In Vitro Effects of PTH (1-84) on Human Skeletal Muscle-Derived Satellite Cells.

Parathyroid hormone (PTH) is a hormone secreted by the parathyroid glands. Despite its well-known characterized anabolic and catabolic actions on the skeleton, the in vitro effects of PTH on skeletal muscle cells are limited and generally performed on animal models. The aim of this study was to evaluate the effects of a short impulse of PTH (1-84) on the proliferation and the differentiation of skeletal muscle satellite cells isolated from human biopsies. The cells were exposed for 30 min to different concentrations of PTH (1-84), from 10-6 mol/L to 10-12 mol/L. ELISA was used to assay cAMP and the myosin heavy-chain (MHC) protein. The proliferation was assayed by BrdU and the differentiation by RealTime-qPCR. A statistical analysis was performed by ANOVA followed by Bonferroni's test. No significant variations in cAMP and the proliferation were detected in the isolated cells treated with PTH. On the other hand, 10-7 mol/L PTH on differentiated myotubes has shown significant increases in cAMP (p ≤ 0.05), in the expression of myogenic differentiation genes (p ≤ 0.001), and in the MHC protein (p ≤ 0.01) vs. untreated controls. This work demonstrates for the first time the in vitro effects of PTH (1-84) on human skeletal muscle cells and it opens new fields of investigation in muscle pathophysiology.

Reverse Expansion for Breast Reconstruction after Skin-sparing and Nipple-sparing Mastectomy: Our First 100 Cases.

Patients with breast cancer have experienced advancements both in oncological treatment and in aesthetics as a result of developments in reconstructive techniques. We aimed to present our experience with the reverse expansion technique, summarizing the results of our first 100 cases of reconstruction after skin-sparing mastectomy and nipple-sparing mastectomy. Methods: From January 2010 to September 2018, 253 breast reconstruction procedures were performed on 100 patients. The reverse expansion technique consists of autologous fat tissue transplantation requiring the combined use of a skin expander and of multiple lipofilling sessions. At the beginning of every session the breast expander was deflated by removing a saline volume similar to that of the fat to be injected. Results: Overall, 56 breast reconstructions after skin-sparing mastectomy and 44 after nipple-sparing mastectomy were performed. An average of 661.5 cm3 of fat per session was harvested and an average of 305.3 cm3 per breast was injected. The average number of sessions to achieve breast reconstruction was 2.53. Only four complications after 253 procedures (1.5%) were reported: one donor site hemorrhage due to genetic lack of coagulation factors, and three surgical site infections. Conclusions: Considering the large number of positive factors such as a fast postoperative recovery, an easy learning curve, a lack of need of a specialized surgical team, a natural look of the breast shape, and the soft consistency of the grafted tissue, we believe this technique could be the first choice for autologous reconstruction after skin-sparing mastectomy and nipple-sparing mastectomy.

Rhino-oropharingeal osteoradionecrotic soft-tissue and bony defect reconstruction with submental artery island flap: a case report.

BACKGROUND: The submental artery island flap is widely used in head and neck reconstruction, since it is easy and quick to harvest, and it can be successfully used for the coverage of perioral, intraoral and facial defects. We used this technique for the reconstruction of a complex soft-tissue and bony defect of rhino-oropharinx. CASE REPORT: Osteoradionecrosis of rhino-oropharingeal posterior wall with C2 necrotic body exposure occurred in a 77-year-old woman. After the failure of reconstruction with a Hadad-Bassagasteguy flap, a submental island flap with cervical spine stabilization was planned to be performed in a one-stage operation. The anterior arc of C1 and odontoid process of C2 were removed and, according to the defect size, a submental island flap was designed in an elliptical fashion. The flap was rotated 180° and tunnelized under the left parapharingeal-prevertebral space, then it was positioned in the rhino-oropharinx and fixed with reabsorbable sutures. The donor site was closed primarily. No peri- or post-operative complications occurred, neither in the recipient nor in the donor-site. At the latest follow-up, 15 months postoperatively, the patient was able to speak without any impairment and started swallowing rehabilitation with good results and an aesthetically satisfactory outcome. CONCLUSION: The submental island flap may be a reliable and versatile flap for reconstruction of head and neck defects, even though in the rhino-oropharingeal posterior wall.

New Robotic System with Wristed Microinstruments Allows Precise Reconstructive Microsurgery: Preclinical Study.

BACKGROUND: Microsurgery allows complex reconstruction of tissue defects after oncological resections or severe trauma. Performing these procedures may be limited by human tremor, precision, and manual dexterity. A new robot designed specifically for microsurgery with wristed microinstruments and motion scaling may reduce human tremor and thus enhance precision. This randomized controlled preclinical trial investigated whether this new robotic system can successfully perform microsurgical needle driving, suturing, and anastomosis. METHODS: Expert microsurgeons and novices completed six needle passage exercises and performed six anastomoses by hand and six with the new robot. Experienced microsurgeons blindly assessed the quality of the procedures. Precision in microneedle driving and stitch placement was assessed by calculating suturing distances and angulation. Performance of microsurgical anastomoses was assessed by time, learning curves, and the Anastomosis Lapse Index score for objective performance assessment. RESULTS: Refined precision in suturing was achieved with the robot when compared with the manual technique regarding suture distances (p = 0.02) and angulation (p < 0.01). The time required to perform microsurgical anastomoses was longer with the robot, however, both expert and novice microsurgeons reduced times with practice. The objective evaluation of the anastomoses performed by novices showed better results with the robot. CONCLUSIONS: This study demonstrated the feasibility of performing precise microsutures and anastomoses using a new robotic system. Compared to standard manual techniques, robotic procedures were longer in time, but showed greater precision.

Reverse Expansion Following Nipple Sparing Mastectomy: A Natural, Safe and Effective Autologous Technique for Breast Reconstruction.

The majority of surgeons choose an implant-based breast reconstruction after mastectomy. Nevertheless, lipofilling is a constantly growing technique allowing a complete breast reconstruction without prosthesis. We introduce our experience using reverse expansion for breast reconstruction following a nipple-sparing mastectomy (NSM) with a subpectoral skin expander. In the period January 2010-August 2021, 106 breast reconstruction procedures were performed on 50 patients after a NSM. We harvested an amount of fat tissue using a 2.5 mm liposuction cannula, we centrifuged it 3 min at 4000 rpm and injected in the recipient site using 3 ml syringes and Coleman cannulas. At the beginning of every session, the breast expander was deflated of a saline volume similar to the one of the fat to be injected. We harvested an average of 679.2 ccs of fat per session and injected an average of 319.3 ccs per breast. The mean number of sessions has been 2.4 per breast. The average number of sessions in a radiotreated patients' subgroup has been slightly higher than a control group. The mean follow-up time was 63.5 months and we observed no complications in 105 over 106 procedures. Lipofilling has proven to be a safe and effective technique for complete breast reconstruction. Our procedure considers the use of a breast expander as a device to prepare the recipient site. Reverse expansion after a NSM allows a like-with-like reconstruction and it might be the first reconstructive choice in a selected group of patients.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Pelvic ring reconstruction with double-barreled fibular free flap: A systematic review.

INTRODUCTION: Pelvic ring reconstruction after internal hemipelvectomy is an extremely challenging surgical procedure, and mandatory reconstruction is to provide a durable and pain-free functional outcome, especially for young, active patients. One of the most widely employed techniques is reconstruction with a double-barreled fibular free flap (DBF). The aim of our work was an in-depth analysis of the outcome of pelvic ring reconstruction performed using the above-mentioned method, in particular looking for a correlation between the fixation technique and either ambulation status or complications. MATERIALS AND METHODS: A systematic review was performed in November 2020 using PubMed and MedLine Ovid databases according to the PRISMA guidelines and the results were statistically analyzed. RESULTS: Studies were published between 1994 and 2015. A DBF was used in each case, with a total of 30 patients. Reconstruction was performed with screws in 13 cases, Cotrel-Dubousset rod fixation in 6, screws and plate in 5, screws with external fixation in 4, and ISOLA in 2. Follow-up time ranged from 3 to 131 months. Functional outcome was excellent in 4 patients and good in 26 patients. Statistical analysis showed no statistical evidence of existing correlation between fixation technique and complications (p = .873), while statistical correlation between age and fixation technique was found (p < .001). CONCLUSION: Reconstruction of pelvic ring with DBF provides an overall good functional outcome. Our data indicate that there is no statistical evidence of existing correlation between the fixation technique and either complications or ambulation status.

Reconstruction after complete mandibular avulsion with double-paddle fibular free flap. A case report.

Reconstruction after maxillofacial trauma is extremely challenging. During the past several decades, the chimeric fibular-free flap has emerged as a leading reconstructive option for head and neck compound defects. This report describes a unique case of total mandibular reconstruction using a double-paddle osteocutaneous fibular free flap after facial traumatic injury. A 45-year-old man presented a severe maxillofacial trauma with complete mandibular avulsion. The shortest segment of a 24-cm fibular flap was used to reconstruct the symphysis while the longest segments were placed to rebuild the mandibular body. Microvascular anastomoses were performed with the external jugular vein and facial artery. The distal skin island (10 × 5 cm) was sutured to cover the endo-oral defect while the proximal one (12 × 6 cm) to restore the external tissues continuity of the facial lower third. The postoperative course was uneventful. One year after flap reconstruction, a first commissuroplasty was performed. After 3 months, secondary commissuroplasty was performed with an Estlander flap to rebuild the right lower lip. At latest follow-up, 60 months postoperatively, the patient was able to tolerate soft diet with maximal mouth opening of more than 4 cm; no impairment to mastication, deglutition, or phonation was observed. Speech was normal and the aesthetic outcome was judged good. Double-paddle fibular free flap allows reconstruction of extremely challenging defects, such in case of complete mandibular avulsion. The proximal perforator can provide extended soft-tissue coverage and greater volume than traditional osteocutaneous flaps, avoiding two flaps simultaneous harvest.

Safety of Reconstructive Microsurgery in the Elderly Population: a Multicentric Prospective Study.

BACKGROUND: Safety of reconstructive microsurgery in elderly patients is still a topic of debate, because no conclusive evidence exists that provides indications and risk evaluation in elderly patients. The purpose of this study, which the Italian Society for Plastic, Reconstructive, and Aesthetic Surgery (SICPRE) has promoted, is to evaluate the safety and the complication risk of elective reconstructive microsurgery in elderly patients as well as to identify patient- or procedure-related risk factors. The secondary aim is to evaluate the predictive role for complications of the Geriatric 8 score (G8). METHODS: A total of 194 consecutive patients from 18 centers, aged 65 or older, who received an elective microsurgical flap between April 2018 and April 2019 were prospectively evaluated. Patient-related, treatment-related, and outcomes data were recorded and statistically analyzed through multiple-adjusted logistic regression models. RESULTS: Our study showed an increased risk of complications and a longer hospitalization in patients aged ≥75 years with the American Society of Anesthesiologists (ASA) score ≥3 (or G8 score ≤11) as compared to patients >65 years of age and <75 years of age who undergo reconstruction with a microsurgical flap. Instead, flap survival did not significantly vary with age, but was associated only with ASA score ≥3 (or G8 score ≤11) and surgeries that last longer than 480 min; however, flap survival (92.3%) was slightly lower than that commonly reported for in the general population. CONCLUSIONS: Reconstructive microsurgery in the elderly is generally safe. The ASA score is easier and quicker than the G8 score and equally useful for risk stratification.

Oromandibular reconstruction with double-skin paddle fibular free flap: A systematic review and meta-analysis.

BACKGROUND: Reconstruction of complex head and neck defects is challenging, especially when more than one soft-tissue subunit is involved. The osteocutaneous fibular flap underwent continual evolution to improve its soft-tissue characteristics, such as including a second skin island. The purpose of this study was to evaluate outcomes regarding oromandibular reconstruction with a double-skin paddle fibular free flap (DSPFFF) using three different techniques: central de-epithelialized skin paddle, distally-based double-skin paddle (DSP), or proximally and distally-based DSP. METHODS: A systematic review was performed in December 2020 using Pubmed and MedLine Ovid databases according to the PRISMA guidelines. A meta-analysis of functional outcome and complications was performed to estimate single incidence rates. RESULTS: A total of 449 patients were included, with a follow-up of 1-84 months, where 330 patients underwent reconstruction with the first technique, 23 patients with the second technique, and 96 patients with the third technique. The meta-analysis showed an overall good functional outcome and a low-complication rate for oromandibular reconstruction with DSPFFF. A better functional outcome and a lower complication rate were found when a distally-based DSPFFF was harvested compared to a proximally and distally-based DSPFFF. CONCLUSION: The DSPFFF was found to be useful and reliable for reconstructing composite and extensive head and neck defects, with an overall good functional outcome and a low-complication rate. The meta-analysis showed a better positive outcome on distally-based DSPFFF rather than proximally and distally-based DSPFFF. In addition, distally-based DSPFFF showed a lower complications rate when compared with proximally and distally-based DSPFFF.

Study of the Expression and Function of Calcium-Sensing Receptor in Human Skeletal Muscle.

Skeletal muscle has an outstanding capacity for regeneration in response to injuries, but there are disorders in which this process is seriously impaired, such as sarcopenia. Pharmacological treatments to restore muscle trophism are not available, therefore, the identification of suitable therapeutic targets that could be useful for the treatment of skeletal reduced myogenesis is highly desirable. In this in vitro study, we explored the expression and function of the calcium-sensing receptor (CaSR) in human skeletal muscle tissues and their derived satellite cells. The results obtained from analyses with various techniques of gene and protein CaSR expression and of its secondary messengers in response to calcium (Ca2+) and CaSR drugs have demonstrated that this receptor is not present in human skeletal muscle tissues, neither in the established satellite cells, nor during in vitro myogenic differentiation. Taken together, our data suggest that, although CaSR is a very important drug target in physiology and pathology, this receptor probably does not have any physiological role in skeletal muscle in normal conditions.

One injection for a great projection: a quick and simple procedure for nipple reconstruction.

Women attach great importance to the presence of a three-dimensional nipple upon completion of the breast reconstruction process. To meet patients' expectations, nipple-areolar complex reconstruction should achieve symmetry in position, size, shape, texture, and color, as well as minimizing donor-site morbidity. However, it is well known that regardless of the reconstructive technique, loss of nipple projection can be reasonably expected. We developed and evaluated a quick, simple, and innovative technique using injectable Integra Flowable Wound Matrix to increase nipple projection after reconstruction. Twenty breast cancer patients who underwent nipple reconstruction resulting in unsatisfactory projection were enrolled in our retrospective study. Nipple projection was measured at the time of surgery and after 6 and 12 months. A visual analogue scale was used to assess patients' satisfaction. Our technique yielded reliable results in terms of the long-lasting maintenance of nipple projection. This method is high-priced, but cost-effective, since one kit may suffice for three patients. Furthermore, our patients were very appreciative of this technique as a single-step, minimally invasive, painless procedure with no reported necessity of re-intervention.

Reconstruction of upper limb soft-tissue defects after sarcoma resection with free flaps: A systematic review.

BACKGROUND AND OBJECTIVES: Upper limb preservation after soft tissue sarcoma (STS) surgical excision is now the accepted gold standard and it often requires reconstruction with free flaps. The purpose of this review is to summarize current literature on upper limb reconstruction with free flaps after STS resection. METHODS: A systematic review was performed in July 2019 in PubMed and MedLine Ovid databases according to the PRISMA guidelines. RESULTS: A total of 17 studies were included in the final analysis, with 132 patients. The most common diagnosis was Malignant Fibrous Histiocytoma. The most frequent timing of flap coverage was immediate. The success rate was almost always 100%. The length of follow-up was reported in 11 studies with a range of 2-187 months. The most commonly reported patient-centered outcome was the MSTS Score. Based on the evidence of the literature collected, we divided the upper limb into four parts (shoulder, elbow and arm, forearm and wrist, and hand) and described the most common and functional free flaps used for reconstruction after STS resection. CONCLUSIONS: Free flaps in the treatment of STS of the upper extremity have a good overall outcome, with a low postoperative complication rate. A wide array of free flaps is available for reconstruction, and the choice of flap is based on defect size, types of tissue required, postoperative functional goal, and surgeon preference. A greater degree of standardization is needed in the reporting of patient-centered outcomes to facilitate future comparative studies.

A Two-Step Immunomagnetic Microbead-Based Method for the Isolation of Human Primary Skin Telocytes/CD34+ Stromal Cells.

Telocytes (TCs), commonly referred to as TCs/CD34+ stromal cells, are a peculiar type of interstitial cells with distinctive morphologic traits that are supposed to exert several biological functions, including tissue homeostasis regulation, cell-to-cell signaling, immune surveillance, and reparative/regenerative effects. At present, the majority of studies investigating these cells are mainly descriptive and focus only on their morphology, with a consequent paucity of functional data. To gain relevant insight into the possible functions of TCs, in vitro analyses are clearly required, but currently, the protocols for TC isolation are only at the early stages and not fully standardized. In the present in vitro study, we describe a novel methodology for the purification of human primary skin TCs through a two-step immunomagnetic microbead-based cell separation (i.e., negative selection for CD31 followed by positive selection for CD34) capable of discriminating these cells from other connective tissue-resident cells on the basis of their different immunophenotypic features. Our experiments clearly demonstrated that the proposed method allows a selective purification of cells exhibiting the peculiar TC morphology. Isolated TCs displayed very long cytoplasmic extensions with a moniliform silhouette (telopodes) and presented an immunophenotypic profile (CD31-/CD34+/PDGFRα+/vimentin+) that unequivocally differentiates them from endothelial cells (CD31+/CD34+/PDGFRα-/vimentin+) and fibroblasts (CD31-/CD34-/PDGFRα+/vimentin+). This novel methodology for the isolation of TCs lays the groundwork for further research aimed at elucidating their functional properties and possible translational applications, especially in the field of regenerative medicine.

Reverse-flow latissimus dorsi myocutaneous flap in a multi-step approach for complex back defect reconstruction: A case report.

Reconstruction of complex back defects is challenging for reconstructive surgeons, as it should preserve function, provide adequate coverage, and minimize morbidity. We present a case of multiple-step reconstruction after resection of a large squamous cell carcinoma recurrence in a 68-year-old man, with local perforator flaps and a reverse-flow latissimus dorsi myocutaneous flap. After radical excision, four propeller perforator flaps were harvested to cover a 30 × 25 cm defect, based on the dorsal branch of the fifth posterior intercostal arteries (right 20 × 9 cm, left 17 × 9 cm) and on the superior gluteal arteries (right 20 × 11 cm, left 21 × 12 cm) bilaterally. In the second step, bilateral propeller perforator flaps based on the fourth lumbar arteries (right 18 × 13 cm, left 23 × 11 cm) were transposed to cover the residual loss of tissues. After 5 months, a recurrence occurred on the left midback. A wide en bloc excision of the last three ribs and pulmonary pleura was performed, and the synthetic mesh used for thoracic wall reconstruction was covered with an ipsilateral 20 × 10 cm reverse-flow latissimus dorsi myocutaneous flap based on the serratus anterior branch. All the flaps healed uneventfully and there were no donor-site complications. Two years postoperatively, the patient had a cosmetically acceptable result without any functional impairment. The reverse-flow latissimus dorsi myocutaneous flap can represent a salvage procedure in back complex defects reconstruction, especially when other local flaps have already been harvested in previous reconstructive procedures.

Mandibular ramus and condyle reconstruction with vascularized proximal fibular epiphyseal transfer in the pediatric patient: A case report.

Mandibular reconstruction in skeletally immature patients is challenging for the Plastic Surgeon. Indeed, it requires replacement of the bony defect with restoration of the growth capability and joint function, when condyle is involved. Vascularized transfer of the proximal epiphysis of the fibula meets all these reconstructive requirements providing an adequate bone stock which also contains a growth plate and an articular surface. The purpose of this article is to report a case of mandibular reconstruction in a 13-year-old boy who underwent resection of a high-grade osteosarcoma involving mandibular angle, ramus, and condyle. A fibular free flap including proximal epiphysis, with its growth plate and the articular surface, was harvested based on the anterior tibial vessels. The fibular head articular surface was placed facing the articular fossa of the temporal bone. A reverse-flow end-to-end anastomosis was performed with the facial vessels. Postoperatively, no infection nor anastomosis complications occurred. Surgical sites healed uneventfully. At latest follow-up, 1 year after surgery, no signs of recurrence were observed. The transferred bone survived and the growth plate was clearly open. Both functional and aesthetic outcomes were rated as good, with maximal mouth opening of more than 4 cm, neither impairment to mastication, deglutition nor phonation was observed. This technique may be a good option for pediatric reconstruction of large bony and articular mandibular defects, where functional restoration of temporomandibular joint and the growing capacity of the bone should be contemporary.

Extensor hallucis longus tendon and soft-tissue reconstruction with palmaris longus tendon included in a radial forearm free flap: A case report.

Reconstruction of foot structures is challenging because of the need to restore both anatomy and function. Extensor hallucis longus (EHL) excision without reconstruction could result in a flexion deformity of the toe at the interphalangeal joint. In this report, we present a case of the use of a palmaris longus tendon included in a fasciocutaneous radial forearm free flap to reconstruct EHL tendon and soft tissues of the distal foot dorsum. A 41-year-old woman presented with a recurrence of myxoinflammatory fibroblastic sarcoma on the medial part of the left foot dorsum. The EHL tendon was sacrificed, leaving a soft-tissue defect of 14 × 5 cm and 14-cm tendon gap. A 14 × 5 cm radial forearm flap with a 16-cm section of palmaris longus tendon was harvested from the left forearm. Radial artery and its comitant vein were anastomosed with dorsalis pedis artery and vein. EHL tendon repair was performed from the composite mass to the proximal and distal stumps. No complication in the postoperative period occurred. At latest follow-up, 12 months postoperatively, the patient showed a normal joint function and was satisfied with the treatment. Palmaris longus tendon included in a radial forearm free flap could be recommended for combined soft tissue and tendon defects, particularly on the foot dorsum.