Contrast Enhanced CT Radiogenomics in a Retrospective NSCLC Cohort: Models, Attempted Validation of a Published Model and the Relevance of the Clinical Context.

RATIONALE AND OBJECTIVE: To develop a radiogenomic predictive model for non-small cell lung cancer (NSCLC) patients studied through contrast enhanced chest computed tomography (CE-CT) targeting the most frequent gene alterations. M&M: A retrospective study of patients with NSCLC imaged with CE-CT before treatment and had their tumor genomics sequenced at our institution was performed. Data was gathered from their imaging studies, their electronic medical records and a web-based database search (cBioPortal.ca). All of the patient data was tabulated for analysis. Two predictive models (M1 & M2) were created using different approaches and a third model was extracted from the literature to also be tested in our population. RESULTS: Out of 157 patients, eighty were male (51%) and 124 (79%) had a history of smoking. The three most prevalent genes were KRAS, TP53 and EGFR. The M1 radiomics-only model median AUC were 0.61 (TP53), 0.53 (KRAS) and 0.64 (EGFR) and for M1 radiomics + clinical were 0.61 (TP53), 0.61 (KRAS) and 0.80 (EGFR). The M2 radiomics-only model median AUC were 0.63 (TP53), 0.60 (KRAS) and 0.65 (EGFR) and for M2 radiomics + clinical were 0.64 (TP53), 0.62 (KRAS) and 0.81 (EGFR). The external EGFR radiomic model showed an AUC of 0.69 and 0.86 for the radiomics-only and combined radiomics + clinical respectively. CONCLUSION: Our study was able to provide robust predictive radiomics model evaluation for the detection of TP53, KRAS and EGFR. We also compared our performance with an already published model and observed how impactful clinical variables can be on models' performance. CLINICAL RELEVANCE STATEMENT: Identifying tumor mutations in patients that can't undergo biopsy is critical for their outcomes. KEYPOINTS: • Tumor genomic profiling is critical for treatment selection • CE-CT radiomics produce robust predictive models comparable to those already published • Clinical variables should be considered/included in predictive models.

Safety of Low-Dose Oral Minoxidil in Patients With Hypertension and Arrhythmia: A Multicenter Study of 264 Patients.

BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.

Trends in urolith composition and factors associated with different urolith types in dogs from the Republic of Ireland and Northern Ireland between 2010 and 2020.

OBJECTIVES: The purpose of this study was to determine changes in urolith trends and factors associated with different urolith types in dogs from the Republic of Ireland and Northern Ireland between 2010 and 2020. MATERIALS AND METHODS: A laboratory database was searched for canine urolith submissions between 2010 and 2020. Trends in urolith composition between 2014 and 2020, and associations between patient characteristics with each urolith type were evaluated. RESULTS: A total of 1162 submissions were included. Struvite (39.0%), calcium oxalate (27.8%) and compound (10.2%) were the most prevalent uroliths. Calcium oxalate urolith (CaOx) incidence significantly increased from 27.8% to 31.2% and that of struvite significantly decreased from 41.7% to 33.0% between 2014 and 2020. Struvite uroliths were overrepresented among females compared to males (odds ratio 8.7, 95% confidence interval 6.6 to 11.5). Males (odds ratio 9.6, 95% confidence interval 6.9 to 13.3) and dogs >7 years of age (odds ratio 4.1, 95%, confidence interval 3.0 to 5.4) were more likely to have CaOx while males (odds ratio 9.6, 95% confidence interval 5.3 to 17.8) and dogs ≤7 year of age, purine uroliths (odds ratio 3.0, 95% confidence interval 1.8 to 5.0). Incidence was higher in bichon frise (odds ratio 1.7, 95% confidence interval 1.3 to 2.4) and Yorkshire terrier (odds ratio 2.8, 95% confidence interval 1.9 to 4.1) for CaOx and higher in shih-tzu for compound uroliths (odds ratio 1.7, 95% confidence interval 1.1 to 2.7) compared to the remaining reported breeds. CLINICAL SIGNIFICANCE: Factors associated with different uroliths were similar to the ones previously reported. Proportion of CaOx submissions increased and that of struvite decreased over the study period which was in agreement with the changes identified in other European countries.

Safety of Low-Dose Oral Minoxidil in Patients With Hypertension and Arrhythmia: A Multicenter Study of 264 Patients. / [Artíulo traducido] Seguridad de minoxidil oral a dosis bajas en pacientes con hipertensión o arritmias: estudio multicéntrico de 264 pacientes.

BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.

Nutritional assessment by ultrasound of the rectus femoris and preperitoneal adipose tissue as predictors of hospitalized patient complications.

INTRODUCTION: Malnutrition and sarcopenia are associated with increased risk of adverse events and worse outcome in hospitalised patients. Ultrasonography is a useful tool in the assessment of body composition. PATIENTS AND METHODS: Twenty-three patients admitted to a hospital ward were recruited. Ultrasonographic variables of muscle tissue and adipose tissue were collected, as well as their variation during admission. These were correlated with anthropometric, clinical and analytical data. RESULTS: We observed a correlation of ultrasound measurements with length of hospitalisation (maximum preperitoneal fat -0.585, rectus femoris thickness - RF -0.539, RF area -0.540), frailty (RF -0.599) and dependency (RF 0.628). RF contractile capacity correlated with reported weekly exercise (0.642). CONCLUSION: RF and preperitoneal fat thickness correlate with the number of days of admission and functional capacity, emerging as prognostic variables.

Vertebral compression fractures managed with brace: risk factors for progression.

PURPOSE: The aim of this study is to identify risk factors for vertebral compression fracture (VCF) progression in patients treated conservatively with a brace. Then, a case-control study was designed. METHODS: All patients over 50 years old with diagnosis of thoracic or lumbar VCF (T5 to L5) in absence of underlying oncological process, treated conservatively with brace, and consecutively attended at our department from January 2017 to June 2021 were retrospectively selected for analysis. Patients missed for follow-up or dead during the first 3 months of follow-up were excluded. RESULTS: Five hundred and eighty-two consecutive patients were recorded. Incomplete follow-up excluded 74 patients and other 19 died in the first three months after diagnosis, so 489 cases were finally analyzed. Median follow-up was 21 (IQR 13;30) weeks. Increased collapse of the vertebral body was found in 29.9% of VCFs with a median time to progression of 9 (IQR 7;13) weeks. Male gender (OR 1.6), type A3 fracture of the AOSpine classification (OR 2.7), thoracolumbar junction location (OR 1.7), and incorrect use of the brace (OR 3.5) were identified as independent risk factors for progression after multivariable analysis. CONCLUSION: Male gender, type A3 fracture of the AOSpine classification, thoracolumbar junction location, and incorrect use of the brace were identified as independent risk factors for VCF progression, which resulted in worse pain control, when treated with brace. Thus, other treatments such as percutaneous vertebral augmentation could be considered to avoid progression in selected cases, since collapse rate has been demonstrated lower with these procedures.

An Italian multicenter retrospective real-life analysis of patients with brain metastases from renal cell carcinoma: the BMRCC study.

BACKGROUND: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC). PATIENTS AND METHODS: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled. Univariate and multivariate models were performed to investigate the impact of clinicopathological features and multimodal treatments on both overall survival (OS) from the BM diagnosis and intracranial progression-free survival (iPFS). RESULTS: The median OS from the BM diagnosis was 18.8 months (interquartile range: 6.2-43 months). Multivariate analysis confirmed the following as positive independent prognostic factors: a Karnofsky Performance Status >70% [hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.26-0.92, P = 0.0026] and a single BM (HR = 0.51, 95% CI 0.31-0.86, P = 0. 0310); in contrast, the following were confirmed as worse prognosis factors: progressive extracranial disease (HR = 1.66, 95% CI 1.003-2.74, P = 0.00181) and only one line of systemic therapy after the BM occurrence (HR = 2.98, 95% CI 1.62-5.49, P = 0.029). Subgroup analyses showed no difference in iPFS according to the type of the first systemic treatment [immunotherapy (IT) or targeted therapy (TT)] carried out after the BM diagnosis (HR = 1.033, 95% CI 0.565-1.889, P = 0.16), and revealed that external radiation therapy (eRT) significantly prolonged iPFS when combined with IT (10.7 months, 95% CI 4.9-48 months, P = 0.0321) and not when combined with TT (9.01 months, 95% CI 2.7-21.2 months, P = 0.59). CONCLUSIONS: Our results suggest a potential additive effect in terms of iPFS for eRT combined with IT and encourage a more intensive multimodal therapeutic strategy in a multidisciplinary context to improve the survival of BMRCC patients.

Duration of the hypotensive effect of prostaglandin analogues measured with the water drinking test in glaucoma patients.

OBJECTIVE: To measure the magnitude and duration of the hypotensive effect of two prostaglandin analogues in glaucoma patients using the water drinking test (WDT). METHODS: Patients received latanoprost or travoprost every 24 h and then every 48 h. Untreated WDT were performed at 7 am and with treatment 12, 36 and 44 h after the last dose; intraocular pressure (IOP) peak, fluctuation and the difference between peak and isolated IOP measurements at consultation times were calculated. RESULTS: Forty-one eyes of 21 patients with primary open-angle glaucoma were included; 22 eyes received latanoprost, and 19 received travoprost. Mean untreated isolated IOP was 17.20 standard deviation (S.D.) 3.73 and 16.95 S.D. 2.61 mmHg and peak pressure 22.45 S.D. 2.91 and 21.58 S.D. 3.79 mmHg, for the latanoprost and travoprost groups, respectively. With treatment, peak pressure was reduced by 22.64% and 20.29% at 12 h, 18.44% and 14.64% at 36 h and 16.17% and 14.46% at 44 h, respectively. The fluctuation without treatment was 4.36 and 5.11 mmHg, and with treatment at 12 h was reduced to 2.77 and 2.89 mmHg, increasing again at 36 and 44 h. CONCLUSIONS: A hypotensive effect was evident up to 44 h after the last dose of latanoprost and travoprost, similar for the two drugs and decreasing over time. IOP fluctuation was only reduced at 12 h.

Clinical Predictors of Pseudohypoxia-Type Pheochromocytomas.

INTRODUCTION: Pheochromocytomas (PCCs) are rare tumors of neural crest origin with divergent transcriptional and metabolic profiles associated with mutational cluster types. Pseudohypoxia-type (PHT) PCCs have a poor prognosis; however diagnostic genetic testing is not always available. We aimed to investigate clinical parameters predictive of PHT PCCs. METHODS: Patients who underwent resection and genetic testing for PCC at two academic centers from 2006-2020 were retrospectively studied. Patients with PHT mutations (SDH-AF2/B/C/D, VHL) were compared to non-pseudohypoxia-type (nonPHT) PCCs to identify widely available clinical parameters predictive of PHT PCCs. Demographic, clinical, and pathologic characteristics were compared using student's T and ANOVA tests. Operative hemodynamic instability was defined as systolic blood pressure (SBP) > 200 mmHg, SBP increase of > 30% relative to baseline, and/or heart rate (HR) > 110 bpm. Mann-Whitney U test was used to assess area under the curve (AUC), sensitivity, and specificity. Recursive partitioning was used to model predictive thresholds for PHT PCC and develop a predictive score. RESULTS: Of the 79 patients included in the cohort, 17 (22%) had PHT and 62 (78%) had nonPHT PCCs. PCC patients with > 2 of the examined predictive clinical parameters (preoperative weight loss [> 10% body weight], elevated preoperative hematocrit [> 50%], normal baseline heart rate [< 100 bpm], and normal plasma metanephrines [< 0.60 nmol/L]) were more likely to have PHT PCCs (AUC = 0.831, sensitivity = 0.882, specificity = 0.694, all p < 0.001). CONCLUSIONS: Widely available preoperative clinical parameters including indicators of erythropoiesis (hemoglobin, hematocrit, and red blood cell count), baseline heart rate, plasma metanephrines, and weight loss may be useful predictors of PHT PCCs and may help guide management of PCCs when genetic testing is unavailable/delayed.

[Clinical and social evaluation of depressed patients in a Psychogeriatric Day Hospital program].

BACKGROUND: The aim of this study was to identify the problems of patients with severe depressive symptoms (GDS>9) according to the HoNOS+65 scale, to evaluate the effectiveness of a partial hospitalization program to reduce severe depressive symptoms, and to identify independent predictors. METHODS: Pre-post study of patients with depression treated at the psychogeriatric Day Hospital (HDPG) of Pamplona (Spain). The scores obtained on the HoNOS+65, MMSE, GDS, BARTHEL, ALSAR, and COTE scales were compared at admission and discharge, and the prognostic factors for no improvement of severe depressive symptoms were determined. RESULTS: The 75.3% of the 81 patients were women, with a mean age of 69.9 years (range: 57-88). At discharge, severe depressive symptoms only remained for 25.9%, who significantly improved on the HoNOS+65 total and COTE scales while problems of physical deterioration were maintained and cognitive ones increased. Patients with GDS <9 at discharge showed significant reductions in all the problems presented at admisión, except for the level of dependency (Barthel). On admission, the patiens who did not improve showed more severe despressive symptoms and greater behavioral and social problems: the three variables were independent predictors for no improvement of severe depressive symptoms. CONCLUSIONS: The HDPG program had a positive impact on patients with severe depressive symptoms. The clinical and social improvement achieved supports the HDPG format as an adequate alternative for the care of elderly patients with severe depressive symptoms.

[Tonic pupil after COVID-19 infection]. / Pupila tónica después de la infección por COVID-19.

The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID-19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis.

Tonic pupil after COVID-19 infection.

The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID 19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis.

Pituitary surgery in elderly patients: a safe and effective procedure.

PURPOSE: The incidence of pituitary adenoma (PA) increases with age. Transsphenoidal surgery (TSS) in elderly patients is often considered to have greater risk compared to the younger population. The aim of this study is to compare surgical results, evolution and postoperative complications between elderly and young patients undergoing TSS. METHODS: Retrospective review of patients undergoing TSS between 2011 and 2018 in our institution. Patients were divided into two cohorts: elderly (≥65 years) and non-elderly (<65 years). Characteristics and outcomes of both groups were compared at diagnosis, before surgery and for an average of 5.9 years of postoperative follow-up. RESULTS: One hundred and twenty-five patients were included, 53 patients were ≥65 years (42%). The elderly patients were more likely to have non-functioning PA (NFPA) (90.5% vs. 45.8%, p: <0.01), a higher proportion of macroadenomas (92.4% vs. 77.8%, p = 0.029) and greater extrasellar extension (88.7% vs. 68.1%, p = 0.007). The elderly group also had more compressive symptoms (54.7% vs. 34.7%, p = 0.035) and hypopituitarism (66% vs. 47.2%, p = 0.029). Overall, surgical and endocrinological outcomes between the two groups were similar. Inpatient mortality in the elderly group was 1.8%. Regarding long-term outcomes, elderly patients had more postoperative hypopituitarism (67.9% vs. 45.8%, p = 0.03) with no differences in permanent diabetes insipidus, less residual tumours (24.5% vs. 40.3%, p = 0.019) and a higher rate of remission after surgery (71.7% vs. 52.8%, p = 0.034). When only NFPA cases were compared, the only significant difference was a higher frequency of macroadenomas in the elderly group. CONCLUSIONS: Our results support the safety and efficacy of TSS in elderly patients with PA. Age should not be considered an exclusion criterion for TSS given that successful results can be achieved if an experienced pituitary team is available.

Radical metastasectomy followed by sorafenib versus observation in patients withclear cell renal cell carcinoma: extended follow -up of efficacy results from the randomized phase II RESORT trial.

Background: The RESORT trial showed no longer relapse free survival (RFS) with sorafenib following radical metastasectomy in metastatic renal cell carcinoma. We present the updated 42-month follow-up data.Methods: The phase II RESORT trial randomized patients to sorafenib or observation within 12 weeks from surgery. RFS was the primary endpoint.Results: We analyzed 68 patients (32 in sorafenib and 36 in the observation arm), randomized between November 2012 and November 2017. Eighty-one percent in the sorafenib arm and 80% in the observation arm had one metastasis . At a median follow-up of 42 months (interquartile range 31-58), in the observation arm the median RFS was 35 months, RFS probability was 57% (95% CI 42-76%) at 24 and 44% (95% CI 30-65%) at 48 months. In the sorafenib arm, median RFS was 21 months, RFS probability was 50% (95% CI 34-71%) at 24 and 32% (95% CI 18-57%) at 48 months (p = 0.342;HR 1.35;95% CI 0.72-2.54). Forty-seven percent and 37.5% of the patients in the two arms, respectively, are disease free. The site of relapses was independent of the previous metastasectomy site.Expert commentary: Sorafenib after metastasectomy did not improve RFS, but surgery in selected patients should be considered in order to potentially improve survival.Clinical trial registration: www.clinicaltrials.gov identifier is NCT0144480.

Isolation and characterization of vibriophage vB_Vc_SrVc9: an effective agent in preventing Vibrio campbellii infections in brine shrimp nauplii (Artemia franciscana).

AIMS: This study describes the physicochemical and genomic characterization of phage vB_Vc_SrVc9 and its potential for phage therapy application against a pathogenic Vibrio campbellii strain. METHODS AND RESULTS: A lytic phage vB_Vc_SrVc9 against V. campbellii was isolated from shrimp farm sediment, and characterized physicochemical and genomically. The use of vB_Vc_SrVc9 phage increased the survival in brine shrimp Artemia franciscana and reduced presumptive V. campbellii to nondetectable numbers. Genomic analysis showed a genome with a single contig of 43·15 kb, with 49 predicted genes and no tRNAs, capable of recognizing and generating complete inhibition zones of three Vibrio sp. CONCLUSIONS: To our knowledge vB_Vc_SrVc9 is a lytic phage that could be used against Vibrio infections, reducing vibrio presence without any apparent impact over the natural microbiota at the family level in 28 libraries tested. SIGNIFICANCE AND IMPACT OF THE STUDY: vB_Vc_SrVC9 is a novel phage and ecofriendly alternative for therapeutic applications and biotechnological purposes because is stable at different environmental conditions, has the potential to eliminate several strains, and has a short latent period with a good burst size. Therefore, the use of phages, which are natural killers of bacteria, represents a promising strategy to reduce the mortality of farmed organisms caused by pathogenic bacteria.

SuperCam Calibration Targets: Design and Development.

SuperCam is a highly integrated remote-sensing instrumental suite for NASA's Mars 2020 mission. It consists of a co-aligned combination of Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), Visible and Infrared Spectroscopy (VISIR), together with sound recording (MIC) and high-magnification imaging techniques (RMI). They provide information on the mineralogy, geochemistry and mineral context around the Perseverance Rover. The calibration of this complex suite is a major challenge. Not only does each technique require its own standards or references, their combination also introduces new requirements to obtain optimal scientific output. Elemental composition, molecular vibrational features, fluorescence, morphology and texture provide a full picture of the sample with spectral information that needs to be co-aligned, correlated, and individually calibrated. The resulting hardware includes different kinds of targets, each one covering different needs of the instrument. Standards for imaging calibration, geological samples for mineral identification and chemometric calculations or spectral references to calibrate and evaluate the health of the instrument, are all included in the SuperCam Calibration Target (SCCT). The system also includes a specifically designed assembly in which the samples are mounted. This hardware allows the targets to survive the harsh environmental conditions of the launch, cruise, landing and operation on Mars during the whole mission. Here we summarize the design, development, integration, verification and functional testing of the SCCT. This work includes some key results obtained to verify the scientific outcome of the SuperCam system.

[Breastfeeding in women who conceived using fertility treatments: a systematic review].

Women subjected to fertility treatment present needs requiring medical attention and decision-making processes before and after delivery that might influence their behaviour in maternal breastfeeding. This review examined the effect of fertility treatments on the start, duration and exclusiveness of maternal lactation based on all the observational studies that compared some result of maternal lactation according to the form of conception. Two reviewers extracted the data and evaluated the risk of bias. The effect of fertility treatments on the results of maternal lactation was small or not significant, and on occasions contradictory. The evidence is limited due to the low number of articles of sufficient quality included. For the time being, fertility treatments do not seem to influence the start, duration and exclusiveness of maternal lactation, but until more and better studies are available, individualized support is recommended for each mother-child dyad according to its characteristics.