Autophagy markers are decreased in bone of osteoporotic patients: a monocentric comparative study.

BACKGROUND: Osteoporosis (OP) is a pathology characterized by bone fragility affecting 30% of postmenopausal women, mainly due to estrogen deprivation and increased oxidative stress. An autophagy involvement is suspected in OP pathogenesis but a definitive proof in humans remains to be obtained. METHODS: Postmenopausal women hospitalized for femoral neck fracture (OP group) or total hip replacement (Control group) were enrolled using very strict exclusion criteria. Western blot was used to analyze autophagy level. RESULTS: The protein expression level of the autophagosome marker LC3-II was significantly decreased in bone of OP patients relative to the control group. In addition, the protein expression of the hormonally upregulated neu-associated kinase (HUNK), which is upregulated by female hormones and promotes autophagy, was also significantly reduced in bone of the OP group. CONCLUSIONS: These results demonstrate for the first time that postmenopausal OP patients have a deficit in bone autophagy level and suggest that HUNK could be the factor linking estrogen loss and autophagy decline. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03175874, 2/6/2017.

Nonsurgical Treatment of Postburn Hypopigmentation: A Literature Review.

The treatment of postburn hypopigmentation was primarily surgical before the advent of new technologies. Medical devices and therapies are emerging to manage scar sequelae that can be disfiguring and associated with severe psychosocial impact. These innovations have been poorly investigated for hypopigmentation, but they represent a real hope. We reviewed all articles published on Pubmed up to June 2022. Included studies had to specifically focus on treating postburn hypopigmented scars. All articles evaluating transient solutions such as make-up, and articles describing inflammation-linked hypopigmentation with no etiological details or no burn injury history were excluded. Through this review, we have highlighted 6 different types of nonsurgical treatments reported in postburn leukoderma potentially allowing definitive results. Electrophoto-biomodulation or E light (combining intensive pulsed light, radiofrequency, and cooling), topical daylight psoralen UVA therapy, and lasers (fractional lasers using pulse energies or CO2FL devices, lasers-assisted drug delivery as local bimatoprost and tretinoin or pimecrolimus) have been explored with encouraging results in hypopigmented burns. Finally, other promising medical strategies include using FK506, a nonsteroidal anti-inflammatory drug, to induce melanogenesis or using melanocyte-stimulating hormones with fractional laser-assisted drug deliveries, which are expected to emerge soon.

Immunosuppressant drug monitor: A non-invasive device to measure tacrolimus level in the saliva of transplanted patients.

Solid organ and vascularized composite allograft transplantation are pivotal in enhancing both life expectancy and quality of life. However, the significant risk of donor tissue rejection requires lifelong immunosuppressive therapy. Tacrolimus, a common component of immunosuppressive regimens, offers effectiveness in preventing organ rejection but poses challenges due to its narrow therapeutic window and toxicity, making it essential to carefully monitor its concentration. Tacrolimus trough levels are currently measured in blood, requiring frequent blood draws from patients, and results are available after 3 to 6 h. To address the need for a fast, minimally-invasive, and simple method to monitor tacrolimus concentrations, we have assessed a new device for at-home analysis, the Immunosuppressant Drug Monitor (IDM) that can extract, identify and quantify tacrolimus in saliva within 15 min. We included males and females hospitalized at Massachusetts General Hospital Transplant Unit, between the ages of 21 and 65 years, and treated with Tacrolimus. Informed consent, demographic and treatment data were collected. Each subject was asked to provide a 5 mL saliva sample that was de-identified and processed by the IDM, while a 5 mL blood sample was drawn and supplied to the MGH clinical lab for analysis by the current standard, immunoassays. The predicted tacrolimus concentration found in saliva was compared to the blood trough level results. 62 samples from 31 different patients were obtained. The male to female ratio and ethnicity distribution were well balanced. The majority of patients were within 30 days of initiating tacrolimus treatment. After IDM calibration and exclusion, 21 samples were measured by the IDM. Using an exponential function fit, the IDM showed a correlation of R2 = 0.39 between the saliva Test Line absorption and the measured tacrolimus concentration in blood, with an average absolute error of 1.8 ng/mL. Our results demonstrate a clear correlation between blood and saliva measurements. The IDM provided promising results to monitor immunosuppressant drug concentrations in patients after transplantation. Future larger studies will further develop the correlation, and the IDM's potential impact on patient outcomes.

Hook nail deformity.

Hook-nail deformity is frequently seen after a fingertip amputation, whether or not flap reconstruction has been done. It is more frequent if the bony support is missing. The deformity results in esthetic and functional impairment which can lead to complete finger amputation. Correction is surgical, but is difficult and surgical series are small. Soft-tissue flap augmentation is simple, but does not add a bony support. Bone augmentation using local flaps is limited by the small size of the distal phalanx remnant. Toe transfer is more logical but, as it is a highly demanding technique, only a few cases have been published. The present study sought to review all the published techniques and their results, to help the reader choose the one best suited to their patient.

Outcomes of Autologous Fat Graft Injection(s) in Treating Sequelae of Digital Trauma: A Case Series.

Background: Sequelae of digital trauma, such as painful scars adherent to tendons and bones, pain of neural origin, cold intolerance, skin and pulp atrophy, occur frequently. Autologous fat graft injections is an interesting option to treat these sequelae. The aim of this study is to describe the outcomes of autologous fat graft injections to treat sequelae of digital trauma. Methods: This retrospective study included all adult patients with digital trauma who underwent an autologous fat grafting procedure at our hospital between 2015 and 2019. The procedure was done at least 6 months after the initial trauma. Outcomes were assessed at least 9 months after the injection and included 2-point epicritic discrimination by Weber test (2-PD) and pulp circumference of the affected finger compared with the contralateral finger, a satisfaction questionnaire concerning the improvement of symptoms, aesthetic aspects and pain related to the operation, evaluation of pain by visual analogue scale, quality of life by SF-36 score and quick disabilities of the arm, shoulder and hand questionnaire (QuickDASH) score. We also assessed whether the patients had reintegrated a previously excluded finger. Results: The study included 14 patients. All patients received one session except for one patient who received two sessions. The average 2-PD of the injured finger was 7 mm compared to 3.57 mm for the contralateral finger. There was no difference in pulp circumference between the treated and contralateral fingers. The mean satisfaction score for symptom improvement and aesthetic improvement was 3.36/5, and the mean score for procedure-related pain was 2.36/5. The mean VAS of the patients was 2.91/10, the mean SF-36 was 60.42/100 and the mean QuickDASH was 40.09/100. Five of the nine patients who had a previously excluded finger were able to reintegrate it. Conclusions: Autologous fat transfer seems to offer some benefit in patients with adherent scars and pulp atrophy. It has little effect on neuropathic pain. Level of Evidence: Level IV (Therapeutic).

Time to return to work after total trapeziometacarpal prosthesis.

OBJECTIVES: This study assessed return to work and prosthesis survival after trapeziometacarpal prosthesis surgery. MATERIAL AND METHODS: A multicenter retrospective study was carried out on patients operated on between 2002 and 2020. All working patients who had undergone trapeziometacarpal prosthesis surgery were included. Return to work was defined as resuming the same full-time position. Postoperative events and their specific treatment and failure to return to work were reported. RESULTS: 240 prostheses in 211 patients were included. The complications rate was 7.5%, with 97% prosthesis survival. 94.3% of patients returned to work, at a mean 48 days (range, 29-210 days; SD, 22.7 days), with no significant difference according to age. Twelve patients did not return to work, half of whom because of prosthetic complications. CONCLUSION: Trapeziometacarpal arthroplasty enables most patients to return to work within 6 weeks. In this series, the prosthetic survival rate was 97%.

Glomus tumor of the scapular neck with axillary nerve compression at the shoulder. A case report.

Background: Glomus tumors, also known as benign acral tumors are extremely rare. Previous glomus tumors from other regions of the body have been linked to neurological compression symptoms, however axillary compression at the scapular neck has never been described. Case presentation: Here, we report a case of axillary nerve compression in a 47-year-old man, secondary to a glomus tumor of the neck of the right scapula, initially misdiagnosed with biceps tenodesis performed and no pain improvement. The magnetic resonance imaging demonstrated a well-contoured, 12 mm tumefaction at the inferior pole of the scapular neck T2-hyperintense and T1-isointense and interpreted as a neuroma. An axillary approach allowed the dissection of the axillary nerve, and the tumor was completely removed. The pathological anatomical analysis resulted in a nodular red lesion measuring 14 × 10 mm, delimited and encapsulated with a definitive diagnostic of glomus tumor. The neurologic symptoms and pain disappeared 3 weeks after surgery and the patient reported satisfaction with the surgical procedure. After 3 months, the results remain stable with a complete resolution of the symptoms. Conclusions: In cases of unexplained and atypical pain in the axillary area, and to avoid potential misdiagnoses and inappropriate treatments, an in-depth exploration for a compressive tumor should be performed as a differential diagnosis.

Radiocarpal fracture-dislocation: Review of the literature, new classification and decision algorithm.

BACKGROUND: Radiocarpal fractures and dislocations are rarely described in the literature. However, the consequences at the functional level are severe, with the loss of almost half of the articular amplitude. The most widespread classification is that of Dumontier, which divides the injury into two categories according to the presence or absence of a fracture. Currently, no classification considers fracture-dislocations in a global and multi-tissue manner; therefore, no therapeutic strategy has been reported. METHODS: We conducted an exhaustive bibliographic search for cohort or case report articles concerning radiocarpal fracture-dislocations published between 1990 and the present. Only descriptions of the injury were identified (noting the type of fracture, direction of displacement and carpal injuries). RESULTS: In all, data were collected from 14 retrospective series and 16 case reports involving 218 patients. Thirty-five and 183 cases involved anterior and posterior displacement, respectively. A fracture of the distal radius was found in 183 cases and 35 cases had a dislocation only, with no significant fracture. Among the posterior displacements, 44 isolated styloid fractures, 62 styloid and posterior marginal fractures, 29 bimarginal fractures (large anterior fragment and small posterior fragment) and 31 fractures of all the fragments described by Medoff with impaction of the central pavement were found. Anterior displacement fractures were found in 17 cases (styloid and/or anterior marginal fracture). We were able to group the different traumatic clinical forms according to a six-category classification. DISCUSSION: A review of the literature highlighted three major components in the management of radiocarpal fracture-dislocations: the bone component, the ligament component and the associated intracarpal lesions. These three components were included in our classification and allowed us to accurately describe all types of radiocarpal fracture-dislocations published in the literature. Authors currently agree on management of the bone component but disagree on that of the ligament component. Particular attention should be paid to intracarpal lesions, which lead to poor outcomes if ignored. Based on our biographical research, we propose a management plan for these complex injuries. LEVEL OF EVIDENCE: VI.

The Impact of Exercise on Motor Recovery after Long Nerve Grafting-Experimental Rat Study.

BACKGROUND: Long nerve grafting often results in unsatisfactory functional outcomes. In this study we aim to investigate the effect of swimming exercise on nerve regeneration and functional outcomes after long nerve grafting. METHODS: A reversed long nerve graft was interposed between C6 and the musculocutaneous nerve in 40 rats. The rats were divided into four groups with 10 in each based on different postoperative swimming regimes for rehabilitation: group A, continuous exercise; group B, early exercise; group C, late exercise; and group D, no exercise (control group). A grooming test was assessed at 4, 8, 12, and 16 weeks postoperatively. Biceps muscle compound action potential (MCAP), muscle tetanic contraction force (MTCF), and muscle weights were assessed after 16 weeks. Histomorphometric analyses of the musculocutaneous nerves were performed to examine nerve regeneration. RESULTS: The grooming test showed all groups except group D demonstrated a trend of progressive improvement over the whole course of 16 weeks. Biceps MCAP, MTCF, and muscle weights all showed significant better results in the exercise group in comparison to the group D at 16 weeks, which is especially true in groups A and B. Nerve analysis at 16 weeks, however, showed no significant differences between the exercise groups and the control group. CONCLUSIONS: Swimming after long nerve grafting can significantly improve muscle functional behavior and volume. The effect is less evident on nerve regeneration. Continuous exercise and early exercise after surgery show more optimal outcomes than late or no exercise. Having a good habit with exercise in the early period is thought as the main reason. Further studies are needed to determine the optimal exercise regimen.

A 3-Dimensional Suture Technique for Flexor Tendon Repair: A Biomechanical Study.

PURPOSE: Flexor tendon injury continues to pose a number of challenges for hand surgeons. Improving mechanical properties of repairs should allow for earlier and unprotected rehabilitation. A 3-dimensional (3D) 4-strand suture technique has been proposed to combine high tensile strength and low gliding resistance without causing suture pullout due to tendon delamination. Our hypothesis is that the 3D technique can result in better mechanical properties than the Adelaide technique. METHODS: Four groups of 10 porcine flexor tendons were sutured using the 3D or Adelaide technique with a 3-0 polypropylene or ultrahigh molecular weight polyethylene (UHMWPE) suture. The axial traction test to failure was performed on each tendon to measure 2-mm gap force and ultimate tensile strength. RESULTS: The mean 2-mm gap force was 49 N for group A (3D + polypropylene), 145 N for group B (3D + UHMWPE), 47 N for group C (Adelaide + polypropylene), and 80 N for group D (Adelaide + UHMWPE). Failure mode was caused by suture breakage for group A (10/10) and mainly by suture pullout for the other groups (8/10 up to 10/10). With the UHMWPE suture, the mean ultimate tensile strength was 145 N for the 3D technique and 80 N for the Adelaide technique. CONCLUSIONS: Porcine flexor tendons repaired using the 3D technique and UHMWPE suture exceeded a 2-mm gap force and tensile strength of 140 N. The ultimate tensile strength was superior to that of the Adelaide technique, regardless of the suture material. CLINICAL RELEVANCE: This in vitro study on porcine flexor tendon suture highlights that the mechanical properties of 3D repair are better than those of 3D repair using the Adelaide technique when a UHMWPE suture is used.

Utilization of the Rat's Tail as a Novel Model for Arterialized Venous Flap.

Arterialized tissues provide longevity and coverage of critically exposed tissue, and in pliable areas of the body, thin flaps are needed. Arterialized venous flaps provide all the aforementioned qualities, yet unpredictability in flap perfusion requires further investigation in experimental studies. Existing animal models are thicker in nature and rarely mimic commonly used venous flaps in clinical practice. A novel design of the rat's tail provides an ideal model for arterialized venous flaps. Eleven venous flaps were harvested from the rats' tail, all presenting with two parallel veins in configuration. Arterialization of veins using the femoral artery was done in either along-valve or against-valve fashion, with the purpose of testing the flap's response to different clinical configurations. The vessel diameter and flap thickness were measured. Flap viability was monitored for 7 days after surgery to ensure stable flap viability. Thickness of the tail flap ranged from 1.0 to 1.2 mm, while the abdomen skin thickness ranged from 1.4 to 1.5 mm. The mean diameter of the lateral veins was 0.85 ± 0.08 mm, which was in between the average femoral artery diameter (mean 0.76 ± 0.1 mm) and the average femoral vein diameter (1.28 ± 0.2 mm). Four of the nine against-valve flaps achieved more than 50% flap survival, while all along-valve flaps achieved flap viability of more than 75%, as evident by indocyanine green imaging. This flap demonstrates similar properties to thin venous flaps used in clinical situations. Standardization of this model can push forth better understanding of the arterialization phenomenon in venous flaps for future studies.

Treatment of hyperpigmentation after burn: A literature review.

OBJECTIFY: Skin pigmentation disorders are one of the most frequent sequelae after burn injury. While these conditions often improve over time, some are permanent and cause severe psychological disorders (especially on the face). Given the frequency of these disorders and their benign nature, the scientific community has great difficulty postponing these patient follow-ups. Publications on their management are rare, and there is no consensus on the gold standard treatment for skin dyschromia. Herein, we performed a literature review including the various treatments currently proposed to manage these hyperpigmentations. METHODS: All reported articles up to February 2021 were reviewed on Pubmed. Studies on the treatment of hyperpigmented scars were included if they were secondary to burn injuries. Excluded articles evaluated transient treatments, such as makeup, and articles on inflammatory hyperpigmentation without etiological details or not secondary to burns. RESULTS: 201 articles were identified, and 13 studies were included. Topical creams used in inflammatory hyperpigmented lesions such as hydroquinone and first-line retinoids are controversial due to their inconstant efficacy. Various types of laser and pulsed light treatments have shown their effectiveness but can also aggravate pigmentation. CONCLUSION: Dyschromia after burn remains a therapeutic challenge. Hyperpigmentations after burn should be treated on a case-by-case basis, using data from the literature, clinical experience and measuring the risk/benefit ratio.

A role for metformin in the treatment of Dupuytren disease?

Dupuytren disease (DD) is a hand-localized fibrotic disorder characterized by a scar-like, collagen-rich cord. Treatment usually comprises surgical removal of the cord, but is associated with a high relapse rate, in some cases requiring finger amputation. There is currently no consensual medical approach for treating DD. Numerous preclinical studies have highlighted antifibrotic properties of metformin, and the aim of this study was to assess a potential antifibrotic role of metformin in DD. Fibroblasts from DD cords (DF) and phenotypically normal palmar fascia (PF) were extracted from surgical specimens and cultured. The fibrotic status of DF and PF was compared at baseline, and under profibrotic (TGF-ß stimulation) and antifibrotic (metformin stimulation) conditions, using quantitative RT-PCR, western blot, immunocytochemistry, and a functional fibroblast contraction assay. At baseline, DF showed higher levels of fibrotic markers and contraction capacity compared with PF. Both types of fibroblasts responded to TGF-ß stimulation. Treatment of DF and PF with metformin did not affect basal levels of fibrotic markers and contraction but largely prevented their induction by TGF-ß. In conclusion, our data show that metformin inhibits TGF-ß-induced expression of fibrotic markers and contraction in hand-derived fibroblasts. This supports the case for a clinical trial to assess the repurposing of metformin as an adjuvant to surgery, to prevent, reduce, or delay recurrence in at-risk DD patients.

Modern and synchronized clinical anatomy teaching based on the BDIE method (board-digital dissection-imaging-evaluation).

PURPOSE: Anatomy has historically been taught via traditional medical school lectures and dissection. In many countries, practical or legal issues limit access to cadaveric dissection. New technologies are favored by students and could improve learning, complementing traditional teaching. METHODS: All students in second-year medicine at a single medical school were submitted to a novel anatomical course with digital tool exposure. We explored a new combined teaching method: a physical blackboard lesson synchronized with digital dissection, imaging and direct evaluation (BDIE). Synchronized dissection is broadcast live in the classroom and in partner medical schools. Following the course, students completed a short survey about their perception of this new anatomic clinical course. RESULTS: The survey included 183 students whom 178 completed the questionnaire, i.e., a 97% response rate. Ninety-nine percent of students thought this synchronized method useful to improve their understanding of anatomy and 90% stated it helped them retain this learning. CONCLUSION: This BDIE method, in conjunction with teaching guidelines and dissection, is highly appreciated by students who consider it helps them to acquire lasting knowledge.

Comparison of Two Rapid Assays for the Detection of BRAF V600 Mutations in Metastatic Melanoma including Positive Sentinel Lymph Nodes.

Testing for the BRAF mutation is mandatory for the management of patients with locally advanced or metastatic melanoma. Molecular analysis based on DNA sequencing remains the gold-standard method for the screening of the different BRAF mutations. These methods must be rapid, sensitive, and specific enough to allow optimal therapeutic management in daily practice and also to include patients in clinical trials. Here, we compared the Idylla BRAF Mutation Test and the anti-BRAF V600E (clone VE1) immunohistochemistry (IHC) in 90 melanoma samples, with a focus on a challenging cohort of 32 positive sentinel lymph nodes. The BRAF status was assessed with both methods independently of the percentage of tumor cells. The concordance rate was calculated excluding both non-contributory analyses and BRAFV600K/R/M mutants due to the specific V600E-IHC test design. The incidence of the BRAFV600E mutation was 33% with both BRAF Idylla and BRAF IHC. The agreement rate was 91% (72/79). Although the agreement rate was high, we suggest that the use of IHC is more suitable for rapid BRAF testing on sentinel lymph node biopsies when associated with a low percentage and scattered tumor cells, which gave a high risk of non-contributory analysis and/or false negative results with the IdyllaTMBRAF Mutation Test.

Flow-Through Arterialized Posterior Interosseous Nerve Grafts for Digital Neurovascular Bundle Defects: Anatomical Study.

BACKGROUND: Digital neurovascular bundle defects are often encountered during crush or avulsion injuries and require complex reconstruction. Use of an arterialized nerve graft (neurovascular graft) serving both as an interpositional arterial conduit and as a nerve graft could be a reconstructive option in these cases. In this anatomical study, the authors aimed to describe a neurovascular graft of the posterior interosseous nerve and a branch of the anterior interosseous artery for neurovascular bundle reconstruction of the fingers. METHODS: Eighteen forearms were injected with red latex in order to collect the anatomical characteristics of the posterior interosseous nerve and the artery running near it. RESULTS: In all cases, the posterior interosseous nerve was followed by a branch of the anterior interosseous artery: the distal dorsal branch of the anterior interosseous nerve. The origin of this artery was proximal to the radiocarpal joint, at an average of 56.5 ± 11.1 mm. The proximal and distal diameters of the branch of the anterior interosseous artery were 1.6 ± 0.2 and 1.1 ± 0.2 mm, respectively. The proximal and distal diameters of the posterior interosseous nerve were 1.2 ± 0.3 mm and 1.1 ± 0.3 mm, respectively. CONCLUSIONS: These results show that a potential free neurovascular graft using the posterior interosseous nerve as nerve graft and the anterior interosseous artery as an arterial bypass to reconstruct both the nerve and arterial tree of the finger could be a useful approach. The authors speculate that this graft could be used to reconstruct the neurovascular bundle of amputated or devascularized digits.

Anatomical study of the clitoris and its implications on female genital mutilation and surgical repair.

BACKGROUND: Worldwide, 200 million girls and women have been subjected to female genital mutilation. To restore the clitoral function and vulvar anatomy, clitoral repair has been performed since the 2000s. Nevertheless, there is a lack of precise and comprehensive data on the clitoral anatomy during surgical repair. This study aimed to precisely describe the terminal anatomies of the dorsal nerve and artery of the clitoris, and the clitoral neurovascular flap advancement for reconstruction in patients with female genital mutilation. METHODS: This study was performed on seven fresh female cadavers. The site of origin, diameter, length, and trajectory of each nerve and artery were recorded. The clitoral neurovascular flap advancement was measured after a midline transection of the suspensory ligament was performed and after extensive liberation of the dorsal bundles at their emergence from the pubic rami. RESULTS: At the distal point of the clitoral body, the width of the dorsal nerve and artery was 1.9 ± 0.3 mm and 0.9 ± 0.2 mm, respectively. The total length of the dorsal bundles was 6.6 cm (± 0.4). The midpart of the suspensory ligament was sectioned, which allowed a mean anteroposterior mobility of 2.7 cm (± 0.2). Extensive dissection of the neurovascular bundles up to their point of emergence from the suspensory ligament allowed a mean mobility of 3.4 ± 0.2 cm. CONCLUSION: We described the anatomical characteristics of the dorsal nerve and artery of the clitoris and the mobility of the clitoral neurovascular flap for reconstruction post clitoridectomy. This was done to restore the anatomic position of the glans clitoris while preserving and potentially restoring clitoral function in patients with female genital mutilation.

Index Finger Pollicization Incisions for Congenital Thumb Aplasia: Review and Design of an Educational Anatomical Model for Skin Incisions.

BACKGROUND: Pollicization of the index finger can be considered the gold standard technique for the treatment of congenital thumb aplasia. The aim of this study was to review the described incisions for pollicization and to create an anatomical framework enabling the study and comparison of these incisions. METHODS: A systematic review was performed to collect descriptions of incision sets. An anatomical model was created from the two upper limbs of the same cadaver. Thumb aplasia was modeled on both hands of this cadaver by severing the thumbs; an index finger pollicization was performed on one of the two hands. Comparative analysis of scar positions, first web size, and neothumb aspect of each incision set was conducted using a surgical glove modeling the skin. The glove was fitted onto the aplastic model to draw the incisions and then onto the pollicized hand to adjust the resulting flaps after cutting. RESULTS: Twelve articles, two textbooks, and one DVD were included in the review, either containing an original description of incisions, or describing an incision pattern with figures and references to the initial author. A total of five different incision sets, described by Buck-Gramcko, Blauth, Foucher, Ezaki, and Malek, were identified and compared using the anatomical model. CONCLUSIONS: This work summarizes five original incisions described for index pollicization in thumb aplasia and presents a standardized and reliable model to study and compare these different sets. The model can be used for educational purposes, either to teach or to optimize an incision set.