The cerebellum modulates thirst.

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin-Ptprd signaling may be a potential therapeutic target for the management of thirst disorders.

Integration of valence and conflict processing through cellular-field interactions in human subgenual cingulate during emotional face processing in treatment-resistant depression.

The subgenual anterior cingulate cortex (sgACC) has been identified as a key brain area involved in various cognitive and emotional processes. While the sgACC has been implicated in both emotional valuation and emotional conflict monitoring, it is still unclear how this area integrates multiple functions. We characterized both single neuron and local field oscillatory activity in 14 patients undergoing sgACC deep brain stimulation for treatment-resistant depression. During recording, patients were presented with a modified Stroop task containing emotional face images that varied in valence and congruence. We further analyzed spike-field interactions to understand how network dynamics influence single neuron activity in this area. Most single neurons responded to both valence and congruence, revealing that sgACC neuronal activity can encode multiple processes within the same task, indicative of multifunctionality. During peak neuronal response, we observed increased spectral power in low frequency oscillations, including theta-band synchronization (4-8 Hz), as well as desynchronization in beta-band frequencies (13-30 Hz). Theta activity was modulated by current trial congruency with greater increases in spectral power following non-congruent stimuli, while beta desynchronizations occurred regardless of emotional valence. Spike-field interactions revealed that local sgACC spiking was phase-locked most prominently to the beta band, whereas phase-locking to the theta band occurred in fewer neurons overall but was modulated more strongly for neurons that were responsive to task. Our findings provide the first direct evidence of spike-field interactions relating to emotional cognitive processing in the human sgACC. Furthermore, we directly related theta oscillatory dynamics in human sgACC to current trial congruency, demonstrating it as an important regulator during conflict detection. Our data endorse the sgACC as an integrative hub for cognitive emotional processing through modulation of beta and theta network activity.

The reliability and discriminant validity of physical, technical, and perceptual-physiological measures during a game-specific basketball activity simulation protocol.

Activity simulation protocols offer useful applications in research and practice; however, the specificity of such protocols to basketball game-play is currently lacking. Consequently, this study aimed to develop a game-specific basketball activity simulation protocol representative of typical playing durations and assess its reliability and discriminant validity. The simulation protocol was modified from an original version (i.e., Basketball Exercise Simulation Test) to incorporate regular breaks indicative of time-outs, free-throws, and substitutions. Twelve competitive male and female adult basketball players competing in the fourth or fifth Spanish basketball division underwent repeated trials of the simulation protocol (min. 4 to max. 14 days apart) for reliability analyses. In turn, 13 competitive male (fifth division), 9 competitive female (fourth division), and 13 recreational male adult basketball players completed the simulation protocol to assess discriminant validity via comparisons between sexes (competitive players) and playing levels (males). A range of physical, technical, and perceptual-physiological variables were collected during and following the simulation protocol. Several physical and heart rate variables displayed the strongest reliability (intraclass correlation coefficient [ICC] = 0.72-0.96; coefficient of variation [CV] = 1.78-6.75%), with physical decrement, technical, blood lactate concentration, and rating of perceived exertion (RPE) variables having the weakest (ICC = 0.52-0.75; CV = 10.34-30.85%). Regarding discriminant analyses between sexes, males demonstrated significantly greater physical outputs in several variables and lower RPE compared to females (p < 0.05, moderate-to-large effects). Comparisons between playing levels revealed competitive males had significantly greater physical outputs across many variables, alongside higher mean heart rate and lower RPE than recreational males (p < 0.05, moderate-to-large effects). This study presents a novel game-specific basketball activity simulation protocol replicating actual playing durations and game configurations that might be successfully applied for both training and research purposes. Reliability statistics are provided for several variables to inform end-users on potential measurement error when implementing the simulation protocol. Discriminant validity of the simulation protocol was supported for several variables, suggesting it may hold practical utility in benchmarking or selecting players. Future research on this topic is encouraged examining wider samples of male and female basketball players at different levels as well as additional forms of validity for the protocol.

Real-world genetic testing outcomes of pan-cancer testing for mismatch repair deficiency.

BACKGROUND: In 2017, the Food and Drug Administration approved pembrolizumab for treatment of any mismatch repair-deficient (dMMR) tumor making MMR immunohistochemistry (IHC) testing beneficial for all tumor types. For the first time, MMR IHC was not performed exclusively to screen for Lynch syndrome (LS). METHODS: In this study, all MMR IHC reports issued between 2017 and 2021 at an academic hospital were reviewed and completion of genetic testing was determined through chart review. Colorectal cancers (CRCs), endometrial cancers (ECs), and noncancerous lesions were excluded. RESULTS: Between 2017 and 2021, MMR IHC was completed in 1939 patients with a malignancy other than CRC or EC. Absent or weak staining for at least one MMR protein was detected in 115 (5.9%) patients and 59 (51%) of those completed germline genetic testing. Overall, the identification rate of LS in this cohort was 0.72%, which is similar to the rate in our previously reported CRC and EC universal screening cohort. A diagnosis of LS was most commonly made in patients with dMMR brain (18.75%) and small intestinal cancers (10.20%). Five additional patients were found to carry a pathogenic variant in a non-LS gene. CONCLUSIONS: Pan-cancer MMR testing for pembrolizumab consideration can identify LS cases at a rate similar to universal CRC and EC screening programs. A persistent challenge is subsequent uptake of genetic testing. MMR testing should be prioritized in brain and small intestinal tumors, and multigene panel testing is recommended in patients with dMMR, as unexpected pathogenic variants in non-LS genes were found as frequently as LS gene variants.

Comparison of Mammography and Mammography with Supplemental Whole-Breast US Tomography for Cancer Detection in Patients with Dense Breasts.

BACKGROUND: Women with dense breasts benefit from supplemental cancer screening with US, but US has low specificity. PURPOSE: To evaluate the performance of breast US tomography (UST) combined with full-field digital mammography (FFDM) compared with FFDM alone for breast cancer screening in women with dense breasts. MATERIALS AND METHODS: This retrospective multireader multicase study included women with dense breasts who underwent FFDM and UST at 10 centers between August 2017 and October 2019 as part of a prospective case collection registry. All patients in the registry with cancer were included; patients with benign biopsy or negative follow-up imaging findings were randomly selected for inclusion. Thirty-two Mammography Quality Standards Act-qualified radiologists independently evaluated FFDM followed immediately by FFDM plus UST for suspicious findings and assigned a Breast Imaging Reporting and Data System (BI-RADS) category. The superiority of FFDM plus UST versus FFDM alone for cancer detection (assessed with area under the receiver operating characteristic curve [AUC]), BI-RADS 4 sensitivity, and BI-RADS 3 sensitivity and specificity were evaluated using the two-sided significance level of α = .05. Noninferiority of BI-RADS 4 specificity was evaluated at the one-sided significance level of α = .025 with a -10% margin. RESULTS: Among 140 women (mean age, 56 years ±10 [SD]; 36 with cancer, 104 without), FFDM plus UST achieved superior performance compared with FFDM alone (AUC, 0.60 [95% CI: 0.51, 0.69] vs 0.54 [95% CI: 0.45, 0.64]; P = .03). For FFDM plus UST versus FFDM alone, BI-RADS 4 mean sensitivity was superior (37% [428 of 1152] vs 30% [343 of 1152]; P = .03) and BI-RADS 4 mean specificity was noninferior (82% [2741 of 3328] vs 88% [2916 of 3328]; P = .004). For FFDM plus UST versus FFDM, no difference in BI-RADS 3 mean sensitivity was observed (40% [461 of 1152] vs 33% [385 of 1152]; P = .08), but BI-RADS 3 mean specificity was superior (75% [2491 of 3328] vs 69% [2299 of 3328]; P = .04). CONCLUSION: In women with dense breasts, FFDM plus UST improved cancer detection by radiologists versus FFDM alone. Clinical trial registration nos. NCT03257839 and NCT04260620 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Mann in this issue.

Management of serum phosphorus over a 1-year follow-up in patients on peritoneal dialysis prescribed sucroferric oxyhydroxide as part of routine care: a retrospective analysis.

BACKGROUND: Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care. METHODS: We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment. RESULTS: The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up). CONCLUSIONS: Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden.

Bright New Resources for Syphilis Research: Genetically Encoded Fluorescent Tags for Treponema pallidum and Sf1Ep Cells.

The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. pallidum ( T. pallidum ) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance of controlled studies to assess differential treponemal gene expression, and generation of loss-of-function mutants to evaluate the contribution of specific genetic loci to T. pallidum virulence. Building on this progress, we engineered the T. pallidum SS14 strain to express a red-shifted Green Fluorescent Protein (GFP) and Sf1Ep cells to express mCherry and blue fluorescent protein (BFP) for enhanced visualization. These new resources improve microscopy- and cell sorting-based applications for T. pallidum , better capturing the physical interaction between the host and pathogen, among other possibilities. Continued efforts to develop and share new tools and resources are required to help our overall knowledge of T. pallidum biology and syphilis pathogenesis reach that of other bacterial pathogens, including spirochetes. Graphical abstract: By employing genetic engineering, T. pallidum was modified to express GFP, and Sf1Ep cells to express mCherry on the cytoplasmic membrane and BFP in the nucleus. These new resources for syphilis research will facilitate experimental designs to better define the complex interplay between T. pallidum and the host during infection.

Hospital nurse staffing variation and Covid-19 deaths: A cross-sectional study.

BACKGROUND: During the Covid-19 pandemic, Covid-19 mortality varied depending on the hospital where patients were admitted, but it is unknown what aspects of hospitals were important for mitigating preventable deaths. OBJECTIVE: To determine whether hospital differences in pre-pandemic and during pandemic nursing resources-average patient-to-registered nurse (RN) staffing ratios, proportion of bachelor-qualified RNs, nurse work environments, Magnet recognition-explain differences in risk-adjusted Covid-19 mortality; and to estimate how many deaths may have been prevented if nurses were better resourced prior to and during the pandemic. METHODS: This is a cross-sectional study of 87,936 Medicare beneficiaries (65-99 years old) hospitalized with Covid-19 and discharged (or died) between April 1 and December 31, 2020, in 237 general acute care hospitals in New York and Illinois. Measures of hospital nursing resources (i.e. patient-to-RN staffing ratios, proportion of bachelor-qualified RNs, nurse work environments, Magnet recognition) in the pre-pandemic period (December 2019 to February 2020) and during (April to June 2021) were used to predict in-hospital and 30-day mortality using adjusted logistic regression models. RESULTS: The mean age of patients was 78 years (8.6 SD); 51 % were male (n = 44,998). 23 % of patients admitted to the hospital with Covid-19 died during the hospitalization (n = 20,243); 31.5 % died within 30-days of admission (n = 27,719). Patients admitted with Covid-19 to hospitals with better nursing resources pre-pandemic and during the pandemic were statistically significantly less likely to die. For example, each additional patient in the average nurses' workload pre-pandemic was associated with 20 % higher odds of in-hospital mortality (OR 1.20, 95 % CI [1.12-1.28], p < 0.001) and 15 % higher odds of 30-day mortality (OR 1.15, 95 % CI [1.09-1.21], p < 0.001). Hospitals with greater proportions of BSN-qualified RNs, better quality nurse work environments, and Magnet recognition offered similar protective benefits to patients during the pandemic. If all hospitals in the study had superior nursing resources prior to or during the pandemic, models estimate many thousands of deaths among patients hospitalized with Covid-19 could have been avoided. CONCLUSIONS: Patients with Covid-19 admitted to hospitals with adequate numbers of RNs caring for patients, a workforce rich in BSN-qualified RNs, and high-quality nurse work environments (both prior to and during the Covid-19 pandemic) were more likely to survive the hospitalization. Bolstering these hospital nursing resources during ordinary times is necessary to ensure better patient outcomes and emergency-preparedness of hospitals for future public health emergencies.

Alternative Models of Nurse Staffing May Be Dangerous in High-Stakes Hospital Care.

BACKGROUND: Hospitals are resurrecting the outdated "team nursing" model of staffing that substitutes lower-wage staff for registered nurses (RNs). OBJECTIVES: To evaluate whether reducing the proportion of RNs to total nursing staff in hospitals is in the best interest of patients, hospitals, and payers. RESEARCH DESIGN: Cross-sectional, retrospective. SUBJECTS: In all, 6,559,704 Medicare patients in 2676 general acute-care US hospitals in 2019. MEASURES: Patient outcomes: in-hospital and 30-day mortality, 30-day readmission, length of stay, and patient satisfaction. Avoidable Medicare costs associated with readmissions and cost savings to hospitals associated with shorter stays are projected. RESULTS: A 10 percentage-point reduction in RNs was associated with 7% higher odds of in-hospital death, 1% higher odds of readmission, 2% increase in expected days, and lower patient satisfaction. We estimate a 10 percentage-point reduction in RNs would result in 10,947 avoidable deaths annually and 5207 avoidable readmissions, which translates into roughly $68.5 million in additional Medicare costs. Hospitals would forgo nearly $3 billion in cost savings annually because of patients requiring longer stays. CONCLUSIONS: Reducing the proportion of RNs in hospitals, even when total nursing personnel hours are kept the same, is likely to result in significant avoidable patient deaths, readmissions, longer lengths of stay, and decreased patient satisfaction, in addition to excess Medicare costs and forgone cost savings to hospitals. Estimates represent only a 10 percentage-point dilution in skill mix; however, the team nursing model includes much larger reductions of 40-50 percentage-points-the human and economic consequences of which could be substantial.

Nurse-sensitive quality and benchmarking in hospitals striving for Magnet® or Pathway® designation: A qualitative study.

AIM: To examine if and how selected German hospitals use nurse-sensitive clinical indicators and perspectives on national/international benchmarking. DESIGN: Qualitative study. METHODS: In 2020, 18 expert interviews were conducted with key informants from five purposively selected hospitals, being the first in Germany implementing Magnet® or Pathway®. Interviews were analyzed using content analysis with deductive-inductive coding. The study followed the COREQ guideline. RESULTS: Three major themes emerged: first, limited pre-existence of and necessity for nurse-sensitive data. Although most interviewees reported data collection for hospital-acquired pressure ulcers and falls with injuries, implementation varied and interviewees highlighted the necessity to develop additional nurse-sensitive indicators for the German context. Second, the theme creating an enabling data environment comprised building clinicians' acceptance, establishing a data culture, and reducing workload by using electronic health records. Third, challenges and opportunities in establishing benchmarking were identified but most interviewees called for a national or European benchmarking system. CONCLUSION: The need for further development of nurse-sensitive clinical indicators and its implementation in practice was highlighted. Several actions were suggested at hospital level to establish an enabling data environment in clinical care, including a nationwide or European benchmarking system. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Involving nurses in data collection, comparison and benchmarking of nurse-sensitive indicators and their use in practice can improve quality of patient care. IMPACT: Nurse-sensitive indicators were rarely collected, and a need for action was identified. The study results show research needs on nurse-sensitive indicators for Germany and Europe. Measures were identified to create an enabling data environment in hospitals. An initiative was started in Germany to establish a nurse-sensitive benchmarking capacity. PATIENT OR PUBLIC CONTRIBUTION: Clinical practitioners and nurse/clinical managers were interviewed.

Assessment of Iron-Based Spin-Orbit Coupling Effects in Pt-Fe Heterobimetallic Lantern Complexes via 57Fe Mössbauer Spectroscopy.

A series of heterobimetallic lantern complexes, [PtFe(SOCR)4(pyX)] where R = Me, X = H (1), X = NH2 (2), X = SMe (3); R = Ph, X = H (4), X = NH2 (5), X = SMe (6), have been prepared and characterized spectroscopically. Compounds 1, 4, and 5 are reported herein for the first time. The high-spin iron(II) sites of 1-6 have been investigated using 57Fe Mössbauer spectroscopy. Although the isomer shift of these species is nearly identical, their quadrupole splitting exhibits a much larger variation. Moreover, the zero-field Mössbauer spectra of 3-5 show surprising changes over time which are likely indicative of small structural distortions. The field dependent Mössbauer study of 1 and 6 revealed a zero field splitting (ZFS) characterized by a relatively large and positive D value. The combined Density Functional Theory (DFT) and ab initio Complete Active Space Self-Consistent Field (CASSCF) investigation of 1-6 indicates that their ground state is best described using a linear combination of {|xz⟩, |yz⟩} states. Our theoretical analysis suggests that the ZFSs and magnitude of the quadrupole splitting of 1-6 are determined by the spin-orbit coupling of the three lowest orbital states which have a T2g parentage.

Cerebellar Functions Beyond Movement and Learning.

The cerebellum has a well-established role in controlling motor functions, including coordination, posture, and the learning of skilled movements. The mechanisms for how it carries out motor behavior remain under intense investigation. Interestingly though, in recent years the mechanisms of cerebellar function have faced additional scrutiny since nonmotor behaviors may also be controlled by the cerebellum. With such complexity arising, there is now a pressing need to better understand how cerebellar structure, function, and behavior intersect to influence behaviors that are dynamically called upon as an animal experiences its environment. Here, we discuss recent experimental work that frames possible neural mechanisms for how the cerebellum shapes disparate behaviors and why its dysfunction is catastrophic in hereditary and acquired conditions-both motor and nonmotor. For these reasons, the cerebellum might be the ideal therapeutic target.

Rate of Change in Cardiac Magnetic Resonance Imaging Measures Is Associated With Death in Duchenne Muscular Dystrophy.

BACKGROUND: Cardiovascular disease is the leading cause of death among patients with Duchenne muscular dystrophy (DMD). Identifying patients at risk of early death could allow for increased monitoring and more intensive therapy. Measures that associate with death could serve as surrogate outcomes in clinical trials. METHODS AND RESULTS: Duchenne muscular dystrophy subjects prospectively enrolled in observational studies were included. Models using generalized least squares were used to assess the difference of cardiac magnetic resonance measurements between deceased and alive subjects. A total of 63 participants underwent multiple cardiac magnetic resonance imaging and were included in the analyses. Twelve subjects (19.1%) died over a median follow-up of 5 years (interquartile range, 3.1-7.0). Rate of decline in left ventricular ejection fraction was faster in deceased than alive subjects (P<0.0001). Rate of increase in indexed left ventricular end-diastolic (P=0.0132) and systolic (P<0.0001) volumes were higher in deceased subjects. Faster worsening in midcircumferential strain was seen in deceased subjects (P=0.049) while no difference in global circumferential strain was seen. The rate of increase in late gadolinium enhancement, base T1, and mid T1 did not differ between groups. CONCLUSIONS: Duchenne muscular dystrophy death is associated with the rate of change in left ventricular ejection fraction, midcircumferential strain, and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve the mortality rate in this population. A decrease in the rate of progression may serve as a valid surrogate outcome for therapeutic trials.

Mercury and selenium distribution in human brain tissue using synchrotron micro-X-ray fluorescence.

Mercury is a well-recognized environmental contaminant and neurotoxin, having been associated with a number of deleterious neurological conditions including neurodegenerative diseases, such as Alzheimer's disease. To investigate how mercury and other metals behave in the brain, we used synchrotron micro-X-ray fluorescence to map the distribution pattern and quantify concentrations of metals in human brain. Brain tissue was provided by the Rush Alzheimer's Disease Center and samples originated from individuals diagnosed with Alzheimer's disease and without cognitive impairment. Data were collected at the 2-ID-E beamline at the Advanced Photon Source at Argonne National Laboratory with an incident beam energy of 13 keV. Course scans were performed at low resolution to determine gross tissue features, after which smaller regions were selected to image at higher resolution. The findings revealed (1) the existence of mercury particles in the brain samples of two subjects; (2) co-localization and linear correlation of mercury and selenium in all particles; (3) co-localization of these particles with zinc structures; and (4) association with sulfur in some of these particles. These results suggest that selenium and sulfur may play protective roles against mercury in the brain, potentially binding with the metal to reduce the induced toxicity, although at different affinities. Our findings call for further studies to investigate the relationship between mercury, selenium, and sulfur, as well as the potential implications in Alzheimer's disease and related dementias.

Validation of a short form of the practice environment scale of the nursing work index: The PES-5.

The Practice Environment Scale of the Nursing Work Index (PES-NWI) has been utilized for two decades globally to measure nurse work environments. Its 31 items in five domains present a substantial respondent burden, threatening survey response rates. The purpose of this study was to derive and validate a short form: the PES-5. We conducted a cross-sectional, secondary analysis of survey data from nurses in 760 hospitals in six U.S. states in 2016 or 2019. One representative item per subscale was selected by highest item-to-subscale R2 from the original PES-NWI publication. Five psychometric properties of the PES-5 were evaluated. The reproduced structure of the full form was confirmed in the 2016 data by the highest R2 for the selected items. The unidimensional structure of the PES-5 was confirmed through confirmatory factor analysis. The correlation between the composite values of the 28-item and 5-item versions was 0.94. The Cronbach's alpha reliability of the PES-5 was >0.80. The intraclass correlation coefficient (ICC 1, k), which evaluates the stability of aggregated values when data are clustered, i.e., nurses are nested within hospitals, was >0.80 in both datasets, demonstrating satisfactory aggregate properties. Construct validity was supported by the selected items being ranked highly in their respective subscales by an expert panel. Criterion validity was supported by an analysis of variance of the PES-5 mean value across responses to a single-item work environment measure. Similar patterns of relationships with other key variables were identified by statistically significant odds ratios in regression models predicting patient mortality from the PES-5. The classification accuracy of the PES-5 was high, with 88% of hospitals classified identically by both versions. The PES-5 shows promise for measurement of nurses' work environments while maximizing response rate by reducing participant burden.

Correction: Nutrikinetics and urinary excretion of phenolic compounds after a 16-week supplementation with a flavanone-rich ingredient.

Correction for 'Nutrikinetics and urinary excretion of phenolic compounds after a 16-week supplementation with a flavanone-rich ingredient' by Jananee Muralidharan et al., Food Funct., 2023, 14, 10506-10519, https://doi.org/10.1039/D3FO02820H.

Magnetic Resonance Imaging-based Prostate Cancer Screening in Carriers of Pathogenic Germline Mutations: Interim Results from the Initial Screening Round of the Prostate Cancer Genetic Risk Evaluation and Screening Study.

BACKGROUND: The risk of early-onset and clinically aggressive prostate cancer is elevated in carriers of certain rare pathogenic germline mutations. The utility of augmenting traditional prostate-specific antigen (PSA)-based screening measures with multiparametric magnetic resonance imaging (MRI) in this population is not yet known. OBJECTIVE: To evaluate MRI-based screening in comparison with traditional PSA-based screening among individuals at an elevated genetic risk for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Male germline carriers of pathogenic/likely pathogenic variants in any of 19 prostate cancer risk genes between the ages of 35 and 74 yr with no prior history of prostate cancer were recruited. Intervention Enrolled participants underwent screening with annual PSA, digital rectal examination (DRE), and triennial multiparametric MRI. Individuals with abnormal DRE, elevated age-adjusted PSA (>1.5 ng/ml for 35-49 yr, >2.0 ng/ml for 50-54 yr, and >3.0 ng/ml for 55-74 yr), or suspicious multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3 lesion) were offered prostate biopsy. Outcome measurements and statistical analysis Endpoints were diagnosis of any and clinically significant prostate cancer, and alternative screening strategies were compared by a decision curve analysis. RESULTS AND LIMITATIONS: To date, 101 males have completed the first round of screening. The greatest proportion of participants are carriers of BRCA2 (n = 44), BRCA1 (n = 35), and ATM (n = 7) variants. Twenty-one have undergone biopsy, resulting in the detection of nine cases of cancer (seven clinically significant). For the detection of clinically significant prostate cancer, abnormal MRI (PI-RADS ≥3) demonstrated 100% sensitivity (7/7) with a negative predictive value (NPV) of 100%, whereas PSA-based screening alone had 57% (4/7) sensitivity with an NPV of 73%. Of six screening strategies evaluated in the decision curve analysis, MRI-based screening alone achieved superior net benefit at all threshold probabilities compared with PSA screening-detecting one additional cancer case per 7.5 patients, while avoiding more unnecessary biopsies at the same threshold probability. CONCLUSIONS: Disease prevalence is high among carriers of prostate cancer-associated pathogenic germline mutations. Early results suggest that MRI-based screening enhances early detection of clinically significant disease beyond PSA screening alone. PATIENT SUMMARY: In this study, we present the interim results from the PROGRESS prostate cancer screening trial. We found that in certain germline carriers of prostate cancer risk mutations, magnetic resonance imaging-based screening enhances detection of prostate cancer while reducing biopsies triggered, in comparison with traditional prostate-specific antigen screening strategies.

Separating Out Pulmonary Sequestration.

Pulmonary sequestration (PS) is a rare congenital anomaly that accounts for 1% to 6% of all pulmonary malformations at birth. It is characterized by a focal area of pulmonary tissue that does not have direct communication with the tracheobronchial tree and does not get blood supply from the pulmonary circulation. We present the case of a 28-year-old female with a history of recurrent pulmonary infections who was found to have intralobar sequestration and underwent curative surgical excision. Because pulmonary sequestration is commonly misdiagnosed, as it can mimic other conditions on chest X-rays, this case illustrates the importance of recognizing pulmonary sequestration as a separate entity and diagnosing/treating it appropriately. The patient presented to the hospital with a one-week history of upper chest pain. Chest radiograph showed mild hyperinflated right lung. Computed tomography angiogram (CTA) revealed an 8.9 x 8.3 cm area of hyper-lucency and decreased normal lung architecture in the right lower lobe with an aberrant arterial blood supply suggestive of intralobar pulmonary sequestration. The patient was referred to cardiothoracic surgery and underwent preoperative outpatient pulmonary function testing, which was unremarkable. The patient subsequently underwent successful robotic resection of the right lower lobe sequestration and the pathology report confirmed PS. A diagnosis of pulmonary sequestration is commonly missed, as it can mimic other conditions on chest X-rays. It can present as a solitary nodule or mass, cystic lesion, consolidation, or an air-fluid level. The period between symptom onset and diagnosis is typically more than five years. While digital subtraction angiography is considered the gold standard for imaging, CTA is now preferred because it allows for clear visualization of lung parenchyma and vascular assisting in surgical planning. For our patient, CTA demonstrated a prominent tubular vessel, which showed less enhancement than the opacified pulmonary artery and pulmonary veins, suggestive of an abnormal vascular supply for the right lower lobe sequestration. Management of intralobar sequestration is curative surgical excision. Both video-assisted thoracoscopic surgery (VATS) and posterolateral thoracotomy are viable options for resection. It should be noted that in symptomatic patients, it is recommended to proceed with surgical resection. However, in asymptomatic individuals with intralobar sequestration (ILS), surgical resection is not required but could be considered as prophylaxis to prevent recurrent infections. Asymptomatic individuals with extralobar sequestration (ELS), on the other hand, should undergo serial monitoring as non-operative management is appropriate. This case highlights the importance of including pulmonary sequestration, especially intralobar sequestration in the differential diagnosis of recurrent localized pulmonary infections, especially in a patient who is otherwise healthy. Although rare, it is important to consider this congenital anomaly when evaluating patients with recurrent localized pulmonary infections, chest pain, or hemoptysis.

Nurses' intention to leave, nurse workload and in-hospital patient mortality in Italy: A descriptive and regression study.

Higher nurse-to-patient ratios are associated with poor patient care and adverse nurse outcomes, including emotional exhaustion and intention to leave. We examined the effect of nurses' intention to leave and nurse-patient workload on in-hospital patient mortality in Italy. A multicentered descriptive and regression study using clinical data of patients aged 50 years or older with a hospital stay of at least two days admitted to surgical wards linked with nurse variables including workload and education levels, work environment, job satisfaction, intention to leave, nurses' perception of quality and safety of care, and emotional exhaustion. The final dataset included 15 hospitals, 1046 nurses, and 37,494 patients. A 10 % increase in intention to leave and an increase of one unit in nurse-patient workload increased likelihood of inpatient hospital mortality by 14 % (odds ratio 1.14; 1.02-1.27 95 % CI) and 3.4 % (odds ratio 1.03; 1.00-1.06 95 % CI), respectively. No other studies have reported a significant association between intention to leave and patient mortality. To improve patient outcomes, the healthcare system in Italy needs to implement policies on safe human resources policy stewardship, leadership, and governance to ensure nurse wellbeing, higher levels of safety, and quality nursing care.