Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer: Updated Overall Survival Outcomes From Phase III PRODIGY.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.

The impact of the new ESTRO-ACROP target volume delineation guidelines for postmastectomy radiotherapy after implant-based breast reconstruction on breast complications.

The European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) updated a new target volume delineation guideline for postmastectomy radiotherapy (PMRT) after implant-based reconstruction. This study aimed to evaluate the impact on breast complications with the new guideline compared to the conventional guidelines. In total, 308 patients who underwent PMRT after tissue expander or permanent implant insertion from 2016 to 2021 were included; 184 received PMRT by the new ESTRO-ACROP target delineation (ESTRO-T), and 124 by conventional target delineation (CONV-T). The endpoints were major breast complications (infection, necrosis, dehiscence, capsular contracture, animation deformity, and rupture) requiring re-operation or re-hospitalization and any grade ≥2 breast complications. With a median follow-up of 36.4 months, the cumulative incidence rates of major breast complications at 1, 2, and 3 years were 6.6%, 10.3%, and 12.6% in the ESTRO-T group, and 9.7%, 15.4%, and 16.3% in the CONV-T group; it did not show a significant difference between the groups (p = 0.56). In multivariable analyses, target delineation is not associated with the major complications (sHR = 0.87; p = 0.77). There was no significant difference in any breast complications (3-year incidence, 18.9% vs. 23.3%, respectively; p = 0.56). Symptomatic RT-induced pneumonitis was developed in six (3.2%) and three (2.4%) patients, respectively. One local recurrence occurred in the ESTRO-T group, which was within the ESTRO-target volume. The new ESTRO-ACROP target volume guideline did not demonstrate significant differences in major or any breast complications, although it showed a tendency of reduced complication risks. As the dosimetric benefits of normal organs and comparable oncologic outcomes have been reported, further analyses with long-term follow-up are necessary to evaluate whether it could be connected to better clinical outcomes.

Comparison of Stored and Fresh Injectable Acellular Adipose Matrix in Soft Tissue Reconstruction in a Murine Model.

BACKGROUND: We previously showed comparable volume effects of injections of acellular adipose matrix (AAM), an adipose tissue-derived extracellular matrix, and conventional fat grafting in a murine model. Thus, AAM could be a novel allogenic injectable product. However, its retention rate poses a concern, as repeated AAM injections may be required in some cases. This study investigated the biological properties and therapeutic value of stored AAM and compared them with those of fresh AAM, in a murine model. METHODS: AAM was manufactured from fresh human abdominoplasty fat. Fresh and stored injectable AAM was prepared within 24 h and 3 months after generation, respectively. Either fresh or stored injectable AAM was injected into the scalp of athymic nude mice (0.2 mL/sample, n = 6 per group). After 8 weeks, graft retention was assessed through weight measurement, and histological analysis was performed, including immunofluorescence staining for CD31 and perilipin. RESULTS: Retention rate was significantly reduced in the stored compared to the fresh injectable AAM group. Nevertheless, histological analysis revealed comparable inflammatory cell presence, with minimal capsule formation, in both groups. Adipogenesis occurred in both groups, with no significant difference in the blood vessel area (%) between groups. CONCLUSIONS: Although the volume effects of stored AAM for soft tissue reconstruction were limited compared to those of fresh injectable AAM, stored AAM had similar capacity for adipogenesis and angiogenesis. This promising allogeneic injectable holds the potential to serve as an effective "off-the-shelf" alternative for repeated use within a 3-month storage period. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .

Effect of Injectable Acellular Adipose Matrix on Soft Tissue Reconstruction in a Murine Model.

BACKGROUND: The extracellular matrix isolated from adipose tissue, known as acellular adipose matrix (AAM), represents a novel biomaterial. AAM functions as a scaffold that not only supports stem cell proliferation and differentiation but also induces adipogenesis and angiogenesis. This study aims to investigate the volumetric effects and microenvironmental changes associated with injectable AAM in comparison to conventional fat grafting. METHODS: AAM was manufactured from fresh human abdominoplasty fat using a mechanically modified method and then transformed into an injectable form. Lipoaspirate was harvested employing the Coleman technique. A weight and volume study was conducted on athymic nude mice by injecting either injectable AAM or lipoaspirate into the scalp (n=6 per group). After eight weeks, graft retention was assessed through weight measurement and volumetric analysis using micro-computed tomography (micro-CT) scanning. Histological analysis was performed using immunofluorescence staining for perilipin and CD31. RESULTS: Injectable AAM exhibited similar weight and volume effects in murine models. Histological analysis revealed comparable inflammatory cell presence with minimal capsule formation when compared to conventional fat grafts. Adipogenesis occurred in both AAM-injected and conventional fat graft models, with no significant difference in the blood vessel area (%) between the two. CONCLUSIONS: In summary, injectable AAM demonstrates effectiveness comparable to conventional fat grafting concerning volume effects and tissue regeneration in soft tissue reconstruction. This promising allogeneic injectable holds the potential to serve as a safe and effective "Off-the-Shelf" alternative in both aesthetic and reconstructive clinical practices. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Dynamic insights into infection risk over time in two-stage implant-based breast reconstruction: a retrospective cohort study.

BACKGROUND: Infections following postmastectomy implant-based breast reconstruction (IBR) can compromise surgical outcomes and lead to significant morbidity. This study aimed to discern the timing of infections in two-stage IBR and associated risk factors. METHOD: A review of electronic health records was conducted on 1096 breasts in 1058 patients undergoing two-stage IBR at Seoul National University Hospital (2015-2020). Infections following the first-stage tissue expander (TE) insertion and second-stage TE exchange were analyzed separately, considering associated risk factors. RESULTS: Over a median follow-up of 53.5 months, infections occurred in 2.9% (32/1096) after the first stage and 4.1% (44/1070) after the second stage. Infections following the first-stage procedure exhibited a bimodal distribution across time, while those after the second-stage procedure showed a unimodal pattern. When analyzing risk factors for infection after the first-stage procedure, axillary lymph node dissection (ALND) was associated with early (≤7 weeks) infection, while both ALND and obesity were independent predictors of late (>7 weeks) infection. For infections following the second-stage procedure, obesity, postmastectomy radiotherapy, a history of expander infection, ALND, and the use of textured implants were identified as independent risk factors. Postmastectomy radiotherapy was related to non-salvaged outcomes after infection following both stages. CONCLUSION: Infections following first and second-stage IBR exhibit distinct timelines reflecting different pathophysiology. Understanding these timelines and associated risk factors will inform patient selection for IBR and aid in tailored postoperative surveillance planning. These findings contribute to refining patient suitability for IBR and optimizing personalized postoperative care strategies.

Distribution of Perigastric Station 4d Lymph Nodes in Vascularized Gastroepiploic Lymph Node Transfer: An Anatomic Study and Case Series.

BACKGROUND: Vascularized gastroepiploic lymph node transfer (VGLNT) is a well-accepted surgical treatment for restoring physiological function in chronic lymphedema. However, the inclusion of substantial lymph nodes (LNs) in the flap remains uncertain. This study aimed to identify the anatomical basis for reliable flap harvest for VGLNT. PATIENTS AND METHODS: The anatomy of perigastric station 4d LNs was studied in healthy cadavers (n = 15) and patients with early gastric cancer (EGC) (n = 27). The omentum was divided into three segments: proximal, middle, and distal from the origin of the right gastroepiploic vessels. The flap dimension, number, location, size of LNs, and caliber of the vessels were reviewed. Eight patients underwent VGLNT for upper/lower limb lymphedema. RESULTS: The mean numbers of LNs in the proximal, middle, and distal segment were 2.5, 1.4, 0.5 in the cadavers, and 4.9, 2.7, 0.7 in the gastrectomy specimens, respectively. The proximal third included a significantly greater number of LNs than the distal third in the cadaveric (p = 0.024) and ECG (p = 0.016) specimens. A total of 95% of the LNs were located within proximal two-thirds of the flap from the vessel origin both in the cadavers (21.0 × 5.0 cm) and in the gastrectomy specimens (20 × 3.5 cm). In VGLNT, the transferred flap was 25.5 ± 6.9 × 4.1 + 0.7 cm in dimension, containing a mean number of 6.5 ± 1.9 LNs. At postoperative 6 months, the volumetric difference was significantly reduced by 22.8 ± 9.2% (p < 0.001). CONCLUSIONS: This study provides a distinct distribution pattern of station 4d LNs. Inclusion of the proximal two-thirds of the flap, which carries majority of the LNs, is recommended for VGLNT.

Hybrid Lymphovenous Anastomosis Surgery Guided by Intraoperative Mesenteric Intranodal Lymphangiography for Refractory Nontraumatic Chylous Ascites: A Case Report.

Refractory chylous ascites can cause significant nutritional and immunologic morbidity, but no clear treatment has been established. This article introduces a case of a 22-year-old female patient with an underlying lymphatic anomaly who presented with refractory chylous ascites after laparoscopic adnexectomy for ovarian teratoma which aggravated after thoracic duct embolization. Ascites (>3,000 mL/d) had to be drained via a percutaneous catheter to relieve abdominal distention and consequent dyspnea, leading to significant cachexia and weight loss. Two sessions of hybrid lymphovenous anastomosis (LVA) surgery with intraoperative mesenteric lymphangiography guidance were performed to decompress the lymphatics. The first LVA was done between inferior mesenteric vein and left para-aortic enlarged lymphatics in a side-to-side manner. The daily drainage of chylous ascites significantly decreased to 130 mL/day immediately following surgery but increased 6 days later. An additional LVA was performed between right ovarian vein and enlarged lymphatics in aortocaval area in side-to-side and end-to-side manner. The chylous ascites resolved subsequently without any complications, and the patient was discharged after 2 weeks. The patient regained weight without ascites recurrence after 22 months of follow-up. This case shares a successful experience of treating refractory chylous ascites with lymphatic anomaly through LVA, reversing the patient's life-threatening weight loss. LVA was applied with a multidisciplinary approach using intraoperative mesenteric lipiodol, and results showed the possibility of expanding its use to challenging problems in the intraperitoneal cavity.

NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses: implications of NETosis inhibition for acne skin inflammation treatment.

Inflammasomes are multiprotein complexes involved in the host immune response to pathogen infections. Thus, inflammasomes participate in many conditions, such as acne. Recently, it was shown that NETosis, a type of neutrophil cell death, is induced by bacterial infection and is involved in inflammatory diseases such as delayed wound healing in patients with diabetes. However, the relationship between inflammasomes and NETosis in the pathogenesis of inflammatory diseases has not been well studied. In this study, we determined whether NETosis is induced in P. acnes-induced skin inflammation and whether activation of the nucleotide-binding domain, leucine-rich family, and pyrin domain-containing-3 (NLRP3) inflammasome is one of the key factors involved in NETosis induction in a mouse model of acne skin inflammation. We found that NETosis was induced in P. acnes-induced skin inflammation in mice and that inhibition of NETosis ameliorated P. acnes-induced skin inflammation. In addition, our results demonstrated that inhibiting inflammasome activation could suppress NETosis induction in mouse skin. These results indicate that inflammasomes and NETosis can interact with each other to induce P. acnes-induced skin inflammation and suggest that targeting NETosis could be a potential treatment for inflammasome-mediated diseases as well as NETosis-related diseases.

Histological Comparison of Nanofat and Lipoconcentrate: Enhanced Effects of Lipoconcentrate on Adipogenesis and Angiogenesis.

BACKGROUND: Nanofat and lipoconcentrate contain adipose-derived stem cells and growth factors, and have wide clinical applications in the regenerative field. This study aimed to investigate the microenvironmental changes associated with nanofat and lipoconcentrate. METHODS: Conventional fat, nanofat, or lipoconcentrate (0.2 mL each, n = 5 per group) were injected subcutaneously into the dorsal flanks of athymic nude mice. The graft weights were measured at postoperative week 4; the grafts and their overlying skin were used for histological analyses. RESULTS: Weights of the lipoconcentrate grafts were significantly greater than those of the conventional fat (p < 0.05) and nanofat (p < 0.01) grafts. There was no significant difference in inflammation, oil cysts, and fibrosis between the conventional fat and nanofat groups. Histological examination of the lipoconcentrate grafts showed less macrophage infiltration and the formation of fibrosis and oil cysts. Additionally, adipogenesis and angiogenesis were induced more in the lipoconcentrate grafts than in the nanofat grafts (p < 0.01). Lipoconcentrate and nanofat improved dermal thickness (p < 0.001 and p < 0.01, respectively, versus the baseline). CONCLUSION: Lipoconcentrate grafts had greater volume and shape retention than conventional fat and nanofat grafts. They had better histological structure and acted as scaffolds for adipogenesis and angiogenesis. Both products showed regenerative effects on dermal thickness; however, only lipoconcentrate grafts had the required volume and regenerative effects, allowing it to serve as a novel adipose-free grafting method for facial rejuvenation and contouring. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Enhanced Effect of Secondary Administration of Adipose-Derived Stromal Cells Concurrent with Fat Grafting.

BACKGROUND: Cell-assisted lipotransfer, a fat graft mixed with adipose-derived stromal cells, is known to enhance fat graft retention. Previously, the authors showed that intravenous injection of adipose-derived stromal cells can improve the survival of grafted fat. In the present study, the authors investigated the effects of a secondary intravenous injection of adipose-derived stromal cells on fat grafting. METHODS: Wild-type C57BL/6J (B6) mice were used as donors for grafted fat and as recipients. Adipose-derived stromal cells were harvested from green fluorescent protein and DsRed B6 mice. The recipient mice were divided into three groups: SI ( n = 10), RI1 ( n = 10), and RI2 ( n = 11). All groups received intravenous injections of green fluorescent protein adipose-derived stromal cells immediately after fat grafting. The RI1 and RI2 groups received repeated intravenous injections of DsRed adipose-derived stromal cells at 1 and 2 weeks, respectively, after fat grafting. The grafted fat volume was measured using micro-computed tomography. RESULTS: Secondarily injected DsRed adipose-derived stromal cells were recruited to the grafted fat and resulted in a higher retention of graft volume and vascular density ( P < 0.05). The stromal-derived factor-1 and C-X-C chemokine receptor type 4 genes related to stem cell homing were highly expressed in the grafted fat and adipose-derived stromal cells ( P < 0.05). The RI2 group showed a higher graft volume and vascular density than the SI and RI1 groups ( P < 0.05). CONCLUSIONS: A secondary intravenous injection of adipose-derived stromal cells at a 2-week interval enhances the effect of adipose-derived stromal cell enrichment in fat grafting. These findings refine clinical protocols and enhance the therapeutic value of cell-assisted lipotransfer. CLINICAL RELEVANCE STATEMENT: In a modified animal model of cell-assisted lipotransfer, the authors demonstrated that secondary intravenous administration of adipose-derived stromal cells improved retention of grafted fat.

Revisiting metformin therapy for the mitigation of diabetic foot ulcer in patients with diabetic kidney disease from real-world evidence.

Diabetic foot ulcer and diabetic kidney disease are diabetes-related chronic vascular complications that strongly correlate with high morbidity and mortality. Although metformin potentially confers a wound-healing advantage, no well-established clinical evidence supports the benefit of metformin for diabetic foot ulcer. Thus, this study investigated the effect of metformin on diabetic foot ulcer from a large diabetic kidney disease cohort for the first time. This retrospective cohort study enrolled 10 832 patients who visited the nephrology department more than twice at two South Korean tertiary-referral centers between 2001 and 2016. The primary outcome was diabetic foot ulcer events; secondary outcomes included hospitalization, amputation, a composite of amputation or vascular intervention, and Wagner Grade ≥ 3. Multivariate Cox analysis and propensity score matching (PSM) were used to balance baseline intergroup differences between metformin users and non-users. In total, 4748 patients were metformin users, and 6084 patients were metformin non-users. Over a follow-up period of 117.5 ± 66.9 months, the diabetic foot ulcer incidence was 5.2%. After PSM, metformin users showed a lower incidence of diabetic foot ulcer events than metformin non-users (adjusted hazard ratio 0.41; p < 0.001). In a sensitivity analysis of 563 patients with diabetic foot ulcer, metformin usage was associated with lower severity in all four secondary outcomes: hospitalization (adjusted hazard ratio 0.33; p < 0.001); amputation (adjusted hazard ratio 0.44; p = 0.001); composite of amputation or vascular intervention (adjusted hazard ratio 0.47; p < 0.001); and Wagner Grade ≥ 3 (adjusted hazard ratio 0.39; p < 0.001). In conclusion, metformin therapy in patients with diabetic kidney disease can lower diabetic foot ulcer incidence and progression.

Multiple Injections of Adipose-Derived Stem Cells Improve Graft Survival in Human-to-Rat Skin Xenotransplantation through Immune Modulation.

BACKGROUND: Adipose-derived stem cells (ADSCs) exert immunomodulatory effects in the treatment of transplant rejection. This study aimed to evaluate the effects of ADSCs on the skin graft survival in a human-to-rat xenograft transplantation model and to compare single and multiple injections of ADSCs. METHODS: Full-thickness human skin xenografts were transplanted into the backs of Sprague-Dawley rats. The rats were injected subcutaneously on postoperative days 0, 3, and 5. The injections were as follows: triple injections of phosphate-buffered saline (PBS group), a single injection of ADSCs and double injections of PBS (ADSC × 1 group), and triple injections of ADSCs (ADSC × 3 group). The immunomodulatory effects of ADSCs on human skin xenografts were assessed. RESULTS: Triple injections of ADSCs considerably delayed cell-mediated xenograft rejection compared with the PBS and ADSC × 1 groups. The vascularization and collagen type 1-3 ratios in the ADSC × 3 group were significantly higher than those in the other groups. In addition, intragraft infiltration of CD3-, CD4-, CD8-, and CD68-positive cells was reduced in the ADSC × 3 group. Furthermore, in the ADSC × 3 group, the expression levels of proinflammatory cytokine interferon-gamma (IFN-γ) were decreased and immunosuppressive prostaglandin E synthase (PGES) was increased in the xenograft and lymph node samples. CONCLUSION: This study presented that triple injections of ADSCs appeared to be superior to a single injection in suppressing cell-mediated xenograft rejection. The immunomodulatory effects of ADSCs are associated with the downregulation of IFN-γ and upregulation of PGES in skin xenografts and lymph nodes.

Recent strategies for neural dynamics observation at a larger scale and wider scope.

The tremendous technical progress in neuroscience offers opportunities to observe a more minor or/and broader dynamic picture of the brain. Moreover, the large-scale neural activity of individual neurons enables the dissection of detailed mechanistic links between neural populations and behaviors. To measure neural activity in-vivo, multi-neuron recording, and neuroimaging techniques are employed and developed to acquire more neurons. The tools introduced concurrently recorded dozens to hundreds of neurons in the coordinated brain regions and elucidated the neuronal ensembles from a massive population perspective of diverse neurons at cellular resolution. In particular, the increasing spatiotemporal resolution of neuronal monitoring across the whole brain dramatically facilitates our understanding of additional nervous system functions in health and disease. Here, we will introduce state-of-the-art neuroscience tools involving large-scale neural population recording and the long-range connections spanning multiple brain regions. Their synergic effects provide to clarify the controversial circuitry underlying neuroscience. These challenging neural tools present a promising outlook for the fundamental dynamic interplay across levels of synaptic cellular, circuit organization, and brain-wide. Hence, more observations of neural dynamics will provide more clues to elucidate brain functions and push forward innovative technology at the intersection of neural engineering disciplines. We hope this review will provide insight into the use or development of recent neural techniques considering spatiotemporal scales of brain observation.

Efficacy of superficial inferior epigastric vein superdrainage in free TRAM and DIEP flap: An indocyanine green angiography study of 68 cases.

BACKGROUND: This study aimed to evaluate the clinical efficacy of venous augmentation using superficial inferior epigastric vein (SIEV) in free transverse rectus abdominis musculocutaneous (TRAM) and deep inferior epigastric artery perforator (DIEP) flap and investigate the factors that hinder the venous superdrainage. METHODS: A retrospective review of 62 free muscle-sparing (MS)-TRAM and 6 DIEP unilateral breast reconstructions from September 2017 to July 2022. Intraoperative indocyanine green angiography was performed on the harvested flap, with the SIEV contralateral to the pedicle side clamped and unclamped for 20 min. The relative ratio of hypoperfused area to the total flap area was calculated and compared quantitatively. The preoperative computed tomography (CT) angiography was reviewed to obtain information on the SIEV diameter and number of midline-crossing medial branches. RESULTS: The participants were categorized into three groups: 42 patients in Group 1 (>3% decrease in hypoperfused area), 20 patients in Group 2 (change in hypoperfused area ranging from -3% to 3%), and six patients in Group 3 (>3% increase in hypoperfused area). The mean number of midline-crossing branches (p = 0.002) and mean difference in the diameter of bilateral SIEVs (p = 0.039) were significantly greater in Group 1 than in the other groups. CONCLUSIONS: Thirty-eight percent (26/68 cases) resulted in sustained or aggravated perfusion after SIEV superdrainage. Superdrainage using the contralateral SIEV in free MS-TRAM/DIEP flap is recommended when there are more than two midline-crossing medial branches of SIEV and when the caliber of SIEV is relatively greater compared with the pedicle side.

Effects of Nanofat in Plastic and Reconstructive Surgery: A Systematic Review.

BACKGROUND: Since the initial introduction by Tonnard in 2013, numerous studies have reported positive findings after employing nanofat; however, concerns exist regarding its effects and mechanisms, and various methods to generate nanofat also remain unclear. The systematic review was conducted to evaluate the efficacy of sole nanofat grafting in plastic and reconstructive surgery. METHODS: The MEDLINE, Embase, Cochrane Central, Web of Science, and Scopus databases were searched for studies related to sole nanofat grafting in plastic and reconstructive surgery (November 23rd, 2022). Outcomes of interest were all clinical results on humans or animals. RESULTS: Twelve studies were included, and no meta-analysis was conducted due to the clinical heterogeneity of the studies. In general, included studies had a low level of evidence. Six studies (n=253) showed significant improvements in scar characteristics via evaluation of the POSAS scales, FACE-Q scale, physician assessment, patient satisfaction, or VSS scale. Four studies described its benefits in skin rejuvenation (wrinkles, fine rhytides, pigmentation, or discoloration) via photographs, questionnaires, or indentation indices. Histological evaluation illustrated overall increases of skin thickness, collagen, and elastic fibers. Three experimental studies showed beneficial effects of nanofat on fat grafting, diabetic wound healing, and hair growth with compelling histological evidence. No severe complication was reported. CONCLUSION: Sole nanofat grafting shows potential benefits in scar treatment and anti-aging with conclusive histological evidence. Clinical studies about fat grafting, wound healing, or hair growth should be conducted, based on the foundation in this systematic review. Nanofat grafting could be a practical and safe procedure.

Norepinephrine preserved flap blood flow compared to phenylephrine in free transverse rectus abdominis myocutaneous flap breast reconstruction surgery: A randomized pilot study.

BACKGROUND: Vasopressors are used in up to 85% of cases during free flap surgery. However, their use is still debated with concerns of vasoconstriction-related complications, with rates up to 53% in minor cases. We investigated the effects of vasopressors on flap blood flow during free flap breast reconstruction surgery. We hypothesized that norepinephrine may preserve flap perfusion better than phenylephrine during free flap transfer. METHODS: A randomized pilot study was performed in patients undergoing free transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction. Patients with peripheral artery disease, allergies to study drugs, previous abdominal operations, left ventricular dysfunction, or uncontrolled arrhythmias were excluded. Twenty patients were randomized to receive either norepinephrine (0.03-0.10 µg/kg/min) or phenylephrine (0.42-1.25 µg/kg/min) (each n = 10) to maintain a mean arterial pressure of 65-80 mmHg. The primary outcome was differences in mean blood flow (MBF) and pulsatility index (PI) of flap vessels after anastomosis measured using transit time flowmetry in the two groups. Secondary outcomes included flap loss, necrosis, thrombosis, wound infection, and reoperation within 7 days postoperatively. RESULTS: After anastomosis, MBF showed no significant change in the norepinephrine group (mean difference, -9.4 ± 14.2 mL/min; p = 0.082), whereas it was reduced in the phenylephrine group (-7.9 ± 8.2 mL/min; p = 0.021). PI did not change in either group (0.4 ± 1.0 and 1.3 ± 3.1 in the norepinephrine and phenylephrine groups; p = 0.285 and 0.252, respectively). There were no differences in secondary outcomes between the groups. CONCLUSION: During free TRAM flap breast reconstruction, norepinephrine seems to preserve flap perfusion compared to phenylephrine. However, further validation studies are required.

Nipple reconstruction using modified C-V flap with purse-string sutures for maintenance of long-term nipple projection.

BACKGROUND: The most common concern in nipple reconstruction is the loss of long-term nipple projection. This study aimed to demonstrate a novel method of nipple reconstruction using a modified C-V flap combined with purse-string sutures in the nipple base to maintain nipple projection. METHODS: From January 2018 to July 2021, patients who underwent nipple reconstruction using the novel modified C-V flap method and conventional C-V flap were retrospectively reviewed. The ratio of projection at the 3, 6, and 12-month postoperative follow-up to the initial nipple projection was calculated and compared. RESULTS: A total of 116 patients were included in this study, which was comprised of 41 patients in the conventional C-V flap group (conventional) and 75 patients in the modified C-V flap with purse-string sutures group (modified). The modified group showed a significantly higher ratio of nipple projection maintenance at postoperative 3 months (79.82%, conventional; 87.25%, modified; p < 0.001), 6 months (68.29%, conventional; 73.18%, modified; p < 0.001), and 12 months (53.98%, conventional; 60.19%, modified; p < 0.001), and a significantly lower revision rate (13/75 patients, 17.33%) than the conventional group (16/41 patients, 39.02%) (p = 0.009) during a mean of 17.67-month follow-up. CONCLUSIONS: Nipple reconstruction using a modified C-V flap with purse-string sutures in the nipple base is a safe and effective method for the maintenance of long-term nipple projection owing to the reduction and stabilization of the nipple base.