviewed for complications requiring additional surgery, including malignancy, bladder perforation, repeat augmentation, bowel obstruction and bladder calculi. Mean and median followup was 13.3 years. RESULTS: Complications occurred in 169 patients (34%) resulting in a total of 254 surgeries. The cumulative risk of further surgery at the bladder level was 0.04 operations per patient per year of augmentation. Three patients (0.6%) had transitional cell carcinoma, of whom all presented with metastatic disease and died. Bladder perforation occurred in 43 patients (8.6%) with a total of 53 events. Of the patients 16 (3.2%) required laparotomy for bowel obstruction and 47 (9.4%) required repeat augmentation. Bladder stones were treated in 75 patients (15%), who required a total of 125 surgeries. CONCLUSIONS: Bladder augmentation provides immeasurable improvements in quality of life but it requires lifelong dedication from the patient, family and health care providers. While the requirements for additional surgery are not trivial, 66% of our patients have not required any further surgery in the augmented bladder.

Treatment of the occult tethered spinal cord for neuropathic bladder: results of sectioning the filum terminale.

PURPOSE: Occult tethered cord syndrome applies to patients with signs and symptoms consistent with a caudal spinal cord malformation despite normal neuroimaging. Although several reports of successful surgical treatment exist, controversy remains with respect to patient selection and efficacy. We present a large series with excellent clinical followup, neuroimaging and urodynamic characterization. MATERIALS AND METHODS: We present our experience with 36 patients at a single institution with preoperative clinical findings, neuroimaging and urodynamics available. Postoperative outcomes were assessed clinically and with urodynamics. We determined predictive parameters to improve patient selection. RESULTS: Approximately 0.04% of pediatric urology clinic visits resulted in neurosurgical referral for the potential of an occult tethered cord. They occurred after failure of a mean of 2 years of aggressive medical management. Daytime urinary incontinence was present in 83% of patients and 47% had encopresis. Preoperative urodynamics were markedly abnormal in all patients with mean bladder capacity 55% of expected capacity. Clinical improvement in urinary symptoms was seen in 72% of patients with resolution of incontinence in 42%. Bowel symptoms improved in 88% of cases, including resolution of encopresis in 53% within 3 months of surgery. Urodynamic improvements were demonstrated in 57% of cases. We were unable to determine preoperative factors that were more likely associated with surgical success. CONCLUSIONS: In a highly select population with severe urinary and fecal dysfunction sectioning a normal-appearing filum terminale can result in significant improvement. We were unable to identify factors that may increase the chance of surgical success.

Spontaneous bladder perforations: a report of 500 augmentations in children and analysis of risk.

PURPOSE: The spontaneous perforation of an augmented bladder is an uncommon but serious complication. To our knowledge our institution has the largest reported series of bladder augmentations. We examined our data to determine the incidence of spontaneous bladder perforation and to delineate associated risk factors. MATERIALS AND METHODS: We performed a retrospective chart review of 500 bladder augmentation procedures performed during the preceding 25 years with a minimum followup of 2 years. RESULTS: Spontaneous perforations occurred in 43 patients (8.6%), for a total of 54 events. The calculated risk was 0.0066 perforations per augmentation-year at risk. Approximately a third of the cases had perforated within 2 years of surgery, a third between 2 and 6 years postoperatively, and a third at more than 6 years after augmentation. Patients who underwent augmentation between 1997 and 2003 had a higher rate of perforation within 2 years of surgery than those operated on between 1978 and 1987. Increased risk of perforation was observed with the use of sigmoid colon and bladder neck surgery. A decreased risk was associated with the presence of a continent catheterizable channel. CONCLUSIONS: We believe that this large and comprehensive series gives valuable insight into this serious complication. The delineation of these potential risk factors serves as a guide for further discussion and investigation.

Partial urogenital mobilization: a limited proximal dissection.

INTRODUCTION: The treatment of urogenital sinus malformations is complex and controversial. Despite numerous and significant contemporary surgical advances, the dissection of the urogenital sinus remains technically challenging. METHODS: Based on total urogenital mobilization, we describe a technique whereby this dissection is limited to the pubourethral ligament. Our short-term results with partial urogenital mobilization (PUM) performed on 15 patients are retrospectively reviewed. RESULTS: There were no intraoperative complications and the short-term cosmetic results are excellent. No patients have developed voiding dysfunction or urinary tract complications. CONCLUSIONS: While total urogenital mobilization is a very effective procedure, we believe that the PUM approach limits potential morbidity in the reconstruction of these complex problems.

Experience with non-cycled artificial urinary sphincters.

OBJECTIVE: To report our experience in children and adolescents with a non-cycled artificial urinary sphincter. While some children with the AUS can void, others require clean intermittent catheterization (CIC) through the sphincter or an alternative site for catheterization; in some of the latter we have either not cycled (pumped) an activated AUS or the AUS has failed, and there is concern about ischaemia in some adults with a non-cycled AUS. PATIENTS AND METHODS: In all, 143 patients who had an AUS placed between 1980 and 2002 were reviewed retrospectively; 15 (10 boys and five girls) no longer cycled (pumped) their AUS. The mean age at AUS insertion was 11 years and the mean (range) follow-up after insertion was 10.4 (1.64-22.2) years. The diagnoses included myelomeningocele in 11, sacral agenesis in three and cloaca in one. Nine patients have an activated functioning AUS and in six the AUS does not function; in the first nine the sphincter has not routinely been cycled (pumped) for a mean (range) of 1.6 (0.6-2.9) years. In the other six with a nonfunctioning AUS the mean (range) observation period is 6.4 (1.5-10) years since the system has not functioned. RESULTS: All patients were completely continent, including the six with a nonfunctioning AUS. After inserting the AUS, two patients voided in combination with CIC (one each urethral and abdominal stoma) and 13 emptied by CIC (nine abdominal stoma, four urethral). There was a mechanical complication in eight patients; three had the AUS repaired and are dry, and five are dry with no repair. In one patient the AUS was never activated. To date there has been no erosion of the cuff in any of the 15 patients with a non-cycled AUS. CONCLUSION: The AUS remains an extremely reliable procedure to achieve continence in children and young adults. It is versatile and can be combined with other procedures that provide an alternative means for catheterization. While some have noted the need to routinely cycle the AUS to prevent erosion, this has not been our experience in these 15 patients.