Economic evaluation of weight loss and transplantation strategies for kidney transplant candidates with obesity.

Novel antiobesity medications, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), have expanded weight loss (WL) options for kidney transplantation (KT) candidates with obesity beyond lifestyle modifications and bariatric surgery. However, varying effectiveness, risk profiles, and costs make strategy choices challenging. To aid decision-making, we used a Markov model to examine the cost-effectiveness of different WL strategies over a 10-year horizon. A target WL of 15% of total body weight was used for the base case scenario, and we compared these strategies to a "liberal" KT strategy of transplanting candidates with obesity. Outcomes included costs (2023 US dollars), quality-adjusted life years, and incremental cost-effectiveness ratios. In analysis, a liberal KT strategy was favored over lifestyle modifications and GLP-1RAs. Among WL strategies, bariatric surgery was the most effective and cost the least, whereas lifestyle modification had the highest cumulative costs and was the least effective. Compared to liberal KT, bariatric surgery costs $45 859 per quality-adjusted life year gained. GLP-1RAs were favored over bariatric surgery only when drug costs were below $5000 per year (base cost $12 077). In conclusion, for KT candidates with obesity, a liberal KT strategy and bariatric surgery are preferred over lifestyle modifications alone and GLP-1RAs based on outcomes and cost-effectiveness.

Early Effect of the Circular Model of Kidney Allocation in the United States.

BACKGROUND: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system on the basis of distance from donor hospital to transplant center within/outside a radius of 250 nautical miles. The effect of this policy on kidney discards and logistics is unknown. METHODS: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared with a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after the onset of COVID-19 and the implementation of KAS250 were evaluated using an interrupted time-series model. Changes in allocation practices (biopsy, machine perfusion, and virtual cross-match) were also evaluated. RESULTS: Post-KAS250 saw a two-fold increase in kidneys imported from nonlocal organ procurement organizations (OPO) and a higher proportion of recipients with calculated panel reactive antibody (cPRA) 81%-98% (12% versus 8%; P <0.001) and those with >5 years of pretransplant dialysis (35% versus 33%; P <0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards after KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased, whereas reliance on virtual cross-match increased, which was associated with shorter CIT. CONCLUSIONS: Early trends after KAS250 show an increase in transplant access to patients with cPRA>80% and those with longer dialysis duration, but this was accompanied by an increase in CIT and a suggestion of worsening kidney discards.

Paraspinous Muscle Flaps in Complex Pediatric Spine Surgeries: A 12-Year Single Institution Experience.

PURPOSE: The benefits of paraspinous flaps in adult complex spine surgery patients are established in the literature; however, their use in pediatric patients has not been well described. This study compares clinical outcomes with and without paraspinous muscle flap closure in pediatric patients who have undergone spine surgery. METHODS: We conducted a retrospective review of all pediatric spine surgeries at the University of California, San Francisco from 2011 to 2022. Patients were divided into 2 cohorts based on whether the plastic surgery service closed or did not close the wound with paraspinous muscle flaps. We matched patients by age, American Society of Anesthesiology classification, prior spinal surgical history, and diagnosis. Surgical outcomes were compared between the 2 cohorts. RESULTS: We identified 226 pediatric patients who underwent at least one spinal surgery, 14 of whom received paraspinous flap closure by plastic surgery. They were matched in a 1:4 ratio with controls (n = 56) that did not have plastic surgery closure. The most common indication for plastic surgery involvement was perceived complexity of disease by the spine surgeon with concern for inadequate healthy tissue coverage (78.6%), followed by infection (21.4%). Postoperative complications were similar between the two groups. The plastic surgery cohort had a higher rate of patients who were underweight (57.1% vs 14.3%, P < 0.01) and had positive preoperative wound cultures (28.6% vs 8.9%, P = 0.05), as well as a higher rate of postoperative antibiotic usage (78.6 vs 17.9%, P < 0.01). There was no difference in recorded postoperative outcomes. CONCLUSIONS: Spine surgeons requested paraspinous flap closure for patients with more complex disease, preoperative infections, history of chemotherapy, or if they were underweight. Patients with paraspinous flap coverage did not have increased postoperative complications despite their elevated risk profile. Our findings suggest that paraspinous muscle flaps should be considered in high-risk pediatric patients who undergo spine surgery.

Soft Tissue Reconstruction After Sacral Neoplasm Resection: The University of California San Francisco Experience.

PURPOSE: Resection of sacral neoplasms such as chordoma and chondrosarcoma with subsequent reconstruction of large soft tissue defects is a complex multidisciplinary process. Radiotherapy and prior abdominal surgery play a role in reconstructive planning; however, there is no consensus on how to maximize outcomes. In this study, we present our institution's experience with the reconstructive surgical management of this unique patient population. METHODS: We conducted a retrospective review of patients who underwent reconstruction after resection of primary or recurrent pelvic chordoma or chondrosarcoma between 2002 and 2019. Surgical details, hospital stay, and postoperative outcomes were assessed. Patients were divided into 3 groups for comparison based on reconstruction technique: gluteal-based flaps, vertical rectus abdominus myocutaneous (VRAM) flaps, and locoregional fasciocutaneous flaps. RESULTS: Twenty-eight patients (17 males, 11 females), with mean age of 62 years (range, 34-86 years), were reviewed. Twenty-two patients (78.6%) received gluteal-based flaps, 3 patients (10.7%) received VRAM flaps, and 3 patients (10.7%) were reconstructed with locoregional fasciocutaneous flaps. Patients in the VRAM group were significantly more likely to have undergone total sacrectomy (P < 0.01) in a 2-stage operation (P < 0.01) compared with patients in the other 2 groups. Patients in the VRAM group also had a significantly greater average number of reoperations (2 ± 3.5, P = 0.04) and length of stay (29.7 ± 20.4 days, P = 0.01) compared with the 2 other groups. The overall minor and major wound complication rates were 17.9% and 42.9%, respectively, with 17.9% of patients experiencing at least 1 infection or seroma. There was no association between prior abdominal surgery, surgical stages, or radiation therapy and an increased risk of wound complications. CONCLUSIONS: Vertical rectus abdominus myocutaneous flaps are a more suitable option for patients with larger defects after total sacrectomy via 2-staged anteroposterior resections, whereas gluteal myocutaneous flaps are effective options for posterior-only resections. For patients with small- to moderate-sized defects, local fasciocutaneous flaps are a less invasive and effective option. Paraspinous flaps may be used in combination with other techniques to provide additional bulk and coverage for especially long postresection wounds. Furthermore, mesh is a useful adjunct for any reconstruction aimed at protecting against intra-abdominal complications.

The Utility of Prevena Negative Pressure Wound Therapy on Groin Incisions for Critical Limb-Threatening Ischemia: A Single Institution Experience.

BACKGROUND: Incisional negative pressure wound therapy (iNPWT) is an adjunctive treatment that uses constant negative pressure suction to facilitate healing. The utility of this treatment modality on vascular operations for critical limb-threatening ischemia (CLTI) has yet to be elucidated. This study compares the incidence of postoperative wound complications between the Prevena Incision Management System, a type of iNPWT, and standard wound dressings for vascular patients who also underwent plastic surgery closure of groin incisions for CLTI. METHOD: We performed a retrospective cohort study of 40 patients with CLTI who underwent 53 open vascular surgeries with subsequent sartorius muscle flap closure. Patient demographics, intraoperative details, and wound complications were measured from 2015 to 2018 at the University of California San Francisco. Two cohorts were generated based on the modality of postoperative wound management and compared on wound healing outcomes. RESULTS: Of the 53 groin incisions, 29 were managed with standard dressings, and 24 received iNPWT. Patient demographics, comorbidities, and operative characteristics were similar between the 2 groups. Patients who received iNPWT had a significantly lower rate of infection (8.33% vs 31.0%, P = 0.04) and dehiscence (0% vs 41.3%, P < 0.01). Furthermore, the iNPWT group had a significantly lower rate of reoperation (0% vs 17.2%, P = 0.03) for wound complications within 30 days compared with the control group and a moderately reduced rate of readmission (4.17% vs 20.7%, P = 0.08). CONCLUSIONS: Rates of infection, reoperation, and dehiscence were significantly reduced in patients whose groin incisions were managed with iNPWT compared with standard wound care. Readmission rates were also decreased, but this difference was not statistically significant. Our results suggest that implementing iNPWT for the management of groin incisions, particularly in patients undergoing vascular operations for CLTI, may significantly improve clinical outcomes.

Dopamine dysfunction in stimulant use disorders: mechanistic comparisons and implications for treatment.

Dopamine system deficiencies and associated behavioral phenotypes may be a critical barrier to success in treating stimulant use disorders. Similarities in dopamine dysfunction between cocaine and methamphetamine use disorder but also key differences may impact treatment efficacy and outcome. This review will first compare the epidemiology of cocaine and methamphetamine use disorder. A detailed account of the pharmacokinetic and pharmacodynamic properties associated with each drug will then be discussed, with an emphasis on effects on the dopamine system and associated signaling pathways. Lastly, treatment results from pharmacological clinical trials will be summarized along with a more comprehensive review of the involvement of the trace amine-associated receptor on dopamine signaling dysfunction among stimulants and its potential as a therapeutic target.

Robotic repair of perineal hernias: a video vignette and review of the literature.

BACKGROUND: Perineal hernias can be secondarily acquired following abdominoperineal resection of the rectum. While transabdominal minimally invasive techniques have traditionally used laparoscopy, there are few studies published on the robotic platform, which has been gaining popularity for other types of hernia repairs. We review the existing literature, share a video vignette, and provide practical tips for surgeons interested in adopting this approach. METHODS: A literature search in Pubmed was performed to include all articles in English describing robotic repair of perineal hernias with identification of variables of interest related to repair. A case presentation with an accompanying video vignette and lessons learned from the experience are provided. RESULTS: Seven case reports (four containing video) published between 2019 and 2022 were included. Most articles (n = 5) utilized the Da Vinci Si or Xi, and most patients (n = 5) had undergone abdominoperineal resection with neoadjuvant chemotherapy to treat rectal cancer. Patients were positioned in Trendelenburg with rightward tilt (n = 2), modified lithotomy (n = 1), or a combination of the two (n = 1). All articles (n = 7) reported closing the defect and using mesh. Three articles describe placing five ports (one camera, three robotic, one assistant). There were no significant intraoperative or postoperative complications reported, and no recurrence noted at 3-27 months follow-up. Based on our experience, as shown in the video vignette, we recommend lithotomy positioning, using porous polypropylene mesh anchored to the periosteum of the sacrum and peritoneum overlying the bladder and side wall, and placing a drain above the mesh. CONCLUSIONS: A robotic transabdominal approach to perineal hernia repair is a viable alternate to laparoscopy based on low complication rates and lack of recurrence. Prospective and longer duration data are needed to compare the techniques.

Long-pulsed neodymium-doped yttrium aluminum garnet for hair reduction in pediatric microtia repair.

Microtia is the term for congenital malformation of the ear in which the external and internal ear are absent or malformed. Surgical reconstruction is a common management approach and occasionally requires hair reduction of the newly constructed auricle. Few studies have investigated lasers for this purpose. We conducted a retrospective chart review of patients seen at a single institution between 2012 and 2021 who underwent laser hair reduction with long-pulsed neodymium-doped yttrium aluminum garnet laser (Nd:YAG). Efficacy ratings were done through review of clinical photographs. Twelve patients were identified with 14 total ears treated. The number of laser treatments varied from 1 to 9 sessions with an average of 5.1 treatments. The majority (8/12) had an "excellent" or "very good" response, one patient had a "good" response, and three were lost to follow-up. Other than pain, there were no side effects documented. Nd:YAG laser was both effective and safe in our pediatric cohort, without any cutaneous side effects in patients with darker skin.

Preventing Rectourethral Fistula Recurrence With Gracilis Flap.

BACKGROUND: Rectourethral fistula (RUF) is an uncommon serious condition with various etiologies including neoplasm, radiation therapy, and surgery. Treatment for RUF remains problematic with a high recurrence rate. Although studies have suggested the recurrence rate of RUF is lower after surgical repair using a gracilis flap, outcomes have varied and the studies were small and inadequately controlled. Here, we compare outcomes of RUF repair with and without gracilis flap to evaluate its efficacy in preventing fistula recurrence and identify risk factors for recurrence. METHODS: We retrospectively reviewed patients who had undergone surgical repair for RUF between 2007 and 2018 at our institution and had at least 30 days of follow-up. Patient demographics, comorbidities, and surgical outcomes were recorded and compared for patients who had gracilis flap repair and those who did not (controls). Single variable logistic regression analysis was used to identify risk factors for recurrence. RESULTS: The gracilis group (n = 24) and control group (n = 12) had similar demographics and comorbidities. Fistula recurrence was far less frequent in the gracilis group (8% vs 50%, P = 0.009). There were no significant differences in other outcomes including length of hospitalization and surgical complications. When recurrent RUF was treated with a muscle flap (gracilis or inferior gluteus), 83% of the group had no additional fistula recurrence. In the control group, history of radiation ( P = 0.04) and urinary incontinence ( P = 0.015) were associated with fistula recurrence. CONCLUSIONS: We recommend using a gracilis flap for RUF repair given its association with lower recurrence without increased surgical complications.

Assessing the Readability of Online Patient Education Resources Related to Gynecomastia.

BACKGROUND: The Internet has a plethora of online patient education resources for many symptoms and diseases. National medical governing bodies recommend that patient education materials are written at or below the eighth-grade level, and the literature suggests that health literacy has been linked to increased adherence to treatment regimens and improved outcomes. The primary aim of the study is to assess the readability of online patient materials relating to gynecomastia and ascertain the availability of patient materials in non-English languages. METHODS: The readability of patient education materials relating to gynecomastia for academic-based websites and nonacademic websites was assessed using the Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), and Simple Measure of Gobbledygook (SMOG). The prevalence of non-English patient education materials was assessed for both academic-based and nonacademic websites. RESULTS: Fifty-eight documents were collected across academic websites. Overall median values were 10.7 for the FKGL, 47.0 for the FRE, and 11.4 for the SMOG. For the 10 nonacademic institutions, the overall median values were 10.6 for the FKGL, 45.2 for the FRE, and 10.8 for the SMOG. No appreciable differences were observed for readability when stratified by region or source. The prevalence of non-English patient materials was 19.1% across institutions. None of the noninstitutional materials had information in non-English languages. CONCLUSIONS: The readability of patient education materials related to gynecomastia is at higher levels than recommended by national organizations. There are limited non-English patient education materials. Future efforts should focus on improving the readability and accessibility of patient materials.

Intracerebral matrix metalloproteinase 9 in fatal diabetic ketoacidosis.

There is increasing awareness that in addition to the metabolic crisis of diabetic ketoacidosis (DKA) caused by severe insulin deficiency, the immune inflammatory response is likely an active multicomponent participant in both the acute and chronic insults of this medical crisis, with strong evidence of activation for both the cytokine and complement system. Recent studies report that the matrix metalloproteinase enzymes and their inhibitors are systemically activated in young Type 1 diabetes mellitus (T1D) patients during DKA and speculate on their involvement in blood-brain barrier (BBB) disruption. Based on our previous studies, we address the question if matrix metalloproteinase 9 (MMP9) is expressed in the brain in the fatal brain edema (BE) of DKA. Our data show significant expression of MMP9 on the cells present in brain intravascular areas. The presence of MMP9 in intravascular cells and that of MMP+ cells seen passing the BBB indicates a possible role in tight junction protein disruption of the BBB, possibly leading to neurological complications including BE. We have also shown that MMP9 is expressed on neurons in the hippocampal areas of both BE/DKA cases investigated, while expression of tissue inhibitor of metalloproteinases 1 (TIMP1) was reduced in the same areas. We can speculate that intraneuronal MMP9 can be a sign of neurodegeneration. Further studies are necessary to determine the role of MMP9 in the pathogenesis of the neurologic catastrophe of the brain edema of DKA. Inhibition of MMP9 expression might be helpful in preserving neuronal function and BBB integrity during DKA.

Three-Dimensional Analysis of Cortical Bone Thickness in Individuals With Non-Syndromic Unilateral Cleft Lip and Palate.

PURPOSE: The aim of this study was to measure the cortical bone thickness of the infrazygomatic crest area in individuals with unilateral cleft lip and palate using cone beam computed tomography for placement of miniplates used for bone anchored maxillary protraction. MATERIALS AND METHODS: CBCT scans were obtained from 31 non-syndromic UCLP children diagnosed with maxillary hypoplasia (17 males, 14 females, mean age: 11.9 years). 5 horizontal and 5 vertical reference planes were drawn at the infrazygomatic crest area. The cortical bone thickness at 25 intersection points on the cleft side and the non-cleft side was measured. RESULTS: The mean cortical bone thickness of the 25 measured points was 1.19 mm on the cleft side and 1.17 mm on the non-cleft side with no significant difference. The greatest cortical bone thickness was found to be at the most superior, posterior point (H+6, V+0), which was 1.49 mm on the cleft side and 1.47 mm on the non-cleft side. The thinnest mean cortical bone thickness was measured at the most inferior, anterior point (H-2, V-8), which was 0.94 mm on the cleft side and 0.95 mm on the non-cleft side. There was no significant difference between males and females.

Short-term adverse effects of early subclinical allograft inflammation in kidney transplant recipients with a rapid steroid withdrawal protocol.

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3-month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3-months posttransplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for acute rejection were identified. These were Group I: No Inflammation (NI, n = 71) and Group II: Subclinical Inflammation (SCI, n = 129). We evaluated differences in kidney function at 24-months and allograft histology score at 12-month biopsy. SCI patients had a higher serum creatinine (1.6 ± 0.7 vs 1.38 ± 0.45; P = .02) at 24-months posttransplant, and at last follow-up at a mean of 42.5 months (1.69 ± 0.9 vs 1.46 ± 0.5 mg/dL; P = .027). The allograft chronicity score (ci + ct + cg + cv) at 12-months posttransplant was higher in the SCI group (2.4 ± 1.35 vs 1.9 ± 1.2; P = .02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (P = .015). De novo donor-specific antibody within 12 months was more prevalent in the SCI group (12/129 vs 1/71, P = .03). SCI is likely not a benign finding and may have long-term implications for kidney allograft function.

Functional MRI and delay discounting in patients infected with hepatitis C.

Hepatitis C virus-infected (HCV+) adults evidence increased rates of psychiatric and cognitive difficulties. This is the first study to use functional magnetic resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. To determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit differences in brain activation during a delay discounting task (DDT), a measure of one's tendency to choose smaller immediate rewards over larger delayed rewards-one aspect of impulsivity. Twenty adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. Mixed effects regression analyses of hard versus easy trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less activation in the left lateral occipital gyrus, precuneus, and superior frontal gyrus. There were also significant interactive effects for hard-easy contrasts in the bilateral medial frontal gyrus, left insula, left precuneus, left inferior parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a positive relationship between impulsivity and activation, while the HCV+ group exhibited a negative relationship. Within the HCV+ group, those with high viral load chose immediate rewards more often than those with low viral load, regardless of choice difficulty; those with low viral load chose immediate rewards more often on hard choices relative to easy choices. Results show that HCV+ patients exhibit greater impulsive behavior when presented with difficult choices, and impulsivity is negatively related to activation in regions important for cognitive control. Thus, interventions that decrease impulsive choice may be warranted with some HCV+ patients.

Otologic Disease Following Palatoplasty In International Cleft Palate Cohort.

OBJECTIVE: Study the prevalence of otologic disease in a pediatric post-palatoplasty population with no prior ear tube placement in resource-deprived countries and assess patient characteristics associated with these abnormal results. DESIGN: Retrospective data review. PARTICIPANTS: Ecuadorian and Chinese children identified during humanitarian cleft lip and palate repair trips with cleft palates undergoing palatoplasty from 2007 to 2010. INTERVENTIONS: Tympanometry and otoacoustic emission (OAE) testing performed following palatoplasty. Patients' parents administered surveys regarding perceived hearing deficits. MAIN OUTCOME MEASURES: Age, gender, Veau classification, follow-up time, laterality, and country of origin were evaluated for possible association with type B tympanogram, "Refer" Otoacoustic results, and presence of hearing difficulty as identified by a parent. Significant predictors were further evaluated with multivariate analysis. RESULTS: The cohorts included 237 patients (129 Ecuadorian, 108 Chinese); mean age: 3.9 years; mean follow-up: 4.2 years. Thirty-nine percent scored type B, 38% failed OAE testing, and 8% of parents noted hearing deficits. The country of origin and a younger age were identified as predictive variables regarding type B tympanogram. Follow-up time, country of origin, and bilateral OAE "Refer" results all significantly predicted parental questionnaire results. Subsequent multivariable analysis further demonstrated effect modification between the 2 variables of age at palatoplasty and country of origin when predicting type B vs type A tympanometry. CONCLUSION: Without otologic intervention, cleft palate children in resource-deprived settings suffer type B tympanometry and failed OAE results with similar to increased incidences to other studied cleft palate populations with otologic interventions available.

Palatal Fistula Risk after Primary Palatoplasty: A Retrospective Comparison of a Humanitarian Organization and Tertiary Hospitals.

BACKGROUND: Humanitarian surgical organizations provide palatoplasties for patients without access to surgical care. Few organizations have evaluated the outcomes of these trips. This study evaluates the palatal fistula rate in patients from two cohorts in rural China and one in the United States. METHODS: This study compared the odds of fistula formation among three cohorts whose palates were repaired between 2005 and 2009. One cohort included 97 Chinese patients operated on by teams from the United States and Canada under the auspices of Resurge International. They were compared to cohorts at Huaxi Stomatology Hospital and the University of California San Francisco (UCSF). Age, fistula presence, and Veau class were compared among cohorts using Chi-square tests. Logistic regression was used to analyze predictors of fistula formation. RESULTS: The fistula risk was 35.4% in patients treated by humanitarian teams, 12.8% at Huaxi University Hospital and 2.5% at UCSF ( P < 0.001). Age and Veau class were associated with fistula formation (Age P = 0.0015; Veau P < 0.001). ReSurge and Huaxi patients had 20.2 and 5.6 times the odds of developing a fistula, respectively, compared to UCSF patients ( P < 0.01, both). A multivariable model controlling for surgical group, age, and gender showed an association between Veau class and the odds of fistula formation. CONCLUSIONS: Chinese children undergoing palatoplasty by international teams had higher odds of palatal fistula than children treated by Chinese surgeons in established institutions and children treated in the United States. More research is required to identify factors affecting complication rates in low-resource environments.

Markers of immune-mediated inflammation in the brains of young adults and adolescents with type 1 diabetes and fatal diabetic ketoacidosis. Is there a difference?

Due to the limited data on diabetic ketoacidosis and brain edema (DKA/BE) in children/adolescents and the lack of recent data on adults with type 1 diabetes (T1D), we addressed the question of whether neuroinflammation was present in the fatal DKA of adults. We performed immunohistochemistry (IHC) studies on the brains of two young adults with T1D and fatal DKA and compared them with two teenagers with poorly controlled diabetes and fatal DKA. C5b-9, the membrane attack complex (MAC) had significantly greater deposits in the grey and white matter of the teenagers than the young adults (p=0.03). CD59, a MAC assembly inhibitory protein was absent, possibly suppressed by the hyperglycemia in the teenagers but was expressed in the young adults despite comparable average levels of hyperglycemia. The receptor for advanced glycation end products (RAGE) had an average expression in the young adults significantly greater than in the teenagers (p=0.02). The autophagy marker Light Chain 3 (LC3) A/B was the predominant form of programmed cell death (PCD) in the teenage brains. The young adults had high expressions of both LC3A/B and TUNEL, an apoptotic cell marker for DNA fragmentation. BE was present in the newly diagnosed young adult with hyperglycemic hyperosmolar DKA and also in the two teenagers. Our data indicate that significant differences in neuroinflammatory components, initiated by the dysregulation of DKA and interrelated metabolic and immunologic milieu, are likely present in the brains of fatal DKA of teenagers when compared with young adults.

Recalcitrant Invasive Skin Cancer of the Scalp: Combined Extirpation and Microsurgical Reconstruction Without Cranioplasty.

BACKGROUND: Recurrent invasive skin cancer of the scalp and calvarium is a difficult problem for which universally accepted treatment protocols have not been established. The authors present their 10-year experience with treatment of this specific subset of scalp reconstruction patients and present a successful treatment algorithm that is well suited to this patient population. METHODS: The authors retrospectively reviewed all patients of microsurgical scalp reconstruction performed from 2005 to 2015 that involved invasive cutaneous malignancies of the scalp and calvarium. RESULTS: Eleven patients met inclusion criteria. There were 9 squamous cell carcinoma, 1 basal cell carcinoma, and 1 melanoma. Seven received radiation prior to resection, 2 were irradiated postoperatively, and 2 were immunosuppressed. Seven had a history of prior scalp reconstruction. The median scalp defect size was 141 cm. All the patients underwent craniectomy and the median cranial defect size was 71 cm. Cranioplasty was not performed in any patient. There were no intraoperative complications or flap loss. Recipient site complications included hematoma in 1, 1 seroma, 2 cerebral spinal fluid leaks, 3 partial skin graft loss. There was 1 donor site seroma in a patient who had a latissimus dorsi flap. All the patients reported satisfaction with the overall result and none were limited in activities by the existing cranial defect. CONCLUSIONS: This is the largest series published to date that focuses exclusively on management of cutaneous malignancies with intracranial invasion. Wide resection with craniectomy, and reconstruction with microvascular free tissue transfer without cranioplasty provides safe and reliable treatment of recalcitrant invasive scalp skin cancers with low morbidity and without major complications. Pre and postoperative radiation is well tolerated with this approach. The patients in this series were of advanced age and of a lifestyle for which cranioplasty is unnecessary for return to regular activities.

Palatal fistula risk after primary palatoplasty: a retrospective comparison of humanitarian operations and tertiary hospitals.

BACKGROUND: Humanitarian surgical organisations provide cleft palate repair for patients without access to surgical care. Despite decades of experience, very little research has assessed the outcomes of these trips. This study investigates the fistula rate in patients from two cohorts in rural China and one in the USA. METHODS: This retrospective study compared the odds of fistula presentation among three cohorts whose palates were repaired between April, 2005, and November, 2009. The primary cohort included 97 Chinese patients operated on in China by surgeons from ReSurge International. A second Chinese cohort of 250 patients was operated on at Huaxi University Hospital by Chinese surgeons. The third cohort of 120 patients from the University of California San Francisco (UCSF) was included for comparison over the same time period; data was taken from medical records. Age, fistula presentation, and Veau Class were compared between the three cohorts with χ(2) tests. Logistic regression was used to analyse predictors of fistula presentation among the three cohorts. This study received institutional review board approval from the UCSF, the Harvard School of Public Health, and physicians at Huaxi University Hospital, and written consent was obtained from study participants in China. FINDINGS: The fistula risk was 35·4% in ReSurge patients, 12·8% for patients at Huaxi University Hospital, and 2·5% for patients at UCSF (p<0·001). At the time of surgery 15·5% of the ReSurge patients were younger than 2 years old, whereas 90·8% of the UCSF children and 41·6% of the Huaxi children were (p<0·001). In the ReSurge cohort, 20·6% of patients had a Veau class of I or II, wheras 40·8% and 58·9% of UCSF and Huaxi patients, respectively, were in class I or II (p<0·001). Age and Veau Class were associated with fistula formation in a univariate analysis. (Veau Class III or IV vs I or II, odds ratio [OR] 6·399 [95% CI 3·182-12·871]; age, OR 1·071 [95% CI 1·024-1·122]). A multivariate model controlling for the surgical group, age at palatoplasty, and sex showed an association between Veau Class and the odds of fistula presentation (Class III or IV vs I or II, OR 5·630 [95% CI 2·677-11·837). In this model, UCSF patients and Huaxi patients had 0·064 and 0·451 times the odds of developing a fistula, respectively, compared with ReSurge patients (p<0·001 both). INTERPRETATION: Chinese children undergoing palatoplasty on surgical missions have higher post-operative odds of palatal fistula than do children treated by local physicians. Children in low-resource settings have higher complication rates than do children in high-resource settings. Older age at palatoplasty and a Veau class III and IV are associated with post-palatoplasty fistula. Furthermore demographic, socioeconomic, and cultural differences could play a part in palatoplasty fistula outcomes between these three populations. More research is needed to determine the effects of post-operative care, the skill of the providers, and the technique used in the surgery that play a role on fistula outcomes after primary palatoplasty, particularly in low-resource environments. FUNDING: None.

Breast Hypoplasia as a Complication of an Untreated Infantile Hemangioma.

We report the case of a mixed infantile hemangioma (IH) involving the right breast that resulted in pronounced hypoplasia of the affected breast, which became apparent after breast development at puberty. No treatment had been performed in infancy or childhood. This case demonstrates that the presence of an IH may affect development of the mammary gland bud and that systemic therapy should be considered in an attempt to minimize this adverse sequela.