Forced Expiratory Volume in One Second Quotient (FEV1Q) as a Prognostic Factor in Amyotrophic Lateral Sclerosis Patients: Comparing Its Predictive Value to Other Lung Function Measurements.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the first and second motor neurons. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) have conventionally served as indicators of respiratory muscle strength. Recently, FEV1Q (FEV1 divided by the sex-specific first percentile values of absolute FEV1 in adults with lung disease) has been suggested as a predictor of mortality. While FVC has been utilized as a prognostic factor, FEV1Q has not yet been examined. METHODS: This retrospective unicenter study evaluated FEV1Q as a predictor of mortality in ALS patients, comparing its predictive efficacy with other measurements, including FEV1, FVC, sniff nasal inspiratory pressure, and maximal inspiratory pressure. The study utilized univariate analysis for each variable employing the Cox proportional hazards model to determine the statistical significance and predictive power of each measurement. RESULTS: Forty-five patients were included, female predominant (60%) and an average age at diagnosis of 69.2 ± 11 years. Almost all (95%) met the criteria for non-invasive ventilation (NIV) and initiated (93%) during the study period, a mean of 137 days after diagnosis. The mortality rate observed was 57%, occurring at a median of 398 days post-diagnosis. On average, patients underwent 1.7 pulmonary function tests, revealing a decline in various parameters, including FEV1, FEV1Q, and FVC. However, only FEV1Q was a statistically significant predictor of mortality (p < 0.0083) in a Cox regression analysis. A negative coefficient for FEV1Q indicated that higher values were associated with a reduced mortality risk, with an average FEV1Q of 2.68 observed at the time of death. CONCLUSION: FEV1Q emerged as the only statistically significant predictor of mortality among the evaluated respiratory measurements in ALS patients. This study is the first to focus on applying FEV1Q in the clinical evaluation of ALS, marking an initial step in understanding its potential role in patient follow-up. However, further studies are needed before these findings can be incorporated into clinical practice.

Early access flow rate predicts vascular access patency-related intervention in the first year: A retrospective cohort study.

INTRODUCTION: Arteriovenous fistulas and grafts are lifelines for most hemodialysis patients, and a low access flow rate often requires patency-related intervention, such as angioplasty or thrombectomy, to prevent access failure. We examined whether early access flow rate, measured after initial fistula/graft cannulation, predicts vascular access patency-related intervention within 1 year. METHODS: This was a single-center retrospective cohort study. Among 172 patients undergoing surgical creation of a fistula/graft, 52 (30.2%) had documented access flow rates measurement by the Transonic™ ultrasound dilution technique, performed within an average of 48 days from initial access cannulation. The need for a patency-related intervention, defined as undergoing a fistulogram, angioplasty, thrombectomy, or surgical revision, was ascertained within 1 year. A receiver-operating characteristic curve (ROC) was generated to evaluate the diagnostic performance of first and average access flow rates for predicting patency-related intervention within 1 year. FINDINGS: Twenty-eight (53.8%) of the 52 study subjects required a patency-related intervention within 1 year. Their characteristics were not significantly different from those who did not require patency-related interventions. However, first access flow rates were significantly lower in patients requiring patency-related intervention compared to those who did not (898 vs. 1471 mL/min; p = 0.003), as were average access flow rates (841 vs. 1506 mL/min; p < 0.001). The ROC analyses revealed that first access flow rates and average access flow rates predicted the need for patency-related intervention within 1 year, with an area under-the-ROC curve of 0.743 (95% confidence interval [CI] 0.608, 0.877) and 0.775 (95% CI 0.648, 0.903), respectively, demonstrating acceptable discrimination. DISCUSSION: In adults undergoing hemodialysis, early access flow rate measurement can predict patency-related intervention within 1 year after initial vascular access cannulation. Additional studies are required to confirm these findings and identify optimal access flow rate cut-off values to predict vascular accesses at higher risk of stenosis.

Impact of Diagnostic and Treatment Delays on Survival and Treatment-Related Toxicities in Portuguese Patients With Head and Neck Cancer.

INTRODUCTION: Delays in diagnosis and initiation of treatment have a negative impact on the prognosis and survival of head and neck cancer (HNC) patients. These delays also involve more intensive treatments with greater toxicity, dysfunction, and morbidity. METHODS: This was a retrospective observational study with patients diagnosed with HNC between January 1, 2018, and December 31, 2021. The main objective was to estimate whether the time to diagnosis (TD) and time until treatment initiation (TIT) translated into changes in the patient's overall survival (OS). Multivariate data analysis was performed with the Cox regression model. Significance was considered for p<0.05. RESULTS: A total of 139 patients were included in this study. Median TD was 126 days and median TIT was 43 days. No association between TD, TIT, treatment toxicity, and OS was found. Being a smoker was associated with a longer TD (p=0.05, hazard ratios {HR}=1.01). TIT was significantly shorter in higher grades (p=0.03, HR=0.57) and during coronavirus disease 2019 (COVID-19) (p=0.04, HR=0.57), but higher in larger disease (tumor {T}) (p=0.04, HR=1.39). A higher T (p=0.01, HR=2.67) and lymph node metastasis (nodes {N}) (p=0.02, HR=2.24) were identified as risk factors with a negative impact on OS, whereas grade was positively correlated (p=0.05, HR=0.32). CONCLUSIONS: Even though there was no correlation between TD and TIT, and OS, action still needs to be taken to shorten these times. T and N remain negative predictive prognostic markers of HNC.

Pressurized liquid extraction of bioactive compounds from grape peel and application in pH-sensing carboxymethyl cellulose films: A promising material to monitor the freshness of pork and milk.

This study produced pH-sensing carboxymethyl cellulose (CMC) films functionalized with bioactive compounds obtained by pressurized liquid extraction (PLE) of grape peel to monitor the freshness of pork and milk. A semi-continuous PLE was conducted using hydroethanolic solution (70:30, v/v) at a flow rate of 5 mL/min, 15 MPa, and 60 °C. The films were produced by the casting technique using CMC (2.5 %, w/v), glycerol (1 %, v/v), and functionalized with 10, 30, and 50 % (v/v) grape peel extract. From the results obtained, LC-MS/MS revealed that PLE extracted twenty-seven phenolic compounds. The main phenolic compounds were kaempferol-3-glucoside (367.23 ± 25.88 µg/mL), prunin (270.23 ± 3.62 µg/mL), p-coumaric acid (236.43 ± 26.02 µg/mL), and procyanidin B1 (117.17 ± 7.29 µg/mL). The CMC films presented suitable color and mechanical properties for food packaging applications. The addition of grape peel extract promoted the pH-sensing property, showing the sensitivity of anthocyanins to pH changes. The films functionalized with grape peel extract presented good release control of bioactive compounds, making them suitable for food packaging applications. When applied to monitor the freshness of pork and milk, the films exhibited remarkable color changes associated with the pH of the food during storage. In conclusion, PLE is a sustainable approach to obtaining bioactive compounds from the grape peel, which can be applied in the formulation of pH-sensing films as a promising sustainable material to monitor food freshness during storage.

Sustainable valorization of pitaya (Hylocereus spp.) peel in a semi-continuous high-pressure hydrothermal process to recover value-added products.

This study evaluated the use of a semi-continuous high-pressure hydrothermal process for the recovery of value-added products from pitaya peel. The process was carried out at 15 MPa, a water flow rate of 2 mL/min, a solvent-to-feed ratio of 60 g water/g pitaya peel, and temperatures ranging from 40 to 210 °C. The results show that extraction temperatures (between 40 and 80 °C) promoted the recovery of betacyanin (1.52 mg/g), malic acid (25.6 mg/g), and citric acid (25.98 mg/g). The major phenolic compounds obtained were p-coumaric acid (144.63 ± 0.42 µg/g), protocatechuic acid (91.43 ± 0.32 µg/g), and piperonylic acid (74.2 ± 0.31 µg/g). The hydrolysis temperatures (between 150 and 210 °C) could produce sugars (18.09 mg/g). However, the hydrolysis process at temperatures above 180 °C generated Maillard reaction products, which increased the total phenolic compounds and antioxidant activity of the hydrolysates. Finally, the use of semi-continuous high-pressure hydrothermal process can be a sustainable and promising approach for the recovery of value-added compounds from pitaya peel, advocating a circular economy approach in the agri-food industry.

Targeting Inhibitor of Apoptosis Proteins to Overcome Chemotherapy Resistance-A Marriage between Targeted Therapy and Cytotoxic Chemotherapy.

Precision oncology is the ultimate goal of cancer treatment, i.e., to treat cancer and only cancer, leaving all the remaining cells and tissues as intact as possible. Classical chemotherapy and radiotherapy, however, are still effective in many patients with cancer by effectively inducing apoptosis of cancer cells. Cancer cells might resist apoptosis via the anti-apoptotic effects of the inhibitor of apoptosis proteins. Recently, the inhibitors of those proteins have been developed with the goal of enhancing the cytotoxic effects of chemotherapy and radiotherapy, and one of them, xevinapant, has already demonstrated effectiveness in a phase II clinical trial. This class of drugs represents an example of synergism between classical cytotoxic chemo- and radiotherapy and new targeted therapy.

Immunotherapy around the Clock: Impact of Infusion Timing on Stage IV Melanoma Outcomes.

Although the impact of circadian timing on immunotherapy has yet to be integrated into clinical practice, chronoimmunotherapy is an emerging and promising field as circadian oscillations are observed in immune cell numbers as well as the expression of immunotherapy targets, e.g., programmed cell death protein-1 and its ligand programmed death ligand 1. Concurrent retrospective studies suggest that morning infusions may lead to higher effectiveness of immune checkpoint inhibitors in melanoma, non-small cell lung cancer, and kidney cancer. This paper discusses the results of a retrospective study (2016-2022) exploring the impact of infusion timing on the outcomes of all 73 patients with stage IV melanoma receiving immunotherapy at a particular medical center. While the median overall survival (OS) was 24.2 months (95% confidence interval [CI] 9.04-39.8), for a median follow-up of 15.3 months, our results show that having more than 75% of infusions in the afternoon results in shorter median OS (14.9 vs. 38.1 months; hazard ratio 0.45 [CI 0.23-0.86]; p < 0.01) with more expressive impacts on particular subgroups: women, older patients, and patients with a lower tumor burden at the outset of immunotherapy. Our findings highlight the potential benefits of follow-up validation in prospective and translational randomized studies.

Multidisciplinary Approach to Spinal Metastases and Metastatic Spinal Cord Compression-A New Integrative Flowchart for Patient Management.

Metastatic spine disease (MSD) and metastatic spinal cord compression (MSCC) are major causes of permanent neurological damage and long-term disability for cancer patients. The development of MSD is pathophysiologically framed by a cooperative interaction between general mechanisms of bone growth and specific mechanisms of spinal metastases (SM) expansion. SM most commonly affects the thoracic spine, even though multiple segments may be affected concomitantly. The great majority of SM are extradural, while intradural-extramedullary and intramedullary metastases are less frequently seen. The management of patients with SM is particularly complex and challenging, with multiple factors-such as the spinal stability status, primary tumor radio and chemosensitivity, cancer biological burden, patient performance status and comorbidities, and patient's oncological prognosis-influencing the clinical decision-making process. Different frameworks were developed in order to systematize and support this process. A multidisciplinary, personalized approach, enriched by the expertise of each involved specialty, is crucial. We reviewed the most recent evidence and proposed an updated algorithmic approach to patients with MSD according to the clinical scenario of each patient. A flowchart-based approach offers an evidence-based management of MSD, providing a valuable clinical decision tool in a context of high uncertainty and quick-acting need.

Semi-continuous flow-through hydrothermal pretreatment for the recovery of bioproducts from jabuticaba (Myrciaria cauliflora) agro-industrial by-product.

The valorization of the by-product of the agro-industrial processing of jabuticaba (Myrciaria cauliflora) was studied by hydrothermal pretreatment. Experiments were carried out in a semi-continuous flow-through process for 45 min, at 15 MPa, a water flow rate of 5 mL min-1, and at different temperatures (60 - 210 °C). The results demonstrate that fructose and glucose were the sugars with the highest concentration in all analyzed treatments. Arabinose and cellobiose were obtained only at higher temperatures (above 130 °C), demonstrating that they were released from the hydrolysis of polysaccharides. The highest cyanidin-3-glucoside yield (1.88 mg g-1) was achieved at 60 °C. The treatments at 135 and 210 °C promoted the degradation of cyanidin-3-glucoside, leading to yields lower than 0.05 mg g-1. At 60 °C, it was possible to recover 74.18 mg g-1 of glucose, 103.77 mg g-1 of fructose, 30.75 mg g-1 of citric acid, and 1.88 mg g-1 of cyanidin-3-glucoside, without the presence of furfural and 5-hydroxymethylfurfural. The results suggest that hydrothermal pretreatment is a promising eco-friendly technology to recover sugars, organic acids, and anthocyanins from jabuticaba by-products in a circular economy framework.

Radiotherapy, Chemotherapy and Immunotherapy-Current Practice and Future Perspectives for Recurrent/Metastatic Oral Cavity Squamous Cell Carcinoma.

Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. While surgical resection is the cornerstone of a multimodal curative approach, some tumors are deemed recurrent or metastatic (R/M) and often not suitable for curative surgery. This mainly occurs due to the extent of lesions or when surgery is expected to result in poor functional outcomes. Amongst the main non-surgical therapeutic options for oral squamous cell carcinoma are radiotherapy, chemotherapy, molecular targeted agents, and immunotherapy. Depending on the disease setting, these therapeutic approaches can be used isolated or in combination, with distinct efficacy and side effects. All these factors must be considered for treatment decisions within a multidisciplinary approach. The present article reviews the evidence regarding the treatment of patients with R/M oral squamous cell carcinoma. The main goal is to provide an overview of available treatment options and address future therapeutic perspectives.

Relationship of glomerular filtration rate and serum CK activity after resistance exercise in women.

The aim of study was to assess the correlation between the changes in serum CK activity after a resistance exercise and renal function measured by glomerular filtration rate (eGFR). Twenty-nine trained women (32 ± 10 years; 157 ± 4 cm; 58.8 ± 6.4 kg) performed a resistance exercise session with 17 exercises with 3 × 12 repetitions in a circuit training fashion. Subjects provided blood samples prior to exercise session (PRE), and at 24, 48, and 72 h following exercise session for creatine kinase (CK) and creatinine. 24-Urine samples were collected before and 72 h after exercises. eGFR was obtained by the three most recommended methods (MDRD; MCQE; Cockcroft-Gault). After the exercise session, serum CK activity increase up 1.68 times (P < 0.01). Serum creatinine increased 25.5% (P = 0.0000) while urinary creatinine decreased on average 6.4% (P = 0.0422). eGFR decreased in all formulas: MDRD by 21.5%, MCQE by 14.2%, and C-G by 17% (all with P < 0.01). Ccr also decreased (-22.9%, P < 0.01). The index of correlation was significant for MDRD (r = -0.924; P < 0.01), C-G (r = -0.884; P < 0.01), and MQCE (r = -0.644; P < 0.05). In conclusion, we observed a significant negative correlation between CK activity and the eGFR indices of renal function.