Predictors of Efficacy of Janus Kinase Inhibitors in Patients Affected by Ulcerative Colitis.

Personalised medicine and the identification of predictors of the efficacy of specific drugs represent the ultimate goal for the treatment of ulcerative colitis (UC) in order to break the current therapeutic ceiling. JAK inhibitors are a new class of advanced therapies, orally administered, showing a good profile of efficacy and safety in both randomised controlled trials (RCTs) and real-world studies. Unfortunately, to date, it is not possible to draw the ideal profile of a patient maximally benefiting from this class of drugs to guide clinicians' therapeutic choices. Baseline clinical activities and inflammatory biomarkers, as well as their early variation after treatment initiation, emerged as the main predictors of efficacy from post hoc analyses of RCTs with tofacitinib. Similar findings were also observed in the real-life studies including mainly patients with a history of pluri-refractoriness to biological therapies. At last, a few new biomarkers have been explored, even though they have not been validated in large cohorts. This paper provides a review of the current knowledge on clinical variables and biomarkers predicting response to JAK inhibitors in UC.

Dynamic Contrast-Enhanced Ultrasound in the Prediction of Advanced Hepatocellular Carcinoma Response to Systemic and Locoregional Therapies.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the sixth most common malignant tumor in the world, with an incidence of 2-8% per year in patients with hepatic cirrhosis or chronic hepatitis. Despite surveillance schedules, it is sometimes diagnosed at an advanced stage, requiring complex therapeutic efforts with both locoregional and systemic treatments. Traditional radiological tools (computed tomography and magnetic resonance) are used for the post-treatment follow-up of HCC. The first follow-up imaging is performed at 4 weeks after resection or locoregional treatments, or after 3 months from the beginning of systemic therapies, and subsequently every 3 months for the first 2 years. For this reason, these radiological methods do not grant the possibility of an early distinction between good and poor therapeutic response. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced ultrasound (DCE-US) have gained the interest of several researchers for their potential role in the early assessment of response to locoregional treatments (chemoembolization) or antiangiogenic therapies in patients with advanced HCC. In fact, DCE-US, through a quantitative analysis performed by specific software, allows the construction of time-intensity curves, providing an evaluation of the parameters related to neoplastic tissue perfusion and its potential changes following therapies. It has the invaluable advantage of being easily repeatable, minimally invasive, and able to grant important evaluations regarding patients' survival, essential for well-timed therapeutic changes in case of unsatisfying response, and eventual further treatment planning.

The Role of Transabdominal Ultrasound Elastography in Gastrointestinal Non-Liver Diseases: Current Application and Future Prospectives.

Ultrasound imaging is the first-line investigation for patients with abdominal symptoms, as it effectively depicts the gastrointestinal tract and enables the diagnosis of multiple pathological conditions. Among different recent ultrasound technological advancements, elastography enables the evaluation of various tissue characteristics, such as neoplastic transformation or fibroinflammatory status. In recent years, ultrasound elastography has been utilized extensively for the study of liver diseases and in numerous other clinical settings, including gastrointestinal diseases. Current guidelines suggest the use of transabdominal ultrasound elastography to characterize bowel wall lesions, to assess gastrointestinal contractility, to diagnose and grade chronic pancreatitis; however, no specific indications are provided. In the present paper, we summarize the evidence concerning the application of different ultrasound elastography modalities in gastrointestinal non-liver diseases.

AAV vector encoding human VEGF165-transduced pectineus muscular flaps increase the formation of new tissue through induction of angiogenesis in an in vivo chamber for tissue engineering: A technique to enhance tissue and vessels in microsurgically engineered tissue.

In regenerative medicine, new approaches are required for the creation of tissue substitutes, and the interplay between different research areas, such as tissue engineering, microsurgery and gene therapy, is mandatory. In this article, we report a modification of a published model of tissue engineering, based on an arterio-venous loop enveloped in a cross-linked collagen-glycosaminoglycan template, which acts as an isolated chamber for angiogenesis and new tissue formation. In order to foster tissue formation within the chamber, which entails on the development of new vessels, we wondered whether we might combine tissue engineering with a gene therapy approach. Based on the well-described tropism of adeno-associated viral vectors for post-mitotic tissues, a muscular flap was harvested from the pectineus muscle, inserted into the chamber and transduced by either AAV vector encoding human VEGF165 or AAV vector expressing the reporter gene ß-galactosidase, as a control. Histological analysis of the specimens showed that muscle transduction by AAV vector encoding human VEGF165 resulted in enhanced tissue formation, with a significant increase in the number of arterioles within the chamber in comparison with the previously published model. Pectineus muscular flap, transduced by adeno-associated viral vectors, acted as a source of the proangiogenic factor vascular endothelial growth factor, thus inducing a consistent enhancement of vessel growth into the newly formed tissue within the chamber. In conclusion, our present findings combine three different research fields such as microsurgery, tissue engineering and gene therapy, suggesting and showing the feasibility of a mixed approach for regenerative medicine.

Innervation of a prefabricated flap: a new experimental model.

INTRODUCTION: Flap innervation by neoaxonogenesis is a promising field of investigation. The authors evaluated the possibility of innervating an acellular collagen scaffold as component of a potential prefabricated flap. MATERIALS AND METHODS: Collagen matrix sheets were implanted around the femoral bundle of a murine model to produce two flaps on proximal and distal nerve stumps based on a flow-through model. After thirty days, nerve regeneration and integration into the collagen matrix were evaluated. The specimens were microscopically analyzed to study Schwann cell colonization and axonal integration with the matrix. Axonal count and density were assessed and statistically evaluated. RESULTS: Qualitative structural and ultrastructural evaluation indicated integration, with axonal fibers merged within the collagen matrix, along with a newly formed vascular network on the proximal flap. Wallerian degeneration occurred inside the distal chamber. Axonal count and density did not show statistically significant differences between the nerve inside the proximal flap and the control side. CONCLUSIONS: Innervation of an acellular matrix can be obtained by direct nerve stump implantation. The flow-through system was relatively easy to build and reliable to provide adequate blood supply. The collagen scaffold may be a promising support or further studies of preinnervated microsurgical flaps.

Vacuum-assisted closure for the treatment of Fournier's gangrene.

BACKGROUND: Fournier's gangrene (FG) is a very aggressive necrotizing fasciitis involving subcutaneous fat and skin of scrotal and perineal regions. Vacuum-assisted closure (VAC) is a well-known method used to treat complex wounds. The authors for the first time enhance a multimodal strategy to treat the FG using VAC, reducing the number of surgical debridements, allowing a one-step surgical reconstruction with locoregional fasciocutaneous flap. METHODS: Six patients with the diagnosis of FG were reviewed retrospectively at our institution. All patients were affected by very extensive FG. The FG Severity Index (FGSI) was used to evaluate the prognosis of the case at admission. Following the acute phase (24-48 h), VAC was used to achieve wound cleaning and prepare the area to a single-stage reconstruction with superomedial thigh flap. Hyperbaric oxygen therapy was also used before final reconstruction. RESULTS: The average FGSI was 10.5, ranging from 8 to 12. All patients survived and were completely healed at the mean follow-up time of 9 months (range 3-30 months). CONCLUSIONS: VAC therapy is effective to clean and prepare the wounds, cutting off the fasciitis process and reducing the hospital stay and patient discomfort. Multidisciplinary treatment is mandatory during this devastating infection.

An anterior-lateral thigh perforator flap on a recipient brachial-radial vein graft for complex wound reconstruction: a case report.

A case of challenging microsurgical reconstruction of a difficult defect in a radiated upper limb is reported. A difficult wound, with tendon and bone exposition, developed on the dorsum of the forearm in a 76-year-old patient; she had been radiated since almost 50 years and her left hand had also been revascularized twice with venous grafts between the humeral artery and the superficial palmar arch. After failure of a local flap, an anterior-lateral thigh perforator flap was successfully transferred with end-to-side anastomoses on the arterialized venous graft. Up to date follow-up shows a good outcome. The Authors discuss the case and review the indications for microsurgical reconstruction in difficult wounds after radiation and ischemic limb conditions.

The use of sentinel node biopsy and selective lymphadenectomy in squamous cell carcinoma of the upper limb. Usefulness of sentinel node biopsy to avoid useless lymphadenectomies in high-risk upper limb SCC.

BACKGROUND: Squamous cell carcinoma (SCC) is the second most common skin cancer in humans. Because the incidence of metastasis from SCC of the skin is rare, regional lymphadenectomy is generally not recommended for the patients with clinically node-negative disease. However, in patients with an intermediate and high risk of metastasis, evaluation of the lymph nodes to detect the absence of metastatic nodal disease is a difficult task. PATIENTS AND METHODS: The authors reviewed the pertinent demographic and surgical data in a consecutive series of six patients with squamous cell carcinoma who underwent sentinel lymph node staging. The tumour size was greater than 2 cm (T2) and the patients had clinically non-palpable regional lymph nodes (N0). All nodes were examined using haematoxylin-eosin staining. Sentinel Lymph Node Biopsy (SLNB) and Selective Lymphadenectomy (SL) using preoperative lymphoscintigraphy and intraoperative radiolymphoscintigraphy and vital dye injections was used to identify the sentinel lymph node avoiding complete axillary node dissection. RESULTS: No false-negative results were observed. At a median follow-up of 10 months (mean 15 months), neither local or regional recurrences in sentinel node-negative basins have been noted. CONCLUSIONS: Sentinel node biopsy is a minimally invasive staging procedure useful in identifying occult regional lymph node disease in selected patients with squamous cutaneous malignancies of the arm. Furthermore sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II squamous cell carcinoma. Although sentinel node-negative patients are a prognostically favourable group, this small series of patients demonstrates that further studies to verify these findings and develop formal guidelines are indicated

The distally based sural flap for lower leg reconstruction: versatility in patients with associated morbidity.

INTRODUCTION: Coverage of soft tissue defects in the lower leg is often made by use of free flap, also because of the improving of anaesthesiology techniques in the last decades. However, there are disadvantages in the use of free flaps like the need for a remote donor site, increased operative time, use of a major vessel to the leg, and microsurgical skills. Besides these, trauma in the lower limb are often cause of damage for a major vessels of the leg, so the use of free flaps in these patients may be related to an higher incidence of complications; also associated pathologies, like diabetes and vascular pathology, can increase the incidence of complications when a free flap is utilized. In all these cases local fascio-cutaneous flaps, like the sural reverse flap, because of their easy and short time harvesting, can be a very good alternative to free flaps. Superficial sural artery flap is a adipofasciocutaneous flap based on the vascular axis of the sural nerve, which gets reverse blood flow through communication with the perforating branch of the peroneal artery, situated in the region of lateral malleolar gutter. PATIENTS AND METHODS: Between 2000 and 2005, 11 patients, mean age 68 (range 58-78 years), were treated at the Plastic and Reconstructive Surgery Unit of Messina University, for soft tissue defects of lower limb and foot, using the distally based sural artery flap. The defects were related to post-traumatic damage of soft tissue, diabetic and vascular ulcers, osteomyelitis and oncological resection. Mean follow-up time was 20 months (range 6-55 months). All patients were pre-operatively assessed for vascular patency of peroneal axis and associated morbidity that could increase risk offlap necrosis. This included diabetes mellitus type II, osteomyelitis and peripheral arterial diseases. RESULTS: All flaps survived with the exception of one that sustained partial skin necrosis, in the ratio of 25% of the skin island. All defects were covered with no major complications and none of the patients required a blood transfusion. Moreover aesthetic results were good with satisfaction of all the patients. CONCLUSION: In our cases we found the sural reverse flap to have a good reliability with low incidence of complication and surgical outcomes. This flap is an excellent option for covering defects of minor deficiency of skin in the third distally of lower limb, ankle and heel. It allows rapid, reliable coverage of defects extending as far distally as the forefoot. Because of the sparing of major vessels, the short surgery time in harvesting the flap, and the good vascular pattern of the flap, we retain the flap a first choose technique for reconstruction in lower leg, especially in politrauma and in patients with associated pathology as vascular diseases or diabetes.

Microsurgical arterovenous loops and biological templates: a novel in vivo chamber for tissue engineering.

BACKGROUND: Microsurgical tissue engineering is an emerging topic in regenerative medicine. Here we describe a new microsurgical model of bioengineering in rats based on the use of an arterovenous loop (AV) implanted into a commercially available crosslinked collagen/glycosaminoglycan template. METHODS: The microvascular loop was created between the femoral artery and vein and covered by the template folded onto itself. The chamber was isolated from the outside tissue by an outer silicon layer to impede tissue ingrowth. RESULTS: At 1-month postimplantation, the tissue chamber was found heavily vascularized, as assessed by laser Doppler perfusion analysis. Histological examination showed that the AV loop was integrated into the collagen matrix of the template and that the whole template was filled with a newly formed soft connective tissue. Most interestingly, the whole scaffold was found heavily vascularized, including the formation of a large number of alpha-SMA-positive arterioles. CONCLUSIONS: The developed microsurgical chamber provides a highly vascular, isolated tool for in vivo tissue engineering.

Dual benefit procedures: combining aesthetic surgery with burn reconstruction.

Burn accounts for a significant proportion of injuries, and of these, the face, neck, and anterior torso are commonly affected. Burn scars remain a lasting reminder of the insult both for the patient and the outside world. There is little doubt that the changes in appearance, and limitations imposed by the burn scar contribute to a negative body image. We present a series of four women, who sustained full thickness burns in childhood with subsequent burn scarring and contracture. These women were noted to have poor body image in areas less affected by burn injury, notably breast ptosis, breast asymmetry and abdominal skin laxity. They were suitable candidates for planned aesthetic procedures, and the skin excised was used to effect synchronous burn reconstruction or contracture release. We believe the potential to use areas of skin excised during aesthetic procedures as possible donor sites of full thickness skin, confers the dual benefits of improved aesthetic and functional outcome, while minimising unnecessary donor site morbidity.

Evidence of significant sternocleidomastoid atrophy following modified radical neck dissection type III.

BACKGROUND: Although modified radical neck dissection type III preserves the spinal accessory nerve, the internal jugular vein, and the sternocleidomastoid muscle, the authors believe there is a significant morbidity to retained structures after neck dissection. Although the effects on accessory nerve function and internal jugular vein patency have been documented, there is little information about sternocleidomastoid morphology and function following modified dissection. METHODS: Using a SonoSite ultrasound machine, the authors assessed sternocleidomastoid muscle morphology, at rest and during contraction, in a cohort of 45 patients who underwent modified radical neck dissection type III with no radiotherapy. All patients had head and neck cancers and received unilateral neck dissection as part of their primary treatment. Static and dynamic measurements were performed at three different levels of the muscle, with the neck in the neutral position. The contralateral neck of the same patient was used as a control. Local muscle asymmetry patterns were calculated using the Absolute Asymmetry Index. RESULTS: Significant sternocleidomastoid atrophy was noted on the side of modified radical neck dissection type III (p < 0.05). The atrophy was particularly marked in the caudal and middle portions of the sternocleidomastoid muscle and was likely related to damage to the segmental blood supply in the caudal and middle portions of the muscle as well as injury to the innervation. CONCLUSION: Despite evidence of significant atrophy, the muscle still underwent morphological changes during contraction that were comparable to those on the normal control side.

A comparison of temporalis transfer and free latissimus dorsi transfer in lower facial reanimation following unilateral longstanding facial palsy.

The ultimate goal in the treatment of facial palsy is the restoration of voluntary and spontaneous movement to the paralyzed side of the face, symmetrical to the normal side. We report our experience treating 40 patients with established facial palsy over a 4-year period. All patients underwent either temporalis transfer or free latissimus dorsi transfer as a single stage to improve lower facial symmetry. We believe that both techniques reliably achieve an increase of movement in facial reanimation after oncological, traumatic, or congenital facial palsy.