Assessing the real benefits of surgery for degenerative lumbar spinal stenosis without instability and spondylolisthesis: a single surgeon experience with a mean 8-year follow-up

Background: The degenerative lumbar spinal stenosis is one of the most commonly treated spinal disorders in older adults; despite its increasing frequency, it is not yet clear what the most effective therapy might be. The aim of this study is to investigate the very long term results of a homogenized cohort of patients suffering from lumbar spinal stenosis: the first subset of patients operated on with laminectomy and the second subset of patients was also advised to undergo laminectomy but never operated on. Methods: Patients from both subgroups were advised to undergo surgery, according to the same criteria, in the period between 2000 and 2010 and were re-evaluated in the period between January and December 2016. Results: Comparing the two subsets of patients, both suffering from clinically relevant LSS, the first subset returns a statistically significant clinical improvement at follow-up. The rate of excellent results decreases over years. Iatrogenic spinal instability incidence was found to be 3.8% in the present cohort. Conclusions: Although the improvement of the first postoperative years decreases over time and despite the lack of general consensus, the lack of established shared guidelines and the limitations of this research, the results support the utilisation of surgery for the management of this condition. Level of Evidence: 3

MicroRNAs delivery into human cells grown on 3D-printed PLA scaffolds coated with a novel fluorescent PAMAM dendrimer for biomedical applications

Many advanced synthetic, natural, degradable or non-degradable materials have been employed to create scaffolds for cell culture for biomedical or tissue engineering applications. One of the most versatile material is poly-lactide (PLA), commonly used as 3D printing filament. Manufacturing of multifunctional scaffolds with improved cell growth proliferation and able to deliver oligonucleotides represents an innovative strategy for controlled and localized gene modulation that hold great promise and could increase the number of applications in biomedicine. Here we report for the first time the synthesis of a novel Rhodamine derivative of a poly-amidoamine dendrimer (G = 5) able to transfect cells and to be monitored by confocal microscopy that we also employed to coat a 3D-printed PLA scaffold. The coating do not modify the oligonucleotide binding ability, toxicity or transfection properties of the scaffold that is able to increase cell proliferation and deliver miRNA mimics (i.e., pre-mir-503) into human cells. Although further experiments are required to optimize the dendrimer/miRNA ratio and improve transfection efficiency, we demonstrated the effectiveness of this promising and innovative 3D-printed transfection system to transfer miRNAs into human cells for future biomedical applications. © 2018, The Author(s)

Biophysical and biological contributions of polyamine-coated carbon nanotubes and bidimensional buckypapers in the delivery of miRNAs to human cells

Recent findings in nanomedicine have revealed that carbon nanotubes (CNTs) can be used as potential drug carriers, therapeutic agents and diagnostics tools. Moreover, due to their ability to cross cellular membranes, their nanosize dimension, high surface area and relatively good biocompatibility, CNTs have also been employed as a novel gene delivery vector system. In our previous work, we functionalized CNTs with two polyamine polymers, polyethyleneimine (PEI) and polyamidoamine dendrimer (PAMAM). These compounds have low cytotoxicity, ability to conjugate microRNAs (such as miR-503) and, at the same time, transfect efficiently endothelial cells. The parameters contributing to the good efficiency of transfection that we observed were not investigated in detail. In fact, the diameter and length of CNTs are important parameters to be taken into account when evaluating the effects on drug delivery efficiency. In order to investigate the biophysical and biological contributions of polymer-coated CNTs in delivery of miRNAs to human cells, we decided to investigate three different preparations, characterized by different dimensions and aspect ratios. In particular, we took into account very small CNTs, a suspension of CNTs starting from the commercial product and a 2D material based on CNTs (ie, buckypapers [BPs]) to examine the transfection efficiency of a rigid scaffold. In conclusion, we extensively investigated the biophysical and biological contributions of polyamine-coated CNTs and bidimensional BPs in the delivery of miRNAs to human cells, in order to optimize the transfection efficiency of these compounds to be employed as efficient drug delivery vectors in biomedical applications

Short report: autistic gastrointestinal and eating symptoms treated with secretin: a subtype of autism

Pervasive Developmental Disorders (PDD) are chronic, lifelong disorders for which there is as yet no effective cure, and medical management remains a challenge for clinicians. The current report describes two patients affected by autistic disorder with associated gastrointestinal symptoms. They received multiple doses of intravenous secretin for a six-month period and were assessed with several specific outcome measures to evaluate drug effect. The administration of secretin led to some significant and lasting improvement in only one case. Gastroesophageal reflux may contribute to some of the behavioural problems and explain the effect of secretin since its suppressive effect on gastric secretion is well known. It is also true that autistic children with gastroesophageal reflux and a higher IQ could constitute a subtype which responds to secretin administration and that could be labelled as a "gastrointestinal subtype"

Short communication: Detection of human Torque teno virus in the milk of water buffaloes (Bubalus bubalis)

Forty-four raw milk and 15 serum samples from 44 healthy water buffaloes reared in Caserta, southern Italy, the most important region in Europe for buffalo breeding, were examined to evaluate the presence of Torque teno viruses (TTV) using molecular tools. Furthermore, 8 pooled pasteurized milk samples (from dairy factories having excellent sanitary conditions) and 6 Mozzarella cheese samples were also tested. Four of the cheese samples were commercial Mozzarella cheese; the remaining 2 were prepared with TTV-containing milk. Human TTV were detected and confirmed by sequencing in 7 samples of milk (approximately 16%). No TTV were found in serum, pooled pasteurized milk, or Mozzarella cheese samples. The samples of Mozzarella cheese prepared with TTV-containing milk did not show any presence of TTV, which provides evidence that standard methodological procedures to prepare Mozzarella cheese seem to affect viral structure, making this food fit for human consumption. The 7 TTV species from water buffaloes were identified as genotypes corresponding to the tth31 (3 cases), sle 1981, sle 2031, and NLC030 (2 cases each) human isolates. Although cross-species infection may occur, detection of TTV DNA in milk but not in serum led us to believe that its presence could be due to human contamination rather than a true infection. Finally, the mode of transmission of TTV has not been determined. Contaminated of the food chain with TTV may be a potential risk for human health, representing one of the multiple routes of infection

Positive end expiratory pressure in acute hypoxemic respiratory failure due to community acquired pneumonia: Do we need a personalized approach?

Background. Acute respiratory failure (ARF) is a life-threatening complication in patients with community acquired pneumonia (CAP). The use of non-invasive ventilation is controversial. With this prospective, observational study we aimed to describe a protocol to assess whether a patient with moderate-to-severe hypoxemic ARF secondary to CAP benefits, in clinical and laboratoristic terms, from the application of a positive end expiratory pressure (PEEP) + oxygen vs oxygen alone. Methods. Patients who benefit from PEEP application (PEEP-responders) were defined as those with partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increase > 20% and/or reduction of respiratory distress during PEEP + oxygen therapy compared to oxygen therapy alone. Clinical characteristics and outcomes were compared between PEEP-responders and PEEP-non responders. Results. Out of 41 patients, 27 (66%) benefit from PEEP application (PEEPresponders), the best response was obtained with a PEEP of 10 cmH2O in 13 patients, 7.5 cmH2O in eight and 5 cmH2O in six. PEEP-responders were less likely to present comorbidities compared to PEEP-non responders. No differences between groups were found in regards to endotracheal intubation criteria fullfillment, intensive care unit admission and in-hospital mortality, while PEEP-responders had a shorter length of hospital stay. Discussion. The application of a protocol to evaluate PEEP responsiveness might be useful in patients with moderate-to-severe hypoxemic ARF due to CAP in order to personalize and maximize the effectiveness of therapy, and prevent the inappropriate PEEP use. PEEP responsiveness does not seem to be associated with better outcomes, with the exception of a shorter length of hospital stay

Noninvasive ventilation weaning in acute hypercapnic respiratory failure due to COPD exacerbation : A real-life observational study

The most recent British Thoracic Society/Intensive Care Society (BTS/ICS) guidelines on the use of noninvasive ventilation (NIV) in acute hypercapnic respiratory failure (AHRF) suggest to maximize NIV use in the first 24 hours and to perform a slow tapering. However, a limited number of studies evaluated the phase of NIV weaning. The aim of this study is to describe the NIV weaning protocol used in AHRF due to acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), patients' characteristics, clinical course, and outcomes in a real-life intermediate respiratory care unit (IRCU) setting. We performed a retrospective study on adult patients hospitalized at the IRCU of San Gerardo Hospital, Monza, Italy, from January 2015 to April 2017 with a diagnosis of AHRF due to COPD exacerbation. The NIV weaning protocol used in our institution consists of the interruption of one of the three daily NIV sessions at the time, starting from the morning session and finishing with the night session. The 51 patients who started weaning were divided into three groups: 20 (39%) patients (median age 80 yrs, 65% males) who completed the protocol and were discharged home without NIV (Completed Group), 20 (39%) did not complete it because they were adapted to domiciliary ventilation (Chronic NIV Group), and 11 (22%) interrupted weaning ex abrupto mainly due to NIV intolerance (Failed Group). Completed Group patients were older, had a higher burden of comorbidities, but a lower severity of COPD compared to Chronic NIV Group. Failed Group patients experienced higher frequency of delirium after NIV discontinuation. None of the patients who completed weaning had AHRF relapse during hospitalization. While other NIV weaning methods have been previously described, our study is the first to describe a protocol that implies the interruption of a ventilation session at the time. The application of a weaning protocol may prevent AHRF relapse in the early stages of NIV interruption and in elderly frail patients

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19–86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS >2 (p < 0.001) and non-complex karyotype (p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors

INCB84344-201: Ponatinib and steroids in frontline therapy for unfit patients with Ph+ acute lymphoblastic leukemia

Tyrosine kinase inhibitors have improved survival for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, prognosis for old or unfit patients remains poor. In the INCB84344-201 (formerly GIMEMA LAL 1811) prospective, multicenter, phase 2 trial, we tested the efficacy and safety of ponatinib plus prednisone in newly diagnosed patients with Ph+ ALL 6560 years, or unfit for intensive chemotherapy and stem cell transplantation. Forty-four patients received oral ponatinib 45 mg/d for 48 weeks (core phase), with prednisone tapered to 60 mg/m2/d from days-14-29. Prophylactic intrathecal chemotherapy was administered monthly. Median age was 66.5 years (range, 26-85). The primary endpoint (complete hematologic response [CHR] at 24 weeks) was reached in 38/44 patients (86.4%); complete molecular response (CMR) in 18/44 patients (40.9%) at 24 weeks. 61.4% of patients completed the core phase. As of 24 April 2020, median event-free survival was 14.31 months (95% CI 9.30-22.31). Median overall survival and duration of CHR were not reached; median duration of CMR was 11.6 months. Most common treatment-emergent adverse events (TEAEs) were rash (36.4%), asthenia (22.7%), alanine transaminase increase (15.9%), erythema (15.9%), and \u3b3-glutamyltransferase increase (15.9%). Cardiac and vascular TEAEs occurred in 29.5% (grade 653, 18.2%) and 27.3% (grade 653, 15.9%), respectively. Dose reductions, interruptions, and discontinuations due to TEAEs occurred in 43.2%, 43.2%, and 27.3% of patients, respectively; 5 patients had fatal TEAEs. Ponatinib and prednisone showed efficacy in unfit patients with Ph+ ALL; however, a lower ponatinib dose may be more appropriate in this population. This trial was registered at www.clinicaltrials.gov as #NCT01641107