Simultaneous Free Flap Breast Reconstruction Combined With Contralateral Mastopexy or Breast Reduction: A Propensity-Matched National Surgical Quality Improvement Program Study on Postoperative Outcomes.

BACKGROUND: Simultaneous free flap breast reconstruction combined with contralateral mastopexy or breast reduction can increase patient satisfaction and minimize the need for a second procedure. Surgeon concerns of increases in operative time, postoperative complications, and final breast symmetry may decrease the likelihood of these procedures being done concurrently. This study analyzed postoperative outcomes of simultaneous contralateral mastopexy or breast reduction with free flap breast reconstruction. METHODS: By using the American College of Surgeons National Surgical Quality Improvement Program database (2010-2020), we analyzed 2 patient cohorts undergoing (A) free flap breast reconstruction only and (B) free flap breast reconstruction combined with contralateral mastopexy or breast reduction. The preoperative variables assessed included demographic data, comorbidities, and perioperative data. Using a neighbor matching algorithm, we performed a 1:1 propensity score matching of 602 free flap breast reconstruction patients and 621 with concurrent contralateral operation patients. Bivariate analysis for postoperative surgical and medical complications was performed for outcomes in the propensity-matched cohort. RESULTS: We identified 11,308 cases who underwent microsurgical free flap breast reconstruction from the American College of Surgeons National Surgical Quality Improvement Program database from the beginning of 2010 to the end of 2020. A total of 621 patients underwent a free flap breast reconstruction combined with contralateral mastopexy or breast reduction. After propensity score matching, there were no significant differences in patient characteristics, perioperative variables or postoperative medical complications between the 2 cohorts. CONCLUSIONS: Simultaneous free flap breast reconstruction combined with contralateral mastopexy or breast reduction can be performed safely and effectively without an increase in postoperative complication rates. This can improve surgeon competence in offering this combination of procedures as an option to breast cancer survivors, leading to better patient outcomes in terms of symmetrical and aesthetically pleasing results, reduced costs, and elimination of the need for a second operation.

Incidence of Complications Associated With Lipectomy Techniques and Patient Body Mass Index: An Institutional and National Analysis Using the Tracking Operations and Outcomes for Plastic Surgeons.

INTRODUCTION: An evaluation of complication rates in different abdominal lipectomy techniques with relationship to body mass index (BMI) and other risk factors. METHODS: We identified patients who underwent an abdominal lipectomy at our institution from January 2015 to July 2020. Those with concurrent hernia repair were excluded. Patients were classified into 2 groups: (1) horizontal lipectomy with or without umbilical translocation and (2) inverted-T lipectomy with translocation. Demographics, operative details, and postoperative complications were collected for 1 year postoperatively. Bivariate analyses were conducted to determine factors associated with type of procedure and complications. Crude and stratum-specific (based on BMI) odds ratios for complications were calculated for the inverted T as compared with the horizontal group. A replicate analysis using the national Tracking Operations and Outcomes for Plastic Surgeons (TOPS) as a single cohort was performed. RESULTS: At our institution, 362 patients (group 1 = 196, group 2 = 166) were included. A total of 40.9% of patients experienced at least one complication at 1 year postoperatively with the complication rate decreasing to 28.0% when analyzed at the 30-day postoperative period. Specifically, wound disruption rates were highest in group 2 (39.8%) compared with group 1 (15.6%; P < 0.0001). The odds of experiencing a complication were greater in the inverted-T group overall and within each stratum of BMI. When dividing the cohort based on BMI class (normal weight, overweight, class I, class II, and class III obesity), the incidence of wound disruption increased as did BMI (2.6%, 22.2%, 27.2%, 48.2%, and 56.3%, respectively; P < 0.0001). The TOPS data set included 23,067 patients and showed an overall complication rate of 13.1% at 30-day postop. Overall, wound disruption rate was 4.6%. Compared with normal weight patients, the odds of experiencing a complication trended higher with each stratum of BMI. Other factors associated with complications included BMI, tobacco use, diabetes, American Society of Anesthesiology, prior massive weight loss, and LOS. CONCLUSIONS: The increasing complication rate within each BMI stratum of the large sample size of the TOPS patient cohort, in addition to our similar institutional trends, suggests that a staged procedure may be more appropriate for higher BMI patients. Surgical technique modification with limited flap undermining in patients undergoing inverted-T lipectomy to preserve flap perfusion may also decrease overall complication rates.

Using TLC-MALDI-TOF to Interrogate In Vitro Peptidyl Proximal Preferences of PARP14 and Glycohydrolase Specificity.

The transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) to target proteins is mediated by a class of human diphtheria toxin-like ADP-ribosyltransferases (ARTDs; previously referred to as poly-ADP-ribose polymerases or PARPs) and the removal of ADPr is catalyzed by a family of glycohydrolases. Although thousands of potential ADPr modification sites have been identified using high-throughput mass-spectrometry, relatively little is known about the sequence specificity encoded near the modification site. Herein, we present a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method that facilitates the in vitro analysis of proximal factors that guide ARTD target selection. We identify a minimal 5-mer peptide sequence that is necessary and sufficient to drive glutamate/aspartate targeting using PARP14 while highlighting the importance of the adjacent residues in PARP14 targeting. We measure the stability of the resultant ester bond and show that non-enzymatic removal is pH and temperature dependent, sequence independent, and occurs within hours. Finally, we use the ADPr-peptides to highlight differential activities within the glycohydrolase family and their sequence preferences. Our results highlight (1) the utility of MALDI-TOF in analyzing proximal ARTD-substrate interactions and (2) the importance of peptide sequences in governing ADPr transfer and removal.

[Moyamoya disease in children] / Moyamoya hos barn.

Moyamoya is a rare condition that affects the blood vessels of the brain in children and young adults. It can cause both ischaemic stroke and cerebral haemorrhage. Although established diagnostic criteria and examinations exist, limited knowledge of the condition often leads to a mistaken or delayed diagnosis. Treatment consists of antiplatelet drugs and surgical revascularisation. Prognosis after successful surgery is good, but the disease requires a dedicated medical team.

Priority setting at the clinical level: the case of nusinersen and the Norwegian national expert group.

BACKGROUND: Nusinersen is one of an increasing number of new, expensive orphan drugs to receive authorization. These drugs strain public healthcare budgets and challenge principles for resource allocation. Nusinersen was introduced in the Norwegian public healthcare system in 2018. A national expert group consisting of physicians was formed to oversee the introduction and continuation of treatment in light of specific start and stop criteria. METHODS: We have studied experiences within the expert group with a special emphasis on their application of the start and stop criteria, rationing of treatment, and experienced moral dilemmas. A research interview with six members of the national expert group was performed, then analysed with manifest content analysis. The analysis was supplemented with publically available sources on priority setting and the process leading up to the introduction of nusinersen and the establishment of the expert group. RESULTS: Sixty-six patients have received treatment within the first 25 months since the national expert group's establishment. Treatment has not been discontinued for any patient. No patients under 18 years of age have been denied treatment, as those who were referred at this age were all deemed to fulfill the start criteria. The expert group has, however, increased geographical treatment equity and facilitated important cooperation at the national level. Furthermore, it has enhanced open and critical discussions of both medical issues and new ethical dilemmas. CONCLUSION: Although facilitating equal access to treatment for SMA patients, the national expert group has not discontinued treatment for any patient. It is suggested that in order for clinicians to be able to ration care for individual patients, they require both adequate support and sufficient formal authority. Start and stop criteria need to be re-evaluated as more knowledge and experience are gained regarding the treatment.

Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

IGDB-2, an Ig/FNIII protein, binds the ion channel LGC-34 and controls sensory compartment morphogenesis in C. elegans.

Sensory organ glia surround neuronal receptive endings (NREs), forming a specialized compartment important for neuronal activity, and reminiscent of glia-ensheathed synapses in the central nervous system. We previously showed that DAF-6, a Patched-related protein, is required in glia of the C. elegans amphid sensory organ to restrict sensory compartment size. LIT-1, a Nemo-like kinase, and SNX-1, a retromer component, antagonize DAF-6 and promote compartment expansion. To further explore the machinery underlying compartment size control, we sought genes whose inactivation restores normal compartment size to daf-6 mutants. We found that mutations in igdb-2, encoding a single-pass transmembrane protein containing Ig-like and fibronectin type III domains, suppress daf-6 mutant defects. IGDB-2 acts in glia, where it localizes to glial membranes surrounding NREs, and, together with LIT-1 and SNX-1, regulates compartment morphogenesis. Immunoprecipitation followed by mass spectrometry demonstrates that IGDB-2 binds to LGC-34, a predicted ligand-gated ion channel, and lgc-34 mutations inhibit igdb-2 suppression of daf-6. Our findings reveal a novel membrane protein complex and suggest possible mechanisms for how sensory compartment size is controlled.

Cerebral Microemboli Detection and Differentiation During Transcatheter Closure of Patent Ductus Arteriosus.

The aim of this prospective study was to determine the frequency and composition of cerebral microemboli in a pediatric population, during transcatheter closure of patent ductus arteriosus (PDA). Multifrequency transcranial Doppler was used to monitor cerebral blood flow velocity (CBFV) and detect microembolic signals (MES) in the middle cerebral artery in 23 patients (median age 18 months). MES were automatically identified and differentiated according to composition; gaseous or solid. The procedure was divided into five periods: Arterial catheterization; venous catheterization; ductal catheterization; angiography; device placement and release. Timing of catheter manipulations and MES were registered and compared. MES were detected in all patients. The median number of signals was 7, (minimum 1, maximum 28). Over 95 % of all MES were gaseous. 11 % were detected during device placement while 64 % were detected during angiographic studies, significantly higher than during any other period (P < 0.001). There was a moderate correlation between the number of MES and volume of contrast used, (R = 0.622, P < 0.01). There was no correlation with fluoroscopic time or duration of procedure. This is the first study to investigate the timing and composition of cerebral microemboli during PDA occlusion. Microemboli were related to specific catheter manipulations and correlated with the amount of contrast used.

Cerebral microemboli detection and differentiation during transcatheter closure of atrial septal defect in a paediatric population.

INTRODUCTION: The aim of this prospective study was to determine the frequency and composition of cerebral microemboli in a paediatric population during transcatheter atrial septal defect closure. METHODS: Multi-frequency transcranial Doppler was used to detect microembolic signals in the middle cerebral artery of 24 patients. Embolic signals were automatically identified and differentiated according to their composition, gaseous or solid. The procedure was divided into five periods: right cardiac catheterisation; left cardiac catheterisation; pulmonary angiography; balloon sizing; and device placement. RESULTS: Microemboli were detected in all patients. The median number of signals was 63 and over 95% gaseous. The total number of microembolic signals detected during two periods - balloon sizing and sheath placement and device placement - was not significantly different (median: 18 and 25, respectively) but was significantly higher than each of the other three periods (p<0.001). In eight patients, the device was opened more than once and the number of embolic signals decreased with each successive device deployment. There was no correlation between the number of microembolic signals and fluoroscopic time, duration of procedure, age, or device size. CONCLUSION: This is the first study to investigate the timing and composition of cerebral microemboli in a paediatric population during cardiac catheterisation. Microembolic signals were related to specific catheter manipulations but were not associated with fluoroscopic time or duration of procedure.

2024 update: European consensus statement on gene therapy for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is one of the most common genetic diseases and was, until recently, a leading genetic cause of infant mortality. Three disease-modifying treatments have dramatically changed the disease trajectories and outcome for severely affected infants (SMA type 1), especially when initiated in the presymptomatic phase. One of these treatments is the adeno-associated viral vector 9 (AAV9) based gene therapy onasemnogene abeparvovec (Zolgensma®), which is delivered systemically and has been approved by the European Medicine Agency for SMA patients with up to three copies of the SMN2 gene or with the clinical presentation of SMA type 1. While this broad indication provides flexibility in patient selection, it also raises concerns about the risk-benefit ratio for patients with limited or no evidence supporting treatment. In 2020, we convened a European neuromuscular expert working group to support the rational use of onasemnogene abeparvovec, employing a modified Delphi methodology. After three years, we have assembled a similar yet larger group of European experts who assessed the emerging evidence of onasemnogene abeparvovec's role in treating older and heavier SMA patients, integrating insights from recent clinical trials and real-world evidence. This effort resulted in 12 consensus statements, with strong consensus achieved on 9 and consensus on the remaining 3, reflecting the evolving role of onasemnogene abeparvovec in treating SMA.

Primary Cutaneous Secretory Carcinoma: A Case Report and Literature Review.

Cutaneous secretory carcinomas (CSCs) are primary neoplasms of the skin that have been just recently described in the literature through case reports and series. In this case, a cutaneous lesion was found on the left temporal region of an 83-year-old male. He was referred to plastic surgery for complete excision, with negative margins confirmed by pathology. Histology, immunostaining, and genetic testing showed characteristics confirming the diagnosis of CSC and were supported by the information present in the current literature. Our patient showed no evidence of nodal disease or recurrence during regular follow-ups. Given the rarity of CSCs, we aim to present our experience regarding the diagnosis, pathological analysis, and management of our patient as well as summarize the present literature to further open avenues of research.

Cognitive function, behaviour and quality of life in children with myotonic dystrophy type 1 in South - Eastern Norway.

BACKGROUND: Cognitive and behavioural problems may be predominant in the clinical picture of myotonic dystrophy (DM1) in childhood. This can lead to a diagnostic delay and thus prevent optimal therapeutic measures. OBJECTIVE: To obtain an overview of children with DM1 in our health region and study their cognitive and behavioural function, quality of life and neurological status. METHODS: Patients diagnosed with DM1 were recruited to this cross-sectional study through local habilitation teams of our health region. Neuropsychological testing and physical examination were performed for the majority. For some patients information was retrieved from medical records and through telephone interviews. A questionnaire was administered regarding quality of life. RESULTS: 27 subjects <18 years diagnosed with DM1 were identified, giving a frequency of DM1 of 4.3/100 000 in this age group. Twenty consented to participate. Five had congenital DM1. Most of the participants had only mild neurological deficits. Two with congenital type had hydrocephalus requiring a shunt. Ten, whereof none with congenital DM1, had a cognitive function within normal range. Three were diagnosed with an autism spectrum disorder, and additional three were reported with autistic traits. Many parents reported social and school problems for their child. CONCLUSIONS: Intellectual disability and varying degrees of autistic behaviour were quite common. Motor deficits were most often mild. A strong focus regarding support at school and in social communication is needed for children growing up with DM1.

Abdominal Wall Reconstruction After Extirpation of a 140-Pound Primary Ovarian Mucinous Adenocarcinoma.

Ovarian cancer is a feared diagnosis for women and clinicians alike. Ovarian mucinous adenocarcinoma is a unique subset of ovarian cancer. As a primary tumor, massive ovarian masses, and more specifically mucinous adenocarcinomas, have been infrequently reported in the medical literature. Team approaches to massive tumor extirpations are essential, as patients often require the expertise of various subspecialists including, but not limited to, gynecologic-oncologists, general surgeons, and plastic and reconstructive surgeons. Here we present a case of a 71-year-old woman with a massive, incapacitating pelvic mass, later found to be a primary ovarian mucinous adenocarcinoma. Once medically optimized, a multi-service team approach was utilized for tumor extirpation and abdominal wall reconstruction. Involved surgical services included Gynecologic-Oncology, General Surgery, and Plastic and Reconstructive Surgery. Exploratory laparotomy for tumor extirpation, hysterectomy, bilateral salpingo-oophorectomy, omentectomy, peritoneal stripping, bilateral inguinal lymphadenectomy, and appendectomy was performed. Extensively thin, devascularized, and attenuated abdominal wall fascia that was adherent to the tumor was removed. The abdominal wall defect was reconstructed and reinforced with inlay and overlays of biologic monofilament mesh. Inverted-T of the vertical and horizontal skin components was performed in a tailor-tacking fashion, assuring the maintenance and protection of the abdominal skin flap vascularity through utilizing the Huger Zones of perfusion. Pathology revealed a stage IA grade 2 mucinous adenocarcinoma of the ovary without evidence of metastasis. No adjuvant therapies were required. The tumor's weight was 140 pounds, and its dimensions were 63 x 41 x 40 cm. It is our hope that presenting this experience will raise awareness of this spectrum of diseases and allow for earlier diagnoses and treatments, as well as exemplify the virtues of a team-based approach in the successful extirpation and subsequent reconstruction of the abdominal wall and skin.

Microsurgery in the Sickle Cell Trait Population: Can it Be Safely and Successfully Performed?

Free-tissue transfer reconstruction in patients with sickle cell anemia risks failure due to polymerization of sickle hemoglobin within the flap microcirculation. However, outcomes vary, as the amount of polymerization is dependent on factors such as disease phenotype/diagnosis, degree of hypoxia, and intracellular dehydration. Most of the literature focuses on patients with sickle cell disease, which produces higher concentrations of sickle hemoglobin and, therefore, is a contraindication to microvascular reconstruction. Fewer reports describe microsurgery in patients with sickle cell trait (SCT) who carry the heterozygous phenotype. Here, we present a case in which a patient with SCT underwent microsurgical breast reconstruction with deep inferior epigastric perforator free-tissue transfer. The 52-year-old woman had previously experienced a failed alloplastic-based reconstruction after radiation therapy for breast cancer. In our case, clinical and Doppler examinations demonstrated that arterial and venous anastomoses had remained patent; so the patient was discharged on postoperative day 4. Blistering developed on postoperative day 8, and by day 15 there was partial necrosis of the inferior-lateral aspect of the deep inferior epigastric perforator flap. Debridement and closure resolved the issue, and at 5 months postprocedure, the flap remained well-perfused and well-incorporated. This case, presented here with patient consent, reports a successful outcome of microsurgical reconstruction in a patient with SCT. It expands the limited evidence to support the safety and feasibility of autologous surgical interventions for patients with the heterozygous phenotype of sickle cell anemia.

Delayed Thoracodorsal Artery Perforator Free Flap for Calcaneal Degloving Injury Reconstruction.

The thoracodorsal artery perforator (TDAP) flap has a long vascular pedicle that is ideal for lower extremity reconstruction, but it generally relies on the presence of a dominant septocutaneous perforator vessel. Surgical delay optimizes flap survival by creating relative ischemia to augment perforator vessels. In this report, we describe the use of a delayed free TDAP flap in the setting of an absent dominant perforator vessel for the reconstruction of a calcaneal degloving injury. A 22-year-old actively smoking patient with a body mass index of 33.5 presented with a nonhealing left heel wound with overlying necrotic changes after traumatic degloving injury. The entire weight-bearing portion of the calcaneal fat pad and the flanking regions were debrided. The TDAP flap was elevated, revealing three small thoracodorsal artery perforators. Given that a dominant perforator was absent, the flap was surgically delayed. Free-tissue transfer occurred 8 days later. This operation was conducted entirely in left lateral decubitus with simultaneous wound preparation and flap harvest. The flap was elevated on two perforators to elongate the pedicle's length and inset to cover exposed calcaneus and pad the heel. Six months postoperatively, the patient is doing well without flap compromise or ulceration. The TDAP flap is a versatile microsurgical tool, and surgical delay extends the utility of this flap when a dominant septocutaneous perforator is unavailable. Recipient site debridement may occur simultaneously with the TDAP delay procedure. Importantly, only one position is required for flap elevation, microsurgical anastomosis, and insetting, thus obviating intraoperative repositioning.

Identification of a Novel PARP14 Site Motif and Glycohydrolase Specificity Using TLC-MALDI-TOF.

Transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) to target proteins is mediated by a class of human poly-ADP-ribose polymerases, PARPs, and removal of ADPr is catalyzed by a family of glycohydrolases. Although thousands of potential ADPr modification sites have been identified using high-throughput mass-spectrometry, relatively little is known about sequence specificity encoded near the modification site. Herein, we present a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method that facilitates the discovery and validation of ADPr site motifs. We identify a minimal 5-mer peptide sequence that is sufficient to drive PARP14 specific activity while highlighting the importance of the adjacent residues in PARP14 targeting. We measure the stability of the resultant ester bond and show that non-enzymatic removal is sequence independent and occurs within hours. Finally, we use the ADPr-peptide to highlight differential activities within the glycohydrolase family and their sequence specificities. Our results highlight: 1) the utility of MALDI-TOF in motif discovery and 2) the importance of peptide sequence in governing ADPr transfer and removal.