Hysterectomy Techniques and Outcomes for Benign Large Uteri: A Systematic Review.

OBJECTIVE: To identify the optimal hysterectomy approach for large uteri in gynecologic surgery for benign indications from a perioperative morbidity standpoint. DATA SOURCES: PubMed and Embase databases were searched from inception through September 19, 2022. Meta-analyses were conducted as feasible. METHODS OF STUDY SELECTION: This review included studies that compared routes of hysterectomy with or without bilateral salpingo-oophorectomy for large uteri (12 weeks or more or 250 g or more) and excluded studies with any concurrent surgery for pelvic organ prolapse, incontinence, gynecologic malignancy, or any obstetric indication for hysterectomy. TABULATION, INTEGRATION, AND RESULTS: The review included 25 studies comprising nine randomized trials, two prospective, and 14 retrospective nonrandomized comparative studies. Studies were at high risk of bias. There was lower operative time for total vaginal hysterectomy compared with laparoscopically assisted vaginal hysterectomy (LAVH) (mean difference 39 minutes, 95% CI, 18-60) and total vaginal hysterectomy compared with total laparoscopic hysterectomy (mean difference 50 minutes, 95% CI, 29-70). Total laparoscopic hysterectomy was associated with much greater risk of ureteral injury compared with total vaginal hysterectomy (odds ratio 7.54, 95% CI, 2.52-22.58). There were no significant differences in bowel injury rates between groups. There were no differences in length of stay among the laparoscopic approaches. For LAVH compared with total vaginal hysterectomy, randomized controlled trials favored total vaginal hysterectomy for length of stay. When rates of blood transfusion were compared between these abdominal hysterectomy and robotic-assisted total hysterectomy routes, abdominal hysterectomy was associated with a sixfold greater risk of transfusion than robotic-assisted total hysterectomy (6.31, 95% CI, 1.07-37.32). Similarly, single studies comparing robotic-assisted total hysterectomy with LAVH, total laparoscopic hysterectomy, or total vaginal hysterectomy all favored robotic-assisted total hysterectomy for reduced blood loss. CONCLUSION: Minimally invasive routes are safe and effective and have few complications. Minimally invasive approach (vaginal, laparoscopic, or robotic) results in lower blood loss and shorter length of stay, whereas the abdominal route has a shorter operative time. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021233300.

Ultrathin Magnesium-Based Coating as an Efficient Oxygen Barrier for Superconducting Circuit Materials.

Scaling up superconducting quantum circuits based on transmon qubits necessitates substantial enhancements in qubit coherence time. Over recent years, tantalum (Ta) has emerged as a promising candidate for transmon qubits, surpassing conventional counterparts in terms of coherence time. However, amorphous surface Ta oxide layer may introduce dielectric loss, ultimately placing a limit on the coherence time. In this study, a novel approach for suppressing the formation of tantalum oxide using an ultrathin magnesium (Mg) capping layer is presented. Synchrotron-based X-ray photoelectron spectroscopy studies demonstrate that oxide is confined to an extremely thin region directly beneath the Mg/Ta interface. Additionally, it is demonstrated that the superconducting properties of thin Ta films are improved following the Mg capping, exhibiting sharper and higher-temperature transitions to superconductive and magnetically ordered states. Moreover, an atomic-scale mechanistic understanding of the role of the capping layer in protecting Ta from oxidation is established based on computational modeling. This work provides valuable insights into the formation mechanism and functionality of surface tantalum oxide, as well as a new materials design principle with the potential to reduce dielectric loss in superconducting quantum materials. Ultimately, the findings pave the way for the realization of large-scale, high-performance quantum computing systems.

Microbiome modulates immunotherapy response in cutaneous squamous cell carcinoma.

The gut microbiome is increasingly recognized to alter cancer risk, progression and response to treatments such as immunotherapy, especially in cutaneous melanoma. However, whether the microbiome influences immune checkpoint inhibitor (ICI) immunotherapy response to non-melanoma skin cancer has not yet been defined. As squamous cell carcinomas (SCC) are in closest proximity to the skin microbiome, we hypothesized that the skin microbiome, which regulates cutaneous immunity, might affect SCC-associated anti-PD1 immunotherapy treatment response. We used ultraviolet radiation to induce SCC in SKH1 hairless mice. We then treated the mice with broad-band antibiotics to deplete the microbiome, followed by colonisation by candidate skin and gut bacteria or persistent antibiotic treatment, all in parallel with ICI treatment. We longitudinally monitored skin and gut microbiome dynamics by 16S rRNA gene sequencing and tumour burden by periodic tumour measurements and histologic assessment. Our study revealed that antibiotics-induced abrogation of the microbiome reduced the tumour burden, suggesting a functional role of the microbiome in non-melanoma skin cancer therapy response.

Chemical Profiles of the Oxides on Tantalum in State of the Art Superconducting Circuits.

Over the past decades, superconducting qubits have emerged as one of the leading hardware platforms for realizing a quantum processor. Consequently, researchers have made significant effort to understand the loss channels that limit the coherence times of superconducting qubits. A major source of loss has been attributed to two level systems that are present at the material interfaces. It is recently shown that replacing the metal in the capacitor of a transmon with tantalum yields record relaxation and coherence times for superconducting qubits, motivating a detailed study of the tantalum surface. In this work, the chemical profile of the surface of tantalum films grown on c-plane sapphire using variable energy X-ray photoelectron spectroscopy (VEXPS) is studied. The different oxidation states of tantalum that are present in the native oxide resulting from exposure to air are identified, and their distribution through the depth of the film is measured. Furthermore, it is shown how the volume and depth distribution of these tantalum oxidation states can be altered by various chemical treatments. Correlating these measurements with detailed measurements of quantum devices may elucidate the underlying microscopic sources of loss.

Microbiome modulates immunotherapy response in cutaneous squamous cell carcinoma.

The gut microbiome is increasingly recognized to alter cancer risk, progression, and response to treatments such as immunotherapy, especially in cutaneous melanoma. However, whether the microbiome influences immune checkpoint inhibitor (ICI) immunotherapy response to non-melanoma skin cancer has not yet been defined. As squamous cell carcinomas (SCC) are in closest proximity to the skin microbiome, we hypothesized that the skin microbiome, which regulates cutaneous immunity, might affect SCC-associated anti-PD1 immunotherapy treatment response. We used ultraviolet radiation to induce SCC in SKH1 hairless mice. We then treated the mice with broad-band antibiotics to deplete the microbiome, followed by colonization by candidate skin and gut bacteria or persistent antibiotic treatment, all in parallel with ICI treatment. We longitudinally monitored skin and gut microbiome dynamics by 16S rRNA gene sequencing, and tumor burden by periodic tumor measurements and histologic assessment. Our study revealed that antibiotics-induced abrogation of the microbiome reduced tumor burden, suggesting a functional role of the microbiome in non-melanoma skin cancer therapy response.

Structure Matters: Asymmetric CO Oxidation at Rh Steps with Different Atomic Packing.

Curved crystals are a simple but powerful approach to bridge the gap between single crystal surfaces and nanoparticle catalysts, by allowing a rational assessment of the role of active step sites in gas-surface reactions. Using a curved Rh(111) crystal, here, we investigate the effect of A-type (square geometry) and B-type (triangular geometry) atomic packing of steps on the catalytic CO oxidation on Rh at millibar pressures. Imaging the crystal during reaction ignition with laser-induced CO2 fluorescence demonstrates a two-step process, where B-steps ignite at lower temperature than A-steps. Such fundamental dissimilarity is explained in ambient pressure X-ray photoemission (AP-XPS) experiments, which reveal partial CO desorption and oxygen buildup only at B-steps. AP-XPS also proves that A-B step asymmetries extend to the active stage: at A-steps, low-active O-Rh-O trilayers buildup immediately after ignition, while highly active chemisorbed O is the dominant species on B-type steps. We conclude that B-steps are more efficient than A-steps for the CO oxidation.

Gynecologic surgical skill acquisition through simulation with outcomes at the time of surgery: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of simulation training vs traditional hands-on surgical instruction on learner operative skills and patient outcomes in gynecologic surgeries. DATA SOURCES: PubMed, Embase, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials from inception to January 12, 2021. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials, prospective comparative studies, and prospective single-group studies with pre- and posttraining assessments that reported surgical simulation-based training before gynecologic surgery were included. METHODS: Reviewers independently identified the studies, obtained data, and assessed the study quality. The results were analyzed according to the type of gynecologic surgery, simulation, comparator, and outcome data, including clinical and patient-related outcomes. The maximum likelihood random effects model meta-analyses of the odds ratios and standardized mean differences were calculated with estimated 95% confidence intervals. RESULTS: Twenty studies, including 13 randomized controlled trials, 1 randomized crossover trial, 5 nonrandomized comparative studies, and 1 prepost study were identified. Most of the included studies (14/21, 67%) were on laparoscopic simulators and had a moderate quality of evidence. Meta-analysis showed that compared with traditional surgical teaching, high- and low-fidelity simulators improved surgical technical skills in the operating room as measured by global rating scales, and high-fidelity simulators decreased the operative time. Moderate quality evidence was found favoring warm-up exercises before laparoscopic surgery. There was insufficient evidence to conduct a meta-analysis for other gynecologic procedures. CONCLUSION: Current evidence supports incorporating simulation-based training for a variety of gynecologic surgeries to increase technical skills in the operating room, but data on patient-related outcomes are lacking.

Surgical Removal of Midurethral Sling in Women Undergoing Surgery for Presumed Mesh-Related Complications: A Systematic Review.

OBJECTIVE: To assess whether some, or all, of the mesh needs to be removed when a midurethral sling is removed for complications. DATA SOURCES: A systematic review and meta-analysis was conducted. MEDLINE, Cochrane, and ClinicalTrials.gov databases from January 1, 1996, through May 1, 2021, were searched for articles that met the eligibility criteria with total, partial, or a combination of anti-incontinence mesh removal. METHODS OF STUDY SELECTION: All study designs were included (N≥10), and a priori criteria were used for acceptance standards. Studies were extracted for demographics, operative outcomes, and adverse events. Meta-analysis was performed when possible. TABULATION, INTEGRATION, AND RESULTS: We double-screened 11,887 abstracts; 45 eligible and unique studies were identified. Thirty-five were single-group studies that evaluated partial mesh removal, five were single-group studies that evaluated total mesh removal, and five were studies that compared partial mesh removal with total mesh removal. All of the studies were retrospective in nature; there were no randomized controlled studies. Comparative studies demonstrated that partial mesh removal had lower rates of postoperative stress urinary incontinence (SUI) than total mesh removal (odds ratio 0.46, 95% CI 0.22-0.96). Single-group studies supported lower rates of postoperative SUI with partial mesh removal compared with total mesh removal (19.2% [95% CI 13.5-25.7] vs 48.7% [95% CI 31.2-66.4]). Both methods were similar with respect to associated pain, bladder outlet obstruction, mesh erosion or exposure, and lower urinary tract symptoms. Adverse events were infrequent. CONCLUSION: Postoperative SUI may be lower with partial mesh removal compared with total mesh removal. Other outcomes were similar regardless of the amount of mesh removed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD 42018093099.

Surveillance for subsequent neoplasms of the CNS for childhood, adolescent, and young adult cancer survivors: a systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Exposure to cranial radiotherapy is associated with an increased risk of subsequent CNS neoplasms among childhood, adolescent, and young adult (CAYA) cancer survivors. Surveillance for subsequent neoplasms can translate into early diagnoses and interventions that could improve cancer survivors' health and quality of life. The practice guideline presented here by the International Late Effects of Childhood Cancer Guideline Harmonization Group was developed with an evidence-based method that entailed the gathering and appraisal of published evidence associated with subsequent CNS neoplasms among CAYA cancer survivors. The preparation of these guidelines showed a paucity of high-quality evidence and highlighted the need for additional research to inform survivorship care. The recommendations are based on careful consideration of the evidence supporting the benefits, risks, and harms of the surveillance interventions, clinical judgment regarding individual patient circumstances, and the need to maintain flexibility of application across different health-care systems. Currently, there is insufficient evidence to establish whether early detection of subsequent CNS neoplasms reduces morbidity and mortality, and therefore no recommendation can be formulated for or against routine MRI surveillance. The decision to start surveillance should be made by the CAYA cancer survivor and health-care provider after careful consideration of the potential harms and benefits of surveillance for CNS neoplasms, including meningioma.

Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma.

PURPOSE: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. METHODS: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing. RESULTS: A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving MYC, MYCN, and FBXW7. Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms. CONCLUSION: Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.

Clinical Outcomes and Complications of Pituitary Blastoma.

CONTEXT: Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome. OBJECTIVE: This work aims to describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases. DESIGN AND SETTING: A multi-institutional case series is presented from tertiary pediatric oncology centers. PATIENTS: Patients included children with pituitary blastoma. INTERVENTIONS: Genetic testing, surgery, oncologic therapy, endocrine support are reported. OUTCOME MEASURES: Outcome measures included survival, long-term morbidities, and germline and tumor DICER1 genotypes. RESULTS: Seventeen pituitary blastoma cases were studied (10 girls and 7 boys); median age at diagnosis was 11 months (range, 2-24 months). Cushing syndrome was the most frequent presentation (n = 10). Cushingoid stigmata were absent in 7 children (2 with increased adrenocorticotropin [ACTH]; 5 with normal/unmeasured ACTH). Ophthalmoplegia and increased intracranial pressure were also observed. Surgical procedures included gross/near-total resection (n = 7), subtotal resection (n = 9), and biopsy (n = 1). Six children received adjuvant therapy. At a median follow-up of 6.7 years, 9 patients were alive; 8 patients died of the following causes: early medical/surgical complications (n = 3), sepsis (n = 1), catheter-related complication (n = 1), aneurysmal bleeding (n = 1), second brain tumor (n = 1), and progression (n = 1). Surgery was the only intervention for 5 of 9 survivors. Extent of resection, but neither Ki67 labeling index nor adjuvant therapy, was significantly associated with survival. Chronic complications included neuroendocrine (n = 8), visual (n = 4), and neurodevelopmental (n = 3) deficits. Sixteen pituitary blastomas were attributed to DICER1 abnormalities. CONCLUSIONS: Pituitary blastoma is a locally destructive tumor associated with high mortality. Surgical resection alone provides long-term disease control for some patients. Quality survival is possible with long-term neuroendocrine management.

Catalytic Oxidation of CO on a Curved Pt(111) Surface: Simultaneous Ignition at All Facets through a Transient CO-O Complex*.

The catalytic oxidation of CO on transition metals, such as Pt, is commonly viewed as a sharp transition from the CO-inhibited surface to the active metal, covered with O. However, we find that minor amounts of O are present in the CO-poisoned layer that explain why, surprisingly, CO desorbs at stepped and flat Pt crystal planes at once, regardless of the reaction conditions. Using near-ambient pressure X-ray photoemission and a curved Pt(111) crystal we probe the chemical composition at surfaces with variable step density during the CO oxidation reaction. Analysis of C and O core levels across the curved crystal reveals that, right before light-off, subsurface O builds up within (111) terraces. This is key to trigger the simultaneous ignition of the catalytic reaction at different Pt surfaces: a CO-Pt-O complex is formed that equals the CO chemisorption energy at terraces and steps, leading to the abrupt desorption of poisoning CO from all crystal facets at the same temperature.

Pleuropulmonary blastoma-like peritoneal sarcoma: a newly described malignancy associated with biallelic DICER1 pathogenic variation.

Since the original description of pathogenic germline DICER1 variation underlying pleuropulmonary blastoma (PPB), the spectrum of extrapulmonary neoplasms known to be associated with DICER1 has continued to expand and now includes tumors of the ovary, thyroid, kidney, eye, and brain among other sites. This report documents our experience with another manifestation: a primitive sarcoma that resembles PPB and DICER1-associated sarcoma of the kidney. These tumors are distinguished by their unusual location in the peritoneal cavity, associated with visceral and/or parietal mesothelium. A total of seven cases were identified through pathology review in children presenting at a median age of 13 years (range 3-14 years). Primary sites of origin included the fallopian tube (four cases), serosal surface of the colon (one case), and pelvic sidewall (two cases). One case had pathologic features of type I PPB, another type Ir (regressed) PPB, and the remaining five had features of type II or III PPB with a mixed primitive sarcomatous pattern with or without cystic elements. All had a pathogenic DICER1 variation identified in germline and/or tumor DNA. PPB-like peritoneal tumors represent a newly described manifestation of DICER1 pathogenic variation whose pathologic features are also recapitulated in DICER1-related renal sarcoma, cervical embryonal rhabdomyosarcoma, and some Sertoli-Leydig cell tumors with heterologous elements. Tumors arising from the fallopian tube or elsewhere in the abdomen/pelvis, especially those with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation, should prompt consideration of germline and tumor DICER1 testing.

Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial.

BACKGROUND: "Head Start" III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma. METHODS: Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction. RESULTS: Between 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ±â€…5% and 62 ±â€…5% for all patients, 61 ±â€…8% and 77 ±â€…7% for localized medulloblastoma, and 35 ±â€…7% and 52 ±â€…7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ±â€…6% and 89 ±â€…6% compared with 26 ±â€…6% and 53 ±â€…7% for classic and 38 ±â€…13% and 46 ±â€…14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex (P <0.0001). Five-year irradiation-free EFS was 78 ±â€…8% for ND and 21 ±â€…5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average. CONCLUSION: We report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.

Bone marrow transplant and pediatric multiple myeloma.

Multiple myeloma is a malignant plasma cell disorder that is rare in the pediatric population, with only approximately 0.3% of cases diagnosed before the age of 30. In this report, we present two patients diagnosed with multiple myeloma between the ages of 12 and 16. Their respective treatment regimens are discussed, including the use of both autologous and allogeneic stem cell transplant.

Measuring Quality in Minimally Invasive Gynecologic Surgery: What, How, and Why?

In healthcare, the goal of maximizing value by improving the quality of care and lowering costs has been notoriously challenging to achieve. The fee-for-service model in gynecology and other fields has historically promoted the reduction of nonsurgical or minimally invasive approaches in favor of complex, often morbid procedures. In this review, we seek to define quality and value in the healthcare field and describe strategies that promote quality over production. We then discuss national, non-specialty-based efforts in the context of Surgical Care Improvement Project measures to improve quality of care. Finally, we present a case study through the Kaiser Permanente Minimally Invasive Hysterectomy Initiative, one such model that successfully built on the quality metrics of the foregoing strategies to improve patient care.