REGOMA-OSS: a large, Italian, multicenter, prospective, observational study evaluating the efficacy and safety of regorafenib in patients with recurrent glioblastoma.

BACKGROUND: In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting. PATIENTS AND METHODS: The major inclusion criteria were histologically confirmed diagnosis of glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function. Regorafenib was administered at the standard dose of 160 mg/day for 3 weeks on/1 week off. Brain magnetic resonance imaging was carried out within 14 days before starting regorafenib and every 8-12 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate, disease control rate (DCR), safety and health-related quality of life. The Response Assessment in Neuro-Oncology (RANO) criteria were used for response evaluation and Common Terminology Criteria for Adverse Events (CTCAE) version 5 for assessment of adverse events (AEs). RESULTS: From September 2020 to October 2022, 190 patients with recurrent glioblastoma were enrolled from 30 cancer centers in Italy: their median age was 58.5 years [interquartile range (IQR) 53-67 years], 68% were male and 85 (44.7%) were in optimal clinical condition (ECOG PS 0). The number of patients taking steroids at baseline was 113 (60%); the second surgery was carried out in 39 (20.5%). O6-methylguanine-DNA methyltransferase (MGMT) was methylated in 80 patients (50.3%) and 147 (92.4%) of the patients analyzed had isocitrate dehydrogenase (IDH) wild type. The median follow-up period was 20 months (IQR 15.6-25.5 months). The median OS was 7.9 months ([95% confidence interval (CI) 6.5-9.2 months] and the median PFS was 2.6 months (95% CI 2.3-2.9 months). Radiological response was partial response and stable disease in 13 (7.3%) and 26 (14.6%) patients, respectively, with a DCR of 21.9%. The median number of regorafenib cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. A dose reduction due to AEs was required in 36% of patients. No deaths were considered as treatment-related AEs. CONCLUSIONS: This large, real-world observational study showed similar OS with better tolerability of regorafenib in patients with relapsed glioblastoma compared with the REGOMA study.

Evaluation of Thermal Decomposition Kinetics of Poly (Lactic Acid)/Ethylene Elastomer (EE) Blends.

The influences of ethylene-based elastomer (EE) and the compatibilizer agent ethylene-butyl acrylate-glycidyl methacrylate (EBAGMA) on the thermal degradation of PLA/EE blends were evaluated by the thermal degradation kinetics and thermodynamic parameters using thermogravimetry. The presence of EE and EBAGMA synergistically improved the PLA thermal stability. The temperature of 10% of mass loss (T10%) of PLA was around 365 °C, while in the compatibilized PLA/EE blend, this property increased to 370 °C. The PLA average activation energy (Ea¯) reduced in the PLA/EE blend (from 96 kJ/mol to 78 kJ/mol), while the presence of EBAGMA in the PLA/EE blend increased the Ea¯ due to a better blend compatibilization. The solid-state thermal degradation of the PLA and PLA/EE blends was classified as a D-type degradation mechanism. In general, the addition of EE increased the thermodynamic parameters when compared to PLA and the compatibilized blend due to the increase in the collision rate between the components over the thermal decomposition.

Negative pressure-assisted endoscopic pilonidal sinus treatment.

BACKGROUND: Endoscopic pilonidal sinus treatment (EPSiT) is a novel minimally invasive option for the treatment of pilonidal sinus disease (PSD). To optimise the postoperative wound management after EPSiT, an ultraportable negative pressure wound therapy (NPWT) device was used. The aim of this study was to assess the clinical outcomes of negative pressure-assisted (NPA) EPSiT. METHODS: All patients with PSD treated by EPSIT from November 2017 to October 2019 were managed postoperatively with a commercially available NPTW dressing applied to the wound. All patients were prospectively entered into a dedicated database. Primary outcome measures were healing rate and return to normal activities. Secondary outcomes were postoperative complications and patient satisfaction. RESULTS: Thirteen male patients underwent NPA EPSiT (mean age 27.8 years, range 16-52 years). Two patients had previous surgery for PSD. The mean follow-up was 14 months (range 4-28 months). In two patients, only partial healing of the tract was achieved. One of these required a further successful NPA EPSiT, while the other one refused any other treatment because of the lack of symptoms. Eight patients were very satisfied and 5 were satisfied with this treatment. CONCLUSIONS: NPA EPSiT is a simple method for improving postoperative wound management, facilitating a quicker recovery and possibly improving overall patient satisfaction.

Initial experience with SphinKeeper™ intersphincteric implants for faecal incontinence in the UK: a two-centre retrospective clinical audit.

AIM: The SphinKeeper™ artificial bowel sphincter implant is a relatively new surgical technique for the treatment of refractory faecal incontinence. This study presents the first experience in two UK tertiary centres. METHOD: This is a retrospective audit of prospectively collected clinical data in relation to technique, safety, feasibility and short-term effectiveness from patients undergoing surgery from January 2016 to April 2019. Baseline data, intra-operative and postoperative complications, symptoms [using St Mark's incontinence score (SMIS)] and radiological outcomes were analysed. RESULTS: Twenty-seven patients [18 women, median age 57 years (range 27-87)] underwent SphinKeeper. In 30% of the patients, the firing device jammed and not all prostheses were delivered. There were no intra-operative complications and all patients were discharged the same or the following day. SMIS significantly improved from baseline [median -6 points (range -12 to +3); P < 0.00016] with 14/27 (51.9%) patients achieving a 50% reduction in the SMIS score. On postoperative imaging, a median of seven prostheses (range 0-10) were identified with a median of five (range 0-10) optimally placed. There was no relationship between number of well-sited prostheses on postoperative imaging and categorical success based on 50% reduction in SMIS (χ2 test, P = 0.79). CONCLUSION: SphinKeeper appears to be a safe procedure for faecal incontinence. Overall, about 50% patients achieved a meaningful improvement in symptoms. However, clinical benefit was unrelated to the rate of misplaced/migrated implants. This has implications for confidence in proof of mechanism and also the need for technical refinement.

Consensus statement of the Italian society of colorectal surgery (SICCR): management and treatment of hemorrhoidal disease.

Hemorrhoidal disease (HD) is the most common proctological disease in the Western countries. However, its real prevalence is underestimated due to the frequent self-medication.The aim of this consensus statement is to provide evidence-based data to allow an individualized and appropriate management and treatment of HD. The strategy used to search for evidence was based on application of electronic sources such as MEDLINE, PubMed, Cochrane Review Library, CINAHL, and EMBASE.These guidelines are inclusive and not prescriptive.The recommendations were defined and graded based on the current levels of evidence and in accordance with the criteria adopted by American College of Chest Physicians. The recommendations were graded A, B, and C.

A survey of dog and cat anaesthesia in a sample of veterinary practices in New Zealand.

AIMS: To survey current anaesthesia practices for dogs and cats in small and mixed animal practices in New Zealand in order to improve anaesthesia education. METHODS: A questionnaire was sent to 440 small and mixed animal practices, including questions regarding the type of practice, preanaesthetic examination, anaesthetic drugs and management, anaesthetic machines, monitoring and topics of interest for continuing professional development. RESULTS: Responses were obtained from 113/440 (26%) practices, with 78 (69%) respondents from small and 35 (31%) from mixed animal practices. A preanaesthetic physical examination was carried out by >95% of respondents and premedication was usually given to dogs (112/113; 99%) and cats (95/113; 85%). Acepromazine was the preferred sedative for dogs and cats, with morphine or buprenorphine. Propofol and alfaxalone were the preferred induction agents, and isoflurane was preferred for maintenance in both dogs and cats. A venous catheter was usually placed for anaesthesia in dogs (59/113; 52%), but less so in cats (39/113; 35%). Perioperative fluid was administered at 10 mL/kg/hour by 62/110 (56%) respondents. Intubation was usually used for anaesthesia in dogs (111/112; 99%), and cats (87/112; 78%). Almost 40% of respondents usually administered supplementary oxygen if patients were not intubated. Local analgesia was used by 69/111 (88%) respondents sometimes or always if applicable. Morphine or buprenorphine, and meloxicam were common choices for post-operative analgesia after neuter surgery in dogs and cats. A semiclosed (non-rebreathing) system was used in animals weighing <10 kg, and a Mapleson E or F non-rebreathing circuit was used by 66/109 (61%) practices. Only 15/111 (14%) practices had a ventilator in their practice. A dedicated anaesthetist was usually used by 104/113 (92%) practices, and apnoea alarms, pulse oximeters, thermometers and oesophageal stethoscopes were the main monitoring devices available in practices. Loco-regional block, pain management, and anaesthetic drugs were the main topics of interest for continuing education. CONCLUSIONS AND CLINICAL RELEVANCE: Responses by the veterinarians taking part in this survey indicated that they had a reasonably good standard of anaesthetic practice. A physical examination was carried out preanaesthesia, and premedication including analgesia was routinely administered to most patients. A dedicated anaesthetist usually monitored patients and most respondents reported they had access to basic anaesthetic monitoring equipment. Areas where changes could lead to improved anaesthetic practice were increased use of I/V catheterisation, endotracheal intubation, and supplementary oxygen, and reduced I/V fluid rates.

Molecular diagnosis of thrombocytopenia-absent radius syndrome using next-generation sequencing.

INTRODUCTION: Thrombocytopenia-absent radius (TAR) syndrome is a rare autosomal recessive disease. Patients are compound heterozygotes for a loss-of-function allele, which in most cases is a large genomic deletion on chromosome 1q21.1 containing the RBM8A gene, and a noncoding variant located in the 5'UTR (rs139428292) or intronic (rs201779890) regions of RBM8A. As the molecular genetic testing in TAR requires multiple techniques for detection of copy-number variations (CNV) and nucleotide substitutions, we tested whether a next-generation sequencing (NGS) approach could identify both alterations. METHODS: Two unrelated families were analyzed with Ion PGM sequencing using a target panel of genes responsible for different forms of inherited thrombocytopenia. A statistical quantitative evaluation of amplicon coverage was performed to detect CNV, in particular those on the RBM8A gene. RESULTS: All the probands were apparently homozygous for the rare allele inherited by the father at the rs139428292 locus, suggesting the presence of a deletion on the maternal chromosome. The statistical analysis confirmed the hemizygous condition of RBM8A. CONCLUSION: We concluded that NGS approaches could be used as a cost-effective method for molecular investigation of TAR as they could simultaneously detect CNV and point mutations.

Cochlear implant and inflammation reaction: Safety study of a new steroid-eluting electrode.

Dexamethasone is a common anti-inflammatory agent added to cochlear implants to reduce hearing loss due to electrode insertion trauma. We evaluated the safety of eluting silicone rods containing 10% dexamethasone in a Guinea pig model. Animals were implanted with a dexamethasone eluting silicone electrode (DER) or with a non-eluting electrode (NER). The control group only underwent a cochleostomy (CS). Prior to implantation and during the two weeks following implantation, the hearing status of the animals was assessed by means of Compound Action Potentials (CAPs) with an electrode placed near the round window. Two weeks after implantation, the mean click threshold shifts were 1 dB ± 10 dB in the DER group, 10 dB ± 10 dB in the NER group and -4 dB ± 10 dB in the control group. After two weeks the bullae of each animal were extracted to verify the presence of macrophages, the percent of tissue growth in the scala tympani and the tissue sealing around cochleostomy. Silicone electrodes samples were also explanted and examined for bacterial infection. Neither bacterial infection nor enhanced number of macrophages were observed. A limited, but not significant, tissue growth was found in the scala tympani between the experimental and the control group. The data suggest that, in the Guinea pig model, the use of DER is apparently safe as an anti-inflammatory slow-release additive to the cochlear implant.

A prospective multicentre observational study of Permacol collagen paste for anorectal fistula: preliminary results.

AIM: Permacol collagen paste (Permacol paste) is a new option for the treatment of anorectal fistula. It functions by filling the fistula tract with an acellular crosslinked porcine dermal collagen matrix suspension. The MASERATI 100 study group was set up to evaluate the clinical outcome of Permacol paste in the treatment of anorectal fistula. This paper reports the results from the initial 30 patients enrolled in the MASERATI 100 prospective, observational clinical trial. METHOD: Patients (N = 30) with anal fistula presenting to 10 European academic surgical units were treated with a sphincter-preserving technique using Permacol paste. Fistula healing was assessed at 1, 3, 6 and 12 months after treatment, with the primary end-point of fistula healing at 6 months post-surgery. Faecal continence and patient satisfaction were recorded at each follow-up visit and adverse events were monitored throughout the follow-up. RESULTS: Of the 28 patients with data at 6 months post-surgery, 15 (54%) were healed, and the healing rate was maintained at 12 months. Healing after treatment with Permacol paste was similar for intersphincteric to transsphincteric fistulae and primary or recurrent fistulae. Only one patient exhibited an adverse event (perianal abscess) that was possibly related to the treatment. At the last outpatient visit, over 60% of patients were satisfied or very satisfied with the operation. CONCLUSION: Permacol paste is shown to be effective in treating primary and recurrent cryptoglandular anorectal fistula with minimal unwanted side effects.

Evaluation and management of hemorrhoids: Italian society of colorectal surgery (SICCR) consensus statement.

Hemorrhoids are one of the most common medical and surgical diseases and the main reason for a visit to a coloproctologist. This consensus statement was drawn up by the Italian society of colorectal surgery in order to provide practice parameters for an accurate assessment of the disease and consequent appropriate treatment. The authors made a careful search in the main databases (MEDLINE, PubMed, Embase and Cochrane), and all results were classified on the basis of the grade of recommendation (A-C) of the American College of Chest Physicians.

The use of an acellular porcine dermal collagen implant in the repair of complex abdominal wall defects: a European multicentre retrospective study.

BACKGROUND: The use of biological materials for the repair of complex abdominal wall defects has increased over the years; however, the role of these materials in routine practice remains unclear. The aim of the study was to evaluate clinical outcomes following the use of Permacol™ porcine collagen surgical implant in complex abdominal wall repair. METHODS: This subset analysis of seven European sites from a multicentre retrospective study included patients undergoing open or laparoscopic surgery and treated with Permacol™ surgical implant. Inguinal, parastomal, diaphragmatic, perineal, and hiatal repairs were excluded. Only patients with at least 12 months of follow-up after surgery were included. RESULTS: A total of 109 patients (56 males and 53 females) were included. Patients had a median of two comorbidities (range 0-6). Thirty-three per cent of patients were treated for recurrent hernia. All but one case used an open approach. Sixty-six per cent were Center for Disease Control wound class II-IV at the time of surgery. Fascial closure was achieved in 69%. Median follow-up length was 720 days (range 368-2857). Recurrence rates at 1 and 2 years were 9.2 and 18.3 %, respectively, and were higher in cases without fascial closure. One-year recurrence was higher following use of an onlay technique (P = 0.025). In a multivariate analysis, among 16 comorbidities examined only fascial closure significantly impacted 1-year recurrence (P = 0.049). CONCLUSIONS: Data from this large retrospective multicentre European study strongly suggest the use of Permacol™ porcine collagen surgical implant to be safe and effective for complex abdominal wall repair. The recurrence rate was impacted by fascial closure.

Evaluation of impact of steroid replacement treatment on bone health in children with 21-hydroxylase deficiency.

There are conflicting data regarding the potential impact of chronic glucocorticoid (GC) therapy on the bone mineral density of patients with congenital adrenal hyperplasia (CAH). Previous studies performed by dual-energy X-ray absorptiometry reported conflicting results. The purpose of this study was to assess the impact of chronic GC replacement treatment in children with classical and non classical CAH due to 21-hydroxylase deficiency (21-OHD) by quantitative ultrasonometry (QUS), an easy, cheap, and radiation-free technique. The study population consisted of nineteen 21-OHD patients (nine males) on lifelong GC treatment. Anthropometric, hormonal, and treatment data were recorded for each patient, and bone quality was assessed by QUS measurements. QUS findings (amplitude-dependent speed of sound and bone transmission time) were normal in 21-OHD patients and did not correlate with duration of treatment, daily, total, and yearly hydrocortisone dose. Furthermore, no significant correlation was found between QUS findings and 17α-hydroxy progesterone, Δ4-androstenedione, and testosterone levels. In conclusion, our results provide reassurance that currently used replacement doses of GC do not have a major impact on bone in patients with CAH. QUS seems to be a reliable tool for screening of bone health in children with 21-OHD.

Tension pneumothorax secondary to nasojejunal feeding tube misplacement in a mechanically ventilated dog.

CASE REPORT: An 11-year-old female terrier-cross underwent general anaesthesia and mechanical ventilation for insulinoma resection. Following tumour removal, three consecutive but unsuccessful attempts were made to place a wire-guided nasojejunal feeding tube (NJFT), using both nostrils, with one tube eventually left in situ in the right nostril. A final successful attempt using a smaller NJFT was made via the left nostril. On withdrawal of the previously, unsuccessfully placed NJFT, the dog developed an acute tension pneumothorax. Severe cardiorespiratory dysfunction ensued, including decreasing arterial haemoglobin O2 saturation, increasing end-tidal CO2, hypotension and tachycardia. Immediate thoracocentesis with air evacuation from the pleural cavity followed by continuous air drainage through bilateral thoracostomy tubes produced marked improvement of cardiorespiratory function. During exploratory thoracotomy performed 1 day later, two lung lesions were identified and over sewn, one in the right middle lobe and the other in the accessory lobe. CONCLUSIONS: This is the first case report to describe in an anaesthetised and mechanically ventilated dog the occurrence and management of a tension pneumothorax as a life-threatening complication secondary to parenchymal injury after NJFT misplacement into the tracheobronchial tree. It illustrates that presence of a cuffed endotracheal tube does not protect against passing a NJFT into the bronchial system.

Monoclonal gammopathy of undetermined significance in pediatric kidney transplant: a possible role of Epstein-Barr virus.

MG is a common event of hematologic malignancies. There are many papers regarding kidney transplantation patients with MGUS in adults, while data in pediatrics are scarce. The etiology and clinical significance of MGUS are unclear both in adults and children. Immunosuppressive drugs, graft antigenicity, and viral infection could play a possible role. The viruses most frequently implicated seem to be EBV or CMV in particular, but their role has to be defined better. However, many investigators have emphasized an impaired balance between an adequate immune response and reactivation of viral infection.

After the introduction into the national newborn screening program: who is receiving genetic counseling for hemoglobinopathies in the Netherlands?

OBJECTIVE: Universal newborn screening for hemoglobinopathies started in The Netherlands in 2007. Herewith severe conditions, such as sickle cell disease, ß-thalassemia major and hemoglobin H disease are putatively identified. Additionally, at least 1,800 carriers of hemoglobin variants associated with severe conditions in homozygote or compound heterozygote forms are identified yearly. Thus far, approximately 60 patients and 800 healthy sickle cell (HbS) carriers are reported each year among 180,000 newborns. Results are sent to the general practitioner with the recommendation to inform and diagnose both parents of the healthy carriers to exclude genetic risk, while patients and their parents are referred directly to a pediatrician. This study was performed to determine how often parents of identified carriers and affected newborns are seen in genetic centers for counseling. METHODS: In this retrospective study, we collected anonymized data from 7 of the 8 Dutch clinical genetic centers from January 1, 2007, until December 31, 2010. RESULTS: After an initial general increase in total counseling intakes, a decline was noticed in the third year, while the requests for prenatal diagnoses remained relatively stable. In 2007 and 2013, genetic counselors were asked for self-reported knowledge. They found hemoglobinopathy counseling complex, but by 2013, they indicated they had acquired sufficient knowledge on most hemoglobinopathy aspects. CONCLUSION: We could not observe a significant increase in genetic counseling for hemoglobinopathy after its introduction into newborn screening. Although 120 HbS carriers and 60 patients are expected to be born from couples at risk annually, only 33 at risk couples out of 540 families of diagnosed newborns received optimal care and information at a genetics center in 4 years.

Guidelines for the use of long-term central venous catheter in children with hemato-oncological disorders. On behalf of supportive therapy working group of Italian Association of Pediatric Hematology and Oncology (AIEOP).

In the last 30 years, the use of long-term central venous catheters (CVC) is increased especially for children with hemato-oncological disorders. However, the use of CVC is associated to complications, as mechanical accidents, thrombosis, and infections that can determine a prolongation of hospital stay, an increase of costs, and sometimes life-threatening conditions that require urgent systemic treatment or CVC removal. CVC removal may be troublesome especially in neonates, infants, or any other "highly needed CVC patients"; in these selected cases, the prevention and treatment of CVC-related complications play a pivotal role and specific surveillance programs are crucial. While extensive literature is focused on CVC management in adults, no guidelines are available for children. To this aim, the first recommendations for the management of CVC infectious complication in pediatric age have been written after pediatric and adult literature review and collegial discussion among members of Supportive Therapy working group of Italian Association of Pediatric Hematology and Oncology. Compared to the adult age, the necessity of peripheral vein cultures for the diagnosis of CVC-related infection remains controversial in children because of the poorer venous asset and a conservative, pharmacologically focused management through CVC remains mandatory, with CVC removal to be performed only in selected cases.

Myocardial damage following cardiac surgery: comparison between single-dose Celsior cardioplegic solution and cold blood multi-dose cardioplegia.

Myocardial protection during cardiac surgery can be accomplished by different cardioplegic solutions. The aim of this study was to assess myocardial damage after heart valve surgery performed with myocardial protection of a single dose of Celsior cardioplegia or with repeated cold blood cardioplegia. After the stratification of 139 valvular patients by means of matching according to cross-clamp and cardiopulmonary bypass time, 32 patients were retained for comparison (16 patients received Celsior and 16 patients received cold blood cardioplegia). Creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) release were evaluated until six days after the operation. Pre-operative characteristics were similar in both groups. In the Celsior group, CK-MB and cTnI values were significantly higher from the first up to the sixth post-operative day. Peak cTnI values were 19.4 ± 13.4 and 9.7 ± 7 ng/mL (p=0.01) in the Celsior and the Cold Blood group, respectively. Peak CK-MB values were 79.6 ± 58.8 and 45.9 ± 20.6 U/L (p=0.07) in the Celsior and the Cold Blood group, respectively. Cold blood cardioplegia reduces perioperative myocardial damage compared to the Celsior solution in elective cardiac valve operations.