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1.
J Viral Hepat ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225298

ABSTRACT

Hepatitis A is a vaccine-preventable disease that typically causes mild illness. Hepatitis A outbreaks associated with person-to-person transmission have been widespread in the United States since 2016. We used public-use US Multiple Cause of Death data to compare characteristics and listed comorbidities among decedents with hepatitis A-listed deaths during non-outbreak (2011-2015) and outbreak (2017-2021) periods and assessed the median age at death among decedents with and without hepatitis A-listed deaths during the outbreak period. From the non-outbreak period to the outbreak period, hepatitis A-listed deaths more than doubled (from 369 to 801), while the hepatitis A-listed age-adjusted mortality rate increased 150% (p < 0.001). When compared with the non-outbreak period, hepatitis A-listed decedents during the outbreak period were more frequently male, aged 18-49 years, non-Hispanic White, died in an inpatient setting, and had hepatitis A listed as their underlying cause of death. The median age at death for hepatitis A-listed decedents was significantly younger during the outbreak period overall and among females (62 and 66 years, respectively) compared with the non-outbreak period (64 and 72 years, respectively, p < 0.001). During the outbreak period, median age at death for hepatitis A-listed decedents was 14 years younger than decedents without hepatitis A listed. Compared with the general US population, decedents with hepatitis A listed on the death certificate died at younger ages during 2017-2021. Efforts are needed to improve hepatitis A vaccination coverage among adults recommended for hepatitis A vaccination to prevent additional premature hepatitis A deaths.

2.
Ned Tijdschr Geneeskd ; 1682024 Aug 22.
Article in Dutch | MEDLINE | ID: mdl-39228326

ABSTRACT

CRISPR-Cas technology is a revolutionary technology to modify DNA sequences. Owing to its effectiveness and accuracy, CRISPR-Cas holds important promises for 'genetic therapy' for various hereditary disorders. CRISPR-Cas enables researchers to modify specific parts of the genome with unprecedented precision, which, in specific cases, can be applied to correct disease-causing DNA variants. However, several important barriers are complicating the clinical implementation trajectory. There are for example concerns regarding the safety, effectiveness and ethical justification. Nevertheless, as CRISPR-Cas becomes more widely known, doctors and healthcare providers are expected to be well aware of the developments surrounding CRISPR-Cas therapy. Professional expertise and clear communication about the possibilities and limitations to patients with genetic disorders are essential, partly to avoid making promises that are unrealistic in the short term. Altogether, geneticists, medical centers and regulators are now facing the challenges to start translating CRISPR-Cas technology into clinical practice, in an effective and ethical manner.


Subject(s)
CRISPR-Cas Systems , Genetic Therapy , Humans , Genetic Therapy/methods , Genetic Therapy/ethics , Genetic Diseases, Inborn/therapy
3.
Laryngoscope ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39162308

ABSTRACT

OBJECTIVE: To evaluate national trends in racial disparities for patients undergoing head and neck reconstructive surgery. METHODS: Retrospective analysis using the 2008 to 2021 American College of Surgeons National Surgical Quality Improvement Program database. Patients receiving microvascular free tissue transfer were eligible for inclusion. Pediatric patients and those treated by non-otolaryngologists were excluded. Outcomes were analyzed with univariate and multivariable models. RESULTS: A total of 5831 head and neck free flap cases were analyzed, 4869 (83.5%) were White, 560 (9.6%) were Black or African American, and 402 (6.9%) were Asian, Native American, or other groups (ANAOG). The proportion of Black or African American patients and ANAOG patients undergoing free tissue transfer increased significantly over the time period (p = 0.047 and p = 0.010, respectively). However, there was a downtrend that started around 2017. In a multivariable model, Black or African American race was not associated with readmission (OR = 0.99 [95% CI 0.74, 1.31], p > 0.05), returning to the operating room (OR = 1.20 [95% CI 0.96, 1.49], p > 0.05), or any post-operative complication (OR = 0.83 [95% CI 0.68, 1.01], p > 0.05). There were also no significant associations found in the ANAOG population on multivariate analysis (p > 0.05 for all). CONCLUSION: The percentage of free tissue transfer performed in patients from minority backgrounds with head and neck cancer has been increasing in the United States. Outcomes after head and neck microvascular reconstruction are similar when stratified by race. However, racial disparities remain and further work is necessary to reduce these disparities. LEVEL OF EVIDENCE: Level IV Laryngoscope, 2024.

4.
ACS Catal ; 14(15): 11545-11553, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39114089

ABSTRACT

Amphiphilic Janus silica particles, tunable with oleophobic-oleophilic properties and low fluorine content (8 wt % F), exhibited prominent foamability for a variety of aromatic alcohols at low particle concentrations (<1 wt %) compared to randomly functionalized silica particles. When selectively loaded with Pd nanoparticles on the oleophilic hemisphere, the particles displayed more than a 2-fold increase in catalytic activity for the aerobic oxidation of benzyl alcohol compared to nonfoam bulk catalysis under ambient O2 pressure. The particles were conveniently recycled with high foamability and catalytic activity maintained for at least five consecutive runs.

6.
Dermatol Online J ; 30(3)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-39090035

ABSTRACT

A simple and rapid method that is not based on race and ethnicity for classifying people with skin of color is of paramount importance in dermatology. The currently used Fitzpatrick classification of sun-reactive skin types is inadequate. Newer scales that have been used in immigration surveys and sociology studies are not applicable in the office setting. A new, non-racial and non-ethnic, colorimetric scale for skin of color has recently been proposed that is simple to perform. The scale has five colors: very light beige (skin color type 1), light brown (skin color type 2), medium brown (skin color type 3), dark brown (skin color type 4) and very dark brown (skin color type 5); an individual with white skin, such as in albinism, would have a skin color type 0 in this classification. In conclusion, the colorimetric scale enables the rapid classification of individuals with skin of color and allows for accurate assessment of skin cancer risk, more appropriate management of cosmetic dermatologic procedures and aesthetic devices, and enhanced ability for focused counseling regarding hair products, skin care interventions, and color-targeted makeup based on the person's skin tone.


Subject(s)
Colorimetry , Skin Pigmentation , Humans , Skin Neoplasms/diagnosis , Dermatology
7.
JACC Heart Fail ; 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39093256

ABSTRACT

Obesity is a common comorbidity among patients with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), with the strongest pathophysiologic link of obesity being seen for HFpEF. Lifestyle measures are the cornerstone of weight loss management, but sustainability is a challenge, and there are limited efficacy data in the heart failure (HF) population. Bariatric surgery has moderate efficacy and safety data for patients with preoperative HF or left ventricular dysfunction and has been associated with reductions in HF hospitalizations and medium-term mortality. Antiobesity medications historically carried concerns for cardiovascular adverse effects, but the safety and weight loss efficacy seen in general population trials of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide/GLP-1 agonists are highly encouraging. Although there are safety concerns regarding GLP-1 agonists in advanced HFrEF, trials of the GLP-1 agonist semaglutide for treatment of obesity have confirmed safety and efficacy in patients with HFpEF.

8.
J Adv Res ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39142441

ABSTRACT

INTRODUCTION: Endometriosis is a chronic inflammatory disease that affects âˆ¼10 % of women. A significant fraction of patients experience limited or no efficacy with current therapies. Tissue adjacent to endometriosis lesions often exhibits increased neurite and vascular density, suggesting that disease pathology involves neurotrophic activity and angiogenesis. OBJECTIVES: We aim to evaluate the potential for key tyrosine-kinase-receptor-coupled neurotrophic molecules to contribute to endometriosis-associated pain in mice. METHODS: Peritoneal fluid was collected from endometriosis patients undergoing surgery and the levels of NGF and VEGFR1 regulators (VEGFA, VEGFB, PLGF, and sVEGFR1) were quantified by ELISA. VEGFR1 regulator concentrations were used to calculate VEGFR1 occupancy. We used genetic depletion, neutralizing antibodies, and pharmacological approaches to specifically block neurotrophic ligands (NGF or BDNF) or receptors (VEGFR1, TRKs) in a murine model of endometriosis-associated pain. Endometriosis-associated pain was measured using von Frey filaments, quantification of spontaneous abdominal pain-related behavior, and thermal discomfort. Disease parameters were evaluated by lesion size and prevalence. To evaluate potential toxicity, we measured the effect of entrectinib dose and schedule on body weight, liver and kidney function, and bone structure (via micro-CT). RESULTS: We found that entrectinib (pan-Trk inhibitor) or anti-NGF treatments reduced evoked pain, spontaneous pain, and thermal discomfort. In contrast, even though calculated receptor occupancy revealed that VEGFR1 agonist levels are sufficient to support signaling, blocking VEGFR1 via antibody or tamoxifen-induced knockout did not reduce pain or lesion size in mice. Targeting BDNF-TrkB with an anti-BDNF antibody also proved ineffective. Notably, changing dosing schedule to once weekly eliminated entrectinib-induced bone-loss without decreasing efficacy against pain. CONCLUSIONS: This suggests NGF-TrkA signaling, but not BDNF-TrkB or VEGF-VEGFR1, mediates endometriosis-associated pain. Moreover, entrectinib blocks endometriosis-associated pain and reduces lesion sizes. Our results also indicated that entrectinib-like molecules are promising candidates for endometriosis treatment.

9.
JAMA Surg ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39167382

ABSTRACT

Importance: The 1-year results of the SECURE trial, a randomized trial comparing a restrictive strategy vs usual care for select patients with symptomatic cholelithiasis for cholecystectomy, resulted in a significantly lower operation rate after restrictive strategy. However, a restrictive strategy did not result in more pain-free patients at 1 year. Objective: To gauge pain level and determine the proportion of pain-free patients, operation rate, and biliary and surgical complications at the 5-year follow-up. Design, Setting, and Participants: This randomized clinical trial was a multicenter, parallel-arm, noninferiority, prospective study. Between February 2014 and April 2017, patients from 24 hospitals with symptomatic, uncomplicated cholelithiasis were included. Uncomplicated cholelithiasis was defined as gallstone disease without signs of complicated cholelithiasis, ie, biliary pancreatitis, cholangitis, common bile duct stones, or cholecystitis. Follow-up data for this analysis were collected by telephone from July 11, 2019, to September 23, 2023. Interventions: Patients were randomized (1:1) to receive usual care or a restrictive strategy with stepwise selection for cholecystectomy. Main Outcomes and Measures: The primary, noninferiority end point was proportion of patients who were pain free as evaluated by Izbicki pain score at the 5-year follow-up. A 5% noninferiority margin was chosen. The secondary end points included cholecystectomy rates, biliary and surgical complications, and patient satisfaction. Results: Among 1067 patients, the median (IQR) age was 49.0 years (38.0-59.0 years); 786 (73.7%) were female, and 281 (26.3%) were male. At the 5-year follow-up, 228 of 363 patients (62.8%) were pain free in the usual care group, compared with 216 of 353 patients (61.2%) in restrictive strategy group (difference, 1.6%; 1-sided 95% lower confidence limit, -7.6%; noninferiority P = .18). After cholecystectomy, 187 of 294 patients (63.6%) in the usual care group and 160 of 254 patients (63.0%) in the restrictive strategy group were pain free, respectively (P = .88). The restrictive care strategy was associated with 387 of 529 cholecystectomies (73.2%) compared with 437 of 536 in the usual care group (81.5%; 8.3% difference; P = .001). No differences between groups were observed in biliary and surgical complications or in patient satisfaction. Conclusions and Relevance: In the long-term, a restrictive strategy results in a significant but small reduction in operation rate compared with usual care and is not associated with increased biliary and surgical complications. However, regardless of the strategy, only two-third of patients were pain free. Further criteria for selecting patients with uncomplicated cholelithiasis for cholecystectomy and rethinking laparoscopic cholecystectomy as treatment is needed to improve patient-reported outcomes. Trial Registration: CCMO Identifier: NTR4022.

10.
Surg Obes Relat Dis ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39129110

ABSTRACT

BACKGROUND: Endometrial cancer (EC) is the strongest obesity-associated malignancy and the fastest-growing cancer in young women. Early identification of EC and other endometrial pathology (malignant and nonmalignant) in women with severe obesity may improve treatment options and uterine preservation. Screening for endometrial pathology using abnormal or postmenopausal uterine bleeding (APUB) as a surrogate in women pursuing metabolic/bariatric surgery may be clinically beneficial, but data supporting this effort are limited. OBJECTIVE: To develop and institute a screening program for APUB as a surrogate for endometrial pathology in bariatric surgery candidates. SETTING: Two, academic metabolic/bariatric surgery programs in Louisiana, United States. METHODS: The Modified SAMANTA is a 10-item questionnaire that was implemented to identify patients with APUB, specifically combining tools designed to identify anovulatory/postmenopausal and heavy menstrual bleeding. Demographic (age, race), body mass index, and questionnaire data were analyzed with respect to positive screening using data from March 2021 through May 2023. RESULTS: Of 1371 eligible women presenting for surgical evaluation, 664 (48.4%) positive screens were identified and referred for gynecologic evaluation to rule out endometrial hyperplasia/cancer or other endometrial pathology. The likelihood of positive screening for APUB was associated with increasing BMI (P = .001) and Black/African American race (P = .003), as well as increasing SAMANTA score (P < .001). In contrast, risk of positive screening was negatively associated with increasing age (P < .001). CONCLUSIONS: Women presenting for metabolic/bariatric surgery have a high prevalence of APUB and, given this dysfunctional bleeding and concurrent obesity, are at greater risk for underlying EC. Potential risk factors for APUB, given their associations with screening positive, include increased body mass index, younger age, and Black/African American race. Standardized screening with appropriate gynecologic referral should be a routine part of the overall evaluation for women with severe obesity.

11.
Surg Obes Relat Dis ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39153899

ABSTRACT

BACKGROUND: Early small bowel obstruction (eSBO) (within 30-days) is a rare but important complication that is associated with high rates of morbidity, including readmission, reintervention, and reoperation. OBJECTIVES: To identify patient-specific and operation-specific characteristics that predispose patients to eSBO and to identify at-risk individuals preoperatively. SETTING: 2015-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP). METHODS: Utilizing the 2015-2021 MBSAQIP PUF, 1,016,484 records were analyzed. Pediatric, revisional, open-conversion, and cases with incomplete data in sex, body mass index, operative-time, 30-day-follow-up variables were excluded. Case details were compared using Fisher's exact & Wilcoxon -Mann -Whitney tests to identify at-risk patients. The likelihood of eSBO was modeled with rare event logistic regression. RESULTS: Incidence of eSBO was .40%. Of the 4103 occurrences of eSBO, RYGB (Roux-en-Y gastric bypass), SG (sleeve gastrectomy), and DS (duodenal switch) accounted for 79.4%, 19.3%, and 1.3%, respectively. Many patient-specific characteristics were significantly associated with eSBO. History of prior foregut surgery, a non-metabolic surgery trained operator, and longer operative times were all associated with increased eSBO (P < .0001). While simultaneously controlling for these factors, eSBO remained higher in DS (OR 9.55, P < .0001) and RYGB (OR 5.18, P < .0001) compared to SG. Increased length of operation (OR 1.03, P < .0001) and non -MS-trained operators (OR 1.33, P < .0001) remained highly significant. Male-sex (OR .70, P < .0001) and diabetes (OR .78, P < .0001) were both protective. CONCLUSIONS: In the largest analysis to date, eSBO remains a rare event. RYGB accounts for the largest proportion of eSBO, however, DS has a higher risk adjusted rate of eSBO.

12.
Neurosurgery ; 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39185896

ABSTRACT

Advocacy, one of the five domains of global neurosurgery, represents a powerful avenue to influence public policy to expand access to safe, timely, and affordable neurosurgical care. In this manuscript, we characterize advocacy in global neurosurgery, describe specific neurosurgeon-led initiatives, and delineate how neurosurgeons can become involved in global neurosurgery advocacy efforts. Advocacy in global neurosurgery involves working together in organized neurosurgery with organizations focused on clinical provisions, training, and policy initiatives. Effective advocacy uses a data-driven approach with myriad facilitators, including collaboration and approach strategies for sharing information and a variety of contextual, ideological, and practical barriers. The main action fronts for global neurosurgery include identifying needs, broadening access, and assuring quality. Neurosurgery-led initiatives transforming public policy have occurred on regional and global scales and accelerated since 2019. Folate fortification of staple foods to prevent neural tube defects represents a recent and notably successful area of advocacy and remains in progress. Neurosurgeons who aspire to become involved in advocacy efforts must obtain competencies and skills distinct from, yet complementary to, the traditional neurosurgical training curriculum.

13.
HPB (Oxford) ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39191539

ABSTRACT

BACKGROUND: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally. METHOD: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts. RESULTS: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC. CONCLUSIONS: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.

14.
Psychiatry Res ; 340: 116123, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39146617

ABSTRACT

BACKGROUND: Chronotype is associated with circadian rhythmicity, a core etiological factor underlying bipolar disorder (BD). Given converging evidence linking late chronotype with poor mental health, the goal of the present study was to examine chronotype (in)stability and its relation to mood symptoms over time. METHODS: Participants with BD I (n = 271), BD II (n = 88), and healthy controls (n = 217) were included (follow-upM=10 years, Range=5-15) from the Prechter Longitudinal Study. Chronotype category and midpoint of sleep, corrected for weekend sleep-debt (MSFsc), were measured with the Munich Chronotype Questionnaire administered every 12 months alongside clinician-rated mood and medication usage. Self-reported mood was measured bi-monthly. Mixed effects models tested whether mood was associated with (in)stability of chronotype category and MSFsc covarying for age, sex, age, and medication. RESULTS: Compared to HC, individuals with BD self-reported having a later chronotype that significantly fluctuated over time. Individuals with BDI showed significantly less stability in MSFsc than HC. Anticonvulsant use was associated with more stability in MSFsc whereas antidepressant use was associated with less stability in MSFsc. CONCLUSIONS: In a large longitudinal cohort, individuals with BD displayed significant instability in circadian typology. Psychopharmacology in BD may have differential impacts on circadian timing that is important to monitor.


Subject(s)
Affect , Bipolar Disorder , Circadian Rhythm , Humans , Bipolar Disorder/physiopathology , Bipolar Disorder/drug therapy , Female , Male , Adult , Longitudinal Studies , Circadian Rhythm/physiology , Affect/physiology , Affect/drug effects , Middle Aged , Sleep/physiology , Sleep/drug effects , Young Adult , Chronotype
15.
Adv Sci (Weinh) ; : e2406255, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39206725

ABSTRACT

The introduction of porosity into ferroelectric ceramics can decrease the effective permittivity, thereby enhancing the open circuit voltage and electrical energy generated by the direct piezoelectric effect. However, the decrease in the longitudinal piezoelectric coefficient (d33) with increasing porosity levels currently limiting the range of pore fractions that can be employed. By introducing aligned lamellar pores into (Ba0.85Ca0.15)(Zr0.1Ti0.9)O3, this paper demonstrates an unusual 22-41% enhancement in the d33 compared to its dense counterpart. This unique combination of high d33 and a low permittivity leads to a significantly improved voltage coefficient (g33), energy harvesting figure of merit (FoM33) and electromechanical coupling coefficient ( k 33 2 $k_{33}^2$ ). The underlying mechanism for the improved properties is demonstrated to be a synergy between the low defect concentration and high internal polarizing field within the porous lamellar structure. This work provides insights into the design of porous ferroelectrics for applications related to sensors, energy harvesters, and actuators.

16.
Am J Otolaryngol ; 45(6): 104500, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39208707

ABSTRACT

OBJECTIVE: Given rising concern regarding antibiotic resistance, our objective was to evaluate antibiotic-resistant infections following leech therapy and to characterize the use of prophylactic antibiotics. METHODS: All reports of adverse events involving hirudotherapy (product code "NRN") were retrieved from the U.S. Food and Drug Administration MAUDE database between 2012 and 2021. Antibiotic resistance was defined by bacterial culture or infection after antibiotic administration. RESULTS: Nineteen cases of antibiotic resistance involving hirudotherapy were identified. Only three cases of antibiotic resistance were discovered on routine testing and the remaining 16 cases were associated with patient injury. Positive blood cultures or fever were present in 26.3 % (n = 5) of cases. Cultures of the infection grew Aeromonas hydrophilia (n = 13; 68.4 %), Vibrio vulnificus (n = 3; 15.8 %), Pseudomonas aeruginosa (n = 2; 10.5 %), and Proteus vulgaris (n = 1; 5.3 %). There were nine (47.4 %) multi-drug resistant infections. Infection was most commonly resistant to fluoroquinolones (n = 9; 47.4 %), trimethoprim-sulfamethoxazole (n = 9; 47.4 %) and ertapenem (n = 4; 21.1 %). CONCLUSION: Antibiotic-resistant infections involving hirudotherapy are frequently resistant to multiple drugs, including fluoroquinolones and trimethoprim-sulfamethoxazole. Resistance to ertapenem, a drug of last resort, was also documented. The findings presented in this study support growing literature that the trend in multi-drug resistance is more severe than previously reported.

18.
Acta Oncol ; 63: 658-668, 2024 Aug 11.
Article in English | MEDLINE | ID: mdl-39129249

ABSTRACT

BACKGROUND AND PURPOSE: This study aims to evaluate neutrophil-to-eosinophil ratio (NER) as a prognostic and/or predictive biomarker in metastatic clear cell renal cell carcinoma (m-ccRCC) treated with nivolumab or ipilimumab/nivolumab. PATIENTS/MATERIALS AND METHODS: We performed a retrospective study on m-ccRCC patients treated with nivolumab or ipilimumab/nivolumab (2012-2022). Baseline NER was calculated and correlated with clinical outcomes: response rate (RR), progression free survival (PFS) and overall survival (OS). Corresponding transcriptomic data were analysed. RESULTS: We included 201 m-ccRCC patients, 76 treated with ipilimumab/nivolumab and 125 with nivolumab. Baseline NER was statistically significantly associated with International Metastatic RCC Database Consortium (IMDC) risk groups. Increased NER was associated with shorter PFS and OS in the total patient series and nivolumab-treated patients. In patients treated with ipilimumab/nivolumab, increased NER was only statistically significantly associated with shorter OS. The impact of baseline NER on PFS and OS was independent of IMDC risk stratification. No clear correlation was found between baseline NER and RECIST response or maximal tumour shrinkage. In two additional databases, NER was also associated with PFS and OS in first-line vascular-endothelial-growth-factor-receptor tyrosine-kinase-inhibitors (VEGFR-TKIs), but not to disease-free survival in the post-nephrectomy setting. Lower NER was associated with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors. INTERPRETATION: Lower baseline NER is associated with better PFS and OS, independent of IMDC risk score, in m-ccRCC patients treated with ipilimumab/nivolumab or nivolumab. It correlates with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors. The predictive power of this biomarker is probably limited and insufficient for patient selection.


Subject(s)
Carcinoma, Renal Cell , Ipilimumab , Kidney Neoplasms , Neutrophils , Nivolumab , Humans , Nivolumab/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/mortality , Ipilimumab/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/mortality , Retrospective Studies , Male , Female , Aged , Middle Aged , Adult , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis , Progression-Free Survival
20.
Int J Sports Physiol Perform ; : 1-12, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39187249

ABSTRACT

PURPOSE: The traditional understanding of how coaches plan for sporting performance is rooted in the assumption that coaches create periodized plans underpinned by physiological principles, thereby providing scientific credibility to their work. In contrast, there remains a paucity of literature exploring how coaches understand or think about their planning practices. The purpose of this study was to generate new knowledge regarding what information coaches actually consider within their planning processes and how they actually approach the task of planning. METHOD: Using rigorous, in-depth interviews, this study examined athletics coaches' understandings of their everyday planning practices, in an attempt to contribute to narrowing the gap between academic research and real-world application. Twenty-eight highly experienced, high-performance track-and-field coaches based in England (female, n = 1; male, n = 27) were recruited. The coaches were from the throwing disciplines (n = 10) and endurance running (n = 18). Coaches were interviewed about their planning process, using a maximum of 3 semistructured interviews per coach, spaced across a full athletics season. In total, this generated 68 hours of data. RESULTS: The analysis demonstrated that, while the participant coaches utilized the principles of periodization, their planning activities were not limited to this issue. The findings highlighted how the coaches conceptualized successful athletic performance in a holistic way; that is, planning is multifaceted in nature. CONCLUSION: This study presents a holistic picture of the complexity of coaches' planning, detailing the considerable time and attention given to planning for athletes' psychological, personal, and social development, to enhance athlete performance and development.

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