Prioritizing sexual and reproductive health research and care for people with cystic fibrosis: A 2023 workshop report from the Cystic Fibrosis Foundation Sexual Health, Reproduction, and Gender (SHARING) Research Working Group.

BACKGROUND: To address sexual and reproductive health (SRH) concerns among people with cystic fibrosis(PwCF), the CF Foundation created the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group. This report summarizes CF community SRH research priorities and workshop discussions/future study planning. METHODS: Pre-workshop, we distributed a community prioritization survey on CF SRH research/care. During the workshop, we used results and reviewed existing research to establish research priorities and design studies to address identified knowledge gaps. RESULTS: A total of 303 respondents (85 % PwCF, 15 % caregivers) completed the survey. Highly-rated SRH topics were: 1) effects of CF modulator therapy on sex hormones; 2) effects of sex hormones on CF; 3) fertility; 4) pregnancy; and 5) SRH/mental health. Twenty-four workshop participants established the need for further research on sex hormones and CF, optimizing SRH care provision, and fertility/ART. CONCLUSION: SRH is an important and emerging area in CF and thoughtful consideration of community perspectives can ensure that future research is relevant and responsive.

Leukostasis With Isolated Central Nervous System Involvement in Chronic Phase of Chronic Myelogenous Leukemia.

Chronic myelogenous leukemia (CML) is a hematologic malignancy with unique significance to the field of hematology and oncology, specifically due to the development of tyrosine kinase inhibitors (TKIs). CML often presents with nonspecific symptoms, and the quality of life in patients with CML has drastically improved as a result of TKIs. However, complications of CML including the risk of transforming into life-threatening blast crises continue to exist. Further, as most patients are asymptomatic in the chronic phase, patients often present with serious complications associated with noncompliance to TKIs. For example, central nervous system (CNS) manifestations of CML have been reported, both as the initial presentation of undiagnosed CML and as known complication of uncontrolled CML. Hyperleukocytosis is a manifestation of uncontrolled CML and leukostasis is a complication, occurring in cases of acute myeloid leukemia (AML). Here we present a rare case of leukostasis in a patient with known CML presenting on computed tomography (CT) as intracranial masses in the chronic phase. Our goal is to discuss this rare case of leukostasis in adult CML and describe its management.

Portal vein thrombosis as the presenting manifestation of JAK2 positive myeloproliferative neoplasm.

Deep venous thrombosis (DVT) is a complication of myeloproliferative neoplasms (MPNs). However, DVTs in unusual sites such as portal vein thrombosis (PVT) are rare and may be the first clinical manifestation of occult MPNs. There is a need for increasing awareness of such manifestations; so, here we discuss a patient who presented with new portal vein thrombosis, underwent further studies, was ultimately diagnosed with JAK2 positive MPN, and started on appropriate treatment with improvement of thrombosis and controlled hematocrit.

Need to study simplification of gastrointestinal medication regimen in cystic fibrosis in the era of highly effective modulators.

INTRODUCTION: The success of highly effective modulator therapy (HEMT) has led to consideration of simpler regimens for people with CF (PwCF) with opportunities to modify burdensome regimens. Despite the intuitive appeal of discontinuing chronic therapies no longer necessary, this process should be pursued systematically to ensure safety, adherence, and validate patient-centered preferences. We designed a questionnaire to determine the state of use of acid-suppressive medications (ASM) and pancreatic enzyme therapy (PERT), current self-withdrawal and provider-directed withdrawal practices, and interest in a standardized withdrawal study. METHODS: In collaboration with CF Foundation (CFF), a questionnaire was developed and distributed to members of Community Voice (CV, comprised of PwCF and their loved ones), and CF providers regarding the need to study simplifying the gastrointestinal (GI) regimen for PwCF on HEMT. RESULTS: Approximately 20-40% of CV or CF providers have decreased or stopped ASM for those on HEMT. For PERT, CV and CF providers have decreased dose (34%-48% and approximately 25%, respectively) more often than having stopped it altogether (13%-24% and 3%-12%, respectively). Cumulatively, there is interest in pursuing research in this area (86% CV and 89% CF providers) and willingness to enroll in such a study (80% CV and 89% CF providers). CONCLUSION: Systematically studying the withdrawal of common GI medications, ASM and PERT, is important to CV and CF providers. Decreases in dosing and withdrawal are already taking place without evidence to support this practice. This questionnaire is the first step in designing a GI medication simplification study in PwCF on HEMT.

Epilepsy research in Africa: A scoping review by the ILAE Pediatric Commission Research Advocacy Task Force.

OBJECTIVE: Despite the high prevalence of epilepsy in Africa, evaluation of epilepsy research trends on the continent is lacking. Without establishing effective research, improvement in care for people with epilepsy cannot be effectively strategized or targeted. METHODS: A scoping review of the peer-reviewed literature on epilepsy from Africa (1989-2019) was conducted. The aim was to understand from this what areas are well researched versus underresearched based on published epilepsy topics. RESULTS: A total of 1227 publications were identified and assessed. A significant increase in publications occurred over the 30 years assessed. African author leadership was evident in most reports. Nine countries had >50 publications identified; the remaining 45 countries had <50 or no publications. Research studies were typically of lower quality (case series and observational studies). Research themes were more focused on clinical epilepsy (descriptive observational studies) and social aspects (qualitative surveys). However, there were a number of unique and strong themes, specifically for neurocysticercosis and nodding syndrome, where strong research collaborations were evident, basic science understandings were explored, and interventional models were established. SIGNIFICANCE: Despite Africa being the continent with the most countries, it is lacking in the quantity, quality, and for some areas, relevance of research on epilepsy. Targeted approaches are needed to upskill the strength of research undertaken with more basic science, interventional, and randomized controlled studies. Themes of research need to promote those with unique African content but also to align with current international research areas that have impact on care delivery, such as epilepsy surgery and epilepsy genetics. For this to be possible, it is important to strengthen research hubs with collaborations that empower Africa to own its epilepsy research journey.

Perceptions of Diabetes Technology Use in Cystic Fibrosis-Related Diabetes Management.

Background: Diabetes technologies are associated with improvements in glycemic control and health-related quality of life among people with type 1 diabetes (T1D). Use and perceptions of continuous glucose monitors (CGM) and insulin pumps within the cystic fibrosis (CF) community have not been well studied. Methods: A 30-item online survey addressing cystic fibrosis-related diabetes (CFRD) diagnosis, CGM and insulin pump use, and perceptions of diabetes technologies was sent to a CF community group, including people with CF (pwCF) and parents of children with CF (cwCF). Results: The response rate was 11% (n = 120; 83 pwCF, 35 cwCF). Sixty-one percent of pwCF and 34% of cwCF reported a diagnosis of CFRD. CGM use was reported by 75% (n = 47) of respondents with CFRD but was discontinued by 19% (n = 9), most commonly due to cost and increased worry about glycemia. Insulin pump therapy was reported by 29% (n = 18 of 62) of respondents with CFRD and was discontinued by 28% (n = 5), most commonly due to pain or skin irritation. Overall, 91% agreed or strongly agreed that CGM facilitated CFRD management. Eighty-one percent agreed with at least five of seven positive statements about CGM as compared with 22% for insulin pumps. Potential embarrassment over device wear, concerns about cost, and pain were commonly held negative perceptions of both technologies. Conclusions: As compared with T1D and despite perceived benefits, rates of sustained diabetes technology use are low in the CFRD community. Better insurance coverage to mitigate cost, better patient education, and confirmation that these technologies improve health and patient-reported outcomes may increase uptake.

DNA2 in Chromosome Stability and Cell Survival-Is It All about Replication Forks?

The conserved nuclease-helicase DNA2 has been linked to mitochondrial myopathy, Seckel syndrome, and cancer. Across species, the protein is indispensable for cell proliferation. On the molecular level, DNA2 has been implicated in DNA double-strand break (DSB) repair, checkpoint activation, Okazaki fragment processing (OFP), and telomere homeostasis. More recently, a critical contribution of DNA2 to the replication stress response and recovery of stalled DNA replication forks (RFs) has emerged. Here, we review the available functional and phenotypic data and propose that the major cellular defects associated with DNA2 dysfunction, and the links that exist with human disease, can be rationalized through the fundamental importance of DNA2-dependent RF recovery to genome duplication. Being a crucial player at stalled RFs, DNA2 is a promising target for anti-cancer therapy aimed at eliminating cancer cells by replication-stress overload.

Uncovering an allosteric mode of action for a selective inhibitor of human Bloom syndrome protein.

BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates. Synthetic lethality analysis implicates BLM as a promising target in a range of cancers with defects in the DNA damage response; however, selective small molecule inhibitors of defined mechanism are currently lacking. Here, we identify and characterise a specific inhibitor of BLM's ATPase-coupled DNA helicase activity, by allosteric trapping of a DNA-bound translocation intermediate. Crystallographic structures of BLM-DNA-ADP-inhibitor complexes identify a hitherto unknown interdomain interface, whose opening and closing are integral to translocation of ssDNA, and which provides a highly selective pocket for drug discovery. Comparison with structures of other RECQ helicases provides a model for branch migration of Holliday junctions by BLM.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) for temporization of hemorrhage in adolescent trauma patients.

BACKGROUND/PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has emerged as an alternative technique for traumatic hemorrhage control in the adult population. The purpose of this study is to describe the details of REBOA placement in adolescent trauma patients. METHODS: Patients 18 years of age or less who received REBOA for aortic occlusion (AO) from August 2013 to February 2017 at 2 urban tertiary care centers were included. RESULTS: 7 adolescent trauma patients received REBOA by trauma surgeons for both blunt (n = 4) and penetrating mechanisms (n = 3); mean age was 17 + 1.5 years, mean admission lactate 13.0 + 4.85 mmol/L, and mean Hgb 10.7 + 2.7 g/dL. 3 patients received REBOA through a 12Fr sheath and 4 through a 7Fr sheath. AO occurred mostly at the distal thoracic aorta (Zone I) (85.7%) and also in the distal abdominal aorta (Zone III) (14.3%). 57% of patients were in arrest with ongoing CPR at the time of REBOA. In-hospital mortality was 57%; all of these patients were in arrest at the time of REBOA, had return of spontaneous circulation (ROSC), and survived to the operating room. No complications from REBOA were identified. CONCLUSION: REBOA appears to be feasible for use in adolescents despite their smaller caliber vessels, even with use of a 12Fr sheath. REBOA results in improved physiology and can bridge adolescent trauma patients presenting in extremis to the operating room. TYPE OF STUDY: Treatment/therapeutic study LEVEL OF EVIDENCE: Level IV.

Age-Dependent Association of Occult Hypoperfusion and Outcomes in Trauma.

BACKGROUND: Occult hypoperfusion (OH), or global hypoperfusion with normal vital signs, is a risk factor for poor outcomes in elderly trauma patients. We hypothesized that OH is associated with worse outcomes than shock in both young and elderly trauma patients. METHODS: We conducted a single-center cohort study of adult (16 years or older) trauma patients from 2016 to 2018 with base excess measured on arrival. Perfusion states were defined as shock if heart rate was >120 beats/min or systolic blood pressure was <90 mmHg; OH if base excess was < -2 mmol/L, heart rate was <120 beats/min, and systolic blood pressure was >90 mmHg; and normal for all others. Patients were stratified as young (younger than 55 years) or elderly (55 years or older). Bayesian regression was used to assess the relationship between arrival perfusion state and mortality or serious complication. RESULTS: Of 3,126 included patients, 808 were elderly. Rates of shock (33% and 31%) and OH (25% and 23%) were similar in young and elderly patients, respectively. OH on arrival was associated with higher odds of mortality or serious complication than normal perfusion, regardless of age group. Compared with shock, OH was associated with an odds ratio of 1.21 (95% CI, 0.97 to 1.52, posterior probability 96%) for poor outcomes in elderly patients and an odds ratio of 0.52 (95% CI, 0.42 to 0.65, posterior probability <1%) for poor outcomes in younger patients. Findings were similar on sensitivity analysis, excluding shock patients with base excess ≥ -2 mmol/L. CONCLUSIONS: In elderly but not younger patients, OH is associated with worse outcomes than shock. Although shock parameters might need to be redefined in elderly patients, more attention is necessary for the diagnosis and treatment of all hypoperfused states in this age group.

Outcomes beyond hospital discharge in infants and children with viral meningitis: A systematic review.

Viruses are the commonest cause of childhood meningitis, but outcomes beyond hospital discharge are poorly described. We undertook a systematic literature review of long-term outcomes following paediatric viral meningitis. A search was carried out using MEDLINE, Embase, and Cochrane Review for studies from 1 January 1990 to 31 December 2018. Studies were included where specific outcome measures were available beyond hospital discharge for children <16 years old with viral meningitis. In total, 3588 papers were identified of which 14 were eligible for inclusion. Four studies reported outcomes in children with nonenterovirus 71 meningitis. A US study of 16 cases demonstrated subtle language difficulties at 3-year follow-up in infants in contrast to an Australian study, which revealed no impairment in language. A Fijian study showed that two out of eight cases had sensorineural hearing loss compared with none in a UK cohort of 668 infants. Three studies evaluated outcomes of enterovirus 71 meningitis in China and Taiwan, two showed cases recovered without sequelae, while one demonstrated an increased risk of attention deficit hyperactivity disorder. Two studies including 141 cases of human parechovirus revealed no evidence of neurodevelopmental sequelae. Conversely, an Australian study demonstrated neurodevelopmental sequelae in 11 out of 77 infants with parechovirus meningitis. Most studies identified in this review demonstrated a high proportion of good clinical outcomes following viral meningitis. However, the data are limited, so robustly conducted neurodevelopmental studies are warranted to inform the evidence-based management of viral meningitis beyond hospital discharge.

Antenatal corticosteroid administration in late-preterm gestations: a cost-effectiveness analysis.

Objective: To evaluate whether administration of antenatal late-preterm betamethasone is cost-effective in the immediate neonatal period.Study design: Cost-effectiveness analysis of late-preterm betamethasone administration with a time horizon of 7.5 days was conducted using a health-system perspective. Data for neonatal outcomes, including respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), and hypoglycemia, were from the Antenatal Betamethasone for Women at Risk for Late-Preterm Delivery trial. Cost data were derived from the Healthcare Cost and Utilization Project from the Agency for Health Care Research and Quality, and utilities of neonatal outcomes were from the literature. Outcomes were total costs in 2017 United States dollars and quality-adjusted life years (QALYs) for each individual infant as well as for a theoretical cohort of the 270 000 late-preterm infants born in 2015 in the USA.Results: For an individual patient, compared to withholding betamethasone, administering betamethasone incurred a higher total cost ($6592 versus $6265) and marginally lower QALYs (0.02002 QALYS versus 0.02006 QALYs) within the studied time horizon. For the theoretical cohort of 270 000 patients, administration of betamethasone was $88 million more expensive ($1780 million versus $1692 million) with lower QALYs (5402 QALYs versus 5416 QALYs), compared to withholding betamethasone. For administration of betamethasone to be cost-effective, the rate of hypoglycemia, RDS, or TTN among late-preterm infants receiving betamethasone would need to be less than 20.0, 4.5, and 2.4%, respectively.Conclusion: Administration of betamethasone in the late-preterm period is likely not cost-effective in the short-term.

Epilepsy diagnosis and management of children in Kenya: review of current literature.

Introduction: The growing impact of non-communicable diseases in low- to middle-income countries makes epilepsy a key research priority. We evaluated peer-reviewed published literature on childhood epilepsy specific to Kenya to identify knowledge gaps and inform future priorities. Methodology: A literature search utilizing the terms "epilepsy" OR "seizure" as exploded subject headings AND "Kenya" was conducted. Relevant databases were searched, generating 908 articles. After initial screening to remove duplications, irrelevant articles, and publications older than 15 years, 154 papers remained for full-article review, which identified 35 publications containing relevant information. Data were extracted from these reports on epidemiology, etiology, clinical features, management, and outcomes. Results: The estimated prevalence of lifetime epilepsy in children was 21-41 per 1,000, while the incidence of active convulsive epilepsy was 39-187 cases per 100,000 children per year. The incidence of acute seizures was 312-879 per 100,000 children per year and neonatal seizures 3,950 per 100,000 live births per year. Common risk factors for both epilepsy and acute seizures included adverse perinatal events, meningitis, malaria, febrile seizures, and family history of epilepsy. Electroencephalography abnormalities were documented in 20%-41% and neurocognitive comorbidities in more than half. Mortality in children admitted with acute seizures was 3%-6%, and neurological sequelae were identified in 31% following convulsive status epilepticus. Only 7%-29% children with epilepsy were on antiseizure medication. Conclusion: Active convulsive epilepsy is a common condition among Kenyan children, remains largely untreated, and leads to extremely poor outcomes. The high proportion of epilepsy attributable to preventable causes, in particular neonatal morbidity, contributes significantly to the lifetime burden of the condition. This review reaffirms the ongoing need for better public awareness of epilepsy as a treatable disease and for national-level action that targets both prevention and management.

Trends in Treatment of T1N0 Esophageal Cancer.

OBJECTIVE: The purpose of this study was to explore nationwide trends in treatment and outcomes of T1N0 esophageal cancer. BACKGROUND: Endoscopic treatment has become an accepted option for early-stage esophageal cancer, but nationwide utilization rates and outcomes are unknown. METHODS: T1N0 esophageal cancers were identified in the National Cancer Database from 2004 to 2014. We assessed trends in treatment; compared endoscopic therapy, esophagectomy, chemoradiation, and no treatment; and performed a subgroup analysis of T1a and T1b patients from 2010 to 2014 (AJCC 7). RESULTS: A total of 12,383 patients with clinical T1N0 esophageal cancer were analyzed. Over a decade, use of endoscopic therapy increased from 12.7% to 33.6%, whereas chemoradiation and esophagectomy decreased, P < 0.01. The rise in endoscopic treatment of T1a disease from 42.7% to 50.6% was accompanied by a decrease in esophagectomies from 21.7% to 12.8% (P < 0.01). For T1b disease, the rise in endoscopic treatment from 16.9% to 25.1% (P = 0.03) was accompanied by decreases in no treatment and chemoradiation, whereas the rate of esophagectomies remained approximately 50%. Unadjusted median survival was longer for patients undergoing resection: esophagectomy, 98.6 months; endoscopic therapy, 77.7 months; chemoradiation, 17.3 months; no treatment, 8.2 months; P < 0.01. Risk-adjusted Cox modeling showed esophagectomy was associated with improved survival [hazard ratio (HR): 0.85], and chemoradiation (HR: 1.79) and no treatment (HR: 3.57) with decreased survival, compared to endoscopic therapy (P < 0.01). CONCLUSIONS: Use of endoscopic therapy for T1 esophageal cancer has increased significantly: for T1a, as an alternative to esophagectomy; and for T1b, as an alternative to no treatment or chemoradiation. Despite upfront risks, long-term survival is highest for patients who can undergo esophagectomy.

Imaging Surveillance for Surgically Resected Stage I Non-Small Cell Lung Cancer: Is More Always Better?

Objective: Routine surveillance imaging for patients with resected non-small cell lung cancer is standard for the detection of disease recurrence and new primary lung cancers. However, surveillance intensity varies widely in practice, and its impact on long-term outcomes is poorly understood. We hypothesized that surveillance intensity was not associated with 5-year overall survival in patients with resected stage I non-small cell lung cancer. Additionally, we examined patterns of recurrence and new primary lung cancer development. Methods: Cancer registrars at Commission on Cancer accredited institutions re-abstracted records to augment National Cancer Database patient data with information on comorbidities, imaging surveillance including intent and result of imaging, and recurrence (2007-2012). Pathologic stage I non-small cell lung cancer patients undergoing computed-tomography surveillance were placed into three imaging surveillance groups based on clinical practice guidelines: high intensity (3 month), moderate intensity (6 month), and low intensity (annual). Kaplan Meier analysis and Cox regression were used to compare overall survival among the three surveillance groups. Results: 2442 patients were identified, with 805 (33%), 1216 (50%), and 421 (17%) patients in the high, moderate, and low surveillance intensity groups, respectively. Five-year overall survival was similar between intensity groups (p=0.547). Surveillance on asymptomatic patients detected 210 (63%) cases of locoregional recurrences and 128 (72%) cases of new primary lung cancer. Conclusions: In a unique national dataset of long-term outcomes for stage I non-small cell lung cancer, surveillance intensity was not associated with 5-year overall survival.

Comparison of Antimicrobial Treatments Applied via Conventional or Handheld Electrostatic Spray To Reduce Shiga Toxin-Producing Escherichia coli on Chilled Beef Outside Rounds.

HIGHLIGHTS: We found no advantage in the use of electrostatic spray to reduce STEC8 on cold beef. Greatest reductions in STEC8 were achieved by lactic acid with conventional spray. Lauric arginate ester was the second best antimicrobial agent at reducing STEC8. Lactic acid reduced pH on the beef surface significantly. There was no effect of antimicrobial solution on temperature increase on beef outside rounds.

Induction Radiation Therapy for Esophageal Cancer: Does Dose Affect Outcomes?

BACKGROUND: Wide variation is seen in the dosage of preoperative induction radiation therapy for esophageal cancer. We investigated associations between outcomes after esophagectomy and dosage of induction radiation therapy. METHODS: Patients undergoing induction radiation therapy (30 to 70 Gy), followed by esophagectomy, were identified from the National Cancer Database and classified as low (<40 Gy), standard (40 to 50.4 Gy), and high dose (>50.4 Gy). Perioperative outcomes and overall survival were compared. Subgroup analysis compared two common dosages: 45 Gy and 50.4 Gy. RESULTS: From 2004 to 2014, 10,738 patients (84.7%) received standard-dose radiation, increasing from 69.7% in 2004 to 93.6% in 2014 (p < 0.001), 1,329 (10.5%) received low-dose radiation, and 608 (4.8%) received high-dose radiation. Higher rates of pathologic complete response (pCR; low: 11.7%, standard: 16.2%, high: 21.0%; p < 0.001) and downstaging (low: 52.0%, standard: 56.4%, high: 63.1%, p = 0.001) were observed as the dosage increased. On multivariable analysis, compared with standard-dose, high-dose radiation was associated with higher 30-day mortality (odds ratio [OR], 2.11; p < 0.001) without a higher likelihood of downstaging or pCR. Low-dose radiation was associated with lower likelihood of downstaging (OR, 0.85; p = 0.04) and pCR (OR, 0.67; p < 0.001) without lowering the risk of 30-day mortality. The dose of 50.4 Gy was associated with higher likelihood of pCR (OR, 1.12; p = 0.04), without affecting 30-day mortality, compared with 45 Gy. CONCLUSIONS: High-dose induction radiation (>50.4 Gy) is associated with increased perioperative death after esophagectomy, without a significant improvement in tumor response. Low-dose radiation (<30 Gy) is associated with worse tumor response without a lower risk of perioperative death. Within standard dosages, 50.4 Gy is associated with higher likelihood of pCR without adversely affecting perioperative mortality compared with 45 Gy.

Postoperative Pneumonia Prevention in Pulmonary Resections: A Feasibility Pilot Study.

BACKGROUND: Pneumonia after pulmonary resection occurs in 5% to 12% of patients and causes substantial morbidity. Oral hygiene regimens lower the incidence of ventilator-associated pneumonias; however, the impact in patients undergoing elective pulmonary resection is unknown. We conducted a prospective pilot study to assess the feasibility of an oral hygiene intervention in this patient cohort. METHODS: Patients undergoing elective pulmonary resection were prospectively enrolled in a single-arm interventional study with time-matched controls. Participants were asked to brush their teeth with 0.12% chlorhexidine three times daily for 5 days before their operations and 5 days or until the time of discharge after their operations. Patients were eligible if they had known or suspected lung cancer and were undergoing (1) any anatomic lung resection or (2) a wedge resection with forced expiratory volume in 1 second or diffusing capacity of lung for carbon monoxide less than 50% predicted. RESULTS: Sixty-two patients were enrolled in the pilot intervention group and compared with a contemporaneous cohort of 611 patients who met surgical inclusion criteria. Preoperative adherence to the chlorhexidine toothbrushing regimen was high: median 100% (interquartile range: 87% to 100%). Postoperatively, 80% of patients continued toothbrushing, whereas 20% declined further participation. Among those who participated postoperatively, median adherence was 86% (interquartile range: 53% to 100%). There was a trend toward reduction in postoperative pneumonia: 1.6% (1 of 62) in the intervention cohort versus 4.9% (30 of 611) in the time-matched cohort (p = 0.35). The number needed to treat to prevent one case of pneumonia was 30 patients. CONCLUSIONS: This pilot study demonstrated patients can comply with an inexpensive perioperative oral hygiene regimen that may be promising for reducing morbidity (Clinical Trials Registry: NCT01446874).

Enhanced Recovery After Surgery (ERAS) in Thoracic Surgery.

Enhanced Recovery After Surgery (ERAS) pathways are protocolled collections of perioperative decisions designed to improve outcomes that are becoming increasingly popular across surgical subspecialties. In this article, we review 5 recent manuscripts focused on ERAS for elective pulmonary resections, focusing on the components of the pathways and the resultant outcomes. Overall, we observed that ERAS protocols can be safely implemented without increasing hospital readmission or mortality. The benefit is largely seen in shortened length of stay, though there is some promise for decreasing rates of important perioperative complications, especially in patients receiving thoracotomies. More research is needed into the specific elements that impact care, as well as the effect on overall patient experience.

UCHL3 Regulates Topoisomerase-Induced Chromosomal Break Repair by Controlling TDP1 Proteostasis.

Genomic damage can feature DNA-protein crosslinks whereby their acute accumulation is utilized to treat cancer and progressive accumulation causes neurodegeneration. This is typified by tyrosyl DNA phosphodiesterase 1 (TDP1), which repairs topoisomerase-mediated chromosomal breaks. Although TDP1 levels vary in multiple clinical settings, the mechanism underpinning this variation is unknown. We reveal that TDP1 is controlled by ubiquitylation and identify UCHL3 as the deubiquitylase that controls TDP1 proteostasis. Depletion of UCHL3 increases TDP1 ubiquitylation and turnover rate and sensitizes cells to TOP1 poisons. Overexpression of UCHL3, but not a catalytically inactive mutant, suppresses TDP1 ubiquitylation and turnover rate. TDP1 overexpression in the topoisomerase therapy-resistant rhabdomyosarcoma is driven by UCHL3 overexpression. In contrast, UCHL3 is downregulated in spinocerebellar ataxia with axonal neuropathy (SCAN1), causing elevated levels of TDP1 ubiquitylation and faster turnover rate. These data establish UCHL3 as a regulator of TDP1 proteostasis and, consequently, a fine-tuner of protein-linked DNA break repair.