Targeted therapy in BRAF mutated aggressive papillary craniopharyngioma: a case report and overview of the literature.

BACKGROUND: Papillary craniopharyngiomas harbor the BRAF V600E mutation, which paves the way for using BRAF inhibitor molecules to treat tumors refractory to standard therapies. Single case reports confirmed the efficacy of targeted therapy. However, most reports were limited by the short follow-up. We describe the long-term course of a patient treated with dual-agent BRAF and MEK inhibitors and review the available literature. CASE REPORT: A 75-year-old male patient had recurrence of a papillary craniopharyngioma after transsphenoidal surgery and Gamma Knife radiosurgery. Review of the pathologic specimen confirmed the presence of the BRAF V600E mutation. Because of the few therapeutic options, we decided to initiate BRAF/MEK inhibitor combined therapy for six months. Rapid reduction of the tumor occurred, but three months after quitting combined medical therapy the tumor recurred. BRAF/MEK inhibitor therapy was resumed and the tumor again showed a marked reduction. The second course was maintained for 20 months and the tumor showed another recurrence within three months, which, again, responded to a third course of targeted therapy. CONCLUSIONS: Our study confirms the excellent response of papillary craniopharyngioma to combined BRAF and MEK inhibitors. However, rapid tumor recurrence is the rule when medical therapy is stopped. Resistance to a second and third course of targeted therapy did not occur, suggesting that tumor mutations affecting the response to drugs seems an uncommon event in papillary craniopharyngioma. The exact role of targeted therapy in the treatment algorithm of papillary craniopharyngiomas has still to be refined.

Clinical and diagnostic findings in COVID-19 patients: an original research from SG Moscati Hospital in Taranto Italy.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide medical challenge due to the scarcity of proper information and remedial resources. The ability to efficiently avoid a further SARS-CoV-2 pandemic will, therefore, depend on understanding several factors which include host immunity, virus behavior, prevention measures, and new therapies. This is a multi-phase observatory study conducted in the SG Moscati Hospital of Taranto in Italy that was converted into COVID-19 Special Care Unit for SARS-Co-V2 risk management. Patients were admitted to the 118 Emergency Pre-Hospital and Emergency Department based on two diagnostic criteria, the nasopharyngeal swab assessed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and CT-scan image characterized by ground glass opacity. Patients were divided into four groups, positive-positive (ER-PP), negative-positive (ER-NP), negative-negative (ER-NN) and a group admitted to the ICU (ER-IC). A further control group was added when the T and B lymphocyte subsets were analyzed. Data included gender, age, vital signs, arterial blood gas analysis (ABG), extensive laboratory results with microbiology and bronchoalveolar lavage fluid (BALF) which were analyzed and compared. Fundamental differences were reported among the groups. Males were significantly higher in PP, ICU, and NP groups, from 2 to 4-fold higher than females, while in the NN group, the number of females was mildly higher than males; the PP patients showed a marked alkalotic, hypoxic, hypocapnia ABG profile with hyperventilation at the time of admission; finally, the laboratory and microbiology results showed lymphopenia, fibrinogen, ESR, CRP, and eGFR were markedly anomalous. The total number of CD4+ and CD8+ T cells was dramatically reduced in COVID-19 patients with levels lower than the normal range delimited by 400/µL and 800/µL, respectively, and were negatively correlated with blood inflammatory responses.

Experimental and Numerical Characterization of the Mechanical Masseter Muscle Response During Biting.

Predictive simulations of the mastication system would significantly improve our understanding of temporomandibular joint (TMJ) disorders and the planning of cranio-maxillofacial surgery procedures. Respective computational models must be validated by experimental data from in vivo characterization of the mastication system's mechanical response. The present pilot-study demonstrates the feasibility of a combined experimental and numerical procedure to validate a computer model of the masseter muscle. An experimental setup is proposed that provides a simultaneous bite force measurement and ultrasound-based visualization of muscle deformation. The direct comparison of the experimentally observed and numerically predicted muscle response demonstrates the predictive capabilities of such anatomically accurate biting models. Differences between molar and incisor biting are investigated; muscle deformation is recorded for three different bite forces in order to capture the effect of increasing muscle fiber recruitment. The three-dimensional (3D) muscle deformation at each bite position and force-level is approximatively reconstructed from ultrasound measurements in five distinct cross-sectional areas (four horizontal and one vertical cross section). The experimental work is accompanied by numerical simulations to validate the predictive capabilities of a constitutive muscle model previously formulated. An anatomy-based, fully 3D model of the masseter muscle is created from magnetic resonance images (MRI) of the same subject. The direct comparison of experimental and numerical results revealed good agreement for maximum bite forces and masseter deformations in both biting positions. The present work therefore presents a feasible in vivo measurement system to validate numerically predicted masseter muscle contractions during mastication.

Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Persistence of polypropylene mesh anisotropy after implantation: an experimental study.

OBJECTIVE: To determine whether anisotropy persisted after incorporation into the host, using a standardised rabbit model for abdominal wall reconstruction. DESIGN: Investigator-initiated prospective-controlled experimental study. SETTING: Centre for Surgical Technologies, Medical Faculty KU-Leuven. SAMPLE: Fifteen New Zealand White rabbits. METHODS: In each rabbit, four full thickness primarily repaired abdominal wall defects were covered by a 4 × 5-cm Prolift+M implant (Johnson & Johnson, Norderstedt, Germany), either with the stiffest (n = 6 rabbits) or most elastic (n = 6) direction parallel to the body axis. Prolift+M contains 32 g/m² polypropylene, reinforced with polyglecaprone fibres. Harvesting was performed after 30, 60 and 120 days (n = 2 each time-point). The abdominal wall of three unoperated rabbits was used as negative control. MAIN OUTCOME MEASURES: Contraction, compliance and maximal strain and stress determined by uniaxial tensiometry. RESULTS: Anisotropy properties persist at lower, more physiological displacements, but not at higher displacements. The stiffness of a mesh-augmented repair in the lower strain range remains above that of native tissue. Eventual mesh contraction was limited to 4.3%. CONCLUSIONS: Anisotropic properties of Prolift+M persist in vivo and shrinkage is minimal. Compliance of mesh-augmented repair remains less than that of native tissue. The functional consequences of this remain to be studied.

Polytherapy in bone regeneration: clinical applications and preliminary considerations.

Polytherapy, namely the simultaneous application of three fundamental elements necessary for bone regeneration (growth factors, osteogenic cells and osteoconductive scaffolds) seems to lead to a very high success rate in the treatment of complex non-union (NU) cases and critical bone defects. NU are reported in 5-10% of long bone fractures. The use of autologous bone grafts has been long-considered the gold standard for the treatment of these cases. However the harvesting procedure from the iliac crest increases surgery time and presents some donor site complications which may be elevated. In recent years, surgeons have some alternatives to autologous grafting such as: application of organic or synthetic bone substitute, application of mesenchymal stromal cells (MSC) or growth factors (GF). In the literature there are many studies available about their application in monotherapy, but unfortunately the healing rate doesn't exceed 90%. Polytherapy seems to be a logical option to improve the healing rate, nevertheless, there are not still extensive studies that validate this strategy and moreover, some questions are not resolved.

Mussel-mimetic tissue adhesive for fetal membrane repair: a standardized ex vivo evaluation using elastomeric membranes.

OBJECTIVE: Iatrogenic preterm premature rupture of membranes (iPPROM), the main complication of invasive interventions in the prenatal period, seriously limits the benefit of diagnostic or surgical prenatal procedures. This study aimed to evaluate preventive plugging of punctured fetal membranes in an ex vivo situation using a new mussel-mimetic tissue adhesive (mussel glue) to inhibit leakage. METHODS: A novel biomechanical test device that tests the closure of injured membranes under near-physiological conditions was used. Mussel glue, a poly(ethylene glycol)-based hydrogel, was used to seal membrane defects of up to 3 mm in mechanically well-defined elastomeric membranes with three different degrees of stiffness. RESULTS: Elastomeric test membranes were successfully employed for testing mussel glue under well-defined conditions. Mussel glue plugs were distended by up to 94%, which translated to an improved sealing efficiency on elastomeric membranes with high stiffness. For the stiffest membrane tested, a critical burst pressure of 48 mbar (36 mmHg) was accomplished in this ex vivo setting. CONCLUSIONS: Mussel glue appears to efficiently seal membrane defects under well-standardized ex vivo conditions. As repaired membranes resist pressures measured in amniotic cavities, mussel glue might represent a novel sealing method for iatrogenic membrane defects.

Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial.

OBJECTIVE: The aim of the study was to compare sequential versus combined diuretic therapy in patients with cirrhosis, moderate ascites and without renal failure. DESIGN: One hundred patients were randomly assigned to the two diuretic treatments. The sequential treatment provided potassium canrenoate at the initial dose of 200 mg/day, then increased to 400 mg/day. Non-responders were treated with 400 mg/day of potassium canrenoate and furosemide at an initial dose of 50 mg/day, then increased to 150 mg/day. The combined treatment provided the initial dose of 200 mg/day of potassium canrenoate and 50 mg/day of furosemide, then increased to 400 mg/day and 150 mg/day, respectively. RESULTS: Most patients who received sequential treatment responded to potassium canrenoate alone (19% to 200 mg/day and 52.63% to 400 mg/day, respectively). Most patients who received the combined treatment responded to the first two steps (40% to the first step and 50% to the second, ie, 400 mg/day of potassium canrenoate plus 100 mg/day of furosemide). Adverse effects (38% vs 20%, p<0.05), in particular, hyperkalaemia (18% vs 4%, p<0.05), were more frequent in patients who received sequential therapy. As a consequence, the per cent of patients who resolved ascites without changing the effective diuretic step was higher in those who received the combined treatment (56% vs 76%, p<0.05). CONCLUSIONS: The combined diuretic treatment is preferable to the sequential one in the treatment of moderate ascites in patients with cirrhosis and without renal failure. NCT00741663. This work is an open randomised clinical trial.

Mediterranean Diet In Healthy Aging.

The World elderly population is expected to double before 2050. Unhealthy habits and unhealthy lifestyles are commonly associated with age-related diseases or their worsening. Modification in daily lifestyle and diet may help preventing age-related diseases onset and efficiently affecting their evolution, thus promoting the Healthy Aging process, concept recently coined to describe the disease-free aging process. This review highlights the role of nutrition science in promoting healthy aging. Since the Mediterranean Model demonstrated to be a useful style in supporting healthy aging, promotion of this correct lifestyle by health policies seems to be the best approach to achieve this target.

Typical CT findings of COVID-19 pneumonia in patients presenting with repetitive negative RT-PCR.

Multiple polymerase chain reaction (RT-PCR) is considered the gold standard diagnostic investigation for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, false negative multiple polymerase chain reaction (RT-PCR) results can be diagnostically challenging. We report three patients with history of fever and different clinical signs. During the height of the pandemic in Italy (March to May 2020), these patients underwent chest computed tomography (CT) scans that showed lung alterations typical of COVID-19 with multiple negative RT-PCR tests and positive serology for SARS-CoV-2. Two of the three patients showed residual pneumonia on CT after the onset of the first clinical signs. One patient presented with diarrhoea without respiratory symptoms. These cases suggest that in the COVID-19 pandemic period, to provide an earlier specific treatment in patients with positive serology, a chest CT scan can be useful in those presenting with a fever or a history of fever associated with persistent mild respiratory symptoms or with abdominal complaints despite repeated negative RT-PCR results.

How cosmetic tightening products modulate the biomechanics and morphology of human skin.

The active and passive mechanical behavior of a cosmetic tightening product for skin anti-aging is investigated based on a wide range of in vivo and in vitro measurements. The experimental data are used to inform a numerical model of the attained cosmetic effect, which is then implemented in a commercial finite-element framework and used to analyze the mechanisms that regulate the biomechanical interaction between the native tissue and the tightening film. Such a film reduces wrinkles and enhances skin consistency by increasing its stiffness by 48-107% and reducing inelastic, non-recoverable deformations (-47%). The substrate deformability influences both the extent of tightening and the reduction of wrinkle amplitude. The present findings allow, for the first time, to rationalize the mechanisms of action of cosmetic products with a tightening action and provide quantitative evidence for further optimization of this fascinating class of biomaterials.

Efficacy and safety of a novel hydrogel (HYADD4-G) in degenerative disc disease patients: a multicentric open label study.

OBJECTIVE: In this premarket clinical study, we evaluated the efficacy and safety of a novel Hydrogel (HYADD4-G) for reducing low back pain (LBP) in patients with degenerative disc disease (DDD). PATIENTS AND METHODS: Twenty-three patients with chronic LBP were enrolled. All patients presented with up to three lumbar black discs (Pfirrmann grade III or IV), LBP of at least 40 mm on the Visual Analogue Scale (VAS), and a Roland-Morris Disability Questionnaire (RMDQ) score of at least 9. Patients received a single 1.5 ml intradiscal injection of HYADD4-G (8 mg/ml), guided by X-ray. Our primary endpoint was the change in VAS score from baseline (day 0) to 4, 12, and 24 weeks. Our secondary endpoints were black disc hydration by Magnetic Resonance Imaging (MRI); the patient's therapeutic response according to the RMDQ; the quality of life, as determined by the EuroQol-5 Dimension (EQ-5D) Index; and a global assessment of patient health status, safety, and local tolerability. RESULTS: Compared with baseline values, VAS score showed a significant reduction at each time point, and across the overall 24-week follow-up period (p < 0.0001). MRI scanning observed a significant reduction in Pfirrmann grade from baseline, by at least one grade, at both week 4 (p = 0.0039) and week 24 (p = 0.0010). Furthermore, compared with baseline values, there was a significant reduction in RMDQ score at each timepoint, and across the entire study period (p < 0.0001). The EQ-5D index increased significantly from baseline to week 24 (p = 0.0001). Finally, mean VAS scores for Patient Global Assessment (PTGA), and Clinical Observer Global Assessment (COGA), decreased significantly at each time point (p < 0.0001), except for week 4. CONCLUSIONS: HYADD4-G proved to be an efficient reliever of low back pain due to DDD.

Metastatic incidence of (PET)CT positive lung hilar and retroperitoneal lymph nodes in esophageal cancer patients.

BACKGROUND: Extra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions. METHODS: All patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012-December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates. RESULTS: From 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up. CONCLUSIONS: The majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy.

A multi-centre retrospective review of second-line therapy in advanced pancreatic adenocarcinoma.

INTRODUCTION: Limited information on second-line treatment in patients with pancreatic adenocarcinoma is available. At time of first-line treatment failure, approximately half of the patients are candidates for further treatment. MATERIAL AND METHODS: A retrospective review of 183 patients submitted to second-line therapy has been performed to identify prognostic factors, provides useful information for patients counseling and generates hypotheses for future studies. Inclusion criteria were: cytological or histologic diagnosis of pancreatic adenocarcinoma and prior gemcitabine-including chemotherapy. Any age, performance status (PS) and chemotherapy regimen were considered. RESULTS: One hundred and eighty-three patients (106 males; 168 metastatic; median age 62 years; median PS 1; 63 submitted to prior curative surgery, 32 to prior radiotherapy) with a median previous progression-free survival (PFS) of 6.7 months were included. Median and 6-month PFS after initiation of salvage therapy were 3.0 months and 20%. Median, 1 and 2 years, overall survival after initiation of salvage therapy were 6.2 months, 17 and 4%, respectively. Previous PFS, CA19.9 levels and age independently predicted OS. CONCLUSION: Re-challenge with gemcitabine and 5-fluorouracil administration may have a role in selected patients.

Long-term follow-up of patients with hyperthyroidism due to Graves' disease treated with methimazole. Comparison of usual treatment schedule with drug discontinuation vs continuous treatment with low methimazole doses: a retrospective study.

Antithyroid drugs may be proposed as the firstline therapy for hyperthyroidism due to Graves' disease since some patients undergo prolonged remission after drug withdrawal. On the other hand, some studies, though controversial, indicated that methimazole (MMI) has some immunomodulating activity. We retrospectively analyzed 384 consecutive patients newly diagnosed with Graves' disease in the years 1990-2002 to ascertain whether long-term therapy with low doses of MMI may prevent relapse of thyrotoxicosis. Two hundred and forty-nine patients were included in our study. The date of reduction of MMI dose to 5 mg/day was considered time 0 for survival analysis. In 121 MMI was discontinued in less than 15 months after time 0 (group D), while in the remaining 128 a daily MMI 2.5-5 mg dose was maintained (group M). One hundred and thirty-five patients were excluded for inadequate response to MMI, relapse of thyrotoxicosis that could be related to an improper withdrawal or reduction of MMI, inadequate or too short followup, iodide contamination, steroid or interferon therapy, pregnancy or post-partum. D and M groups did not differ for clinical and hormonal parameters except age, which was lower in D (p=0.019). Age > vs < 35 yr was relevant in survival analysis; therefore patients were divided in 2 groups according to this age cut-off. In younger patients relapse of thyrotoxicosis occurred in 15 patients of group D 2.4-39.6 months (median 19.0) after time 0, and 8 M after 5.9-40.0 (21.3) months, while 14 D and 5 M maintained euthyroidism until the end of the observation after 31.8-95.3 (56.6) months and 30.4-62.1 (46.5) months, respectively. Survival analysis indicated that the risk of relapse was similar in group D and M. In older patients relapse of thyrotoxicosis occurred in 40 patients of group D after 8.2-65.8 (25.4) months and 29 M after 5.8-62.5 (22.4) months, while 52 D and 86 M maintained euthyroidism until the end of the observation, 20.1-168.0 (46.7) months and 24.1-117.4 (53.4) months respectively. Survival analysis indicated that the risk of relapse was increased in group D. Therefore long-term treatment with low doses of MMI seems to prevent relapse in Graves' disease in patients above 35 yr of age. This should be confirmed in a prospective study.

Corrugated diaphragm shape design study for hemocompatible pulsatile ventricular assist devices.

We aim to maximize the pumping volume of a pulsatile ventricular assist device, where the diaphragm is covered with an endothelial cell layer. These cells are estimated to survive a cyclic strain up to fifteen percent. To increase the pumping volume under this strain constraint we use an approach based on corrugation of the diaphragm in its reference configuration. The paper explains the parametrization scheme for finding corrugation shapes, addresses modeling and evaluation schemes and reports on the results of a parameter study. The results show that corrugated diaphragm shapes are effective for increasing pumping volumes under a strain constraint.

The suture retention test, revisited and revised.

A systematic investigation of the factors affecting the suture retention test is performed. The specimen width w and the distance a of the suture bite from the specimen free edge emerge as the most influential geometrical parameters. A conservative approach for the quantification of suture retention strength is identified, based on the use of a camera to monitor the incipient failure and detect the instant of earliest crack propagation. The corresponding critical force, called break starting strength, is extremely robust against test parameter variations and its dependence on the specimen geometry becomes negligible when a≥ 2mm and w≥ 10mm. Comparison of suture retention and mode I crack opening tests reveals a linear correlation between break starting strength and tearing energy. This suggests that the defect created by the needle and the load applied by the suture thread lead to a fracture mechanics problem, which dominates the initiation of failure.

Correlating diameter, mechanical and structural properties of poly(l-lactide) fibres from needleless electrospinning.

The development and application of nanofibres requires a thorough understanding of the mechanical properties on a single fibre level including respective modelling tools for precise fibre analysis. This work presents a mechanical and morphological study of poly-l-lactide nanofibres developed by needleless electrospinning. Atomic force microscopy (AFM) and micromechanical testing (MMT) were used to characterise the mechanical response of the fibres within a diameter range of 200-1400 nm. Young's moduli E determined by means of both methods are in sound agreement and show a strong increase for thinner fibres below a critical diameter of 800 nm. Similar increasing trends for yield stress and hardening modulus were measured by MMT. Finite element analyses show that the common practice of modelling three-point bending tests with either double supported or double clamped beams is prone to significant bias in the determined elastic properties, and that the latter is a good approximation only for small diameters. Therefore, an analytical formula based on intermediate boundary conditions is proposed that is valid for the whole tested range of fibre diameters, providing a consistently low error in axial Young's modulus below 10%. The analysis of fibre morphology by differential scanning calorimetry and 2D wide-angle X-ray scattering revealed increasing polymer chains alignment in the amorphous phase and higher crystallinity of fibres for decreasing diameter. The combination of these observations with the mechanical characterisation suggests a linear relationship between Young's modulus and both crystallinity and molecular orientation in the amorphous phase. STATEMENT OF SIGNIFICANCE: Fibrous membranes have rapidly growing use in various applications, each of which comes with specific property requirements. However, the development and production of nanofibre membranes with dedicated mechanical properties is challenging, in particular with techniques suitable for industrial scales such as needleless electrospinning. It is therefore a key step to understand the mechanical and structural characteristics of single nanofibres developed in this process, and to this end, the present work presents changes of internal fibre structure and mechanical properties with diameter, based on dedicated models. Special attention was given to the commonly used models for analyzing Young's modulus of single nanofibers in three-point bending tests, which are shown to be prone to large errors, and an improved robust approach is proposed.

Development of a Novel Human Cell-Derived Tissue-Engineered Heart Valve for Transcatheter Aortic Valve Replacement: an In Vitro and In Vivo Feasibility Study.

Transcatheter aortic valve replacement (TAVR) is being extended to younger patients. However, TAVR-compatible bioprostheses are based on xenogeneic materials with limited durability. Off-the-shelf tissue-engineered heart valves (TEHVs) with remodeling capacity may overcome the shortcomings of current TAVR devices. Here, we develop for the first time a TEHV for TAVR, based on human cell-derived extracellular matrix and integrated into a state-of-the-art stent for TAVR. The TEHVs, characterized by a dense acellular collagenous matrix, demonstrated in vitro functionality under aortic pressure conditions (n = 4). Next, transapical TAVR feasibility and in vivo TEHV functionality were assessed in acute studies (n = 5) in sheep. The valves successfully coped with the aortic environment, showing normal leaflet motion, free coronary flow, and absence of stenosis or paravalvular leak. At explantation, TEHVs presented full structural integrity and initial cell infiltration. Its long-term performance proven, such TEHV could fulfill the need for next-generation lifelong TAVR prostheses.

Carbapenem-Resistant Klebsiella Pneumoniae Infections Early After Liver Transplantation: A Single-Center Experience.

The aims of this study were to define in a cohort of 310 liver transplant recipients, the incidence of post-liver transplantation (LT) non-carbapenem-resistant Klebsiella pneumoniae (CRKP) and CRKP infections, pre- and post-LT CRKP colonization, CRKP-associated mortality, and risk factors for non-CRKP and CRKP infections. Every patient was screened for CRKP immediately before and after LT. The 6-month survival rate was 95%. Fifty-two patients became infected (16.5%): 8 by CRKP (2.5%) and 44 (14%) by a non-CRKP micro-organism. Median onset of CRKP infections occurred at postoperative (POD) 12 (range, 4-70). CRKP colonization occurred in 20 patients (6%): 10 before LT (3 infected and died) and 10 after (5 infected, 3 died). CRKP- versus non-CRKP-infected patients had higher rates of intensive care unit (ICU) and hospital mortality (50% vs 20% and 62.5% vs 36%; P ≤ .001), septic shock (87% vs 34%; P = .0057; confidence interval [CI], 9.8-71.5), prolonged mechanical ventilation (100% vs 64%; P = .043, CI, 3.5-51.9), and renal replacement therapy (87% vs 41%; P = .0177; CI, 2.8-65). The small number of CRKP-infected patients did not allow the definition of specific risk factors for CRKP infection. At univariate analysis, pre- and post-LT colonization (odds ratio [OR], 10.76; CI, 2.6-44; OR, 14.99; CI, 3.83-58.66, respectively), relaparotomy (OR, 9.09; CI, 4.01-20.6), retransplantation (OR, 7.45; CI, 3.45-16), bile leakage (OR, 61.28; CI, 9.23-80), and early allograft dysfunction (EAD; OR, 5.7; CI, 3-10.7) were significantly associated with infections, making CRKP colonization (any time) and post-LT surgical and medical complications critical factors for post-LT CRKP infections.