Liposomal and Nonliposomal Bupivacaine for Mohs Surgery: A Systematic Review.

BACKGROUND: Lidocaine is the most commonly used local anesthetic for Mohs micrographic surgery (MMS), but given its limited half-life, postoperative pain remains a significant concern for patients. Bupivacaine is used in various surgical subspecialty procedures and has demonstrated improved pain control compared with lidocaine. However, its role in MMS is insufficiently explored. OBJECTIVE: To systematically review the current literature for reports on use of bupivacaine, traditional nonliposomal and newer liposomal formulations, for MMS. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The MEDLINE, PubMed, and EMBASE databases were queried for articles presenting original data on the use of bupivacaine for MMS. RESULTS: Of 483 potentially relevant articles, 3 studies met final inclusion criteria, capturing a total of 253 patients involved in primary investigations comparing bupivacaine to traditional local anesthesia for MMS. Bupivacaine was well-tolerated and associated with comparable or modestly reduced intraoperative and postoperative pain and opioid use. CONCLUSION: Bupivacaine may have a role in prolonging intraoperative anesthesia, reducing acute postoperative pain, and reducing postoperative opioid use after MMS. However, large, prospective studies are needed to solidify the generalizability and clinical utility of these findings.

Pinch Grafting: A Systematic Review of Modern Perspectives and Applications in Dermatologic Surgery and Wound Healing.

BACKGROUND: Pinch grafting has experienced a resurgence in interest in recent years, stemming from its simplicity, safety, and potential in restoring tissue integrity. While historically employed for chronic nonhealing wounds, pinch grafts have shown promise following surgical procedures, particularly those involving the lower extremities. OBJECTIVE: To systematically review the literature and present an updated overview of the current applications of pinch grafting. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In collaboration with a medical reference librarian, the PubMed, Embase, Scopus, and Web of Science databases were searched for studies reporting on the use of pinch grafting from 2000 onward. The references of each included article were also screened. RESULTS: Ten articles met final inclusion criteria. In total, 300 patients underwent pinch grafting for treatment of skin ulceration, while an additional 35 cases were performed as an alternative to primary closure following skin cancer resection. Overall, pinch grafting was safe and well tolerated, with minimal adverse outcomes reported. CONCLUSION: Pinch grafting is a safe, straightforward, and effective technique to promote the healing of chronic wounds. While the procedure shows early promise in emerging applications within dermatologic surgery, only about 10% of the reported cases involved this indication, reflecting a need for further research in this area.

Hidradenocarcinoma: A Case Series From the Scripps Clinic With a Systematic Review of the Literature.

BACKGROUND: Hidradenocarcinoma (HAC) is a rare adnexal carcinoma. To the best of the authors' knowledge, there are no published systematic reviews on HAC. OBJECTIVE: To incorporate a case series from the authors' institution and systematically integrate reported information to provide a reference tool for optimization of diagnosis and management. METHODS: A comprehensive MEDLINE search was conducted from database inception to 2021 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This yielded 225 studies with 165 cases of HAC. References of included articles were also searched. In addition, 9 patients with HAC were identified from the authors' institution over the past 10 years. RESULTS: The mean age of HAC presentation is 60 years with a slight male predilection (60%). The head and neck is the most commonly affected region. Over 36% of cases either presented with metastatic disease or went on to metastasize. The most common treatment type was wide local excision, followed by Mohs micrographic surgery. CONCLUSION: Early detection with accurate histologic interpretation is prudent in all cases of HAC. Wide local excision is the current first-line treatment. However, Mohs micrographic surgery offers complete marginal analysis with evidence of reduced risk of metastasis and better outcomes compared with wide local excision. Currently, there are no National Comprehensive Cancer Network guidelines for the treatment of HAC, and consensus guidelines are limited to tumor and nodal metastasis staging provided by the American Joint Committee on Cancer, eighth edition. Thus, this case series and systematic review integrates important aspects of diagnosis, workup, and management of HAC.

Neurotropic melanoma arising from a neurocristic hamartoma.

Neurotropic melanoma is a rare type of malignant melanoma with nerve invasion or neural differentiation. Neurocristic cutaneous hamartoma is a rare, benign tumor of the skin and superficial soft tissue that arises from aberrant migration of neural crest cells. We report a rare case of a 74-year-old man with a clinically diagnosed giant congenital nevus of the right mid-back, histopathologically confirmed to be a neurocristic cutaneous hamartoma, who developed neurotropic spindle cell melanoma within the lesion. The patient was treated with serial re-excisions until clear margins were achieved.

The Role of Matrix Metalloproteinase-13 (MMP13) in TGFß/BMP Pathway Regulation of Fibro-Adipogenic Progenitor (FAP) Differentiation.

BACKGROUND/AIMS: Muscle fibrosis and fatty infiltration (FI) are common complications seen in various muscle disease states. Recent studies indicate that muscle residential fibro/adipogenic progenitors (FAPs) are the major cellular source for muscle fibrosis and FI. We previously showed that MMP13 knockout (KO) mice have significantly increased FI, suggesting an important role of MMP13 in muscle FI. However, how MMP13 affects the differentiation of FAPs remains unknown. METHODS: In order to assess the role of MMP-13 on FAP differentiation, we isolated FAPs from wildtype C57BL/6 and MMP13 knock out mice with FACS using CD31-, CD45-, Integrin α7- and Sca-1+ markers. FAPs were cultured in 24 well plate after FACS.in standard media till 80% confluent and then switched to adipogenic medium. In order to study the role of TGFß and BMP in their differentiation, FAPs from both wildtype and MMP13 KO mice were treated with TGFß1 (5 ng/ml). For MMP13 inhibitor treatment, FAPs from wildtype mice were incubated in adipogenic medium containing 10 µM MMP13 inhibitor (or vehicle) for 2 weeks. Immunofluorescence and gene expression analysis were used to assess FAP adipogenic and fibrogenic differentiation. FAPs were stained with Perilipin A (FITC, adipogenesis marker) and αSMA (Red, fibroblast marker), and DAPI. Real time PCR was performed for gene expression evaluation. A two-tailed Anova was used for statistical comparisons between groups, withp ≤ 0.05. Data are presented as mean ± standard deviation. RESULTS: In this study, we isolated FAPs from wildtype C57BL/6 and MMP13 KO mice and evaluated their adipogenic and fibrogenic differentiation in vitro. MMP13 KO FAPs demonstrated enhanced adipogenesis but reduced fibrogenesis compared to wildtype FAPs. Treating wildtype FAPs with an MMP13 inhibitor simulated phenotypes seen in MMP13 KO FAPs. In order to assess the role of MMP13 on TGFß/BMP signaling in regulating FAP differentiation, we treated wildtype and MMP13 KO FAPs with TGFß1, BMP7, TGFß inhibitor, and BMP inhibitor. TGFß1 treatment significantly enhanced fibrogenesis, but inhibited adipogenesis of wildtype FAPs. However, treatment with BMP7 showed the opposite effect. Interestingly, the effect of TGFß1/BMP7 was voided in MMP13 KO FAPs. Treating wildtype FAPs with MMP13 inhibitor also abolished the effect of TGFß1/BMP7 in FAP differentiation. CONCLUSION: Results from this study showed that TGFß1 inhibits FAP adipogenesis but stimulates FAP fibrogenesis. BMP7 was shown to promote FAP adipogenesis but reduce its fibrogenesis. The role of the TGFß/BMP signaling pathway regulating FAP differentiation was found to be MMP13 dependent. This study suggests that MMP13 is a critical downstream effector in TGFß/BMP pathway which may serve as a new therapeutic target for muscle fibrosis and FI.

Effects of High Gamma Doses on the Structural Stability of Metal-Organic Frameworks.

Four different MOFs were exposed to γ rays by a cobalt-60 source reaching a maximum dose of 5 MGy. The results showed that the MIL-100 (Cr) and MIL-100 (Fe) did not exhibit obvious structural damage, suggesting their excellent radiation stability. MIL-101 (Cr) showed good radiation stability up to 4 MGy, but its structure started degrading with increasing radiation dose. Furthermore, the results showed that the structure of AlFu MOFs started to decompose at a gamma dose of 1 MGy, exhibiting a much lower tolerance to γ radiation. At this radiation energy, the dominant interaction of the gamma-ray with MOFs is the Compton effect and the radiation stability of MOFs can be improved by prolific aromatic linkers, high linker connectivity, and good crystallinity. The results of this study indicate that MIL-100 and MIL-101 MOFs have a good potential to be employed in nuclear applications, where relatively high radiation doses play a role, for example, nuclear waste treatment and radionuclides production.

Extraocular Sebaceous Carcinoma Treated With Mohs Micrographic Surgery-A 24-Year Retrospective Review of Tumor Characteristics and Treatment Outcomes.

BACKGROUND: Extraocular sebaceous carcinoma (SC) is rare, with distinct features from its ocular counterpart. These neoplasms have been associated with Muir-Torre syndrome (MTS). Associated internal malignancies include gastrointestinal and genitourinary. OBJECTIVE: Assess for local recurrence, metastasis, disease-specific death, and additional malignancies in patients with extraocular SC treated with Mohs micrographic surgery (MMS) at a single referral center. METHODS: Review of patients with extraocular SC treated with MMS between 1995 and 2019. Follow-up was obtained by chart review. RESULTS: Thirty-eight patients with 41 tumors were identified (25, 66% male). During a mean follow-up of 5.9 ± 5 years, one case of metastasis was identified in an incompletely treated case. No recurrence was identified in the remaining 40 tumors. Five of 41 (12%) tumors had aggressive histologic features. Seven of 38 (18%) patients had a diagnosis of MTS or associated risk factors. There was no association between MTS or its risk factors and high-risk tumors. CONCLUSION: There were no incidences of local recurrence, metastasis, or disease-specific death in cases treated completely with MMS. Metastasis and disease-specific death occurred in an incompletely treated case, highlighting the risk associated with aggressive tumors.

Beige fibro-adipogenic progenitor transplantation reduces muscle degeneration and improves function in a mouse model of delayed repair of rotator cuff tears.

BACKGROUND: Muscle atrophy and fatty infiltration (FI) are common occurrences following rotator cuff (RC) tears. Tears of all sizes are subject to muscle degeneration. The degree of muscle degeneration following RC tears is highly correlated with repair success and functional outcomes. We have recently discovered that muscle fibro-adipogenic progenitors (FAPs) can differentiate into uncoupling protein 1 (UCP-1)-expressing beige adipocytes and induce muscle regeneration. This study evaluated the potential of local cell transplantation of beige adipose FAPs (BAT-FAPs) to treat RC muscle degeneration in a murine model of RC repair. METHODS: BAT-FAPs were isolated from muscle in UCP-1 reporter mice by flow cytometry as UCP-1+/Sca1+/PDGFR+/CD31-/CD45-/integrin α7-. C57/BL6J mice underwent supraspinatus tendon tear with suprascapular nerve transection followed by repair 2 or 6 weeks after the initial injury. At the time of repair, mice received either no additional treatment, phosphate-buffered saline injection, or BAT-FAP injection. Functional outcomes were assessed by gait analysis. Mice were humanely killed at 6 weeks after cell transplantation. Supraspinatus muscle FI, fibrosis, muscle fiber size, and vascularity were analyzed and quantified via ImageJ. Analysis of variance with post hoc Tukey test and P <.05 was used to determine statistical significance. RESULTS: Cell transplantation diminished fibrosis, FI, and atrophy and enhanced vascularization in both delayed repair models. Cell transplantation resulted in improved shoulder function as assessed with gait analysis in both the delayed repair models. CONCLUSIONS: BAT-FAPs significantly reduced muscle degeneration and improved shoulder function after RC repair. BAT-FAPs hold significant promise as a therapeutic adjunct to repair for patients with advanced RC pathology.

Reversal of Fatty Infiltration After Suprascapular Nerve Compression Release Is Dependent on UCP1 Expression in Mice.

BACKGROUND: In large rotator cuff tears, retraction of the supraspinatus muscle creates suprascapular nerve traction and compression. However, suprascapular nerve transection, when used in previous models, is different from chronic compression of the suprascapular nerve in patients. To define the role of suprascapular nerve chronic injury in rotator cuff muscle atrophy and fatty infiltration, we developed a novel reversible suprascapular nerve compression mouse model. QUESTIONS/PURPOSES: We asked: (1) Can suprascapular nerve injury be induced by compression but reversed after compression release? (2) Can muscle fatty infiltration be induced by suprascapular nerve compression and reversed after compression release? (3) Is white fat browning involved in fatty infiltration resorption? METHODS: Mice in a common strain of C57BL/6J were randomly assigned to suprascapular nerve transection (n = 10), nerve compression (n = 10), nerve compression and release (n = 10), or sham control (n = 10) groups. To study the role or white fat browning on muscle fatty infiltration, additional UCP1 reporter mice (n = 4 for nerve compression and n = 4 for nerve compression release) and knockout mice (n = 4 for nerve compression and n = 4 for nerve compression release) were used. Nerve injury was testified using osmium tetroxide staining and neural muscular junction staining and then semiquantified by counting the degenerating axons and disrupted junctions. Muscle fatty infiltration was evaluated using Oil Red O staining and then semiquantified by measuring the area fraction of fat. Immunofluorescent and Oil Red O staining on UCP1 transgenic mice was conducted to testify whether white fat browning was involved in fatty infiltration resorption. Ratios of UCP1 positively stained area and fat area to muscle cross-section area were measured to semiquantify UCP1 expression and fatty infiltration in muscle by blinded reviewers. Analysis of variance with Tukey post hoc comparisons was used for statistical analysis between groups. RESULTS: Suprascapular nerve injury was induced by compression but reversed after release. The ratios of degenerating axons were: sham control: 6% ± 3% (95% confidence interval [CI], 3%-10%); nerve compression: 58% ± 10% (95% CI, 45%-70% versus sham, p < 0.001); and nerve compression and release: 15% ± 9% (95% CI, 5%-26% versus sham, p = 0.050). The supraspinatus muscle percentage area of fatty infiltration increased after 6 weeks of nerve compression (19% ± 1%; 95% CI, 18%-20%; p < 0.001) but showed no difference after compression release for 6 weeks (5% ± 3%; 95% CI, 1%-10%; p = 0.054) compared with sham (2% ± 1%; 95% CI, 1%-3%). However, the fat area fraction in UCP1 knockout mice did not change after nerve compression release (6% ± 1%; 95% CI, 4%-8% at 2 weeks after compression and 5% ± 0.32%; 95% CI, 4%-6% after 2 weeks of release; p = 0.1095). CONCLUSIONS: We developed a clinically relevant, reversible suprascapular nerve compression mouse model. Fatty infiltration resorption after compression release was mediated through white fat browning. CLINICAL RELEVANCE: If the mechanism of browning of white fat in rotator cuff muscle fatty infiltration can be confirmed in humans, a UCP1 agonist may be an effective treatment for patients with suprascapular nerve injury.

Roux-en-Y gastric bypass increases systemic but not portal bile acid concentrations by decreasing hepatic bile acid uptake in minipigs.

Roux-en-Y gastric bypass (RYGB) surgery is widely used in the management of morbid obesity. RYGB improves metabolism independently of weight loss by still unknown mechanisms. Bile acids (BAs) are good candidates to explain this benefit, since they regulate metabolic homeostasis and their systemic concentrations increase upon RYGB. Here we analyzed the mechanisms underlying the increase in systemic BA concentrations after RYGB and the role of the liver therein. To this aim, we used the Göttingen-like minipig, a human-size mammalian model, which allows continuous sampling and simultaneous analysis of pre-hepatic portal and systemic venous blood. BA concentrations and pool composition were measured in portal blood, containing intestinal reabsorbed BAs and compared to systemic blood during a standardized meal test before and after RYGB. Systemic total BA concentrations increased after RYGB, due to an increase in conjugated BAs. Interestingly, the ratio of portal:systemic conjugated BAs decreased after RYGB, indicating a role for the liver in systemic BA concentrations changes. In line, hepatic expression of BA transporter genes decreased after RYGB. Our results show that the increase in systemic BAs after surgery is due to decreased selective hepatic recapture. Thus, alterations in hepatic function contribute to the increase in systemic BAs after RYGB.

Are lifetime affective disorders predictive of long-term outcome in severe adolescent anorexia nervosa?

Depression and anxiety are commonly associated with anorexia nervosa (AN) and contribute to difficulties in social integration, a negative factor for outcome in AN. The link between those disorders and AN has been poorly studied. Thus, our objective was to investigate (1) the link between outcome nine years after hospitalisation for AN and the occurrence of lifetime anxious or depressive comorbidities; (2) the prognostic value of these comorbidities on patient outcome; 181 female patients were hospitalised for AN (between 13 and 22 years old), and were re-evaluated for their psychological, dietary, physical and social outcomes, from 6 to 12 years after their hospitalisation. The link between anxious and depressive disorders (premorbid to AN and lifetime) and the outcome assessment criteria were tested through multivariate analyses; 63% of the participants had good or intermediate outcome, 83% had presented at least one anxiety or depression disorder in the course of their lives, half of them before the onset of AN. Premorbid obsessive compulsive disorders (OCD), BMI at admission, and premenarchal AN all contribute to poor prognosis. Social phobia and agoraphobia affect the subjects' quality of life and increase eating disorder symptoms. These results encourage a systematic assessment of, and care for, anxiety and depression comorbidities among female adolescent patients with a particular focus on premorbid OCD.

Influence of Roux-en-Y gastric bypass on plasma bile acid profiles: a comparative study between rats, pigs and humans.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is the most widely used bariatric surgery procedure, which induces profound metabolic and physiological effects, such as substantial improvements in obesity, type 2 diabetes and their comorbidities. Increasing evidence identifies bile acids (BAs) as signaling molecules that contribute to the metabolic improvement after RYGBP. However, how and to what extent BAs mediate the metabolic effects of RYGBP still remains unclear and requires mechanism of action studies using preclinical models. In this study, we compared plasma BA profiles before and after RYGBP in two animal models, rats and pigs, with humans to evaluate their translational potential. METHODS: Plasma BAs were profiled in rats, pigs and humans by liquid chromatography coupled with tandem mass spectrometry before and after RYGBP. RESULTS: RYGBP increased baseline plasma total BA concentrations in humans and in the two animal models to a similar extent (∼3-fold increase), despite differences in presurgery BA levels and profiles between the models. However, qualitatively, RYGBP differently affected individual plasma BA species, with similar increases in some free species (cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)), different increases in glyco-conjugated species depending on the model and globally no increase in tauro-conjugated species whatever the model. CONCLUSIONS: The tested animal models share similar quantitative RYGBP-induced increases in peripheral blood BAs as humans, which render them useful for mechanistic studies. However, they also present qualitative differences in BA profiles, which may result in different signaling responses. Such differences need to be taken into account when translating results to humans.

Successful Treatment of Chronic Venous Ulcers With a 1,320-nm Endovenous Laser Combined With Other Minimally Invasive Venous Procedures.

BACKGROUND: Venous ulcers are very common with few curative treatment options. OBJECTIVE: To report the closure rate and clinical characteristics of active venous ulcers in a vein clinic using endovenous laser ablation (EVLA) with a 1,320-nm laser. METHODS AND MATERIALS: A prospective database was kept consisting of patients with an active venous ulcer at the time of consultation in a single-practitioner academic vein clinic from March 2007 to May 2014. A database was maintained and charts were reviewed with attention to the length of time the patient reported having the ulcer, procedures performed, and time to ulcer healing. RESULTS: Thirty-one patients were identified at consultation with venous ulceration. One patient's ulcer was healed with conservative medical management before receiving treatment. The remaining 30 patients were treated with a combination of EVLA of the great and/or short saphenous veins, foam sclerotherapy of insufficient varicose and reticular veins, and phlebectomy as appropriate. Two patients were lost to follow up after partial treatment. Ulcer healing occurred in more than 93% (27/29) of patients with a median healing time of 55 days from the time of first treatment. The median follow-up time after treatment was 448 days. CONCLUSION: Endovenous laser ablation with a 1,320-nm laser in combination with foam sclerotherapy and phlebectomy as appropriate is effective treatment of chronic venous ulcers and should be considered as a treatment option for patients with C6 venous insufficiency. To the authors' knowledge, this is the largest, prospective series of chronic venous ulcers treated with EVLA. Further randomized controlled studies are needed to confirm these findings.

Loading of osseointegrated implants for bone conduction hearing at 3 weeks: 3-year stability, survival, and tolerability.

The objective of this study was to ascertain the long-term safety of loading osseointegrated implants for bone conduction hearing 3 weeks post-surgery. Thirty consecutive adult patients were implanted with the Baha BI300 (Cochlear Bone Anchored Solutions) in our tertiary referral center. Implants were loaded with the sound processor 3 weeks post-surgery. Follow-up examinations were performed at 10 days; 3, 4, 6, 8, and 12 weeks; 6 months; and 1, 2, and 3 years after implant surgery. At each follow-up visit, implant stability quotient (ISQ) values were recorded by means of resonance frequency analysis, and soft tissue status was evaluated according to Holgers' classification. ISQ trends, implant survival, and soft tissue reactions were compared to a population of 52 patients with the same type of implants loaded from 6 weeks post-surgery as part of another study. Subjective benefit was measured by means of the Glasgow Benefit Inventory (GBI). After an initial dip in ISQ at 10 days after implantation, a gradually increasing trend in ISQ was found until 6 months in both populations, after which ISQ values remained above baseline values. Implant survival was 97 % in the study population and 96 % in the comparison population. Clinically relevant soft tissue reactions were found in 0.9 % (study population) and 1.7 % (comparison population) of all visits. Patients reported subjective benefit; the mean GBI score was 22.8. In conclusion, loading these implants at 3 weeks post-surgery is safe based on the current study, as long-term results show high ISQ values and good implant survival and tolerability.

Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus.

Aspergillus fumigatus is a saprotrophic fungus whose spores are ubiquitous in the atmosphere. It is also an opportunistic human pathogen in immunocompromised individuals, causing potentially lethal invasive infections, and is associated with severe asthma and sinusitis. The species is only known to reproduce by asexual means, but there has been accumulating evidence for recombination and gene flow from population genetic studies, genome analysis, the presence of mating-type genes and expression of sex-related genes in the fungus. Here we show that A. fumigatus possesses a fully functional sexual reproductive cycle that leads to the production of cleistothecia and ascospores, and the teleomorph Neosartorya fumigata is described. The species has a heterothallic breeding system; isolates of complementary mating types are required for sex to occur. We demonstrate increased genotypic variation resulting from recombination between mating type and DNA fingerprint markers in ascospore progeny from an Irish environmental subpopulation. The ability of A. fumigatus to engage in sexual reproduction is highly significant in understanding the biology and evolution of the species. The presence of a sexual cycle provides an invaluable tool for classical genetic analyses and will facilitate research into the genetic basis of pathogenicity and fungicide resistance in A. fumigatus, with the aim of improving methods for the control of aspergillosis. These results also yield insights into the potential for sexual reproduction in other supposedly 'asexual' fungi.

Complications of Morbid Obesity in Total Joint Arthroplasty: Risk Stratification Based on BMI.

This study stratifies complication risk in primary total joint arthroplasty (TJA) based on body mass index (BMI). Demographics, co-morbidities, perioperative variables, and complications were reviewed for 22,808 patients. Chi-squared, one-way ANOVA, univariate and multivariable regression analysis were performed. Increasing BMI led to an increase (P<0.05) in combined complications, acute kidney injury (AKI), cardiac arrest (CA), reintubation, reoperation, and superficial infection (SI). Univariate analysis for BMI>40 revealed an increase in combined complications (15.21-vs-17.40%), AKI (1.93-vs-3.87%), CA (0.22-vs-0.57%), reintubation (0.47-vs-0.95%), reoperation (2.36-vs-3.37%), and SI (0.82-vs-1.65%). Multivariable regression showed BMI>40 as an independent predictor for combined complications (OR=1.18), AKI (OR=1.79), CA (OR=3.94), reintubation (OR=2.56), reoperation (OR=1.44), and SI (OR=2.11). Morbid obesity confers increased risk for complications in TJA.