Treatment of Recurrent Tracheocutaneous Fistulas in the Irradiated Neck with a Two Layers-Two Flaps Combined Technique.

The development of a tracheocutaneous fistula (TCF) is a well-documented complication after tracheostomy, especially in chronic morbid patients, in whom tubes or cannulas are left in place over time, or in irradiated patients. Surgical treatments are therefore needed which range from simple curettage and dressings to local skin flaps, muscle flaps and, in the more complex cases, microsurgical free tissue transfers. We present a novel combined technique used to successfully treat recurrent TCFs in irradiated patients, involving a superiorly based turnover fistula flap and a sternocleidomastoid transposition flap.

Haematological recovery in poor and good haematopoietic stem cell mobilisers.

OBJECTIVES: Evaluate whether poor mobilisers had delayed haematopoietic (neutrophil and platelet) recovery despite receiving similar cell dose as good mobilisers. BACKGROUND: Autologous haematopoietic progenitor cell (HPC) transplantation is indicated to treat some haematological malignancies. This procedure requires HPC mobilisation from bone marrow to peripheral blood. Cell dose is important for a fast haematological recovery. Despite being poor mobilisers, some patients can collect enough cell numbers for transplantation. RESULTS: Fifteen poor mobiliser patients (peak of CD34+ cells ≤10 µL(-1) in peripheral blood) were transplanted at our institution. Haematological recovery (neutrophil ≥ 500 µL(-1) ) in this group was compared to that observed in the group of 16 patients of good mobilisers (peak of CD34+ cells ≥20 µL(-1) in peripheral blood) who received similar cell dose (2·637 ± 0·1744 × 10(6) kg(-1) vs 2·727 ± 0·1746 × 10(6) kg(-1) ; P = 0·7177). The poor mobiliser group had neutrophil and platelet recovery later than the good mobiliser group (on day 12, range 9-14 vs day 10, range 9-22, P = 0·0381 for neutrophil, and on day 22·89 ± 11·16 and 14·08 ± 4·821, P = 0·0193 for platelet). Mortality rates and transfusion requirements were not different between the groups. CONCLUSION: Poor mobilisers have delayed neutrophil and platelet recovery after autologous HPC transplantation despite having received the same cell dose as good mobilisers.

Minimal residual disease negativity in elderly patients with acute myeloid leukemia may indicate different postremission strategies than in younger patients.

In the present analysis, we evaluated whether in elderly acute myeloid leukemia (AML) patients (>60 years), minimal residual disease (MRD) assessed by flow cytometry may have a role in guiding choice of postremission strategies. We analyzed 149 young and 61 elderly adults who achieved morphological CR after induction course of EORTC/GIMEMA protocols. Elderly patients reached a postconsolidation MRD negative status less frequently than younger ones (11 vs 28 %, p = 0.009). MRD negativity resulted in a longer 5-year disease-free survival (DFS) both in elderly (57 vs 13 %, p = 0.0197) and in younger patients (56 vs 31 %, p = 0.0017). Accordingly, 5-year cumulative incidence of relapse (CIR) of both elderly (83 vs 42 %, p = 0.045) and younger patients (59 vs 24 % p = NS) who were MRD positive doubled that of MRD negative ones. Nevertheless, CIR of MRD negative elderly patients was twofold higher than that of younger MRD negative ones (42 vs 24 %, p = NS). In conclusion, elderly patients in whom chemotherapy yields a MRD negative CR have duration of DFS and rate of CIR significantly better than those who remain MRD positive. Nonetheless, the high CIR rate observed in the elderly suggests that MRD negativity might have different therapeutic implications in this population than in the younger counterpart.

A rapid genetic counselling and testing in newly diagnosed breast cancer is associated with high rate of risk-reducing mastectomy in BRCA1/2-positive Italian women.

BACKGROUND: Risk-reducing mastectomy (RRM) decreases breast cancer (BC) risk in BRCA1/2 mutation carriers by up to 95%, but the Italian attitude towards this procedure is reluctant. PATIENTS AND METHODS: This is an observational study with retrospective design, using quantitative and qualitative research methods, aimed at evaluating the attitude towards RRM by rapid genetic counselling and testing (RGCT), at the time of BC diagnosis, compared with traditional genetic counselling and testing (TGCT), after previous BC surgery. Secondary aims were to investigate patient satisfaction after RRM and the rate of occult tumour in healthy breasts. A total of 1168 patients were evaluated: 1058 received TGCT, whereas 110 underwent RGCT. RESULTS: In TGCT, among 1058 patients, 209 (19.7%) mutation carriers were identified, with the rate of RRM being 4.7% (10 of 209). Conversely in RGCT, among 110 patients, 36 resulted positive, of which, 15 (41.7%) underwent bilateral mastectomy at the BC surgery time, showing an overall good satisfaction, measured by interpretative phenomenological analysis 12 months after the intervention. CONCLUSIONS: Our study shows that RGCT in patients with a hereditary profile is associated with a high rate of RRM at the BC surgery time, this being the pathway offered within a multidisciplinary organization.

Muscle-only versus chimeric musculocutaneous gastrocnemius pedicled flap in complex orthoplastic reconstructions of the knee region: A retrospective study.

BACKGROUND: The knee region represents a challenging area of soft tissue reconstruction. Specifically, in the context of total knee arthroplasty (TKA) or following high-energy trauma with fractures and hardware fixation, soft tissue defects can expose critical structures such as joint, bone or tendon, besides the implant/plates themselves, with dramatic consequences in terms of postoperative infection and hardware contamination. METHODS: A retrospective study was conducted on a prospectively maintained database from January 2016 to February 2021. Inclusion criteria involved all patients who underwent an implant-associated infection of the knee and upper third of the leg coupled with a soft tissue reconstruction (STR) using the traditional gastrocnemius muscle (GM) pedicled flap or the chimeric GM-MSAP (medial sural artery perforator) flap. RESULTS: Thirty-eight patients were included (group A, GM flap, 22 patients; group B, chimeric GM-MSAP flap, 16 patients). No statistically significant differences were detected in terms of age, comorbidities, defect size, follow-up, and flap complications. A statistically significant difference was seen among the groups in terms of successful flap re-raise (required because of a persistent infection of the implant or in a two-stage procedure setting, including the use of a cemented spacer) in favour of the GM-MSAP group. CONCLUSION: The chimeric GM-MSAP, being safer to reraise if required, can be a significantly more powerful tool in those cases in which a two-stage procedure is planned or when there is a high probability for secondary intervention need, reducing the need to convert to either free flap coverage or amputation.

The role of MTHFR polymorphisms in the risk of lipedema.

OBJECTIVE: This study examines the role of MTHFR gene polymorphism (rs1801133) in women with lipedema (LIPPY) body composition parameters compared to a control group (CTRL). SUBJECTS AND METHODS: We carried out a study on a sample of 45 LIPPY and 50 women as a CTRL. Body composition parameters were examined by Dual-energy X-ray Absorptiometry (DXA). A genetic test was performed for the MTHFR polymorphism (rs1801133, 677C>T) using a saliva sample for LIPPY and CTRL groups. Mann-Whitney tests evaluated statistically significant differences between four groups (carriers and non-carriers of the MTHFR polymorphism for LIPPY and CTRL groups) on anthropometric/body composition parameters to identify patterns. RESULTS: LIPPY showed significantly higher (p<0.05) anthropometric parameters (weight, BMI, waist, abdominal, hip circumferences) and lower waist/hip ratio (p<0.05) compared to the CTRL group. The association between the polymorphism alleles related to the rs1801133 MTHFR gene and the body composition values LIPPY carriers (+) showed an increase in fat tissue of legs and fat region of legs percentage, arm's fat mass (g), leg's fat mass (g), and leg's lean mass (g) (p<0.05) compared to CTRL (+). Lean/fat arms and lean/fat legs were lower (p<0.05) in LIPPY (+) than in CTRL (+). In the LIPPY (+), the risk of developing the lipedema disease was 2.85 times higher (OR=2.85; p<0.05; 95% confidence interval = 0.842-8.625) with respect to LIPPY (-) and CTRL. CONCLUSIONS: The presence or absence of MTHFR polymorphism offers predictive parameters that could better characterize women with lipedema based on the association between body composition and MTHFR presence.

Sigmoid intramural hematoma and hemoperitoneum: an early severe complication after stapled hemorrhoidopexy.

Stapled hemorrhoidopexy is a widely used surgical technique for treating hemorrhoids, although severe complications have been reported. The authors report a rare case of extensive ascending intramural hematoma of the sigmoid colon complicating stapled hemorrhoidopexy, with perforation and hemoperitoneum. Diagnosis was established at CT scan and treatment consisted of drainage, suturing, and diverting colostomy. This reported case is the ninth described in the literature, but, so far, it is not known what preventive measures to use in order to avoid such a rare complication. Adoption of a correct surgical technique remains the step of utmost importance in order to prevent such a severe postoperative complication.

How can cells sense the elasticity of a substrate? An analysis using a cell tensegrity model.

A eukaryotic cell attaches and spreads on substrates, whether it is the extracellular matrix naturally produced by the cell itself, or artificial materials, such as tissue-engineered scaffolds. Attachment and spreading require the cell to apply forces in the nN range to the substrate via adhesion sites, and these forces are balanced by the elastic response of the substrate. This mechanical interaction is one determinant of cell morphology and, ultimately, cell phenotype. In this paper we use a finite element model of a cell, with a tensegrity structure to model the cytoskeleton of actin filaments and microtubules, to explore the way cells sense the stiffness of the substrate and thereby adapt to it. To support the computational results, an analytical 1D model is developed for comparison. We find that (i) the tensegrity hypothesis of the cytoskeleton is sufficient to explain the matrix-elasticity sensing, (ii) cell sensitivity is not constant but has a bell-shaped distribution over the physiological matrix-elasticity range, and (iii) the position of the sensitivity peak over the matrix-elasticity range depends on the cytoskeletal structure and in particular on the F-actin organisation. Our model suggests that F-actin reorganisation observed in mesenchymal stem cells (MSCs) in response to change of matrix elasticity is a structural-remodelling process that shifts the sensitivity peak towards the new value of matrix elasticity. This finding discloses a potential regulatory role of scaffold stiffness for cell differentiation.

The interleukin-1 cluster gene region is associated with multiple sclerosis in an Italian Caucasian population.

BACKGROUND: Polymorphisms of the interleukin-1 (IL-1) gene family have been proposed as potential variants for different diseases including multiple sclerosis (MS). With respect to MS, IL-1 beta (-511 C/T; rs16944), IL-1 beta (+3954 C/T; rs1143634), IL-1 alpha (-889 C/T; rs1800587), IL-1 alpha (+4845 G/T; rs17561), and the variable number of tandem repeats in intron 2 of the IL-1 receptor antagonist (IL-1RN) gene polymorphisms have been studied in different ethnic groups, leading to conflicting results. METHODS: This study investigates the association between IL-1 genes and MS by means of 70 markers spanning the 1.1 Mb region where the IL-1 genes map and exploring both the linkage disequilibrium (LD) and the haplotype structure in a case-control design including 410 subjects (160 patients and 250 controls). RESULTS: From allelic/genotypic tests, significant association was found for several polymorphisms including the IL-1 beta (-511 C/T) variant (P-adjusted = 4.5 x 10(-4)) and some polymorphisms around the IL-1RN gene. The 'block-step' pattern obtained from both the LD map and pairwise analysis identifies four LD regions. Region 1 showed a significant association with MS for the global test (P < 0.0001) and haplotypes containing the IL-1 beta (-511 C/T) variant still demonstrate highly significant association with disease (P-value range: 9.9 x 10(-5) to 0.02). CONCLUSIONS: Our findings support the existence of a causative variant for MS within this candidate region in a representative Italian Caucasian population and, in particular, the role of the IL-1 beta (-511 C/T) variant warrants further investigation.

Short Report - Medical nutrition therapy for critically ill patients with COVID-19.

No Abstract Available.

The role of IL-6 gene polymorphisms in the risk of lipedema.

OBJECTIVE: Lipedema is a disorder of adipose tissue characterized by abnormal subcutaneous fat deposition, leading to swelling and enlargement of the lower limbs and trunk. The aim of this study was to evaluate the lipedema phenotype by investigating the role of polymorphisms related to IL-6 (rs1800795) gene in people with diagnosis of lipedema. The second aim was to identify indicators of body composition, useful for a differential analysis between subjects with lipedema and the control group. PATIENTS AND METHODS: Two groups are involved in the study, 45 women with lipedema (LIPPY) and 50 women randomly chosen from the population as Control (CTRL). Clinical and demographical variables recorded include weight, height, body mass index (BMI) and circumference measurements. Body composition (Fat mass, FM; lean mass, LM) was assessed by Dual-energy X-ray Absorptiometry (DXA). The genetic tests for IL-6 (rs18oo795) gene were performed for both groups, using a saliva sample. RESULTS: The study of the relationship between the IL-6 (rs1800795) gene polymorphism, the anthropometric values and the body composition indices has provided the following significant results: subjects with diagnosis of lipedema present statistically significant increased values with regard to weight, BMI, waist, abdomen and hip circumferences, arms, legs and whole FM (% and kg), gynoid FM (kg), legs LM (kg) and ASMMI. Moreover, the value of the waist hip ratio was found to be decreased. CONCLUSIONS: For the first time, we suggested that IL-6 gene polymorphism could characterize subjects with lipedema respect to Normal Weight Obese and obese subjects. The intra-group comparisons (LIPPY carriers vs. LIPPY non-carriers and CTRL carriers vs. CTRL non-carriers) showed no statistically significant values. In contrast, the inter-group comparisons (LIPPY non-carriers vs. CTRL non-carriers and LIPPY carriers vs. CTRL carriers) resulted statistically significant. We have identified other indices, such as leg index, trunk index, abdominal index, total index, that could be promising clinical tools for diagnosis of the lipedema phenotype and for predicting the evolution of the disease.

A novel sax-stent method in treatment of ascending aorta and aortic arch aneurysms evaluated by finite element simulations.

OBJECTIVES: A novel stent method to simplify treatment of proximal ascending aorta and aortic arch aneurysms was developed and investigated by finite element analysis. Therapy of ascending aortic and aortic arch aneurysms is difficult and challenging and is associated with various complications. METHODS: A 55mm wide×120mm long stent was designed without the stent graft and the stent was deployed by an endovascular method in a virtual patient-specific aneurysm model. The stress-strain analysis and deployment characteristics were performed in a finite element analysis using the Abaqus software. RESULTS: The stent, when embedded in the aortic wall, significantly reduced aortic wall stresses, while preserving the side coronary ostia and side branches in the aortic arch. When tissue growth was modeled computationally over the stent struts the wall stresses in aorta was reduced. This effect became more pronounced when increasing the thickness of the tissue growth. There were no abnormal stresses in the aorta, coronary ostium and at the origin of aortic branches. The stent reduced aneurysm expansion cause by hypertensive condition from 2mm without stenting to 1.3mm after stenting and embedding. CONCLUSION: In summary, we uncovered a simple treatment method using a bare nitinol stent without stent graft in the treatment of the proximal aorta and aortic arch aneurysms, which could eventually replace the complex treatment methods for this disease.

Mesenchymal stromal cell infusion to treat steroid-refractory acute GvHD III/IV after hematopoietic stem cell transplantation.

Acute GvHD (aGvHD) is a life-threatening complication of hematopoietic stem cell transplantation. Frontline therapy for aGvHD consists of corticosteroid administration. However, ∼25% of the patients have a steroid-refractory disease, a sign of poor prognosis. An alternative therapy for steroid-refractory aGvHD is infusion of mesenchymal stromal cells (MSCs). Herein, we report the results of 46 patients treated with MSC infusion as salvage therapy for steroid-refractory aGvHD III/IV (78% grade IV). Patients received a median cumulative dose of MSCs of 6.81 × 106/kg (range, 0.98-29.78 × 106/kg) in a median of 3 infusions (range, 1-7). Median time between the onset of aGvHD and the first MSC infusion was 25.5 days (range, 6-153). Of the patients, 50% (23/46) presented clinical improvement. Of these, 3 patients (13%) had complete response, 14 (61%) had partial response and 6 (26%) had transient partial response. The estimated probability of survival at 2s year was 17.4%. Only 2 patients (4.3%) presented acute transient side effects (nausea/vomiting and blurred vision) during cell infusion. No patient had late or severe side effects because of MSC infusion. These results suggest that this therapeutic modality is safe and should be considered for steroid-refractory aGvHD, especially in countries where other second-line agents are less available.

Expression and function of neurotrophins and their receptors in human melanocytes.

Melanocytes and cells of the nervous system are of common ectodermal origin and neurotrophins (NT) have been shown to be released by human keratinocytes. We investigated the expression and function of NT [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, NT-4/-5] and their receptors in human melanocytes. Human melanocytes produce all NT in different amounts, whereas they only release NT-4. NT-4 release is downregulated, whereas NT-3 is upregulated by ultraviolet (UVB) irradiation. Melanocytes treated with phorbol 12-myristate 13-acetate (PMA) express TrkA and TrkB, but not TrkC. NT fail to stimulate melanocyte proliferation, whereas they stimulate the synthesis of tyrosinase and tyrosinase-related protein-1 (TRP-1). Finally, NT-3, NT-4 and NGF increase melanin production. Taken together, these results demonstrate an intriguing interaction between melanocytes and the nervous system. We speculate that NT could be considered the target of therapy for disorders of skin pigmentation.

Unstructured hexahedral mesh generation of complex vascular trees using a multi-block grid-based approach.

The trend towards realistic numerical models of (pathologic) patient-specific vascular structures brings along larger computational domains and more complex geometries, increasing both the computation time and the operator time. Hexahedral grids effectively lower the computational run time and the required computational infrastructure, but at high cost in terms of operator time and minimal cell quality, especially when the computational analyses are targeting complex geometries such as aneurysm necks, severe stenoses and bifurcations. Moreover, such grids generally do not allow local refinements. As an attempt to overcome these limitations, a novel approach to hexahedral meshing is proposed in this paper, which combines the automated generation of multi-block structures with a grid-based method. The robustness of the novel approach is tested on common complex geometries, such as tree-like structures (including trifurcations), stenoses, and aneurysms. Additionally, the performance of the generated grid is assessed using two numerical examples. In the first example, a grid sensitivity analysis is performed for blood flow simulated in an abdominal mouse aorta and compared to tetrahedral grids with a prismatic boundary layer. In the second example, the fluid-structure interaction in a model of an aorta with aortic coarctation is simulated and the effect of local grid refinement is analyzed.

Severe Acute Anemia After Liver Transplantation in an Elderly Jehovah's Witness Treated With High-dose Erythropoietin and Ferric Carboxymaltose: A Case Report.

BACKGROUND: There is no standard treatment for patients with severe anemia who refuse blood transfusion or cannot receive red blood cells. CASE REPORT: After an orthotopic liver transplantation, an elderly Jehovah's Witness who refused blood transfusion presented with severe acute anemia with hemorrhagic shock. The calculated red blood cell loss was near 70%. Associated with surgical treatment and supportive measures, the patient was treated with high-dose erythropoietin and ferric carboxymaltose. RESULTS: The patient presented a rapid increase in hemoglobin concentration and reticulocyte count with resolution of hemorrhagic shock after the proposed pharmacologic treatment combined with local hemostatic measures. She was transferred to a low-risk unit 4 days after transplantation and was discharged from the hospital on day 10. The hemoglobin concentration was normal 35 days after the bleeding event. CONCLUSION: This case demonstrated that a protocol with high-dose erythropoietin and ferric carboxymaltose may be an option for patients with severe anemia who refuse blood transfusion or cannot receive red blood cells.

From teams to hierarchy: a short-lived innovation in a hospital for the elderly.

An institution created to deliver rehabilitative care to the elderly is the object of this discussion. Three years of careful planning had produced a facility with a unique spatial design, a 'team approach' rather paper documents the confrontation, during the first year, between this innovative plan and the realities of operation. When the study ended, reality was gaining the advantage over the plan.

Effect of postoperative radiation on the incorporation of tibial bone grafts in the rabbit.

A dose of 48 Gy of X-irradiation given over two to five weeks after grafting caused no significant delay in the rate of healing and only a small and statistically non-significant decrease in the torsional strength of the graft-bone junction of either vascularised or non-vascularised bone grafts of the tibiae of rabbits. Healing was faster and the union between the graft and adjacent bone developed torsional strength significantly more rapidly with vascularised than with non-vascularised grafts. These findings suggest that postoperative radiotherapy is unlikely to have a significantly deleterious effect on the healing of bone grafts used to repair defects produced by excision of malignant bone tumours.

Age-associated changes of memory (CD45RO+) and naive (CD45R+) T cells.

1. The total number of lymphocytes and the percentage of CD45RO+ (putative memory T cell) and CD45R+ (putative naive T cell) were determined in 15 cord blood samples, 66 healthy children ranging in age from 1 to 18 years, 16 adults (23-59 years) and 16 aged individuals (60-96 years). 2. The total number of lymphocytes decreased with age and reached the adult range in children aged 11-14 years. CD45R+ T cells were the predominant cell type in cord blood and decreased with age up to the adult group, while the percentage of CD45RO+ T cells was low in cord blood and increased with age. No significant difference was observed between the adult and the aged groups for either lymphocyte subset. 3. These data support the view that CD45RO+ and CD45R+ T-cell subsets represent maturational stages of T cells.

Simultaneous bimaxillary alveolar ridge augmentation by a single free fibular transfer: a case report.

Class VI atrophy according to Cawood still represents a major challenge in pre-prosthetic surgery. Reconstruction of mandibular and maxillary bony defects using microvascular techniques is safe and reliable. The fibula, due to its morphological properties, is ideal for alveolar ridge augmentation and its donor site morbidity is the lowest among vascularized bone flaps. In this paper, we report the first case, to our knowledge, of extreme atrophy of both jaws, successfully treated by simultaneous bony augmentation of the maxillary and mandibular alveolar ridges with just one free fibula flap. Pre-operative planning, surgical technique and prosthetic restoration are discussed in detail.