Effect of temperature on the protective efficacy of a live attenuated vaccine against herpesviral haematopoietic necrosis in goldfish.

The live attenuated vaccine P7-P8 strain against herpesviral haematopoietic necrosis, which is caused by cyprinid herpesvirus 2 (CyHV-2), exhibits high protective efficacy in goldfish at 25°C, the predominant temperature for this disease; however, the effect of water temperature during the vaccination period on efficacy has not been determined. In this study, an in vitro experiment revealed that the vaccine strain grew between 15 and 30°C in the goldfish cell line RyuF-2. Subsequent in vivo efficacy tests were conducted with vaccination temperatures ranging from 15 to 30°C. During the vaccination period, organs were sampled to determine the vaccine growth dynamics. Blood plasma was collected to assess anti-CyHV-2 antibody titres. The protective efficacy of the vaccine at 15, 20, 25, and 30°C after subsequent virulent CyHV-2 challenge resulted in a relative percentage survival of 73.3%, 77.8%, 100%, and 77.8%, respectively, which indicated that the vaccine is effective over this temperature range. The vaccine virus load in the spleen was lowest at 15°C (103.7 DNA copies/mg) and highest at 25°C (106.5 DNA copies/mg). This indicates that the vaccine virus load over 104 DNA copies/mg may elicit sufficient acquired immunity. No significant differences in antibody titre were observed between groups, which suggests that cell-mediated immunity can be fundamentally involved in protection.

Minimizing Nipple-Areolar Complex Complications in Prepectoral Breast Reconstruction After Nipple-Sparing Mastectomy.

PURPOSE: Nipple-areolar complex (NAC) viability remains a significant concern following prepectoral tissue expander (TE) reconstruction after nipple-sparing mastectomy (NSM). This study assesses the impact of intraoperative TE fill on NAC necrosis and identifies strategies for mitigating this risk. METHODS: A chart review of all consecutive, prepectoral TEs placed immediately after NSM was performed between March 2017 and December 2022 at a single center. Demographics, mastectomy weight, intraoperative TE fill, and complications were extracted for all patients. Partial NAC necrosis was defined as any thickness of skin loss including part of the NAC, whereas total NAC necrosis was defined as full-thickness skin loss involving the entirety of the NAC. P < 0.05 was considered statistically significant. RESULTS: Forty-six patients (83 breasts) with an average follow-up of 22 months were included. Women were on average 46 years old, nonsmoker (98%), and nondiabetic (100%) and had a body mass index of 23 kg/m2. All reconstructions were performed immediately following prophylactic mastectomies in 49% and therapeutic mastectomies in 51% of cases. Three breasts (4%) were radiated, and 15 patients (33%) received chemotherapy. Mean mastectomy weight was 346 ± 274 g, median intraoperative TE fill was 150 ± 225 mL, and median final TE fill was 350 ± 170 mL. Partial NAC necrosis occurred in 7 breasts (8%), and there were zero instances of complete NAC necrosis. On univariate analysis, partial NAC necrosis was not associated with any patient demographic or operative characteristics, including intraoperative TE fill. In multivariable models controlling for age, body mass index, mastectomy weight, prior breast surgery, and intraoperative TE fill, partial NAC necrosis was associated with lower body mass index (odds ratio, 0.53; confidence interval [CI], 0.29-0.98; P < 0.05) and higher mastectomy weight (odds ratio, 1.1; CI, 1.01-1.20; P < 0.05). Prior breast surgery approached significance, as those breasts had a 19.4 times higher odds of partial NAC necrosis (95% CI, 0.88-427.6; P = 0.06). CONCLUSIONS: Nipple-areolar complex necrosis following prepectoral TE reconstruction is a rare but serious complication. In this study of 83 breasts, 7 (8%) developed partial NAC necrosis, and all but one were able to be salvaged.

Clinical effectiveness of postoperative prostaglandin E1 administration in reducing flap necrosis following microsurgical reconstruction.

BACKGROUND: Extensive experimental evidence has suggested the potential efficacy of prostaglandin E1 (PGE1) in enhancing flap survival, leading to its widespread empirical use following free flap operation. However, the translation of these experimental findings into clinical benefits remains uncertain. This study aimed to assess the clinical effectiveness of postoperative PGE1 administration on the outcomes of microsurgical reconstruction. METHODS: A retrospective review was conducted for patients who underwent free flap-based reconstruction between September 2020 and November 2022, dividing into two cohorts. For all consecutive cases conducted during the formal half, PGE1 was administered for postoperative 7 days (PGE1 cohort), and for those during the latter, PGE1 was not given (non-PGE1 cohort). The profiles of perfusion-related complications (PRC) were compared between the two cohorts. Further analyses after propensity-score matching were performed. RESULTS: In total, 274 cases were analyzed, consisting of 142 in PGE1 and 132 in non-PGE1 cohort. Baseline characteristics were similar between the two cohorts, except for higher rates of comorbidities and chronic wound-related defects in the PGE1 cohort. Overall PRC developed in 37 cases (13.5%), including 6 (2.1%) total loss and 38 (10.2%) partial necrosis. Compared to the control, the PGE1 cohort exhibited significantly lower rates of overall PRC and partial flap necrosis. This difference remained significant on multivariable analyses. The rate of total flap loss did not differ between the cohorts. Consistent associations were observed in the propensity-score matching analysis. CONCLUSION: Postoperative administration of PGE1 appears to be associated with reduced risks for the development of partial flap necrosis.

Strategies to avoid mastectomy skin-flap necrosis during nipple-sparing mastectomy.

BACKGROUND: Nipple-sparing mastectomy is associated with a higher risk of mastectomy skin-flap necrosis than conventional skin-sparing mastectomy. There are limited prospective data examining modifiable intraoperative factors that contribute to skin-flap necrosis after nipple-sparing mastectomy. METHODS: Data on consecutive patients undergoing nipple-sparing mastectomy between April 2018 and December 2020 were recorded prospectively. Relevant intraoperative variables were documented by both breast and plastic surgeons at the time of surgery. The presence and extent of nipple and/or skin-flap necrosis was documented at the first postoperative visit. Necrosis treatment and outcome was documented at 8-10 weeks after surgery. The association of clinical and intraoperative variables with nipple and skin-flap necrosis was analysed, and significant variables were included in a multivariable logistic regression analysis with backward selection. RESULTS: Some 299 patients underwent 515 nipple-sparing mastectomies (54.8 per cent (282 of 515) prophylactic, 45.2 per cent therapeutic). Overall, 23.3 per cent of breasts (120 of 515) developed nipple or skin-flap necrosis; 45.8 per cent of these (55 of 120) had nipple necrosis only. Among 120 breasts with necrosis, 22.5 per cent had superficial, 60.8 per cent had partial, and 16.7 per cent had full-thickness necrosis. On multivariable logistic regression analysis, significant modifiable intraoperative predictors of necrosis included sacrificing the second intercostal perforator (P = 0.006), greater tissue expander fill volume (P < 0.001), and non-lateral inframammary fold incision placement (P = 0.003). CONCLUSION: Modifiable intraoperative factors that may decrease the likelihood of necrosis after nipple-sparing mastectomy include incision placement in the lateral inframammary fold, preserving the second intercostal perforating vessel, and minimizing tissue expander fill volume.

Nipple Sparing Mastectomy Technique to Reduce Ischemic Complications: Preserving Important Blood Flow Based on Breast MRI.

BACKGROUND: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction is commonly performed. However, nipple areolar complex (NAC) and mastectomy skin necrosis represent significant complications requiring reoperation and revision. Breast MRI, often obtained for oncologic assessment, can visualize the dominant breast and NAC vascular supply. This study describes the surgical technique utilizing breast MRI blood flow information to preserve important NAC blood supply, thereby, reducing ischemic complications. METHODS: After IRB approval, a prospectively maintained database of all NSM by a single breast surgeon from 2018 to 2020 formed the study group. Preoperative contrast enhanced Breast MRI analysis determined the dominant NAC blood supply. Intraoperatively, the dominant Internal Mammary Artery Perforator (IMP) to the NAC was preserved (IMP-NSM). The IMP-NSM surgical technique preserving the IMP blood flow, evaluation of breast MRI blood flow patterns, surgical findings, and ischemic complications were analyzed. RESULTS: 114 NSM were performed in 74 patients (mean age: 49 years [range, 22-73 years], BMI 25.8 kg/m2 [range, 19-41 kg/m2]). Breast MRI identified the dominant IMP to the NAC in 92%. IMP preservation was successful in 89% (101/114). Necrosis requiring NAC removal occurred in 0.9% (1/114), and skin necrosis reoperation in 1.8% (2/114). Including all post-operative necrosis occurred in 10.5% (12/114), statistically significantly lower compared to the literature for NSM assessing MRI blood flow data without surgical IMP preservation (necrosis 24.4%, p < 0.001) (Bahl et al. in J Am Coll Surg 223(2):279-285, 2016) utilizing Doppler for IMP preservation (necrosis 37%, p < 0.001) (Swistel et al. in Plast Reconstr Surg Glob Open 2(8):e198, 2014) and dividing the IMP in all (necrosis 31.4%, p < 0.001) (Ahn et al. in Eur J Surg Oncol 44(8):1170-1176, 2018). CONCLUSIONS: The IMP-NSM surgical technique preserves the dominant blood supply to the NAC, thereby, decreasing ischemic complications.

Umbilicus Necrosis During Mesh Repair of Rectus Diastasis for Abdominoplasty: Practical Tips for Prevention and Treatment.

Rectus muscles widened by pregnancy are handled in dramatically different ways in standard abdominoplasty and mesh abdominoplasty. Patients with significant abdominal wall laxity and/or umbilical hernia repair are treated with the use of retrorectus mesh placement. In these conditions the risk of damaging the blood supply to the umbilicus might be greater. Despite the fact that it is of no functional significance in adults, the umbilicus is a key esthetic landmark of the anterior abdominal wall. For both patients and surgeons alike, its absence, distortion, or misplacement after surgery can be distressing and can be a source of frequent patient complaint. Umbilical stalk necrosis represents an underreported yet important complication for patients following mesh abdominoplasty. We advance some recommendations for patients undergoing abdominoplasty with mesh repair of rectus diastasis and/or concomitant umbilical hernia mesh repair via the open approach. This information should help influence intraoperative decision-making to prevent the development of this undesirable complication.Level of Evidence V: 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 .

Utility of Indocyanine Green Angiography for Preventing Pre-expanded Extended Lower Trapezius Myocutaneous Flap Necrosis: How to Make the Correct Decision for Hypoperfused Areas.

BACKGROUND: Designing a skin flap that perfectly covers the anatomical and dynamic territories is challenging. Tissues capturing territories beyond may be insufficiently perfused, and these hypoperfused areas can lead to partial flap necrosis. Indocyanine green angiography (ICGA) is an effective tool for identifying hypoperfused areas. This retrospective study proposes a standardized strategy for managing the hypoperfused areas identified by ICGA in pre-expanded extended lower trapezius myocutaneous (e-LTMC) flaps. METHODS: Patients who underwent pre-expanded e-LTMC flap surgery with perfusion assessment using ICGA between June 2016 and January 2022 were identified. A standardized protocol was applied, and patients were divided into four groups according to different management options for hypoperfused areas detected by ICGA. Preoperative and operative variables of interest and postoperative outcomes, including flap necrosis and flap survival length, were collected and analyzed. RESULTS: Sixty-nine flaps were included in the study. No total flap necrosis was observed. Partial necrosis occurred in 10 flaps. Significant differences were observed in the incidence of full-thickness necrosis between the management groups. The incidence of flap necrosis in cases where management relied on ICGA findings was significantly lower than that of cases where management did not rely on ICGA findings. There were no differences in the relative survival length of the flap between cases with and without intervention for the hypoperfused areas. CONCLUSION: The proposed standard strategy effectively reduced the necrosis rate of the pre-expanded e-LTMC flap, thus it is sensible to act on the ICGA findings. Prophylactic resection of the hypoperfused area should be recommended. Where resection may lead to poor reconstructive outcomes, flap trimming or a second flap should be the preferred option.

Preventing Soft Tissue Complications in Secondary Aesthetic Breast Surgery Using Indocyanin Green Angiography.

BACKGROUND: Secondary cosmetic breast surgery after primary augmentation with implant can be associated with an increased risk of adverse events. Partial/complete nipple-areola complex necrosis is particularly feared. In this preliminary study, the authors propose the utilization of indocyanine green (ICG) angiography to assess the blood supply of breast tissue after implant removal. OBJECTIVES: The main objective was to prevent skin and gland necrosis in revision breast surgery. METHODS: The authors performed a retrospective comparative analysis of 33 patients who underwent secondary breast surgery between 2018 and 2021 by a single surgeon (M.S.). Breast tissue perfusion was assessed in 16 patients by intraoperative ICG angiography at the end of implant removal and possible capsulectomy. Non-stained/non-fluorescent areas were judged to be low perfusion areas and were excised with short scar mastopexy. RESULTS: In the ICG angiography group, 7 patients (44%) showed an area of poor perfusion along the inferior pole; all of these patients underwent subglandular breast augmentation. Resection of the poor perfusion areas allowed an uneventful postoperative course. In the non--- ICG angiography group (17 patients), 5 patients experienced vertical-scar dehiscence/necrosis. We found a statistically significant association between the non-ICG angiography group and vertical scar dehiscence/necrosis, and also between vertical scar dehiscence/necrosis and subglandular implant placement (P = 0.04). CONCLUSIONS: Safer secondary surgery can be offered to patients undergoing secondary aesthetic breast procedures, especially when the first augmentation surgery is unknown-for example, implant plane, type of pedicle employed, if the implant is large and subglandular, and if capsulectomy is performed.

[Vascular occlusion following profile harmonization of the chin with hyaluronic acid fillers]. / Vasculaire occlusie na profielharmonisatie van de kin met hyaluronzuur fillers.

The use of dermal fillers for cosmetic procedures has increased rapidly both worldwide and in the Netherlands in recent years, which has led to an absolute increase in reported side effects and complications. Although most of these complications are mild, serious complications such as vascular occlusion can also occur. In this article, we describe a case of a 35-year-old woman who showed signs of reduced tissue perfusion and the early stage of skin necrosis following injection of hyaluronic acid fillers in the chin. This complication was successfully treated by ultrasound-guided injection of hyaluronidase, resulting in a full recovery without residual symptoms. To minimize the risk of serious complications treatment with hyaluronic acid fillers should be carried out by an experienced practitioner.

Use of ICG Angiography in Head and Neck Reconstruction With the Supraclavicular Artery Island Flap.

PURPOSE: Adequate distal skin paddle perfusion is essential to preventing postoperative flap necrosis in head and neck reconstruction. To describe the use of indocyanine green angiography (ICGA), to assess skin paddle perfusion in the setting of head and neck reconstruction with the supraclavicular artery island flap at a single institution and assess the effect of ICGA use on the rate of postoperative skin paddle necrosis. METHODS: A retrospective cohort study consistently of patients who underwent head and neck reconstruction with a supraclavicular artery island flap for any indication at a tertiary medical center from 2010 to 2018. The predictor variable was ICGA use. The primary outcome was rate of skin paddle necrosis. Secondary outcomes included rates of post-operative overall complications, dehiscence, fistula, and reoperation. Covariates included demographic, operative, flap perfusion assessment, and postoperative variables. Retrospective assessment of distal flap perfusion was performed on available ICGA video recordings. Descriptive and bivariate statistics were computed. Statistical significance was set at P ≤ .05. RESULTS: A total of 104 patients were included and ICGA was used in 23 cases. In 10 of these cases, flap trimming was performed due to concern of flap hypoperfusion on ICGA. The median relative distal flap perfusion was 16.7 ± 2.6% in trimmed flaps, compared to 35 ± 13.2% in untrimmed flaps. ICGA use was not associated with rate of skin paddle necrosis (P = .76). CONCLUSIONS: ICGA is a viable method of assessing intraoperative supraclavicular artery island skin paddle perfusion and can help determine the need for distal flap trimming when tissue viability based on clinical findings alone is uncertain. ICGA use for skin paddles with uncertain perfusion on intraoperative clinical findings prevented a potential increase in postoperative necrosis compared to that of skin paddles with adequate perfusion on intraoperative clinical findings. Future studies are required to determine the minimum distal perfusion value that indicates hypoperfusion and the need for flap modification.

Strategy for preventing skin paddle necrosis in mandibular reconstruction with free fibula osteocutaneous flap.

BACKGROUND: Non-thrombotic skin paddle necrosis occasionally occurs during mandibular reconstructions with free fibula osteocutaneous flaps. The number of perforators, size of the skin paddle, and ischemia time of the flap are considered as causes of skin paddle necrosis. The importance of donor side selection has also been highlighted. This study aimed to investigate the leading cause of skin paddle necrosis and the optimal reconstructive procedure. METHODS: A total of 66 patients who underwent mandibular reconstruction using a free fibula osteocutaneous flap were retrospectively analyzed. Skin paddle necrosis, number of cutaneous perforators, size of the skin paddle, and ischemia time of the flap were investigated. An incorrect "laterality" was defined as a skin paddle (septum) covering the reconstruction plate. Donor-site morbidity was recorded. RESULTS: Skin paddle necrosis occurred in 15.2% of patients. An incorrect laterality was associated with a higher incidence of skin paddle necrosis (odds ratio, 22.0; 95% confidence interval, 2.5-195; p = .005). Donor-site morbidity was noted in 18.8% of the patients, without any significant difference in terms of the donor side with and without skin graft (p = .592). The postoperative activities of daily living were not affected. CONCLUSIONS: To prevent skin paddle necrosis, donor side selection is an important safety strategy during mandibular reconstruction with free fibula osteocutaneous flap. The postoperative activities of daily living were found to be little affected by differences in the donor side.

The Effect of Quilting Sutures on the Tension Required to Advance the Abdominal Flap in Abdominoplasty.

BACKGROUND: Quilting sutures attaching the abdominal flap to the aponeurosis contribute to the prevention of seroma formation following abdominoplasty. The sutures distribute the tension over the subcutaneous tissue along the flap length, theoretically decreasing tension at the distal (cutaneous) end of the flap. This is expected to reduce the risks of necrosis, dehiscence, and enlarged or hypertrophic scars. OBJECTIVES: This study sought to verify whether quilting sutures decrease the tension required to advance the dermal-fat flap in abdominoplasty. METHODS: Thirty-four women undergoing abdominoplasty with quilting sutures participated in the study. The tensile force required for flap advancement was measured with a digital force gauge before and after placement of quilting sutures and then compared. Differences in tensile force were tested for correlations with BMI, age, weight of flap tissue removed, number of previous pregnancies, and postoperative complications, including seroma formation, hematoma, necrosis, dehiscence, and enlarged or hypertrophic scars. RESULTS: A mean reduction in tension of 27.7% was observed at the skin suture after the placement of quilting sutures (P < 0.001). No significant correlation was found between reduced flap tension and BMI, age, weight of tissue removed, or number of births. One case of seroma formation and 2 cases of enlarged scars were observed, but no case of hematoma, necrosis, or wound dehiscence was detected. CONCLUSIONS: The use of quilting sutures to attach the abdominal flap to the aponeurosis of the anterior abdominal wall reduced tension at the advancing edge of the flap in abdominoplasty.

British Association of Urological Surgeons (BAUS) and Nurses (BAUN) consensus document: management of the complications of long-term indwelling catheters.

OBJECTIVE: To look at best evidence and expert opinion to provide advice in the form of a consensus statement lead by Female, Neurological and Urodynamic Urology (FNUU) section of the British Association of Urological Surgeons (BAUS) in conjunction with the British Association of Urological Nurses (BAUN). METHODS: Initially a literature search was performed with incorporation of aspects of the existing guidance and further informed by UK best practice by core members of the group. The document then underwent reviews by the FNUU Executive Committee members, the BAUN executive committee, a separate experienced urologist and presented at the BAUS annual meeting 2020 to ensure wider feedback was incorporated in the document. RESULTS: Complications of long-term indwelling catheters include catheter-associated urinary tract infections (CAUTI), purple urine bag syndrome, catheter blockages, bladder spasms (causing pain and urinary leakage), loss of bladder capacity, urethral erosion ("catheter hypospadias")/dilatation of bladder outlet and chronic inflammation (metaplasia and cancer risk). CONCLUSIONS: We have provided a list of recommendations and a troubleshooting table to help with the management of the complications of long term catheters.

[Immediate outcomes of pancreatoduodenectomy after different digestive reconstruction procedures]. / Blizhaishie rezul'taty pankreatoduodenal'noi rezektsii posle razlichnykh variantov rekonstruktsii pishchevaritel'noi sistemy.

OBJECTIVE: To study the immediate results of pancreatoduodenectomy depending on digestive reconstruction procedure. MATERIAL AND METHODS: We analyzed 242 patients who underwent pancreatoduodenectomy for the period from January 2013 to December 2019. There were 32 combined procedures: 28 (11.6%) with portal vein resection and 8 (3.3%) simultaneous operations (right-sided hemicolectomy - 4, right-sided adrenalectomy - 2, gastrectomy with splenectomy - 2). Pancreatic stump was inserted into the jejunum in 156 (64.5%) patients, into the stomach - in 86 (35.5%) cases. RESULTS: Postoperative period was uneventful in 180 (74.4%) patients. Eighty postoperative complications were observed in 62 (25.6%) patients; 221 (91.3%) patients were discharged, 21 (8.7%) patients died. Pancreatic necrosis was the most common postoperative event and provoked 65 (82.5%) various complications (38 (72.1%) in patients with pancreaticojejunostomy and 20 (71.5%) in those with pancreaticogastrostomy). Incidence of complications was similar in both groups. However, pancreaticojejunostomy was followed by severe pancreatic fistula type C in 12 (23.1%) patients, type B in 24 (46.1%) cases. In case of pancreaticogastrostomy, pancreatic fistula type C occurred in 4 (14.3%) cases, type B - in 8 (28.6%) patients. CONCLUSION: Pancreatic necrosis was the most common postoperative event after pancreatoduodenectomy. Fewer severe pancreatic fistulae (type C) were recorded after pancreaticogastrostomy although these patients had lower density of the pancreas and unclear pancreatic duct. Choice of pancreatic-digestive anastomosis should be determined by features of pancreatic parenchyma, pancreatic duct diameter. Nevertheless, final decision is a prerogative of surgeon. Pancreaticogastrostomy is especially advisable in minimally invasive PDEs that will simplify inclusion of the pancreas into digestive system and reduce the incidence of complications and mortality.

Dendrobium Alkaloids Promote Neural Function After Cerebral Ischemia-Reperfusion Injury Through Inhibiting Pyroptosis Induced Neuronal Death in both In Vivo and In Vitro Models.

Pyroptosis is a newly identified lytic form of programmed cell death which is characterized by plasma membrane blebbing and rupture. Pyroptosis occurs in cerebral ischemia injury, and contributes to the activation and secretion of the inflammatory cytokines interleukin (IL)-1ß, IL-18, and IL-6. Previous reports have found that Dendrobium alkaloids (DNLA) can exert neuroprotective effects against oxygen-glucose deprivation/reperfusion (OGD/R) damage in vitro, but the mechanisms underlying these effects remain elusive. In this study, we investigated whether DNLA exerted therapeutic benefits against cerebral ischemia-reperfusion (CIR) damage via ameliorating pyroptosis and inflammation. OGD/R damage was induced in HT22 cells pretreated with DNLA (0.03, 0.3, or 3 mg/ml, 24 h prior to OGD/R), MCC950 (10 ng/ml, 1 h prior), and VX765 (10 ng/ml, 1 h prior). Neuronal apoptosis, necrosis, pyroptosis, and pathological changes were analyzed 24 h following OGD/R. Further to this, male C57/BL mice pretreated with different concentrations of DNLA (0.5 or 5 mg/kg, ip.) for 24 h and VX765 (50 mg/kg, ip., 1 h before CIR) underwent transient middle cerebral artery occlusion and reperfusion. We found that DNLA pretreatment resulted in a lower neurologic deficit score, a reduced infarct volume, fewer pyroptotic cells, and reduced levels of inflammatory factors 24 h after CIR. Furthermore, DNLA administration also reduced the levels of the pyroptosis-associated proteins Caspase-1 and gasdermin-D, particularly in the hippocampal CA1 region. Similar decreases were observed in the levels of the inflammatory factors IL-1ß, IL-6, and IL-18. OGD/R-associated ultrastructural damage was seen to improve following DNLA administration, likely due to the regulation of the tight junction protein Pannexin-1 by DNLA. Overall, these findings demonstrate that DNLA can protect against CIR damage through inhibiting pyroptosis-induced neuronal death, providing new therapeutic insights for CIR injury.

Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis.

Necroptosis is a regulated, nonapoptotic form of cell death initiated by receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL) proteins. It is considered to be a form of regulated necrosis, and, by lacking the "find me" and "eat me" signals that are a feature of apoptosis, necroptosis is considered to be inflammatory. One such "eat me" signal observed during apoptosis is the exposure of phosphatidylserine (PS) on the outer plasma membrane. Here, we demonstrate that necroptotic cells also expose PS after phosphorylated mixed lineage kinase-like (pMLKL) translocation to the membrane. Necroptotic cells that expose PS release extracellular vesicles containing proteins and pMLKL to their surroundings. Furthermore, inhibition of pMLKL after PS exposure can reverse the process of necroptosis and restore cell viability. Finally, externalization of PS by necroptotic cells drives recognition and phagocytosis, and this may limit the inflammatory response to this nonapoptotic form of cell death. The exposure of PS to the outer membrane and to extracellular vesicles is therefore a feature of necroptotic cell death and may serve to provide an immunologically-silent window by generating specific "find me" and "eat me" signals.

Arterial Supercharging Is More Beneficial to Flap Survival Due to Quadruple Dilation of Venules.

BACKGROUND: "Choke vessels" are communicating conduits between adjacent perforasomes in the skin. Most researches focus mainly on the arterial aspect of the "choke vessels" and neglect the venous aspect, an imbalance needed to be addressed. MATERIALS AND METHODS: The study was divided into parts I, II, and III. Part I was for observation of the vascular morphological evolution in the choke zone after flap harvest in rats. Part II was for determination of the importance of the dilation of the arterial and venous components of "choke vessels" by preserving the iliolumbar artery (ILA group) or vein (ILV group). A laser Doppler flowmeter and a speckle flow imaging system were adopted for monitoring the hemodynamic impact caused by the different manipulation. Part III was for corroboration of part II by manipulation of other vessels. RESULTS: In part I, the arteries and veins between the iliolumbar and intercostal perforasomes underwent modest dilation, whereas the venules between the veins nearly quadrupled in diameter. In part II, flaps in the ILA group were much more intensive in blood perfusion than flaps in the ILV group. The flap necrosis rate was 0.31 ± 0.07 in the ILV group, being significantly larger than 0.10 ± 0.03 in the ILA group. Part III confirmed that venous superdrainage is less efficacious in reducing flap necrosis than arterial supercharging, in which the position of the additional artery was far more important than the diameter. CONCLUSIONS: The extensive dilation of the venous component of choke vessels makes a more potent compensatory role for venous drainage after flap harvest, indicating arterial supercharging is better in augmenting flap viability than venous superdrainage.

Sodium Valproate Improves Skin Flap Survival via Gamma-Aminobutyric Acid and Histone Deacetylase Inhibitory System.

Sodium valproate interacts with biological systems through different mechanisms such as activation of gamma-aminobutyric acid (GABA)-sensitive chloride channels and inhibition of histone deacetylase. In this study, we examined the effect of sodium valproate in random-pattern skin flap of rats and investigated its mechanisms of action. Different types of experiments were carried out. In acute treatment, different doses of sodium valproate (50, 100, 150, 300 mg/kg) were injected intraperitoneally 1 h before surgery. In chronic treatment, the substance was injected each day for 2 wk. The size of skin necrosis was measured 1 wk after the surgery. The rate of secondary healing, amount of weight gain, hair growth, and wound regeneration were measured 2 wk after operation. In acute treatment, sodium valproate (100 mg/kg) reduced significantly the length of skin necrosis (P < 0.05). Administration of bicuculline (competitive antagonist of GABAA, 20 mg/kg) increased the length of skin necrosis (P < 0.05). In addition, administration of 100 mg/kg of sodium valproate and subeffective dose of bicuculline (10 mg/kg) prevented the protective effect of sodium valproate on skin flap necrosis (P < 0.05). In the chronically treated skin flap group, 100 mg/kg of sodium valproate reduced the length of necrosis (P < 0.01). Weight gain in the valproate group was more than that in the control group (P < 0.05). Skin also healed faster in the sodium valproate group than in the control group (P < 0.001). Combination therapy of sodium valproate and trichostatin A (330 nmol/kg) reversed the effect of valproate (P < 0.05). This study demonstrate that sodium valproate accelerates skin secondary healing in a rat model of skin flap probably through a GABA and histone deacetylase-dependent mechanism.

Erdosteine salvages cardiac necrosis: Novel effect through modulation of MAPK and Nrf-2/HO-1 pathway.

Isoproterenol (ISO) induced oxidative stress and inflammation is involved in the pathogenesis of myocardial necrosis. To optimize the effect of erdosteine against myocardial necrosis, male albino Wistar rats were divided into eight groups (n = 6), that is, normal, ISO-control, erdosteine pretreatment with ISO. Rats were administered erdosteine orally for 28 days. Two doses of ISO (85 mg/kg), s.c. were given to ISO-C and erdosteine treatment groups on the 27th and 28th day. On the 29th day, hemodynamic parameters were recorded and the heart was excised for further parameters. In ISO-C rats, significantly increased levels of inflammatory markers, pro-oxidants, and structural damage were observed as compared with normal group. Furthermore, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed an increased expression of apoptotic proteins. Erdosteine at 80 mg/kg reversed the deleterious effects of ISO and normalized myocardium. Erdosteine showed anti-inflammatory, antiapoptotic, and antioxidant activities through inhibition of MAPK and Nrf-2/HO-1 pathways. To conclude, erdosteine was found protective in ISO-induced myocardial necrosis through MAPK and Nrf-2/HO-1 pathway.

Indocyanine green angiography for preventing postoperative mastectomy skin flap necrosis in immediate breast reconstruction.

BACKGROUND: Breast cancer will affect one in eight women during their lifetime. The opportunity to restore the removed tissue and cosmetic appearance is provided by reconstructive breast surgery following skin-sparing mastectomy (SSM). Mastectomy skin flap necrosis (MSFN) is a common complication following SSM breast reconstruction. This postoperative complication can be prevented by intraoperative assessment of mastectomy skin flap viability and intervention when tissue perfusion is compromised. Indocyanine green fluorescence angiography is presumed to be a better predictor of MSFN compared to clinical evaluation alone. OBJECTIVES: To assess the effects of indocyanine green fluorescence angiography (ICGA) for preventing mastectomy skin flap necrosis in women undergoing immediate breast reconstruction following skin-sparing mastectomy. To summarise the different ICGA protocols available for assessment of mastectomy skin flap perfusion in women undergoing immediate breast reconstructions following skin-sparing mastectomy. SEARCH METHODS: We searched the Cochrane Breast Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 3, 2019), MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov in April 2019. In addition, we searched reference lists of published studies. SELECTION CRITERIA: We included studies that compared the use of ICGA to clinical evaluation to assess mastectomy skin vascularisation and recruited women undergoing immediate autologous or prosthetic reconstructive surgery following SSM for confirmed breast malignancy or high risk of developing breast cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias of the included nonrandomised studies and extracted data on postoperative outcomes, including postoperative MSFN, reoperation, autologous flap necrosis, dehiscence, infection, haematoma and seroma, and patient-related outcomes. The quality of the evidence was assessed using the GRADE approach and we constructed two 'Summary of finding's tables: one for the comparison of ICGA to clinical evaluation on a per patient basis and one on a per breast basis. MAIN RESULTS: Nine nonrandomised cohort studies met the inclusion criteria and involved a total of 1589 women with 2199 breast reconstructions. We included seven retrospective and two prospective cohort studies. Six studies reported the number of MSFN on a per breast basis for a total of 1435 breasts and three studies reported the number of MSFN on a per patient basis for a total of 573 women. Five studies reported the number of other complications on a per breast basis for a total of 1370 breasts and four studies reported the number on a per patient basis for a total of 613 patients. Therefore, we decided to pool data separately. Risk of bias for each included nonrandomised study was assessed using the Newcastle-Ottawa Scale for cohort studies. There was serious concern with risk of bias due to the nonrandomised study design of all included studies and the low comparability of cohorts in most studies. The quality of the evidence was found to be very low, after downgrading the quality of evidence twice for imprecision based on the small sample sizes and low number of events in the included studies. Postoperative complications on a per patient basis We are uncertain about the effect of ICGA on MSFN (RR 0.79, 95% CI 0.40 to 1.56; three studies, 573 participants: very low quality of evidence), infection rates (RR 0.91, 95% CI 0.60 to 1.40; four studies, 613 participants: very low quality of evidence), haematoma rates (RR 0.87, 95% CI 0.30 to 2.53; two studies, 459 participants: very low quality of evidence) and seroma rates (RR 1.68, 95% CI 0.41 to 6.80; two studies, 408 participants: very low quality of evidence) compared to the clinical group. We found evidence that ICGA may reduce reoperation rates (RR 0.50, 95% CI 0.35 to 0.72; four studies, 613 participants: very low quality of evidence). One study considered dehiscence as an outcome. In this single study, dehiscence was observed in 2.2% of participants (4/184) in the ICGA group compared to 0.5% of participants (1/184) in the clinical group (P = 0.372). The RR was 4.00 (95% CI 0.45 to 35.45; one study; 368 participants; very low quality of evidence). Postoperative complications on a per breast basis We found evidence that ICGA may reduce MSFN (RR 0.62, 95% CI 0.48 to 0.82; six studies, 1435 breasts: very low quality of evidence), may reduce reoperation rates (RR 0.65, 95% CI 0.47 to 0.92; five studies, 1370 breasts: very low quality of evidence) and may reduce infection rates (RR 0.65, 95% CI 0.44 to 0.97; five studies, 1370 breasts: very low quality of evidence) compared to the clinical group. We are uncertain about the effect of ICGA on haematoma rates (RR 1.53, CI 95% 0.47 to 4.95; four studies, 1042 breasts: very low quality of evidence) and seroma rates (RR 0.71, 95% CI 0.37 to 1.35; two studies, 528 breasts: very low quality of evidence). None of the studies reported patient-related outcomes. ICGA protocols: eight studies used the SPY System and one study used the Photodynamic Eye imaging system (PDE) to assess MSFN. ICGA protocols in the included studies were not extensively described in most studies. AUTHORS' CONCLUSIONS: Although mastectomy skin flap perfusion is performed more frequently using ICGA as a helpful tool, there is a lack of high-quality evidence in the context of randomised controlled trials. The quality of evidence in this review is very low, since only nonrandomised cohort studies have been included. With the results from this review, no conclusions can be drawn about what method of assessment is best to use during breast reconstructive surgery. High-quality randomised controlled studies that compare the use of ICGA to assess MSFN compared to clinical evaluation are needed.