Salvage of Nipple-Areolar Complex Ischemia With Dimethyl Sulfoxide: A Case Series.

BACKGROUND: Nipple-areolar complex (NAC) necrosis is a known risk of breast surgery, particularly mastectomy. Disruption of the underlying blood supply to the NAC can lead to ischemia and subsequent necrosis. Nitroglycerin paste is currently used to combat NAC ischemia but has limited efficacy and an unfavorable side effect profile. Topical dimethyl sulfoxide (DMSO) has been shown to increase tissue perfusion in microsurgery and various skin flaps, but its role in the treatment and prevention of NAC ischemia has not been reported. Through a prospective case series, this study aims to introduce DMSO as a safe treatment for NAC ischemia after breast surgery. METHODS: Patients treated by 2 breast surgeons and a single plastic surgeon who underwent nipple-sparing mastectomy or breast reduction and developed NAC ischemia were identified via a prospectively maintained database. Ischemic changes were diagnosed, and treatment to the affected NAC with DMSO was initiated at the conclusion of the procedure, or postoperative day 1 in most cases, and continued 4 times daily until ischemic changes had resolved clinically. Collected demographic, surgical, and outcome variables were analyzed using descriptive statistics. RESULTS: Eleven patients with a mean age of 47.8 ± 9.5 years (range, 35-61 years) and mean body mass index of 26.0 ± 4.4 kg/m2 (range, 20.7-33.4 kg/m2) were identified. The mean duration of time between surgery and the clinical diagnosis of NAC ischemia was 1.3 ± 2.8 days (range, 0-7 days). The average length of time from DMSO initiation to clinical improvement or resolution of NAC ischemia was 7.5 ± 2.5 days (range, 5-12 days). All patients demonstrated significant improvement or complete resolution of NAC ischemia following serial topical DMSO application. CONCLUSIONS: This study demonstrates DMSO is a safe treatment for threatened NACs. All patients in this series showed either dramatic improvement or resolution of NAC ischemia after DMSO application, and threatened NACs of all 11 patients were successfully salvaged. These promising results set the basis for ongoing randomized controlled studies to determine the efficacy of DMSO treatment for NAC ischemia.

Considerations for Surgical Treatment of Neurogenic Thoracic Outlet Syndrome: A Meta-Analysis of Patient-Reported Outcomes.

PURPOSE: It remains unclear whether first rib resection (FRR), performed via a supraclavicular (SCFRR) or transaxillary (TAFRR) approach, is necessary for patients with neurogenic thoracic outlet syndrome (nTOS). In a systematic review and meta-analysis, we performed a direct comparison of patient-reported functional outcomes following different surgical approaches for nTOS. METHODS: The authors searched PubMed, Embase, Web of Science, Cochrane Library, PROSPERO, Google Scholar, and the gray literature. Data were extracted based on the procedure type. Well-validated patient-reported outcome measures were analyzed in separate time intervals. Random-effects meta-analysis and descriptive statistics were used where appropriate. RESULTS: Twenty-two articles were included, with 11 discussing SCFRR (812 patients), 6 discussing TAFRR (478 patients), and 5 discussing rib-sparing scalenectomy (RSS; 720 patients). The mean difference between preoperative and postoperative Disabilities of the Arm, Shoulder and Hand score was significantly different comparing RSS (43.0), TAFRR (26.8), and SCFRR (21.8). The mean difference between preoperative and postoperative visual analog scale scores was significantly higher for TAFRR (5.3) compared to SCFRR (3.0). Derkash scores were significantly worse for TAFRR compared to RSS or SCFRR. RSS had a success rate of 97.4% based on Derkash score, followed by SCFRR and TAFRR at 93.2% and 87.9%, respectively. RSS had a lower complication rate compared to SCFRR and TAFRR. There was a difference in complication rates: 8.7%, 14.5%, and 3.6% for SCFRR, TAFRR, and RSS, respectively. CONCLUSIONS: Mean differences in Disabilities of the Arm, Shoulder and Hand scores and Derkash scores were significantly better for RSS. Higher complication rates were reported after FRR. Our findings suggest that RSS is an effective option for the treatment of nTOS. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Healing Exposed Calvarial Hardware Using Negative-Pressure Wound Therapy and Vashe Wound Solution: Case Report.

OBJECTIVE: The management of cranioplasty infections has historically been explantation followed by delayed reimplantation/reconstruction. This treatment algorithm necessitates surgery, tissue expansion, and prolonged disfigurement. In this report, the authors describe a treatment approach consisting of serial vacuum-assisted closure (VAC) with hypochlorous acid (HOCl) solution (Vashe Wound Solution; URGO Medical) as a salvage strategy. METHODS: A 35-year-old man who sustained head trauma, neurosurgical complications, and severe syndrome of the trephined (SOT; devastating neurologic decline treated by cranioplasty) underwent titanium cranioplasty with free flap. Three weeks postoperation, he presented with pressure-related wound dehiscence/partial flap necrosis, exposed hardware, and bacterial infection. Given the severity of his precranioplasty SOT, hardware salvage was critical. He was treated with serial VAC with HOCl solution for 11 days followed by VAC for 18 days and definitive split-thickness skin graft placement over resulting granulation tissue. Authors also conducted a literature review of cranial reconstruction infection management. RESULTS: The patient remained healed 7 months postoperatively without recurrent infection. Importantly, his original hardware was retained, and his SOT remained resolved. Findings from the literature review support the use of conservative modalities to salvage cranial reconstructions without hardware removal. CONCLUSIONS: This study investigates a new strategy for managing cranioplasty infections. The VAC with HOCl solution regimen was effective in treating the infection and salvaging the cranioplasty, thus obviating the complications associated with explantation, new cranioplasty, and recurrence of SOT. There is limited literature on the management of cranioplasty infections using conservative treatments. A larger study to better determine the efficacy of VAC with HOCl solution is underway.

Characteristics and Treatment of Patients Diagnosed With Paradoxical Adipose Hyperplasia After Cryolipolysis: A Case Series and Scoping Review.

BACKGROUND: Paradoxical adipose hyperplasia (PAH), a rare side effect of CoolSculpting (cryolipolysis), is characterized by fatty enlargement of the treatment area occurring months after the procedure. OBJECTIVES: The purpose of this study was to report a retrospective case series of patients diagnosed with PAH at the authors' institution, increase the collective understanding of this complication and subsequent management, and raise the question of who should ethically perform cryolipolysis. METHODS: All participants diagnosed with PAH by a plastic surgeon at a large academic medical center were identified. Demographic information, medical history, procedure details, time to PAH diagnosis, and corrective surgical intervention details were collected. Mean duration of time from cryolipolysis treatment to diagnosis of PAH was calculated, along with other descriptive statistics. A scoping review of all PAH literature published in PubMed, Embase, and Web of Science was also conducted. RESULTS: Four patients diagnosed with PAH after cryolipolysis were identified for inclusion in this study. The calculated incidence of PAH at our center was 0.67%. All patients requested therapy for PAH and subsequently underwent either liposuction, abdominoplasty, or both. The mean duration of in-person follow-up time after final surgical treatment of PAH was 13.8 + 19.8 months (range, 2.8-43.5). Fortunately, no patients showed signs of PAH recurrence, and 3 out of 4 patients did not show signs of residual deformity. CONCLUSIONS: Findings from this patient cohort and scoping review provide evidence that although revisions may be required, conventional body contouring methods, not in the armamentarium of non-plastic surgeon practitioners, effectively alleviated PAH.

Cyclophosphamide/fludarabine nonmyeloablative allotransplant for acute myeloid leukemia.

We compared survival outcomes following myeloablative allotransplant (MAT) or cyclophosphamide/fludarabine (Cy/Flu) nonmyeloablative allotransplant (NMAT) for 165 patients with acute myelogenous leukemia (AML) in remission or without frank relapse. Patients who received NMAT were more likely to be older and have secondary AML and lower performance status. At a median follow-up of 61 months, median event-free survival and overall survival survival were not different between NMAT and MAT in univariate as well as multivariate analyses. Cy/Flu NMAT may provide similar disease control and survival when compared with MAT in patients with AML in remission or without frank relapse.

Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly.

BACKGROUND: Postoperative delirium, a common complication in the elderly, can occur following any type of surgery and is associated with increased morbidity and mortality; it may also be associated with subsequent cognitive problems. Effective therapy for postoperative delirium remains elusive because the causative factors of delirium are likely multiple and varied. METHODS: Patients 65 yr or older undergoing elective knee arthroplasty were prospectively evaluated for postoperative Diagnostic and Statistical Manual of Mental Disorders-IV delirium. Exclusion criteria included dementia, mini-mental state exam score less than 24, delirium, clinically significant central nervous system/neurologic disorder, current alcoholism, or any serious psychiatric disorder. Delirium was assessed on postoperative days 2 and 3 using standardized scales. Patients' preexisting medical conditions were obtained from medical charts. The occurrence of obstructive sleep apnea was confirmed by contacting patients to check their polysomnography records. Data were analyzed using Pearson chi-square or Wilcoxon rank sum tests and multiple logistic regressions adjusted for effects of covariates. RESULTS: Of 106 enrolled patients, 27 (25%) developed postoperative delirium. Of the 15 patients with obstructive sleep apnea, eight (53%) experienced postoperative delirium, compared with 19 (20%) of the patients without obstructive sleep apnea (P = 0.0123, odds ratio: 4.3). Obstructive sleep apnea was the only statistically significant predictor of postoperative delirium in multivariate analyses. CONCLUSIONS: This is the first prospective study employing validated measures of delirium to identify an association between preexisting obstructive sleep apnea and postoperative delirium.

Effect of Sirolimus levels between days 11 and 20 after allogeneic stem cell transplantation on the risk of hepatic sinusoidal obstruction syndrome.

Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT). Sirolimus plus tacrolimus is an accepted regimen for graft-versus-host disease (GVHD) prophylaxis, with both agents implicated as risk factors for SOS. We analyzed 260 consecutive patients who underwent allogeneic HSCT following myeloablative conditioning using total body irradiation (TBI)-based (n = 151) or chemotherapy only (n = 109) regimens, with sirolimus plus tacrolimus for GVHD prophylaxis. SOS occurred in 28 patients at a median of 22 (range, 12-58) days. Mean sirolimus trough levels were higher between days 11 and 20 following transplant in patients who developed SOS (10.3 vs. 8.5 ng/ml, P = 0.008), with no significant difference in mean trough levels between days 0 and 10 (P = 0.67) and days 21-30 (P = 0.37). No differences in mean tacrolimus trough levels during the same time intervals were observed between those developing SOS and others. On multivariable analysis, a mean sirolimus trough level ≥ 9 ng/ml between days 11 and 20 increased the risk of SOS (hazard ratio 3.68, 95% CI: 1.57-8.67, P = 0.003), together with a longer time from diagnosis to transplant (P = 0.004) and use of TBI (P = 0.006). Our results suggest that mean trough sirolimus levels ≥ 9 ng/mL between days 11 and 20 post transplant may increase the risk of SOS and should be avoided.

A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas.

Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P increases Akt phosphorylation by 2.5-fold, with an EC(50) of 57 nM. Blockade of NK1R lowers basal phosphorylation of Akt, indicating the presence of a constitutively active form of NK1R; similar results are seen in U251 MG and DBTRG-05 glioblastoma cells. Linkage of NK1R to Akt implicates NK1R in apoptosis of glioblastoma cells. Indeed, treatment of serum-starved U373 cells with substance P reduces apoptosis by 53 +/- 1% (p < 0.05), and treatment with NK1R antagonist L-733,060 increases apoptosis by 64 +/- 16% (p < 0.01). Further, the blockade of NK1R in human glioblastoma cells with L-733,060 causes cleavage of Caspase-3 and proteolysis of poly (ADP-ribose) polymerase. Experiments designed to elucidate the mechanism of NK1R-mediated Akt phosphorylation revealed total involvement of non-receptor tyrosine kinase Src and phosphatidyl-3-kinase, a partial involvement of epidermal growth factor receptor, and no involvement of mitogen-activated protein/extracellular signal-related kinase. Taken together, the results of the present study indicate a key role for NK1R in glioblastoma apoptosis.

Toward a research-based assessment of dyslexia: using cognitive measures to identify reading disabilities.

One hundred five participants from a random sample of elementary and middle school children completed measures of reading achievement and cognitive abilities presumed, based on a synthesis of current dyslexia research, to underlie reading. Factor analyses of these cognitive variables (including auditory processing, phonological awareness, short-term auditory memory, visual memory, rapid automatized naming, and visual processing speed) produced three empirically and theoretically derived factors (auditory processing, visual processing/speed, and memory), each of which contributed to the prediction of reading and spelling skills. Factor scores from the three factors combined predicted 85% of the variance associated with letter/sight word naming, 70% of the variance associated with reading comprehension, 73% for spelling, and 61% for phonetic decoding. The auditory processing factor was the strongest predictor, accounting for 27% to 43% of the variance across the different achievement areas. The results provide practitioner and researcher with theoretical and empirical support for the inclusion of measures of the three factors, in addition to specific measures of reading achievement, in a standardized assessment of dyslexia. Guidelines for a thorough, research-based assessment are provided.

Mechanisms regulating the origins of the vertebrate vascular system.

In order to sustain growth, differentiation, and organogenesis, vertebrate embryos must form a functional vascular system early in embryonic development. Intrinsic interest in this process as well as the promise of potential clinical applications has led to significant progress in understanding the mechanisms governing the formation of the vascular system, however the earliest stages of vascular development--the emergence of committed endothelial precursors from the mesoderm--remain unclear. A review of the current literature reveals an unexpected diversity and heterogeneity with respect to where vascular endothelial cells originate in the embryo, when they become committed and the mechanisms governing how endothelial cells acquire their identity. Spatially, a widespread region of the early mesoderm possesses the ability to give rise to vascular endothelial cells; temporally the process is not limited to a small window during embryogenesis, but rather, may continue throughout the lifespan of the organism. On the molecular level, recent findings point to several determinative pathways that regulate, modulate, and extend the scope of the Flk1/VEGF signaling system. An expanding array of novel gene products implicated in endothelial cell type determination appear to act synergistically, with different combinations of factors leading to diverse cellular responses, varying patterns of differentiation, and considerable heterogeneity of endothelial cell types during embryogenesis.