Treatment of presumed aseptic non-union of the humeral shaft by osteosynthesis combining intramedullary nailing and screw plate.

In 2020, the most common treatment for presumed aseptic non-union of the humeral shaft seems to be decortication, often associated with bone autografting, and stabilized by a screw plate. We propose to evaluate an original technique of rigid osteosynthesis combining intramedullary nailing and screw plate. Between January 2004 and January 2020, 45 patients underwent treatment of presumed aseptic non-union of the humeral shaft by osteosynthesis combining intramedullary nailing and a screw plate. The minimum radio-clinical follow-up was one year postoperatively. The series included 19 men and 26 women with a mean age of 53 years (range 19-84 years). Bone consolidation was achieved in 43 patients, a rate of 95.5%. Comparing patients who achieved bone consolidation with the two failed consolidations did not reveal any statistically significant factor. Interobserver agreement was almost perfect (k=0.93) for the use of the RUST for humeral shaft fractures treated with intramedullary nailing and screw plate. In our study, the treatment of presumed aseptic non- union of the humeral shaft with an osteosynthesis combining intramedullary nailing and screw plate gives, with 95.5% of bone consolidation, results equal to or even superior to the different treatments currently described in the literature.

The management of endoscopic retrograde cholangio- pancreatography-related infections risk: results of an italian survey at regional level.

Background and aim: Among the Endoscopic retrograde cholangiopancreatography (ERCP) adverse events, an increasingly arising problem is the transmission of Multi Drug Resistant (MDR) Bacteria through duodenoscopes. The aim of this survey was to evaluate the current clinical practice of management of ERCP associated infections in Emilia-Romagna, Italy. Methods: An online survey was developed including 12 questions on management of ERCP associated infections risk. The survey was proposed to all 12 endoscopy centers in Emilia Romagna that perform at least > 200 ERCPs per year. Results: 11 centers completed the survey (92%). Among all risk factors of ERCP infections, hospitalization in intensive care units, immunosuppressant therapies, and previous MDR infections have achieved a 80 % minimum of concurrence by our respondents. The majority of them did not have a formalized document in their hospital describing categories and risk factors helpful in the detection of patients undergoing ERCP with an high-level infective risk (9/11, 82%). Most centers (8/11, 72%) do not perform screening in patients at risk of ERCP infections. Post procedural monitoring is performed by 6 of 11 centers (55%). Conclusion: Our survey showed that, at least at regional level, there is a lack of procedures and protocols related to the management of patients at risk of ERCP infections.

Ion concentrations in nasal airway surface liquid: a prediction model for the identification of cystic fibrosis carriers.

BACKGROUND: Cystic fibrosis (CF) carriers seem to have a higher risk to develop chronic rhino-sinusitis (CRS), although the full underlying mechanisms are unknown. Ion concentrations in nasal airway surface liquid (ASL) may be influenced by the heterozygosity for CF gene mutation, with possible impacts on the development of CRS. METHODS: A cheap and feasible standardized technique was designed to measure the ion levels in nasal ASL. With this purpose we collected, under basal conditions, samples from the nasal cavity of 165 adults: 14 homozygous for CF, 83 carriers and 68 healthy controls. Sodium (Na) and Chlorine (Cl) concentrations were then evaluated among different groups. RESULTS: Statistical analysis revealed a significant difference of Na and Cl values between controls and carriers and between controls and homozygotes. Receiver operating characteristic (ROC) curves and derived indicators (Youden's index and Area Under the Curve, AUC) were used to further evaluate the diagnostic capability of Na and Cl concentrations to differentiate heterozygotes from controls. ROC curves demonstrated that the optimal diagnostic cut-off value of Na is at 124, and the optimal cut-off value of Cl is at 103,2. CONCLUSION: ASL sampling can be considered a new diagnostic tool for providing quantitative information on nasal ion composition. According to our findings, Na and Cl concentrations of nasal ASL could represent a useful tool to assess heterozygotes and healthy controls.

Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study.

OBJECTIVES: Clinical variables were investigated in the 'treatment resistant depression (TRD)- III' sample to replicate earlier findings by the European research consortium 'Group for the Study of Resistant Depression' (GSRD) and enable cross-sample prediction of treatment outcome in TRD. EXPERIMENTAL PROCEDURES: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. RESULTS: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD-I. CONCLUSION: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD-III enabled robust prediction of treatment outcome in TRD-I.

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets.

Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses and a major cause of morbidity worldwide. Currently available antidepressants are effective for most patients, although around 30% are considered treatment resistant (TRD), a condition that is associated with a significant impairment of cognitive function and poor quality of life. In this respect, the identification of the molecular mechanisms contributing to TRD represents an essential step for the design of novel and more efficacious drugs able to modify the clinical course of this disorder and increase remission rates in clinical practice. New insights into the neurobiology of TRD have shed light on the role of a number of different mechanisms, including the glutamatergic system, immune/inflammatory systems, neurotrophin function, and epigenetics. Advances in drug discovery processes in TRD have also influenced the classification of antidepressant drugs and novel classifications are available, such as the neuroscience-based nomenclature that can incorporate such advances in drug development for TRD. This review aims to provide an up-to-date description of key mechanisms in TRD and describe current therapeutic strategies for TRD before examining novel approaches that may ultimately address important neurobiological mechanisms not targeted by currently available antidepressants. All in all, we suggest that drug targeting different neurobiological systems should be able to restore normal function but must also promote resilience to reduce the long-term vulnerability to recurrent depressive episodes.

New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.

Defining the biology of intrahepatic cholangiocarcinoma: molecular pathways and early detection of precursor lesions.

Intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of the biliary tract with growing incidence and dismal prognosis. It is responsible for 10-20% of primary liver cancer worldwide, but early diagnosis is still a challenge and few treatment options are available. Aim of this review is to summarize the current knowledge about biological features and arising molecular patterns of this disease. The identification of emerging biomarkers and early detection of precursor lesions shall play a key role in the perspective of future tailored targeted therapies.

Barriers against split-dose bowel preparation for colonoscopy.

OBJECTIVE: Although split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients' attitude towards split regimen and patient-related factors associated with its uptake. DESIGN: In a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4 L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire. RESULTS: Of the 1447 patients (mean age 59.2±13.5 years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p<0.001, χ2 for linear trend). At multivariate analysis, colonoscopy appointment before 10:00 (OR 0.14, 95% CI 0.11 to 0.18), travel time to endoscopy service >1 h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split-dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92). CONCLUSION: Patient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered. TRIAL REGISTRATION NUMBER: NCT02287051; pre-result.

Neuronal cell adhesion genes and antidepressant response in three independent samples.

Drug-effect phenotypes in human lymphoblastoid cell lines recently allowed to identify CHL1 (cell adhesion molecule with homology to L1CAM), GAP43 (growth-associated protein 43) and ITGB3 (integrin beta 3) as new candidates for involvement in the antidepressant effect. CHL1 and ITGB3 code for adhesion molecules, while GAP43 codes for a neuron-specific cytosolic protein expressed in neuronal growth cones; all the three gene products are involved in synaptic plasticity. Sixteen polymorphisms in these genes were genotyped in two samples (n=369 and 90) with diagnosis of major depressive episode who were treated with antidepressants in a naturalistic setting. Phenotypes were response, remission and treatment-resistant depression. Logistic regression including appropriate covariates was performed. Genes associated with outcomes were investigated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) genome-wide study (n=1861) as both individual genes and through a pathway analysis (Reactome and String databases). Gene-based analysis suggested CHL1 rs4003413, GAP43 rs283393 and rs9860828, ITGB3 rs3809865 as the top candidates due to their replication across the largest original sample and the STAR*D cohort. GAP43 molecular pathway was associated with both response and remission in the STAR*D, with ELAVL4 representing the gene with the highest percentage of single nucleotide polymorphisms (SNPs) associated with outcomes. Other promising genes emerging from the pathway analysis were ITGB1 and NRP1. The present study was the first to analyze cell adhesion genes and their molecular pathways in antidepressant response. Genes and biomarkers involved in neuronal adhesion should be considered by further studies aimed to identify predictors of antidepressant response.

Large diameter fully covered self-expanding metal stent placement for palliation of proximal malignant esophageal strictures.

In patients with malignant esophageal strictures within 6 cm from the upper esophageal sphincter, self-expanding metal stents placement represents a challenge because there is an increased risk of complications. The aim of this study was to assess the safety and effectiveness of large-diameter WallFlex(®) fully covered self-expanding metal stents for palliation of patients with proximal malignant esophageal strictures. From March 2010 to December 2012, 12 patients with proximal strictures (4-6 cm from the upper esophageal sphincter) and six with very proximal strictures (<4 cm from the upper esophageal sphincter) were palliated with this fully covered self-expanding metal stent and included in the study. Technical success was 100% and clinical success was 94%. The mean baseline dysphagia score was 3.2, and 1 week after stenting it improved significantly to 1.3 (P < 0.001). Early complications occurred in four patients, more frequently in patients with very proximal strictures as compared with patients with proximal strictures (P = 0.02). Late complications occurred in five patients, and there were no differences between patients with very proximal strictures or proximal strictures (P = 0.245). The mean survival after stent placement was 119 days, and no differences between patients with very proximal strictures versus proximal strictures were found (P = 0.851). There was no stent-related mortality or 30-day mortality. Our results suggested that a large-diameter fully covered self-expanding metal stent is an effective and secure device for palliation of patients with proximal malignant esophageal strictures.

Satisfaction of patients' next of kin in a 'Hub & Spoke' ICU network.

This study aimed to gauge the opinions of patients' next of kin regarding transfer of patients from the specialist 'Hub' intensive care unit, to 'Spoke' intensive care units near home. We included 213 consecutive patients with severe trauma or severe acute neurological conditions admitted to the Hub intensive care unit over a 21-month period, who were repatriated to Spoke intensive care units for ongoing intensive care. One year after admission to the Hub intensive care unit, two thirds of patients' next of kin said they would have preferred patients to have been treated only in the Hub intensive care unit, and not repatriated. They perceived Hub intensive care unit care to be important, and would have preferred that their relatives be hospitalised there until intensive treatment was completed. The next of kin's preference was associated with severe acute neurological conditions (p ≤ 0.0001). Although centralised Hub & Spoke intensive care unit networks are appropriate to ensure specialised care, repatriation to local hospitals may not be appropriate for patients with severe neurological conditions.

PPP3CC gene: a putative modulator of antidepressant response through the B-cell receptor signaling pathway.

Antidepressant pharmacogenetics represents a stimulating, but often discouraging field. The present study proposes a combination of several methodologies across three independent samples. Genes belonging to monoamine, neuroplasticity, circadian rhythm and transcription factor pathways were investigated in two samples (n=369 and 88) with diagnosis of major depression who were treated with antidepressants. Phenotypes were response, remission and treatment-resistant depression. Logistic regression including appropriate covariates was performed. Genes associated with outcomes were investigated in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) genome-wide study (n=1861). Top genes were further studied through a pathway analysis. In both original samples, markers associated with outcomes were concentrated in the PPP3CC gene. Other interesting findings were particularly in the HTR2A gene in one original sample and the STAR*D. The B-cell receptor signaling pathway proved to be the putative mediator of PPP3CC's effect on antidepressant response (P=0.03). Among innovative candidates, PPP3CC, involved in the regulation of immune system and synaptic plasticity, seems promising for further investigation.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

BACKGROUND: The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS: We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS: Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION: We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

Update on oncoplastic breast surgery.

Oncoplastic surgery of the breast (OPS) has generated great excitement over the past years and has become an integrated component of the surgical treatment of breast cancer. Oncoplastic surgical procedures associate the best surgical oncologic principles to achieve wide tumor-free margins with the best principles of plastic surgery to optimize cosmetic outcomes. Thanks to oncoplastic techniques, the role of breast conserving surgery (BCS) has been extended to include a group of patients who would otherwise require mastectomy to achieve adequate tumor clearance. As OPS continues to gain acceptance and diffusion, an optimal and systematic approach to these techniques is becoming increasingly necessary. This article has the aim to review the essential principles and techniques associated with oncoplastic surgery, based on the data acquired through an extensive search of the PUBMED and MEDLINE database for articles published using the key words "breast cancer oncoplastic surgery". This review analyzes possible the advantages", classifications, indications, and the criteria for a proper selection of oncoplastic techniques to facilitate one's ability to master these procedures and make OPS a safe and an effective procedure.

The role of oxidized regenerate cellulose to prevent cosmetic defects in oncoplastic breast surgery.

BACKGROUND: Breast conserving surgery (BCS) combined with postoperative radiotherapy has become the gold standard of locoregional treatment for the majority of patients with early-stage breast cancer, offering equivalent survival and improved body image and lifestyle scores as compared to mastectomy. In an attempt to optimize the oncologic safety and cosmetic results of BCS, oncoplastic procedures (OPP) have been introduced in recent years combining the best principles of surgical oncology with those of plastic surgery. However, even with the use of OPP, cosmetic outcomes may result unsatisfying when a large volume of parenchyma has to be removed, particularly in small-medium size breasts. AIM: The aim of this article is to report our preliminary results with the use of oxidized regenerate cellulose (ORC) (Tabotamp fibrillar, Johnson & Johnson; Ethicon, USA) as an agent to prevent cosmetic defects in patients undergoing OPP for breast cancer and to analyze the technical refinements that can enhance its efficacy in optimizing cosmetic defects. METHODS: Different OPP are selected based on the location and size of the tumor as well as volume and shape of the breast. After excision of the tumor, glandular flaps are created by dissection of the residual parenchyma from the pectoralis and serratus muscles and from the skin. After careful haemostasis, five layers of ORC are positioned on the pectoralis major in the residual cavity and covered by advancement of the glandular flaps. Two additional layers of ORC are positioned above the flaps and covered by cutaneous-subcutaenous flaps. RESULTS: The use of ORC after OPP has shown promising preliminary results, indicating a good tolerability and positive effects on cosmesis. CONCLUSIONS: This simple and reliable surgical technique may allow not only to reduce the rate of post-operative bleeding and infection at the surgical site but also to improve cosmetic results.

The Gastro-Laryngeal Tube for interventional endoscopic biliopancreatic procedures in anesthetized patients.

The Gastro-Laryngeal Tube (G-LT) is a modification of the laryngeal tube which provides a dedicated channel for the insertion of an endoscope while acting as a supraglottic airway for ventilation. The aim of this study was to assess the safety and effectiveness of this device in patients undergoing anesthesia for interventional endoscopic biliopancreatic procedures (IEBPPs).A total of 22 patients were included in the study. The G-LT was inserted successfully in all patients. Arterial oxygen saturation was stable; the mean value was 97.9%. The IEBPPs were performed successfully in all patients through the endoscopic channel, with a mean duration of 99 minutes. The maneuverability of the endoscope was considered good in all patients. There were two cases of sore throat after the procedures, two cases of asymptomatic erosion of the upper esophageal mucosa, one case of Mallory-Weiss syndrome, and one case of pancreatitis after endoscopic retrograde cholangiopancreatography.Our results suggest that the G-LT is an effective and secure device for airway management and for use during IEBPPs.

Cholangioscopy using a new type of cholangioscope for the diagnosis of biliary tract disease: a case series.

We present an initial report regarding the clinical usefulness of peroral cholangioscopy, using a new type of cholangioscope, the Polyscope. Peroral cholangioscopy was performed in four patients with strictures after orthotopic liver transplantation (OLT) which were suspected of being ischemic biliary lesions, in three with indeterminate biliary strictures, in three with suspected retained bile duct stones, and in two for evaluation of the intraductal spread of adenomatous tissue after an ampullectomy. In all cases peroral cholangioscopy was performed successfully without complications. On the basis of direct viewing and/or tissue sampling a correct diagnosis was reached in all cases: in all patients who underwent OLT the strictures were not ischemic; the indeterminate strictures were all benign; and, in patients with suspected stones, complete clearance was confirmed. Intraductal spread was confirmed in one patient and excluded in the other. In our experience, peroral cholangioscopy using a Polyscope is a safe and effective method for diagnosing bile duct lesions.