Citations

ObjectiveThis scoping review aims to explore the current body of literature to characterize how short‐term surgical trips (STSTs) in Otolaryngology‐Head and Neck Surgery (OtoHNS) contribute to surgical, educational, and sustainability‐based outcomes in low‐ and middle‐income countries (LMICs). We aim to use these data to synthesize aspects of STSTs that are successful with the hopes of shaping future global efforts.Data SourcesData sources included Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus.Review MethodsA comprehensive search was conducted on several databases from inception to October 14, 2021. We included primary studies exploring any surgical or educational outcomes of global short‐term surgical endeavors within LMICs. Data were then extracted to evaluate the heterogenous body of literature that exists, characterizing the surgical, educational, and sustainability‐based outcomes.ResultsForty‐Seven studies were included in the final analysis. Most publications were focused on surgical interventions (39 of 47; 82.9%); 13 (27.7%) studies included education as the primary aim and 12 (25.5%) considered sustainability a significant aim. Of the 94 first and last authors, there were zero first authors and only one last author with an LMIC affiliation. Twenty‐six studies (55%) mentioned that any patients were seen in follow‐up, ranging from one day to five years.ConclusionOur scoping review demonstrates that most STSTs have focused primarily on surgical procedures with a lack of appropriate long‐term follow‐up. However, the available outcome‐based information presented helps identify factors that characterize a strong short‐term global surgical program.Level of EvidenceNA Laryngoscope, 134:32–39, 2024

Abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

Mortality reviews are intended to produce transparent, non-punitive personal and organisational learning that leads to systematic improvement in care. Mayo Clinic has a well-established care review process that has accomplished that objective within our system. The establishment of a new hospital, a joint venture between Mayo Clinic and Sheikh Shakhbout Medical City (SSMC) in Abu Dhabi, provided a unique opportunity to share this care review process internationally. During a baseline measurement period, only 78.3% of mortality reviews at SSMC were completed within 45 days, 16.7 percentage points below the target of 95%. A collaboration between SSMC and Mayo Clinic aimed to accelerate the design and implementation of a care review process system. Collaboration was constrained by travel restrictions imposed by COVID-19, language barriers, legal privacy concerns, and differing electronic health records. Mayo Clinic facilitated a 12-week virtual engagement with SSMC using weekly video meetings, education and training regarding Mayo Clinic’s care review process. The engagement led to implementation of weekly mortality review huddles, restructuring of the mortality review committee to be multidisciplinary, use of a standardised taxonomy to characterise opportunities to improve care and creation of an education/communication plan regarding identified improvement opportunities using change management strategies. After the care review process for mortality reviews was instituted, SSMC achieved and sustained a target of 100% of mortality reviews completed within 45 days. The new process resulted in improved mortality review indicators and provided quality feedback to staff with engagement in performance improvement efforts. A virtual collaboration led to successful implementation of a care review process and substantial gains in the effectiveness of the quality programme at SSMC. This could serve as a model to assist other organisations, even if in-person engagement is hindered.

Abstract Cardiovascular disease is a major cause of mortality among oncologic patients. As cancer therapies continue to evolve and advance, cancer survival rates have been increasing and so has the burden of cardiovascular disease within this population. For this reason, cardio-oncology plays an important role in promoting multidisciplinary care with the primary care provider, oncology, and cardiology. In this review, we discuss the roles of different providers, strategies to monitor patients receiving cardiotoxic therapies, and summarize cancer therapy class-specific toxicities. Continued collaboration among providers and ongoing research related to cardiotoxic cancer therapies will enable patients to receive maximal, evidence-based, comprehensive care.

AbstractThe current study was aimed to investigate the beneficial effect of sumatriptan, a 5‐hydroxytryptamine 1B/1D (5HT1B/1D) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/1D receptors and suppressing pro‐inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5 ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1 mg/kg, i.p) 30 min before gastric ulcer induction. GR‐127935 (0.01 mg/kg, i.p, a selective 5HT1B/1D antagonist) was administered 30 min before sumatriptan (0.1 mg/kg) injection. Macroscopic assessments (J‐score), ELISA analysis of tumour necrosis factor‐alpha (TNF‐α) and interleukin‐1beta (IL‐1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J‐score, TNF‐α, IL‐1β and microscopic features. Sumatriptan (0.1 mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J‐score, TNF‐α, IL‐1β and microscopic lesions. Concurrent administration of GR‐127935 (0.01 mg/kg) with sumatriptan (0.1 mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin‐, WRS‐ and ethanol‐induced gastric damage in rats via the possible involvement of the 5HT1B/1D receptors.

ABSTRACT Triple negative breast cancer (TNBC) continues to be the subtype of breast cancer with the highest rates of recurrence and mortality. The lack of expression of targetable proteins such as the estrogen receptor and absence of HER2 amplification have made relying on cytotoxic chemotherapy necessary for decades. In the operable setting, efforts to improve outcomes have focused on escalation of systemic therapy and a shift toward preoperative delivery followed by a response adapted approach to postoperative systemic therapy. An improved understanding of tumor biology has resulted in the identification of subsets of patients with specific molecular features, leading to testing and approval of multiple new targeted therapies for this disease. Furthermore, advances in drug development have led to the approval of antibody-drug conjugates that are redefining classification schemes for breast cancer. This review focuses on the modern management of TNBC, with particular focus on recent updates in the treatment of operable disease, and an overview of the most recent promising advances in the therapeutic landscape of metastatic disease. It discusses the practical challenges and unanswered questions resulting from the approval of neoadjuvant immunotherapy and shares an approach in the clinic on topics for which evidence is lacking. In addition, it provides a glimpse into the future, highlighting challenges and opportunities for biomarker based right-sizing of preoperative therapy, refining evaluation of response to preoperative therapy after surgery, early diagnosis and detection of relapse, and areas of needed research for metastatic TNBC.

Abstract Background Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. Methods Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. Results Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. Conclusions BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

AbstractIntroduction/AimsMost persons with amyotrophic lateral sclerosis (ALS) live at home with support of family caregivers, with escalating complexity of care over the trajectory of the disease requiring resources and support to mitigate negative physical, social, and emotional outcomes.MethodsThis scoping review identifies the home health/home care needs of persons with ALS and their caregivers as a basis for creating a home health medical standard. We used the PRISMA Extension for Scoping Reviews (PRISMA‐ScR) to examine studies describing home care needs published between 2011 and 2021.ResultsOur search yielded 481 articles, of which 44 were included with a total of 3592 (9–273) participants. Most studies used a cross‐sectional design and 20 (45%) were rated as high quality. We grouped the needs identified as emotional/psychological, assistive devices and technology, information and education, and human resources and professional services. Most studies demonstrated persistent unmet needs and that available interventions were helpful while needs generally were not met proactively, despite the predictable trajectory.DiscussionThis review describes biopsychosocial and equipment interventions over the trajectory of ALS with implications for anticipatory planning by clinicians, as well as policy for coverage of necessary services and supports. Interdisciplinary expert teams could develop consensus around needs across the trajectory and recommended services and supports. To make knowledge more accessible, encourage availability of services, and clarify the need for coverage of services, we aim to develop an expert consensus‐based ALS home health medical standard guidance document in collaboration with the American Association of Neuromuscular and Electrodiagnostic Medicine.

AbstractIntraneuronal accumulation of misfolded α-synuclein is the pathological hallmark of Parkinson’s disease and dementia with Lewy bodies, often co-occurring with variable degrees of Alzheimer’s disease related neuropathology. Genetic association studies have successfully identified common variants associated with disease risk and phenotypic traits in Lewy body disease, yet little is known about the genetic contribution to neuropathological heterogeneity.Using summary statistics from Parkinson’s disease and Alzheimer’s disease genome-wide association studies, we calculated polygenic risk scores and investigated the relationship with Lewy, amyloid-β and tau pathology. Associations were nominated in neuropathologically defined samples with Lewy body disease from the Netherlands Brain Bank (n = 217) and followed up in an independent sample series from the Mayo Clinic Brain Bank (n = 394). We also generated stratified polygenic risk scores based on single-nucleotide polymorphisms annotated to eight functional pathways or cell types previously implicated in Parkinson’s disease and assessed for association with Lewy pathology in subgroups with and without significant Alzheimer’s disease co-pathology.In an ordinal logistic regression model, the Alzheimer’s disease polygenic risk score was associated with concomitant amyloid-β and tau pathology in both cohorts. Moreover, both cohorts showed a significant association between lysosomal pathway polygenic risk and Lewy pathology, which was more consistent than the association with a general Parkinson’s disease risk score and specific to the subset of samples without significant concomitant Alzheimer’s disease related neuropathology.Our findings provide proof of principle that the specific risk alleles a patient carries for Parkinson’s and Alzheimer’s disease also influence key aspects of the underlying neuropathology in Lewy body disease. The interrelations between genetic architecture and neuropathology are complex, as our results implicate lysosomal risk loci specifically in the subset of samples without Alzheimer’s disease co-pathology. Our findings hold promise that genetic profiling may help predict the vulnerability to specific neuropathologies in Lewy body disease, with potential relevance for the further development of precision medicine in these disorders.

Abstract Patients with blood culture-negative endocarditis due to Bartonella infection frequently presented with fever, cytopenias, kidney failure, and positive PR3-ANCA. Bartonella IgG titers were variable. Patients commonly underwent surgery with overall low mortality.