Negative Prognostic Factor Research Articles

The prognostic value of myosteatosis in pancreatic cancer: A systematic review and meta-analysis

Background and aimsThe phenomenon of myosteatosis, characterized by the accumulation of ectopic fat within and surrounding skeletal muscle, has been identified as a potential adverse factor in the prognosis of individuals with cancer. This systematic review and meta-analysis sought to examine the association between myosteatosis and survival rates as well as postoperative complications in patients diagnosed with pancreatic cancer (PC). MethodsA systematic search was conducted on Web of Science, Embase, and Pubmed until March 25, 2024, to identify pertinent articles assessing the prognostic significance of myosteatosis in patients with PC, utilizing the search terms: myosteatosis, PC, and prognosis. The selected studies were utilized to investigate the prognostic impact of myosteatosis on the survival of PC patients. Forest plots and pooled effects models were employed to present the findings of this meta-analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). A total of 565 studies were initially identified from the three databases, with 14 retrospective cohort studies ultimately included in the final quantitative analysis. ResultsThe meta-analysis revealed a significant association between myosteatosis and both overall survival (OS) [Hazard Ratio (HR): 1.55, 95% Confidence Interval (CI): 1.40-1.72, P < 0.001, I2=0.0%] and recurrence-free survival (RFS) (HR 1.48, 95% CI: 1.17-1.86, P = 0.001, I2=0.0%) in patients diagnosed with PC. Subgroup analyses revealed that myosteatosis continued to be a negative prognostic factor in PC across various treatment modalities, patient populations, and myosteatosis assessment methods. Additionally, myosteatosis was identified as a risk factor for postoperative complications, with a pooled odds ratio of 2.20 (95% CI: 1.45-3.35, P < 0.001, I2=37.5%). All included studies achieved NOS scores of 6 or higher, indicating a relatively high level of methodological quality. ConclusionThese results suggest that myosteatosis is significantly associated with both survival outcomes and postoperative complications in patients with PC.

Sleep disturbances in probable multiple system atrophy

BackgroundMultiple system atrophy (MSA) is a fatal alpha-synucleinopathy characterized by variable combinations of parkinsonism, autonomic and cerebellar dysfunction. Sleep in MSA is highly compromised due to various sleep disturbances. Disrupted sleep-wake cycles in MSA contribute to poor health-related quality of life and are negative prognostic factors. ObjectivesWe aimed to study the various sleep disturbances; the effect of parkinsonian and cerebellar phenotypes on sleep; and the correlation of sleep parameters with disease severity in an Asian-Indian cohort of probable MSA patients. MethodsWe recruited 60 probable MSA patients (MSA-P = 19; MSA-C = 41). Disease severity was assessed using UPDRS-III, UMSARS-I and UMSARS-II. Detailed history and relevant sleep questionnaires were applied to evaluate the sleep disturbances. ResultsSleep disturbances were universally observed in probable MSA patients in this cohort. These include REM behavior disorder (RBD)-95 %; poor sleep quality-80 %; secondary insomnia and intermittent awakenings-100 %; excessive daytime sleepiness-26 %; risk for obstructive sleep apnea-51.7 % and snoring-85 %. MSA patients reported 38.2 ± 22.9 percentage improvement in sleep with the medications. There was no significant difference between probable MSA-P and MSA-C patients in any of the sleep parameters. Sleep quality was poor in patients with pre-motor RBD than post-motor RBD (p < 0.01). Poor sleep quality had a moderate positive correlation with RBD duration. Disease severity positively correlated with RBD duration and poor sleep quality. ConclusionsSleep disturbances, the negative prognostic factors, were universally observed in this Asian Indian MSA cohort. This study provides supporting evidence that RBD might play a possible role in MSA disease severity, progression, and sleep quality.

The effect of midline shift on survival time in dogs with structural brain disease diagnosed on MRI.

The effect of midline shift identified on brain MRI on survival time in dogs with structural brain disease is relatively unknown. This retrospective single-centered cohort study reviewed medical and imaging data of 77 dogs with structural brain lesions evident on MRI. Images were reviewed for the presence of midline shift, brain edema, foramen magnum herniation, and ventriculomegaly. Kaplan-Meier method and Cox regression analysis were undertaken to compare survival between dogs with and without midline shift. Midline shift was present in 40 of 77 (52%) dogs and absent in 37 of 77 (48%). Univariate analysis revealed that dogs with midline shift had a median survival time of 34.5 days (95% CI, 4-108 days) compared with 241 days (95% CI, 133,- days) in dogs without midline shift (hazard ratio=2.67, 95% CI, 1.5-4.49). Multivariate Cox regression analysis revealed a hazard ratio of 3.6 (95% CI, 1.7-7.6; P-value<.001) for dogs with midline shift. Shorter median survival times remained significant in all groups after segregation based on etiological diagnosis. The significantly shorter survival times observed herein for dogs with midline shifts, regardless of etiologic cause, provide further evidence that midline shift holds value as a negative prognostic factor in diagnostic imaging.

Examination of Sarcopenia with Obesity as a Prognostic Factor in Patients with Colorectal Cancer Using the Psoas Muscle Mass Index

Background: Sarcopenia, the age-related loss of muscle mass, is a negative prognostic factor in gastrointestinal cancer. Sarcopenia combined with visceral obesity (sarcopenic obesity) is associated with poor outcomes. We explored the influence of obesity and other factors on the prognosis of patients with colorectal cancer diagnosed with sarcopenia. Methods: We enrolled 211 patients with colorectal cancer diagnosed with preoperative sarcopenic obesity who underwent radical resection at Osaka University Hospital between January 2009 and January 2012. Muscle mass was assessed using the psoas muscle mass index. Obesity was evaluated by measuring the visceral fat area in the umbilical region. Patients were categorized into two groups: sarcopenia with obesity (SO) and sarcopenia without obesity (non-SO). Overall survival, cancer-specific survival, and cancer-related relapse-free survival (CRRFS) were compared between the two groups. Patient characteristics, including age, sex, body mass index, serum albumin, C-reactive protein, tumor markers, prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and geriatric nutritional risk index (GNRI), were also analyzed. Results: CRRFS was significantly shorter in the SO group than in the non-SO group (p = 0.028). PNI, mGPS, and GNRI were not identified as significant prognostic factors for CRRFS. Multivariate analysis highlighted sarcopenic obesity, elevated carcinoembryonic antigen levels, and unfavorable histological types as significant predictors of poor CRRFS outcomes. Conclusions: Sarcopenic obesity is an independent predictor of poor prognosis in patients with CRC. Thus, interventions aimed at increasing muscle mass and reducing visceral fat could potentially improve the prognosis of these patients.

Impact of chronic kidney disease on the course and outcome of COVID-19

COVID-19 is primarily a respiratory disease. However, patients with COVID-19 are at high risk for acute kidney injury or exacerbation of preexisting kidney disease, especially those with comorbidities such as hypertension, coronary artery disease, chronic liver disease, chronic kidney disease, and malignancies. We reviewed studies that assessed the association between chronic kidney disease and SARS-CoV-2 coronavirus infection and infection outcomes, including hospitalization, severe COVID-19, need for intensive care, COVID-19 progression, and death. The studies showed varied and often contradictory results, as the baseline data differ in many parameters, such as the period of the pandemic, quality and size of the sample, and degree of comorbidity. Nevertheless, the studies consistently revealed that chronic kidney disease is an unfavorable factor with regard to SARS-CoV-2 infection. Furthermore, concomitant chronic kidney disease predisposes patients with COVID-19 to severe COVID-19, viral pneumonia, development of acute respiratory distress syndrome, acute kidney injury, and other complications, which in turn are negative prognostic factors for mortality. Patients with chronic kidney disease who survived COVID-19 are more likely to develop post-COVID syndromes with various persistent or recurrent symptoms than convalescents without renal comorbidity. These patients require long-term monitoring and optimization of therapy and are priority for vaccination.

Evaluating estimated health care resource utilization and costs in patients with myelofibrosis based on transfusion status and anemia severity: A retrospective analysis of the Medicare Fee-For-Service claims data.

Myelofibrosis (MF) is a rare but aggressive myeloproliferative neoplasm that commonly affects older patients, with a mean age of onset of older than 60 years. At least a third of patients with primary MF are anemic at diagnosis, and nearly all patients become anemic over time; approximately half require red blood cell transfusions within a year of diagnosis. Anemia and transfusion dependence are leading negative prognostic factors for overall survival and are associated with diminished quality of life and increased health care-related economic burden in patients with MF. To describe baseline characteristics, health care resource utilization (HCRU), and costs as a function of transfusion status and anemia severity in patients diagnosed with MF among the US Medicare Fee-For-Service (FFS) population. This retrospective cohort study included patients diagnosed with MF appearing in the 100% Medicare FFS database enrolled between January 1, 2012, and December 31, 2020. Patients were segmented into hemoglobin level cohorts (no, mild, moderate, and severe anemia) and transfusion status cohorts (transfusion independent [TI], transfusion requiring [TR], or transfusion dependent [TD]). Across cohorts, demographics and disease characteristics were assessed at baseline; per patient per month all-cause HCRU and medical and pharmacy costs were reported during follow-up. All results were summarized descriptively. The transfusion status cohort (N = 1,749) included TI (n = 980), TR (n = 559), and TD (n = 210) patients; the anemia severity cohort (N = 365) included patients with no (n = 100), mild (n = 128), moderate (n = 99), and severe (n = 38) anemia. On average, TR and TD patients or those with moderate or severe anemia had numerically higher Deyo-Charlson Comorbidity Index scores than those who were TI or had mild or no anemia. TR and TD cohorts reported numerically greater all-cause outpatient, inpatient, and emergency department utilization vs the TI cohort. All-cause costs were numerically higher in the TD and TR cohorts vs the TI cohort ($14,655 and $14,249 vs $8,191). Incremental increases in HCRU and costs were also observed with increasing anemia severity. All-cause medical and pharmacy costs for no, mild, moderate, and severe anemia cohorts were $4,689, $7,268, $10,439, and $13,590, respectively. This retrospective analysis of the US Medicare FFS database descriptively evaluated patients by transfusion status and anemia severity and showed that costs and HCRU were numerically lower for patients with transfusion independence compared with those with transfusion dependence. Similar trends were seen when comparing patients based on anemia status, with numerically lower HCRU and cost observed with decreasing anemia severity.

Food Aversion, Systemic Inflammation and Intramuscular Adipose Tissue are Mortality Predictors in Advanced Lung Cancer Patients

ABSTRACTBackgroundCancer cachexia, systemic inflammation and muscle wasting are associated with poor survival in non–small cell lung cancer (NSCLC) patients (pts). We hypothesized whether neutrophil‐to‐lymphocyte ratio (NLR) and intramuscular adipose tissue/skeletal muscle index (IMAT/SMI) would predict prognosis in metastatic NSCLC (mNSCLC). In addition, we verified the role of a cancer cachexia questionnaire (EORTC‐QLQ‐CAX24) in the survival prediction.MethodsWe analysed a prospective cohort of 128 treatment‐naive mNSCLC pts (April 2017 to May 2020). We evaluated QoL using the EORTC‐QLQ‐C30 and EORTC‐QLQ‐CAX24 scales. We used the baseline NLR as a surrogate of systemic inflammation. We did evaluate IMAT/SMI using baseline plain computed tomography imaging. Cox multivariate regression, including age, sex, ECOG‐PS and histology as covariates, was performed.ResultsElevated NLR (hazard ratio [HR] 1.26, 95% confidence interval [CI]: 1.01–1.59, p = 0.038), IMAT/SMI ratio (HR 1.37, 95% CI: 1.03–1.84, p = 0.032) and high CAX24 scores for food aversion (HR 1.52, 95% CI: 1.13–2.03, p = 0.006) were associated with worse prognosis in mNSCLC. Indeed, higher ECOG‐PS (Spearman rho = 0.208, p = 0.027), CAX24 scores for food aversion (Spearman rho = 0.197, p = 0.036), loss of control (Spearman rho = 0.212, p = 0.024) and eating and weight loss worry domains (Spearman rho = 0.219, p = 0.020) were associated with elevated NLR levels.ConclusionsElevated NLR, IMAT/SMI ratio and CAX24 score for food aversion are independently associated with worse survival in mNSCLC. These data underscored the importance of cachexia features as negative prognostic factors in mNSCLC and revealed the EORTC‐QLQ‐CAX24 questionnaire as a new tool for helping clinical decision‐making.Trial Registration: ClinicalTrials.gov identifier: NCT03960034 and NCT04306094

Impact of Sarcopenia on Treatment Outcomes and Toxicity in Locally Advanced Rectal Cancer

Background and Objectives: Sarcopenia, a condition characterized by muscle mass loss, is prevalent in up to 68% of rectal cancer patients and has been described as a negative prognostic factor, impacting overall survival and tumor response. While there are extensive data on rectal cancer globally, only a handful of studies have evaluated the role of sarcopenia in locally advanced rectal cancer (LARC). Our study aimed to investigate the relationship between sarcopenia, overall response rate, and toxicity in patients who underwent total neoadjuvant treatment (TNT) for LARC. Materials and Methods: We performed a retrospective study of patients with rectal cancer treated with TNT and surgery with curative intent between 2021 and 2023 at Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj-Napoca. Sarcopenia was assessed on MRI images by measuring the psoas muscle area (PMA) at the level of the L4 vertebra before and after neoadjuvant therapy. The primary endpoints were the overall complete response rate (oCR) and acute toxicity. Results: This study included 50 patients with LARC. The oCR rate was 18% and was significantly associated with post-treatment sarcopenia (OR 0.08, p = 0.043). Patients who did not achieve a clinical or pathologic complete response had, on average, an 8% muscle loss during neoadjuvant therapy (p = 0.022). Cystitis and thrombocytopenia were significantly associated with post-treatment sarcopenia (p = 0.05 and p = 0.049). Conclusions: Sarcopenia and loss of psoas muscle during neoadjuvant therapy were negatively associated with tumor response in locally advanced rectal cancer. Thrombocytopenia and cystitis are more frequent in sarcopenic than non-sarcopenic patients undergoing neoadjuvant chemoradiation for rectal cancer.

Complimentary Role of Comprehensive Palliative Care Treatment to Intrathecal Therapy: Case Report

Intrathecal therapy with implanted devices is often reported in some recommendations.for the management of difficult cancer pain However, data is often biased by optimistic view and poor assessment.We report a case of patient in which a comprehensive and complex palliative care treatment was effective in managing a patient who was implanted a subcutaneous port for intrathecal analgesiaThis patient had many characteristics of a difficult pain, really defined as refractory due to various negative prognostic pain factors, such as neuropathic pain and psychological distress..A comprehensive pain management with a balanced approach including both interventional therapy and palliative care simultaneously, allowed to achieve optimal pain control. Terms such as intractable or refractory pain, have been ambiguously used in literature to select patients as candidates for implated pumps. A meaningful evaluation and a comprehensive treatment should be mandatory when using intrathecal anlgesia in patients with very difficult pain conditions.

Cardiovascular disease and psychiatric disorders: An-up-to date review.

Cardiovascular diseases (CVD) and mental health disorders (MHD) are respectively the first and second most prevalent diseases in high-income countries and the two most relevant causes of disability worldwide. The close association between the two conditions has been known for a long time and research has been able to document how the co-morbidity between cardiovascular disorders and mental health disorders is a negative prognostic factor for both conditions. This strong connection and the relevance of the impact of the association have led to define a new branch of cardiology, known as behavioral cardiology. The aim of the new branch is just to study the nexus CVD-MHD in order to prevent or decrease the burden of MHD on CVD and vice versa. This review describes the epidemiological evidence of the relationship between MHD on CVD at the state of the art among clinical research.

Post-injury treatment with 7,8-dihydroxyflavone attenuates white matter pathology in aged mice following focal traumatic brain injury

Traumatic brain injury (TBI) is a major cause of morbidity and mortality, not least in the elderly. The incidence of aged TBI patients has increased dramatically during the last decades. High age is a highly negative prognostic factor in TBI, and pharmacological treatment options are lacking. We used the controlled cortical impact (CCI) TBI model in 23-month-old male and female mice and analyzed the effect of post-injury treatment with 7,8 dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor (BDNF)-mimetic compound, on white matter pathology. Following CCI or sham injury, mice received subcutaneous 7,8-DHF injections (5 ​mg/kg) 30 ​min post-injury and were sacrificed on 2, 7 or 14 days post-injury (dpi) for histological and immunofluorescence analyses. Histological assessment with Luxol Fast Blue (LFB)/Cresyl Violet stain showed that administration of 7,8-DHF resulted in preserved white matter tissue at 2 and 7 dpi with no difference in cortical tissue loss at all investigated time points. Treatment with 7,8-DHF led to reduced axonal swellings at 2 and 7 dpi, as visualized by SMI-31 (Neurofilament Heavy Chain) immunofluorescence, and reduced number of TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labelling)/CC1-positive mature oligodendrocytes at 2 dpi in the perilesional white matter. Post-injury proliferation of Platelet-derived Growth Factor Receptor (PDGFRα)-positive oligodendodrocyte progenitor cells was not altered by 7,8-DHF. Our results suggest that 7,8-DHF can attenuate white matter pathology by mitigating axonal injury and oligodendrocyte death in the aged mouse brain following TBI. These data argue that further exploration of 7,8-DHF towards clinical use is warranted.

Efficacy and outcome analysis: monotherapy and combination therapy of S-1 for patients with advanced non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related mortality worldwide. S-1, a fluorouracil derivative known for its efficacy and minimal adverse effects in various solid tumors, offers hope for advanced non-small cell lung cancer (NSCLC) patients. This study conducted a retrospective, single-center analysis to investigate the effectiveness and safety of S-1 monotherapy and combination therapy as second-line or subsequent treatment for advanced NSCLC. A total of 52 patients diagnosed with advanced NSCLC at Zhejiang Cancer Hospital (Hangzhou, China) from January 1, 2018, to August 31, 2023 were included in a retrospective study. Among these patients, 13 received S-1 monotherapy while 39 received S-1 in combination therapy. The study aimed to analyze the short-term efficacy, long-term outcome, prognostic factors, and treatment-related adverse events (AEs). The objective response rate (ORR) was 28.8%, with a median progression-free survival (PFS) of 2.7 months [95% confidence interval (CI): 2.1-2.8] and a median overall survival (OS) of 9.5 months (95% CI: 6.3-12.6) for the entire cohort. The combination therapy with S-1 was determined to be a significant independent predictor of OS, while treatment line was identified as an independent negative prognostic factor for OS. The most prevalent AE observed was anemia, affecting 12 patients (23.1%). The majority of AEs were classified as grade 1-2, with only 3 patients (5.7%) experiencing grade 3-4 AEs. Further prospective studies are recommended to fully assess the therapeutic value of this treatment approach. Results indicated that both S-1 monotherapy and combination therapy showed promising efficacy and were well tolerated as second-line or later-line treatments for patients with advanced NSCLC. Further prospective studies are recommended to fully assess the therapeutic value of this treatment approach.

Diet and exercise in relation to lower extremity artery disease.

Adherence to the Mediterranean diet (MeD) has been associated with a reduced incidence of peripheral arterial disease (PAD)/lower extremity arterial disease (LEAD) in observational trials and in a randomized trial. In secondary prevention, a lower hazard ratio for composite major adverse cardiovascular events has been associated with better adherence to MeD in a relatively small, randomized trial. This has not been confirmed in a sub-analysis of a large interventional trial of dual antithrombotic treatment. The effects of vegetarian, vegan or low carbohydrate/ketogenic diets on the incidence and outcomes of PAD/LEAD are not known. While abdominal obesity is associated with diabetes mellitus and PAD/LEAD, the lowest incidence of PAD/LEAD has been found in subjects with a body mass index 25-29.9 kg/m2. Malnutrition is a negative prognostic factor for survival of patients with chronic limb threatening ischemia. Physical activity (PA) is an acute stressor, but habitual recreational PA results in beneficial adaptations and improved health. In observational studies, lower levels of exercise and lower physical fitness have been associated with more prevalent PAD/LEAD. In contrast to coronary artery disease, that shows a reverse J-shaped relationship between long-term endurance exercise and coronary atherosclerosis, such a relationship is not known for PAD/LEAD. A general recommendation for maintaining cardiovascular health is performing regular moderate-intensity exercise with some vigorous-intensity aerobic PA, and resistance exercise at least twice a week. Combinations of healthy behaviors are more effective in preventing PAD/LEAD than a single behavioral component. In treatment of PAD/LEAD causing intermittent claudication, supervised walking training is recommended among measures of first-line treatment, while unsupervised walking training should be considered as an alternative.

Renal Cell Carcinoma With Tumor Thrombus Extending Into the Inferior Vena Cava and the Right Atrium Demonstrated by 68 Ga-DOTATATE PET/CT.

Approximately 10% of all renal cell carcinoma (RCC) patients develop a venous tumor thrombus, a major negative prognostic factor. Surgical excision is commonly required for RCC patients with tumor thrombus. Accurate preoperative diagnosis and assessment of tumor thrombus level is vital because the level of thrombus may influence treatment decisions. MRI, contrast-enhanced CT, 18 F-FDG PET/CT, and 68 Ga-PSMA PET/CT have been used to diagnose and evaluate the extent of tumor thrombus in RCC. However, no case of RCC with inferior vena cava tumor thrombus showing 68 Ga-DOTATATE uptake has been reported yet. Herein, we report a case of metastatic RCC with tumor thrombus in the inferior vena cava on 68 Ga-DOTATATE PET/CT.

Utility of atezolizumab plus bevacizumab, carboplatin, and paclitaxel combination for the treatment of advanced non-squamous non-small cell lung cancer patients with malignant pleural effusion.

Malignant pleural effusion (MPE) remains a negative prognostic factor in non-small cell lung cancer (NSCLC), even after the emergence of immune checkpoint inhibitors. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Bevacizumab, a humanized monoclonal antibody against VEGF, is a key agent for patients who develop MPE. However, it is unclear whether MPE is a poor prognostic factor in patients with advanced non-squamous NSCLC receiving treatment with the atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP) regimen. Moreover, the effect of ABCP on MPE control is unknown. This study aimed to elucidate the efficacy and safety of ABCP for non-squamous NSCLC patients with MPE. We retrospectively analyzed consecutive patients with advanced non-squamous NSCLC who received treatment with ABCP (January 2019-September 2023). Patients were divided into two groups (non-MPE and MPE), and treatment outcomes were compared. In the MPE group, treatment efficacy for MPE control and toxicity were evaluated. Of the 46 patients enrolled, 17 and 29 were included in the non-MPE and MPE groups, respectively. The objective response and disease control rates were not significantly different between the non-MPE and MPE groups (76.5% vs. 51.7%, P=0.13; 88.2% vs. 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 vs. 10.1 months, P=0.87; 16.0 vs. 19.9 months, P=0.87, respectively). In the MPE group, 25 patients (86.2%) achieved MPE control lasting >8 weeks from the initiation of treatment with ABCP; the median progression-free survival without an unequivocal increase in MPE was 15.0 months. The incidence rates of grade ≥3 non-immune- and immune-related adverse events were 83% and 17%, respectively. There was no treatment-related death. The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE.

Comparison of manual versus automated thermal lid therapy with expression for meibomian gland dysfunction in patients with dry eye disease.

To compare two types of lipid expression procedures to treat dry eye disease. Standardized treatment and evaluation methods were used in patients treated with either manual thermoelectric lipid expression (MiBoFlo) or automated lipid expression (Lipiflow) of the Meibomian glands. This was a contemporaneous, non-randomized study of both treatment methods. Treatment was per the manufacturers' recommendation. The primary outcome included two types of dry eye questionnaires as well as objective analysis of ocular surface including tear break up time, Schirmer testing, Osmolarity, and fluorescein staining. Baseline characteristics analyzed included floppy lid, conjunctivochalasis and lagophthalmos. Statistical analysis was performed correcting for baseline factors such as age and co existing pathology using multivariable analysis. Both treatments improved the results of the OSDI and SPEED dry eye questionnaire results. Both treatments resulted in improvement of many objective findings including SPK, lissamine green staining and tear break up time with the MiBoFlo showing more improvement than Lipiflow. OSDI was more sensitive to improvement of symptoms than the SPEED questionnaire. Manual expression with MiBoFlo device resulted in statistically more improvement in questionnaire scores than did automated expression with Lipiflow. Negative prognostic factors for symptomatic improvement included blepharitis, autoimmune disease and ocular allergies. Thermal lid therapy along with mechanical expression of lipids from the meibomian glands successfully treats dry eye symptoms and signs. Manual therapy with MiBoFlo resulted in more subjective and objective improvement scores than automated therapy with the Lipiflow device.

Germline Polymorphisms Associated with Overall Survival in Lung Adenocarcinoma: Genome-Wide Analysis.

Lung cancer remains a global health concern, with substantial variation in patient survival. Despite advances in detection and treatment, the genetic basis for the divergent outcomes is not understood. We investigated germline polymorphisms that modulate overall survival in 1464 surgically resected lung adenocarcinoma patients. A multivariable Cox proportional hazard model was used to assess the association of more than seven million polymorphisms with overall survival at the 60-month follow-up, considering age, sex, pathological stage, decade of surgery and principal components as covariates. Genes in which variants were identified were studied in silico to investigate functional roles. Six germline variants passed the genome-wide significance threshold. These single nucleotide polymorphisms were mapped to non-coding (intronic) regions on chromosomes 2, 3, and 5. The minor alleles of rs13000315, rs151212827, and rs190923216 (chr. 2, 3 and 5, respectively) were found to be independent negative prognostic factors. All six variants have been reported to regulate the expression of nine genes, seven of which are protein-coding, in different tissues. Survival-associated variants on chromosomes 2 and 3 were already reported to regulate the expression of NT5DC2 and NAGK, with high expression associated with the minor alleles. High NT5DC2 and NAGK expression in lung adenocarcinoma tissue was already shown to correlate with poor overall survival. This study highlights a potential regulatory role of the identified polymorphisms in influencing outcome and suggests a mechanistic link between these variants, gene expression regulation, and lung adenocarcinoma prognosis. Validation and functional studies are warranted to elucidate the mechanisms underlying these associations.

Genomic Landscape of Myelodysplastic/Myeloproliferative Neoplasms: A Multi-Central Study.

The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.

Comorbidity and Disease Activity in Multiple Sclerosis

Multiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant to clinicians and clinical trialists. To evaluate the association of comorbidities with disease activity in clinical trials of disease-modifying therapies (DMTs) in populations with MS. A 2-stage meta-analytic approach was used in this cohort study of individual participant data from phase 3 clinical trials of MS DMTs that had 2 years of follow-up and were conducted from November 2001 to March 2018. Data were analyzed from February 2023 to June 2024. Comorbidity burden and individual comorbidities present at trial enrollment, including hypertension; hyperlipidemia; functional cardiovascular disease, ischemic heart, cerebrovascular, and peripheral vascular disease; diabetes; autoimmune thyroid and miscellaneous autoimmune conditions; migraine; lung and skin conditions; depression; anxiety; and other psychiatric disorders. The main outcome was evidence of disease activity (EDA) over 2 years of follow-up, defined as confirmed relapse activity, disability worsening, or any new lesions on magnetic resonance imaging. A total of 16 794 participants with MS were included from 17 clinical trials (67.2% female). Over the 2-year follow-up, 61.0% (95% CI, 56.2%-66.3%; I2 = 97.9%) of the pooled trials had EDA. After adjusting for multiple factors, the presence of 3 or more comorbidities was associated with an increased hazard of EDA (adjusted hazard ratio [AHR], 1.14; 95% CI, 1.02-1.28) compared with no comorbidity. Presence of 2 or more cardiometabolic conditions was also associated with an increased hazard of EDA (AHR, 1.21; 95% CI, 1.08-1.37) compared with no cardiometabolic comorbidity. Presence of 1 psychiatric disorder was associated with an increased hazard of EDA (AHR, 1.07; 95% CI, 1.02-1.14). In this study, a higher burden of comorbidity was associated with worse clinical outcomes in people with MS, although comorbidity could potentially be a partial mediator of other negative prognostic factors. Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice.

Differences in Trunk Acceleration-Derived Gait Indexes in Stroke Subjects with and without Stroke-Induced Immunosuppression.

Background: Stroke-induced immunosuppression (SII) represents a negative rehabilitative prognostic factor associated with poor motor performance at discharge from a neurorehabilitation unit (NRB). This study aims to evaluate the association between SII and gait impairment at NRB admission. Methods: Forty-six stroke patients (65.4 ± 15.8 years, 28 males) and 42 healthy subjects (HS), matched for age, sex, and gait speed, underwent gait analysis using an inertial measurement unit at the lumbar level. Stroke patients were divided into two groups: (i) the SII group was defined using a neutrophil-to-lymphocyte ratio ≥ 5, and (ii) the immunocompetent (IC) group. Harmonic ratio (HR) and short-term largest Lyapunov's exponent (sLLE) were calculated as measures of gait symmetry and stability, respectively. Results: Out of 46 patients, 14 (30.4%) had SII. HR was higher in HS when compared to SII and IC groups (p < 0.01). HR values were lower in SII when compared to IC subjects (p < 0.01). sLLE was lower in HS when compared to SII and IC groups in the vertical and medio-lateral planes (p ≤ 0.01 for all comparisons). sLLE in the medio-lateral plane was higher in SII when compared to IC subjects (p = 0.04). Conclusions: SII individuals are characterized by a pronounced asymmetric gait and a more impaired dynamic gait stability. Our findings underline the importance of devising tailored rehabilitation programs in patients with SII. Further studies are needed to assess the long-term outcomes and the role of other clinical features on gait pattern.