Effectiveness of a drain in surgical treatment of sacrococcygeal pilonidal disease. Results of a randomized and controlled clinical trial on 803 consecutive patients.

PURPOSE: The aim of this study was to evaluate the influence of cavity drainage in the surgical treatment of sacrococcygeal pilonidal sinuses. METHODS: The study was prospectively carried out in 803 patients randomized into two groups of respectively 401 and 402 patients. In the first group, primary excision and closure were associated with drainage of the wound; in the second group, the wound was not drained. We have analyzed time off work, time to walk without pain, time to sitting on the toilet without pain, recurrences, and wound infections. We have also evaluated the satisfaction rate and esthetic results. RESULTS: On comparing time off work, time to walk without pain, and time to sitting on toilet without pain postoperatively, there were no significant differences between the two groups. A significant difference between the two groups with regard to wound infection rates (p = 0.5) and recurrence rates (p = 0.6) was not observed. In order to prevent prolonged inpatient stay and social intolerance, this study suggests that the post-operative period is tolerated by a few when a drain was used. The visual analog scale (VAS) in the drained group was 3.2 ± 0.9, and VAS in the non-drained group was 3.5 ± 0.9 with a significant statistical difference (p = 0.0001). As regards the cosmetic appearance of the scar after surgery, we achieved a high satisfaction rate among patients in either group with 82.9% good cosmetic results. CONCLUSIONS: The use of a drain, in our experience, appears to be useless in achieving a quick healing of the sacral wound; in addition, it has a low satisfaction rate

Management challenges arising from COVID-19: reorganization of a healthcare setting and insights for patiet transfer workflows

The condition for the healthcare services’ provision, in a context of healthcare reorganization without increasing resources, is identified in the correct allocation of patients. During the COVID-19 pandemic and also in the times to come, access to high-intensity care will be subject to several challenges. There is, therefore, the need to promptly recognize the degree of patients complexity. It is essential to define criteria that make possible the identification of the patient correct allocation from the first access to the facility. In general, patient allocation should follow a multidisciplinary approach based both on the framing of needs by health professionals, and on an assessment that can make improvements to the health performance of the organization. Starting from the identification of three gaps in the literature: (1) low research rate for the study of inter-departmental workflows; (2) low research rate for studying the elements of patient transfer management; (3) and low research rate to analyze the coordination between medical and non-medical professionals, this work aims to identify the critical issues related to the introduction of a new setting in a hospital in Central Italy. To achieve the objective, a qualitative research study has been carried out. The results highlighted two aspects relating to the criticalities of the new structure. These will need to be taken into account to best support patient transfer activities. Analyzing clinical, organizational, managerial, and technical problems in an integrated way will help improve the management efficiency of healthcare organizations as a whole

Value-based health-care principles in health-care organizations

Purpose: This study aims to analyze the value-based health-care model in defining a strategy to guide the evolution of health-care organizations toward a value-oriented model. To improve the quality of care by ensuring economic sustainability, it is necessary to redefine the concept of competition in healthcare and align it with the concept of maximizing value for patients. Design/methodology/approach: Performance measurement is a crucial aspect of the analysis of health-care organizations. Porter developed an effective analytical technique and presented the measurement of health-care outcomes based on health conditions, the efficiency of health-care organizations and the type of service provided. Findings: Clinical outcomes and data on the costs of care of each patient are essential to evaluate improvement in treatment value over time. Engaging in the evaluation of what happens to patients in their course of care enables the expansion of the measurement of outcomes because it measures all the health services related to it. Originality/value: Building a health-care system based on the value and continuous improvement of care and services provided is a goal shared by many countries and international organizations. Today, the analysis of outcomes is important for making informed decisions, directing and planning clinical and organizational changes by improving the quality of care and services

Stem Cell Transplantation in Acute Myeloid Laeukemia

Allogeneic hematopoietic stem cell transplantation represents the only potentially curative therapeutic approach for Acute Myeloid Leukemia. The choice to perform an allogeneic hematopoietic transplant is the result of a decision-making process that considers disease-related factors (AML-risk category and the state of disease at the time of transplant), the type of donor available and his characteristics (HLA compatibility, gender, CMV serostatus) and the individual risk associated with the procedure itself. The choice of the appropriate conditioning regimen depends on the patient’s age and comorbidities. While the introduction of reduced intensity regimen and the availability of alternative donors allows more patients to be eligible for transplantation, myeloablative conditioning remains the standard of care for fit patients. Disease relapse is the leading cause of treatment failure and new strategies attempting at reducing the relapse incidence post transplantation are currently being investigated

Ruolo dell’imaging TC nella valutazione post-mortem dei soggetti deceduti per caduta da altezze elevate: nostra esperienza

The CT-v can therefore be considered an effective method as an aid in the autopsy evaluation of individuals who died for various causes; in particular, in the case of deaths due to accidental falls from high altitudes, is able to identify the primary cause of death and all the epiphenomena due to precipitation

Early hip fracture surgery and rehabilitation. How to improve functional quality outcomes. A retrospective study

Introduction: Hip fractures are one of the major disability causes associated with a high morbidity and mortality rate. Early surgery and stable fixation could be associated with better pain control, possibly lower mortality rates, and early recovery of autonomy. Aim: The aim of this study was to analyze a population affected by hip fractures exploring the effects of an early surgery and rehabilitation approach in relation to functional outcomes. Materials and methods: This study included 140 adult patients (mean age 79.35±11.71, range 66-94 years) with hip fractures admitted to the orthopedic unit of the University Hospital of Messina who underwent surgery and a rehabilitation program while hospitalized. Exclusion criteria were patients not surgically treated or discharged with no rehabilitation sessions. Clinical outcomes were evaluated post-surgery and before discharge as follows: pain quantification using the visual analogue scale and functional evaluation using the Barthel Index. A rehabilitation protocol was started within 48 hours after surgery. Results: The study sample resulted in 140 patients. Eighty-seven of them (63.14%) underwent hip replacement surgery, and 53 patients (37.86%) underwent internal fixation surgery. The greater part of the sample (68.42%) had surgery within 48 hours. Patients with more comorbidities had worse clinical outcomes, as shown by the Barthel Index, timing of verticalization and walking, and pain control. Between admission and discharge, the Barthel Index score improved, as did the pain complained of by most patients. Conclusions: A direct connection between orthopedics and the rehabilitation team, even after discharge, should be established and promptly organized to gain the best clinical outcomes. Indeed, we propose the triad early verticalization, pain control, and Barthel Index as a possible tool to define functional quality outcomes in post hip fracture surgery

Valproic Acid Synergizes With Cisplatin and Cetuximab in vitro and in vivo in Head and Neck Cancer by Targeting the Mechanisms of Resistance

Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. The combination of cisplatin (CDDP) plus cetuximab (CX) is one of the standard first-line treatments in this disease. However, this therapeutic regimen is often associated with high toxicity and resistance, suggesting that new combinatorial strategies are needed to improve its therapeutic index. In our study, we evaluated the antitumor effects of valproic acid (VPA), a well-known antiepileptic agent with histone deacetylase inhibitory activity, in combination with CDDP/CX doublet in head and neck squamous cell carcinoma (HNSCC) models. We demonstrated, in HNSCC cell lines, but not in normal human fibroblasts, that simultaneous exposure to equitoxic doses of VPA plus CDDP/CX resulted in a clear synergistic antiproliferative and pro-apoptotic effects. The synergistic antitumor effect was confirmed in four different 3D-self-assembled spheroid models, suggesting the ability of the combined approach to affect also the cancer stem cells compartment. Mechanistically, VPA enhanced DNA damage in combination treatment by reducing the mRNA expression of ERCC Excision Repair 1, a critical player in DNA repair, and by increasing CDDP intracellular concentration via upregulation at transcriptional level of CDDP influx channel copper transporter 1 and downregulation of the ATPAse ATP7B involved in CDDP-export. Valproic acid also induced a dose-dependent downregulation of epidermal growth factor receptor (EGFR) expression and of MAPK and AKT downstream signaling pathways and prevent CDDP- and/or CX-induced EGFR nuclear translocation, a well-known mechanism of resistance to chemotherapy. Indeed, VPA impaired the transcription of genes induced by non-canonical activity of nuclear EGFR, such as cyclin D1 and thymidylate synthase. Finally, we confirmed the synergistic antitumor effect also in vivo in both heterotopic and orthotopic models, demonstrating that the combined treatment completely blocked HNSCC xenograft tumors growth in nude mice. Overall, the introduction of a safe and generic drug such as VPA into the conventional treatment for R/M HNSCC represents an innovative and feasible antitumor strategy that warrants further clinical evaluation. A phase II clinical trial exploring the combination of VPA and CDDP/CX in R/M HNSCC patients is currently ongoing in our institute

Next Generation Molecular Diagnosis of Hereditary Spastic Paraplegias: An Italian Cross-Sectional Study

Hereditary spastic paraplegia (HSP) refers to a group of genetically heterogeneous neurodegenerative motor neuron disorders characterized by progressive age-dependent loss of corticospinal motor tract function, lower limb spasticity, and weakness. Recent clinical use of next generation sequencing (NGS) methodologies suggests that they facilitate the diagnostic approach to HSP, but the power of NGS as a first-tier diagnostic procedure is unclear. The larger-than-expected genetic heterogeneity-there are over 80 potential disease-associated genes-and frequent overlap with other clinical conditions affecting the motor system make a molecular diagnosis in HSP cumbersome and time consuming. In a single-center, cross-sectional study, spanning 4 years, 239 subjects with a clinical diagnosis of HSP underwent molecular screening of a large set of genes, using two different customized NGS panels. The latest version of our targeted sequencing panel (SpastiSure3.0) comprises 118 genes known to be associated with HSP. Using an in-house validated bioinformatics pipeline and several in silico tools to predict mutation pathogenicity, we obtained a positive diagnostic yield of 29% (70/239), whereas variants of unknown significance (VUS) were found in 86 patients (36%), and 83 cases remained unsolved. This study is among the largest screenings of consecutive HSP index cases enrolled in real-life clinical-diagnostic settings. Its results corroborate NGS as a modern, first-step procedure for molecular diagnosis of HSP. It also disclosed a significant number of new mutations in ultra-rare genes, expanding the clinical spectrum, and genetic landscape of HSP, at least in Italy

Potential clinical impact of T-cell lymphocyte kinetics monitoring in patients with B cell precursors acute lymphoblastic leukemia treated with blinatumomab: a single-center experience

Blinatumomab is a bispecific anti-CD3 and anti-CD19 antibody that acts as a T-cell engager: by binding CD19+ lymphoblasts, blinatumomab recruits cytotoxic CD3+ T-lymphocytes to target the cancer cells. Here we describe seven different patients affected by B-cell precursor acute lymphoblastic leukemia (Bcp-ALL) and treated with blinatumomab, on which we evaluated the potential association between the amount of different T-cells subsets and deep molecular response after the first cycle, identified as a complete remission in the absence of minimal residual disease (CR/MRD). The immune-system effector cells studied were CD3+, CD4+ effector memory (T4-EM), CD8+ effector memory (T8-EM), and T-regulatory (T-reg) lymphocytes, and myeloid-derived suppressor cells (MDSC). Measurements were performed in the peripheral blood using flow cytometry of the peripheral blood at baseline and after the first cycle of blinatumomab. The first results show that patients with a higher proportion of baseline T-lymphocytes achieved MRD negativity more frequently with no statistically significant difference (p=0.06) and without differences in the subpopulation count following the first treatment. These extremely preliminary data could potentially pave the way for future studies, including larger and less heterogeneous cohorts, in order to assess the T-cell kinetics in a specific set of patients with potential synergy effects in targeting myeloid-derived suppressor cells (MDSC), commonly known to have an immune evasion mechanism in Bcp-ALL

Impairment of circulating endothelial progenitors in Down syndrome

<p>Abstract</p> <p>Background</p> <p>Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.</p> <p>Methods</p> <p>Circulating endothelial progenitors of Down syndrome affected individuals were isolated, <it>in vitro </it>cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of <it>CXCL12 </it>gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.</p> <p>Results</p> <p>We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.</p> <p>Conclusions</p> <p>Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.</p