Propeller Flap Reconstruction Following Pilonidal Cyst Excision: A Single-Center Experience With Same-Day Discharge.

INTRODUCTION: Reconstruction following pilonidal cyst resection must balance risk of recurrence, healing time, and resumption of functional routine. Propeller flaps provide a reliable and effective reconstructive option. This study highlights our experience with propeller flap reconstruction following pilonidal cyst resection and demonstrates the efficacy of same-day discharge. METHODS: A single-institution retrospective chart review was performed for propeller flap reconstructions completed from March 2018 to July 2022. Patient demographics, pilonidal cyst details, operative details, and postoperative outcomes were collected. Primary outcomes included flap survival, flap complications, and pilonidal disease recurrence. RESULTS: Twenty-eight outpatient propeller flap reconstructions following pilonidal cyst resections were identified in 26 patients, with two patients receiving a second propeller flap due to recurrence. Most patients were male (n = 15, 57.7%) with a mean age at time of index operation of 25.5 ± 5.8 years and mean body mass index of 26.5 ± 4.1 kg/m2. Mean symptom duration prior to index surgery was 39.3 months. Mean skin defect size following resection was 28.3 ± 15.3 cm2, with a mean flap size of 44.7 ± 35.5 cm2. Flap survival was 100% (n = 28), with five flaps (17.9%) experiencing minor wound complications and one patient (3.8%) requiring return to the operating room. Mean time to functional improvement was 24.0 ± 22.8 days. Pilonidal disease recurrence occurred in three patients (11.5%). Mean follow-up was 4.1 ± 5.4 months. CONCLUSIONS: Propeller flaps provide a successful and reliable reconstructive option for pilonidal disease defects. Because patients in our cohort experienced favorable outcomes and functional improvement, we advocate for same-day discharge in order to reduce hospital and patient burden.

Postoperative Glycemic Response in High-Risk Type II Diabetics Receiving Below-Knee Amputation: Does Intraoperative Dexamethasone Make an Impact?

Despite known risks of hyperglycemia on postoperative complications, the influence of intraoperative dexamethasone on blood glucose has yet to be evaluated within the diabetic limb salvage population. This study aimed to assess the effect of intraoperative dexamethasone on postoperative blood glucose in diabetic patients undergoing atraumatic major lower extremity amputations. A single-center retrospective review of diabetic patients undergoing below-knee amputation between January 2017 and December 2022 was performed. Blood glucose levels for the 5 days before and after amputation were recorded and compared with the primary endpoints of postoperative hyperglycemia (>200 mg/dL) and glucose variability (>200 mg/dL). Cohorts were divided by patients who did and did not receive intraoperative administration of dexamethasone. Three hundred eighty-one were screened for eligibility with 180 patients included. Of these, 50 patients received dexamethasone intraoperatively (38.5%). Average pre- and postoperative blood glucose, rate of pre- and postoperative hyperglycemia, perioperative glucose variability, and postoperative dehiscence and infection were comparable between cohorts. On multivariate analysis, intraoperative administration of dexamethasone was not associated with postoperative hyperglycemia (p = .104) or perioperative blood glucose variability > 200 mg/dL (p = .334). Perioperative blood glucose variability > 200 mg/dL was associated with higher odds of surgical site infection (SSI) (odds ratio 5.12, p = .003). Administration of intravenous dexamethasone to diabetic patients undergoing below-knee amputation is not associated with postoperative hyperglycemia or complications. This study confirms previous findings that high glucose is a predictor of SSI. Concerted effort by a multidisciplinary team to attain tight glycemic control is critical to optimizing healing.

A Multidisciplinary Approach to End-Stage Limb Salvage in the Highly Comorbid Atraumatic Population: An Observational Study.

Background: The use of free tissue transfer (FTT) is efficacious for chronic, non-healing lower extremity (LE) wounds. The four pillars of managing patient comorbidities, infection control, blood flow status, and biomechanical function are critical in achieving successful limb salvage. The authors present their multidisciplinary institutional experience with a review of 300 FTTs performed for the complex LE limb salvage of chronic LE wounds. Methods: A single-institution, retrospective review of atraumatic LE FTTs performed by a single surgeon from July 2011 to January 2023 was reviewed. Data on patient demographics, comorbidities, preoperative management, intraoperative details, flap outcomes, postoperative complications, and long-term outcomes were collected. Results: A total of 300 patients who underwent LE FTT were included in our retrospective review. Patients were on average 55.9 ± 13.6 years old with a median Charlson Comorbidity Index of 4 (IQR: 3). The majority of patients were male (70.7%). The overall hospital length of stay (LOS) was 27 days (IQR: 16), with a postoperative LOS of 14 days (IQR: 9.5). The most prevalent comorbidities were diabetes (54.7%), followed by peripheral vascular disease (PVD: 35%) and chronic kidney disease (CKD: 15.7%). The average operative LE FTT time was 416 ± 115 min. The majority of flaps were anterolateral thigh (ALT) flaps (52.7%), followed by vastus lateralis (VL) flaps (25.3%). The immediate flap success rate was 96.3%. The postoperative ipsilateral amputation rate was 12.7%. Conclusions: Successful limb salvage is possible in a highly comorbid patient population with a high prevalence of diabetes mellitus, peripheral vascular disease, and end-stage renal disease. In order to optimize patients prior to their LE FTT, extensive laboratory, arterial, and venous preoperative testing and diabetes management are needed preoperatively. Postoperative monitoring and long-term follow-up with a multidisciplinary team are also crucial for long-term limb salvage success.

An Algorithmic Approach to Dual-System Venous Drainage for DIEP Flap Breast Reconstruction.

BACKGROUND: Few studies compared the use of the deep venous system alone versus combined superficial and deep venous drainage in DIEP flaps. The objective of this study is to compare DIEP flap breast reconstruction using either the deep venous system alone versus dual-system venous drainage and to propose an algorithm for flap design and orientation and veins selection to facilitate consistent use of dual-system venous drainage. METHODS: Patients undergoing DIEP flap breast reconstruction between March 2017 and April 2021 were retrospectively reviewed. Flaps were divided into two groups: deep venous system only (Group 1) or dual-system (Group 2). Outcomes included takeback to the operating room (OR), flap loss and thrombosis and operative time. RESULTS: A total of 244 DIEP flaps in 162 patients met inclusion criteria. A total of 130 flaps were included in Group 1 (53.3%) and 114 flaps were included in Group 2 (46.7%). Sixteen flaps (6.6%) required immediate takeback to the OR and takeback rates were not significantly different between groups (p=0.606). Flap loss rate was significantly higher in Group 1: 2.5% vs Group 2: 0%; p=0.031. Flap thrombosis occurred in 8 flaps (3.3%) and tended to occur more frequently in Group 1 but this finding did not reach significance (Group 1: 5.4% vs Group 2: 0.9%; p=0.071). CONCLUSIONS: The use of dual-system venous drainage in DIEP flap breast reconstruction decreases the rate of flap loss. Our algorithm can be used to guide selection of flap laterality, rotation, and veins and recipient vessels to facilitate routine use of dual-system venous drainage.

A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development.

Disrupted-In-Schizophrenia-1 (DISC1), originally identified at the breakpoint of a chromosomal translocation that is linked to a rare familial schizophrenia, has been genetically implicated in schizophrenia in other populations. Schizophrenia involves subtle cytoarchitectural abnormalities that arise during neurodevelopment, but the underlying molecular mechanisms are unclear. Here, we demonstrate that DISC1 is a component of the microtubule-associated dynein motor complex and is essential for maintaining the complex at the centrosome, hence contributing to normal microtubular dynamics. Carboxy-terminal-truncated mutant DISC1 (mutDISC1), which results from a chromosomal translocation, functions in a dominant-negative manner by redistributing wild-type DISC1 through self-association and by dissociating the DISC1-dynein complex from the centrosome. Consequently, either depletion of endogenous DISC1 or expression of mutDISC1 impairs neurite outgrowth in vitro and proper development of the cerebral cortex in vivo. These results indicate that DISC1 is involved in cerebral cortex development, and suggest that loss of DISC1 function may underlie neurodevelopmental dysfunction in schizophrenia.

Saphenous Vein Interposition Grafts in Lower Extremity Reconstruction: Appraisal of Technique and Case Series.

Vascular microanastomosis is technically challenging in patients with calcified recipient and donor vessels. Inside-to-outside suturing can prevent plaque rupture and ensure full-thickness intimal approximation. Although this is the preferred technique for anastomosis of atherosclerotic vessels, direct connection of calcified arteries necessitates outside-to-inside suturing on one side of the anastomosis. Furthermore, it is difficult to achieve optimal vessel wall approximation in the setting of luminal size mismatch and rigid vasculature. We previously reported on the use of a saphenous vein interposition graft as a novel technique to achieve a flow-sparing anastomosis in patients with diffuse atherosclerosis who are undergoing free tissue transfer. This study further assesses outcomes of this technique in a series of patients and demonstrates a flap success rate of over 93% in patients with calcified recipient and donor microvasculature.

Serial Excision for Treatment of Non-melanoma Skin Cancer.

Mohs micrographic surgery (MMS) has become the predominant modality of excision for non-melanoma skin cancers (NMSC). Patients are referred for MMS under the assumption that it is the most effective procedure for definitive removal of the cancer while also allowing for maximal tissue preservation to achieve optimal cosmesis. The objective of this study was to investigate outcomes of serial excision (SE) as an alternative excision modality for NMSC. METHODS: Patients undergoing SE for basal cell carcinoma or squamous cell carcinoma by the senior author from 2009 to 2020 were retrospectively reviewed. Patient demographics, lesion characteristics, and excision characteristics were recorded. The primary outcome was the number of excisions required to achieve negative margins. RESULTS: In total, 129 patients with 205 NMSC lesions were retrospectively reviewed. An estimated 69 lesions (33.7%) were located in high risk areas, as defined by the National Comprehensive Cancer Network. Negative margins were achieved in 191 (93.2%) lesions. In 88.3% of lesions (n = 181/205), negative margins were achieved in 2 or less excisions. 12 lesions (5.9%) were referred for MMS. CONCLUSIONS: Our results demonstrate that SE is an effective modality for definitive removal of NMSC. Recent research reveals that SE is much less expensive than MMS, and therefore places a smaller financial burden on the patient and the healthcare system as a whole. Relative to MMS, SE offers similar if not increased benefits for lower cost. Our findings highlight the need to critically reassess the select indications for MMS.

Amputation versus Free Flap: Long-Term Outcomes of Microsurgical Limb Salvage and Risk Factors for Amputation in the Diabetic Population.

BACKGROUND: Reconstructive microsurgery is an effective limb-saving option for nonhealing lower extremity wounds in diabetic patients. However, the ability to predict the future need for amputation is unclear. This article seeks to identify risk factors for amputation following microsurgical free tissue transfer in the diabetic lower extremity. METHODS: Diabetic patients undergoing lower extremity free flap surgery between August of 2011 and January of 2018 performed by a single surgeon were identified retrospectively. Patient comorbidities, reconstructive conditions and flap traits, microsurgical outcomes, and long-term outcomes were examined. Variables conferring risk for future amputation were examined by means of regression analysis. RESULTS: Sixty-four patients met the criteria. The overall immediate flap success rate was 94 percent (60 of 64). Long term, 50 patients (78.1 percent) underwent successful salvage, and 14 patients (21.9 percent) required major amputation. Acute flap loss resulted in four amputations, and delayed complications (hematoma, infection, recurrent nonhealing) resulted in 10 amputations. The average time to amputation was 5.6 months. Risk factors for amputation were end-stage renal disease (OR, 30.7; p = 0.0087), hindfoot wounds (OR, 4.6; p = 0.020), elevated hemoglobin A1C level greater than 8.4 percent (OR, 1.4; p = 0.05), and positive wound cultures (OR, 6.1; p = 0.003). CONCLUSIONS: Multiple comorbidities and poor glucose control were identified as risk factors for amputation after free flap limb salvage. However, successful limb preservation is possible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Aspergillus fumigatus extract differentially regulates antigen-specific CD4+ and CD8+ T cell responses to promote host immunity.

Invasive aspergillosis is a major cause of morbidity and mortality in the severely immunocompromised. The paucity of information about the mechanisms by which Aspergillus-derived factors regulate antigen-specific T cell responses in vivo poses a significant hurdle for devising effective immunization strategies to treat or prevent aspergillosis. By monitoring adoptively transferred T cell receptor transgenic, naive CD4+ (OT-II) and CD8+ (OT-I) T cells specific for distinct peptides of a nominal antigen, chicken ovalbumin (OVA), we demonstrate that sensitization with Aspergillus fumigatus (Af) extract plus OVA protein considerably enhances OT-I and OT-II T cell activation, which results in clonal expansion, primarily as a result of increased proliferation. The sensitization provided by Af extract promotes OT-I expansion accompanied by differentiation into interferon-gamma-producing cytotoxic cells. It is surprising that no effector differentiation of the induced OT-II response was observed. Moreover, the Af extract-induced OT-I and OT-II T cell expansion was transient, as considerable contraction in the numbers of detectable OT-I and OT-II T cells was evidenced by Day 10. In agreement with these observations, sensitization with Af extract plus OVA marginally promoted host immunity against an OVA-expressing thymoma (E.G7) challenge, and the protection was enhanced by resensitization with Af extract and OVA. Our results demonstrate the ability of Af extract to differentially regulate antigen-specific CD4+ and CD8+ T cell responses, resulting in limited augmentation of host immunity. This information suggests that strategies to target CD4+ T cell effector maturation may promote host immunity to Aspergillus and unexpectedly demonstrates the use for Af extract as a CD8+ T cell adjuvant.

Heat shock proteins as vaccine adjuvants in infections and cancer.

In addition to maintaining cell homeostasis under physiological and stress conditions, some heat shock proteins (HSPs) are potent inducers of immunity and have been harnessed as vaccine adjuvants targeted to cancers and infections. HSPs are a group of ubiquitous intracellular molecules that function as molecular chaperones in numerous processes, such as protein folding and transport, and are induced under stress conditions, such as fever and radiation. Certain HSPs are potent inducers of innate and antigen-specific immunity. They activate dendritic cells partly through toll-like receptors, activate natural killer cells, increase presentation of antigens to effector cells and augment T-cell and humoral immune responses against their associated antigens. Their roles in priming multiple host defense pathways are being exploited in vaccine development for cancer and infectious diseases.

Modeling the combination of amphotericin B, micafungin, and nikkomycin Z against Aspergillus fumigatus in vitro using a novel response surface paradigm.

Response surface methods for the study of multiple-agent interaction allow one to model all of the information present in full concentration-effect data sets and to visualize and quantify local regions of synergy, additivity, and antagonism. In randomized wells of 96-well plates, Aspergillus fumigatus was exposed to various combinations of amphotericin B, micafungin, and nikkomycin Z. The experimental design was comprised of 91 different fixed-ratio mixtures, all performed in quintuplicate. After 24 h of drug exposure, drug effect on fungal viability was assessed using the tetrazolium salt 2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium-hydroxide} (XTT) assay. First, we modeled each fixed-ratio combination alone using the four-parameter Hill concentration-effect model. Then, we modeled each parameter, including the 50% inhibitory concentration (IC(50)) effect, versus the proportion of each agent using constrained polynomials. Finally, we modeled the three-agent response surface overall. The overall four-dimensional response surface was complex, but it can be explained in detail both analytically and graphically. The grand model that fit the best included complex polynomial equations for the slope parameter m and the combination index (equivalent to the IC(50) for a fixed-ratio concentration, but with concentrations normalized by the respective IC(50)s of the drugs alone). There was a large region of synergy, mostly at the nikkomycin Z/micafungin edge of the ternary plots for equal normalized proportions of each drug and extending into the center of the plots. Applying this response surface method to a huge data set for a three-antifungal-agent combination is novel. This new paradigm has the potential to significantly advance the field of combination antifungal pharmacology.

Effect of amphotericin B and micafungin combination on survival, histopathology, and fungal burden in experimental aspergillosis in the p47phox-/- mouse model of chronic granulomatous disease.

Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase characterized by recurrent life-threatening bacterial and fungal infections. We characterized the effects of single and combination antifungal therapy on survival, histopathology, and laboratory markers of fungal burden in experimental aspergillosis in the p47phox-/- knockout mouse model of CGD. CGD mice were highly susceptible to intratracheal Aspergillus fumigatus challenge, whereas wild-type mice were resistant. CGD mice were challenged intratracheally with a lethal inoculum (1.25 x 10(4) CFU/mouse) of A. fumigatus and received one of the following regimens daily from day 0 to 4 after challenge (n = 19 to 20 per treatment group): (i) vehicle, (ii) amphotericin B (intraperitoneal; 1 mg/kg of body weight), (iii) micafungin (intravenous; 10 mg/kg), or (iv) amphotericin B plus micafungin. The rank order of therapeutic efficacy based on prolonged survival, from highest to lowest, was as follows: amphotericin B plus micafungin, amphotericin B alone, micafungin alone, and the vehicle. Lung histology showed pyogranulomatous lesions and invasive hyphae, but without hyphal angioinvasion or coagulative necrosis. Treatment with micafungin alone or combined with amphotericin B produced swelling of invasive hyphae that was not present in mice treated with the vehicle or amphotericin B alone. Assessment of lung fungal burden by quantitative PCR showed no significant difference between treatment groups. Serum galactomannan levels were at background despite documentation of invasive aspergillosis by histology. Our findings showed the superior efficacy of the amphotericin B and micafungin combination compared to either agent alone after A. fumigatus challenge and also demonstrated unique features of CGD mice as a model for experimental aspergillosis.