Results of a prospective observational study of autologous peripheral blood mononuclear cell therapy for no-option critical limb-threatening ischemia and severe diabetic foot ulcers.

BACKGROUND: Cell therapy with autologous peripheral blood mononuclear cells (PB-MNCs) may help restore limb perfusion in patients with diabetes mellitus and critical limb-threatening ischemia (CLTI) deemed not eligible for revascularization procedures and consequently at risk for major amputation (no-option). Fundamental is to establish its clinical value and to identify candidates with a greater benefit over time. Assessing the frequency of PB circulating angiogenic cells and extracellular vesicles (EVs) may help in guiding candidate selection. METHODS: We conducted a prospective, non-controlled, observational study on no-option CLTI diabetic patients that underwent intramuscular PB-MNCs therapy, which consisted of more cell treatments repeated a maximum of three times. The primary endpoint was amputation rate at 1 year following the first treatment with PB-MNCs. We evaluated ulcer healing, walking capability, and mortality during the follow-up period. We assessed angiogenic cells and EVs at baseline and after each cell treatment, according to primary outcome and tissue perfusion at the last treatment [measured as transcutaneous oxygen pressure (TcPO2)]. RESULTS: 50 patients were consecutively enrolled and the primary endpoint was 16%. TcPO2 increased after PB-MNCs therapy (17.2 ± 11.6 vs 39.1 ± 21.8 mmHg, p < .0001), and ulcers healed with back-to-walk were observed in 60% of the study population (88% of survivors) during follow-up (median 1.5 years). Patients with a high level of TcPO2 (≥ 40 mmHg) after the last treatment showed a high frequency of small EVs at enrollment. CONCLUSIONS: In no-option CLTI diabetic patients, PB-MNCs therapy led to an improvement in tissue perfusion, a high rate of healing, and back-to-walk. Coupling circulating cellular markers of angiogenesis could help in the identification of patients with a better clinical benefit over time.

Bioactive Glass in a Multi Drug Resistance Osteomyelitis in Diabetic Foot: Case Report.

Diabetic foot osteomyelitis (DFO) is a clinical problem with high risk of amputation. The treatment of DFO is still an unsolved challenge. Surgical therapy, antibiotic therapy or conservative treatment are still debated for the timing and the consequences. Long antibiotic therapies expose the selection of multidrug-resistant bacteria. Nowadays the use of new bone substitutes aims to support the load of the bone segments and to ensure the eradication of the infectious process after surgical treatment. A case report of digital osteomyelitis due to a multidrug resistant bacteria was treated with a conservative treatment and use of bioglass (Bonalive) that has the ability to inhibit bacterial growth. A long follow-up shows the resolution of infectious process, no ulcer recurrence and persistent recovery of its ability to walk. Our results agree with literature data and suggest that bioglass may be considered a useful option to manage DFO and achieve healing with a very conservative approach.

Effectiveness of Sucrose Octasulfate Dressing in the Treatment of Neuro-Ischaemic Diabetic Foot Heel Ulcers: A Retrospective Single arm Study.

The study aimed to evaluate the effectiveness of the use of sucrose octasulfate impregnated dressing (TLC-NOSF [Technology Lipido-Colloid-Nano-OligoSaccharide Factor]) in the management of persons with neuro-ischaemic heel diabetic foot ulcers (DFUs). Consecutive patients who referred for an active non-infected neuro-ischaemic heel DFU belonging to grade IC (superficial) or IIC (deep to tendons, muscle or capsule) according to Texas University Classification were included. All patients were managed by a pre-set limb salvage protocol in the respect of International guidelines and the TLC-NOSF dressing was used as primary and specific dressing. Patients were evaluated any 2 to 4 weeks until wound healing or different outcomes. Primary outcome was the rate of complete wound healing after 24 weeks of follow-up. The secondary outcomes assessed the healing time, the rate of wound regression, the re-ulceration in the case of complete healing and the safety. Thirty patients were included. The mean age was 67 ± 11 years, 17 (56.7%) were male, all of them were affected by type 2 diabetes with a mean duration of 18 ± 7 years. Twenty patients (66.7%) showed deep ulcers (grade 2 of Texas University Classification); the mean TcPO2 at the inclusion was 42 ± 7 mm Hg. Twenty-two patients (73.3%) healed by Week 24. The mean time of healing was 84 ± 32 days, 2 (6.7%) patients had ulcer relapse after healing, 28 (93.3%) had wound regression >50%, 2 (6.7%) had mild infection, 1 (3.3%) reported major amputation. No serious adverse events related to TLC-NOSF dressing or local reactions were reported. This current study showed the potential benefit of sucrose octasulfate for treating neuro-ischaemic heel DFUs in addition to the standard of care.

The Immune-Centric Revolution in the Diabetic Foot: Monocytes and Lymphocytes Role in Wound Healing and Tissue Regeneration-A Narrative Review.

Monocytes and lymphocytes play a key role in physiologic wound healing and might be involved in the impaired mechanisms observed in diabetes. Skin wound macrophages are represented by tissue resident macrophages and infiltrating peripheral blood recruited monocytes which play a leading role during the inflammatory phase of wound repair. The impaired transition of diabetic wound macrophages from pro-inflammatory M1 phenotypes to anti-inflammatory pro-regenerative M2 phenotypes might represent a key issue for impaired diabetic wound healing. This review will focus on the role of immune system cells in normal skin and diabetic wound repair. Furthermore, it will give an insight into therapy able to immuno-modulate wound healing processes toward to a regenerative anti-inflammatory fashion. Different approaches, such as cell therapy, exosome, and dermal substitute able to promote the M1 to M2 switch and able to positively influence healing processes in chronic wounds will be discussed.

Foot Revascularization Avoids Major Amputation in Persons with Diabetes and Ischaemic Foot Ulcers.

The study aims to evaluate the effectiveness of foot revascularization in persons with diabetic foot ulcers (DFUs) and below-the-ankle (BTA) arterial disease. Consecutive patients referred for a new active ischaemic DFU requiring lower limb revascularization were considered. Among those, only patients with a BTA arterial disease were included. Revascularization procedures were retrospectively analysed: in the case of successful foot revascularization (recanalization of pedal artery, or plantar arteries or both) or not, patients were respectively divided in two groups, successful foot perfusion (SFP) and failed foot perfusion (FFP). Healing, minor and major amputation at 12 months of follow-up were evaluated and compared. Eighty patients (80) were included. The mean age was 70.5 ± 10.9 years, 55 (68.7%) were male, 72 (90%) were affected by type 2 diabetes with a mean duration of 22.7 ± 11.3 years. Overall 45 (56.2%) patients healed, 47 (58.7%) had minor amputation and 13 (16.2%) major amputation. Outcomes for SFP and FFP were respectively: healing (89.3 vs. 9.1%, p < 0.0001), minor amputation (44.7 vs. 78.8%, p = 0.0001), major amputation (2.1 vs. 36.3%, p < 0.0001). Failed foot revascularization resulted an independent predictor of non-healing, minor amputation, and major amputation. Foot revascularization is mandatory to achieve healing and avoid major amputation in persons with ischaemic DFU and BTA arterial disease.

Advancement of thyroid surgery video recording: A comparison between two full HD head mounted video cameras.

BACKGROUND: The aim of this study was to test two different video cameras and recording systems used in thyroid surgery in our Department. This is meant to be an attempt to record the real point of view of the magnified vision of surgeon, so as to make the viewer aware of the difference with the naked eye vision. MATERIALS AND METHODS: In this retrospective study, we recorded and compared twenty thyroidectomies performed using loupes magnification and microsurgical technique: ten were recorded with GoPro® 4 Session action cam (commercially available) and ten with our new prototype of head mounted video camera. RESULTS: Settings were selected before surgery for both cameras. The recording time is about from 1 to 2 h for GoPro® and from 3 to 5 h for our prototype. The average time of preparation to fit the camera on the surgeon's head and set the functionality is about 5 min for GoPro® and 7-8 min for the prototype, mostly due to HDMI wiring cable. Videos recorded with the prototype require no further editing, which is mandatory for videos recorded with GoPro® to highlight the surgical details. CONCLUSION: the present study showed that our prototype of video camera, compared with GoPro® 4 Session, guarantees best results in terms of surgical video recording quality, provides to the viewer the exact perspective of the microsurgeon and shows accurately his magnified view through the loupes in thyroid surgery. These recordings are surgical aids for teaching and education and might be a method of self-analysis of surgical technique.

A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas.

BACKGROUND: The INI1/SMARCB1 gene protein product has been implicated in the direct pathogenesis of schwannomas from patients with one form of schwannomatosis [SWNTS1; MIM # 162091] showing a mosaic pattern of loss of protein expression by immunohistochemistry [93% in familial vs. 55% in sporadic cases]. AIM OF STUDY: To verify whether such INI1/SMARCB1 mosaic pattern could be extended to all schwannomas arising in the sporadic and familial schwannomatoses [i.e. to SMARCB1-related (SWNTS1) or LZTR1-related (SWNTS2) schwannomatosis or to SMARCB1/LZTR1-negative schwannomatosis] and whether it could be involved in classical NF2 or solitary peripheral schwannomas METHODS: We blindly analysed schwannoma samples obtained from a total of 22 patients including (a) 2 patients (2 males; aged 38 and 55 years) affected by non-familial SMARCB1-associated schwannomatosis (SWTNS1); (b) 1 patient (1 female; aged 33 years) affected by familial schwannomatosis (SWTNS1/ SMARCB1 germ line mutations); (c) 5 patients (3 males, 2 females; aged 33 to 35 years) affected by non-familial (sporadic) LZTR1-associated schwannomatosis (SWNTS2); (d) 3 patients (3 males; aged 35 to 47 years) affected by familial schwannomatosis (SWTNS2/ LZTR1 germ line mutations); (e) 2 patients (1 male, 1 female; aged 63 and 49 years, respectively) affected by non-familial schwannomatosis (SWTNS, negative for SMARCB1, LZTR1 and NF2 gene mutations); (f) 4 patients (3 males, 1 females; aged 15 to 24 years) affected by classical NF2 (NF2: harbouring NF2 germ line mutations; and (g) 5 patients (3 males, 2 females; aged 33 to 68 years) who had solitary schwannomas. [follow-up = 15-30 years; negative for constitutional/somatic mutation analysis for the SMARCB1, LZTR1 and NF2 genes] were (blindly) analyzed. The INI1/SMARCB1 immunostaining pattern was regarded as (1) diffuse positive nuclear staining [= retained expression] or (2) mosaic pattern [mixed positive/negative nuclei = loss of expression in a subset of tumour cells]. RESULTS: All solitary peripheral schwannomas and NF2-associated vestibular schwannomas showed diffuse nuclear INI1/SMARCB1 staining in 97-100% of neoplastic cells; schwannomas obtained from all cases of non-familial and familial schwannomatosis and NF2-associated non-vestibular schwannomas showed a mosaic pattern ranging from 10 to 70% of INI1/SMARCB1-positive expression. We did not record a complete lack of nuclear staining. CONCLUSIONS: The present data suggests that (a) mosaic loss of immunohistochemical INI1/SMARCB1 expression, despite the interlesional variability, is a reliable marker of schwannomatosis regardless of the involved gene and it might help in the differential diagnosis of schwannomatosis vs. solitary schwannomas and (b) INI1/SMARCB1 expression is not useful in the differential with mosaic NF2, since NF2-associated peripheral schwannomas show the same immunohistochemical pattern.

Microsurgical approach for unusual and unexpected malignant fibrous histiocytoma of the forearm: A case report.

Soft tissue sarcomas are rare tumors with a dismal prognosis. Among the most common histological types of sarcomas of the extremities, malignant fibrous histiocytoma (MFH) is the one with the highest incidence. Surgery is considered to be the first choice of treatment for MFH. To the best of our knowledge, this is the first case report in the literature of a patient with MFH within the abductor pollicis longus (APL) muscle. This unusual location was also unexpected by the treating surgeons, as the preoperative magnetic resonance imaging localized the tumor inside a different muscle. A 79-year-old Caucasian man presented with a swelling in the middle third of the dorsal aspect of the left forearm. MFH was diagnosed following biopsy and instrumental diagnostic examinations. Surgical excision and simultaneous reconstruction was performed by the same microsurgical team, achieving an excellent functional outcome. The present case highlights the significance of microsurgical approach for improving strategic planning in oncologic surgery. Accurate surgical dissection, performed by a team of microsurgeons, allowed for the identification of the unusual and unexpected tumor localization within the APL muscle. For this reason, a change of surgical strategy allowed for preservation of the extensor digitorum communis muscle, which would otherwise have to be resected, with tendon transfer and successful restoration of the thumb abduction function.

Breast Mondor's disease: Diagnosis and management of six new cases of this underestimated pathology.

Mondor's disease is an unusual and little-known pathology of the breast, characterized by superficial thrombophlebitis. The causes are still unresolved. Most of the patients do not fall under case studies of the scientific literature, given the reported incidence rate between 0.5% and 0.8%. The Mondor's disease patients are not always properly identified, and they are frequently treated as outpatients, even considering the benign course of the disease which often spontaneously resolves without any medical therapy. We report here six new cases of Mondor's disease, two of them were likely due to a trauma and were easily resolved with the use of non-steroidal anti-inflammatory drugs; the third one was apparently due to the stretching of the mammary veins in a patient with gigantomastia; the fourth one was subsequent to hormonal stimulation for in vivo fertilization and following gestation; and the last two cases (one was a man) were diagnosed after undergoing surgery for breast carcinoma.

Misdiagnosis of plexiform neurofibroma of the medial plantar nerve: case report.

Plexiform neurofibromas are benign tumors of the peripheral nerve. Diagnosis may be challenging, if they present mimicking other peripheral nerve pathologies. We report the case of a patient who had severe foot pain, which progressively hampered her walking ability, erroneously attributed to recurrent Morton's neuroma. Diagnosis of plexiform neurofibroma of her right medial plantar nerve was made 15 years after the appearance of symptoms. Pain and function recovered after radical neurotomy of the medial plantar nerve. A correct diagnosis is an essential starting point in the treatment of neurofibromas and a misdiagnosis may lead to an inappropriate treatment.

Spinal neurofibromatosis with central nervous system involvement in a set of twin girls and a boy: further expansion of the phenotype.

BACKGROUND: Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations. OBJECTIVES: The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature. METHODS AND RESULTS: In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1-like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature. CONCLUSIONS: This article presents the first report on (1) spinal neurofibromatosis in a set of affected monozygotic twins; (2) the earliest onset of the disease; and (3) the occurrence of high signal lesions in the brain at MRI.

Unexpected granular cell tumor in abdominal wall: case report and literature review.

Granular cell tumors (GCTs) are uncommon benign neoplasms deriving from Schwann cells of the peripheral nerve fibers. Although these tumors can be found anywhere in the body, the most frequent site is the tongue, followed by the chest wall and the arm. The abdominal wall is an extremely rare site for GCTs. These tumors are generally asymptomatic and have a slow growth rate. Today, thanks to their immunoreactivity to S-100 and CD68, the differential diagnosis is more straightforward than in the past. We report on a young patient affected by a GCT located in the upper third of the right rectus abdominis muscle. En bloc excision through a diamond-shaped skin incision allowed us to make a correct histological diagnosis, which was confirmed by the immunohistochemical findings. GCT, which is very rare in abdominal wall muscles, should be considered in the differential diagnosis, and surgical excision is the treatment of choice.