Poor Treatment Research Articles

In vitro T cell responses to PD-1 blockade are reduced by IFN-α but do not predict therapy response in melanoma patients

PD-1 blockade therapy has revolutionized melanoma treatment, but still not all patients benefit and pre-treatment identification of those patients is difficult. Increased expression of inflammatory markers such as interleukin (IL)-6 in blood of patients correlates with poor treatment response. We set out to study the effect of inflammatory cytokines on PD-1 blockade in vitro. For this, we studied the effect of IL-6 and type I interferon (IFN) in vitro on human T cells in a mixed leukocyte reaction (MLR) in the absence or presence of PD-1 blockade. While IL-6 reduced IFN-γ secretion by T cells in both the presence and absence of PD-1 blockade, IFN-α specifically reduced the IFN-γ secretion only in the presence of PD-1 blockade. IFN-α reduced T cell proliferation independent of PD-1 blockade and reduced the percentage of cells producing IFN-γ only in the presence of PD-1 blockade. Next we determined the type I IFN score in a cohort of 22 melanoma patients treated with nivolumab. In this cohort, we did not find a correlation between clinical response and type I IFN score, nor between clinical response and IFN-γ secretion in vitro in a MLR in the presence of PD-1 blockade. We conclude that IFN-α reduces the effectiveness of PD-1 blockade in vitro, but that in this cohort, type I IFN score in vivo, nor IFN-γ secretion in vitro in a MLR in the presence of PD-1 blockade correlated to decreased therapy responses in patients.

Investigation of ferroptosis-associated molecular subtypes and immunological characteristics in lupus nephritis based on artificial neural network learning

BackgroundLupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) with poor treatment outcomes. The role and underlying mechanisms of ferroptosis in LN remain largely unknown. We aimed to explore ferroptosis-related molecular subtypes and assess their prognostic value in LN patients.MethodsMolecular subtypes were classified on the basis of differentially expressed ferroptosis-related genes (FRGs) via the Consensus ClusterPlus package. The enriched functions and pathways, immune infiltrating levels, immune scores, and immune checkpoints were compared between the subgroups. A scoring algorithm based on the subtype-specific feature genes identified by artificial neural network machine learning, referred to as the NeuraLN, was established, and its immunological features, clinical value, and predictive value were evaluated in patients with LN. Finally, immunohistochemical analysis was performed to validate the expression and role of feature genes in glomerular tissues from LN patients and controls.ResultsA total of 10 differentially expressed FRGs were identified, most of which showed significant correlation. Based on the 10 FRGs, LN patients were classified into two ferroptosis subtypes, which exhibited significant differences in immune cell abundances, immune scores, and immune checkpoint expression. A NeuraLN-related protective model was established based on nine subtype-specific genes, and it exhibited a robustly predictive value in LN. The nomogram and calibration curves demonstrated the clinical benefits of the protective model. The high-NeuraLN group was closely associated with immune activation. Clinical specimens demonstrated the alterations of ALB, BHMT, GAMT, GSTA1, and HAO2 were in accordance with bioinformatics analysis results, GSTA1 and BHMT were negatively correlated with the severity of LN.ConclusionThe classification of ferroptosis subtypes and the establishment of a protective model may form a foundation for the personalized treatment of LN patients.

MUC16 as a serum-based prognostic indicator of prometastatic gastric cancer

Metastatic gastric cancer (GC) presents significant clinical challenges due to its poor prognosis and limited treatment options. To address this, we conducted a targeted protein biomarker discovery study to identify markers predictive of metastasis in advanced GC (AGC). Serum samples from 176 AGC patients (T stage 3 or higher) were analyzed using the Olink Proteomics Target panels. Patients were retrospectively categorized into nonmetastatic, metastatic, and recurrence groups, and differential protein expression was assessed. Machine learning and gene set enrichment analysis (GSEA) methods were applied to discover biomarkers and predict prognosis. Four proteins (MUC16, CAIX, 5’-NT, and CD8A) were significantly elevated in metastatic GC patients compared to the control group. Additionally, GSEA indicated that the response to interleukin-4 and hypoxia-related pathways were enriched in metastatic patients. Random forest classification and decision-tree modeling showed that MUC16 could be a predictive marker for metastasis in GC patients. Additionally, ELISA validation confirmed elevated MUC16 levels in metastatic patients. Notably, high MUC16 levels were independently associated with metastatic progression in T3 or higher GC. These findings suggest the potential of MUC16 as a clinically relevant biomarker for identifying GC patients at high risk of metastasis.

Online mindfulness-based cognitive therapy for treatment-resistant depression: a parallel-arm randomized controlled feasibility trial.

Treatment-resistant depression (TRD) presents a significant challenge, affecting approximately 30% of individuals diagnosed with major depressive disorder and leading to poor treatment responses. Innovations in digital mental health, especially online mindfulness-based cognitive therapy (eMBCT), offer promising avenues for enhancing access to effective mental health care for individuals with TRD in a clinical setting. The aim of this study was to examine the feasibility of eMBCT in an individual clinical context to decrease depressive symptoms for TRD. Conducted at the Institute of Psychiatry of the Federal University of Rio de Janeiro, Brazil, this parallel-arm, randomized controlled feasibility trial involved outpatients diagnosed with TRD, aged 18 and above. Of the 39 outpatients invited, 28 were randomized into two groups: an intervention group receiving the eMBCT program (n = 15) and a control group (n = 13). The intervention, consisting of an 8-week course, was delivered via live video sessions. Following the assessment period, participants in the control group were offered the eMBCT intervention. Assessments using standardized questionnaires were conducted at the start and end of the study. Within the eMBCT group, improvements were observed in depression symptoms (Z = -3.423; p = 0.001; effect size r = 0.78), anxiety symptoms (Z = -3.361; p = 0.001; effect size r = 0.77), with no significant changes in the control group. Comparatively, the eMBCT group showed significant reductions in depression symptoms and improvements in clinical global impressions over the control group (BDI2: U = 30.5; p = 0.015; effect size r = 0.47, CGI1: U = 21.0; p = 0.004; effect size r = 0.56). eMBCT in an individual format combined with medication, appears to be a feasible treatment for TRD, decreasing symptoms of depression. In a future trial the control group may have a manualized intervention. The Brazilian Clinical Trials Registry: (https://ensaiosclinicos.gov.br/rg/RBR-6zndpbv) and RBR-6zndpbv.

Depression among Tuberculosis Patients and its Association with Medication Adherence of Anti-Tuberculosis Drugs Literature Review

Introduction: Tuberculosis or known as TBC is one of communicable disease that caused by the bacillus Mycobacterium tuberculosis. This disease is the major of public health problem due to it can spread easily from the patients to the healthy people by air transmission. In order to stop the transmission and improve the health status of the community, treatment is needed for patients with tuberculosis. But, almost people with tuberculosis patients had poor treatment and the factor that contribute to their adherence is depression. Depression and tuberculosis are frequently coexisting in individuals. Depression lead them having negative perception about the treatment and get misconceptions about TB disease. Therefore, most of tuberculosis patients with depression are having lower level of medication adherence. Objective: The purpose of this literature review is to analyze the association between depression among tuberculosis patients with medication adherence of anti-tuberculosis. Method:.This study uses the literature review method to review the results of research that has been published by previous researchers. The literature sources obtained were the results of searches from three online databases, namely Google scholars, Pubmed, and Scopus. which published in the range of 2018-2024. Result: Depression was significantly associated with medication adherence among people who had tuberculosis Conclusion: Depression appears to be a strong risk factor for treatment failure and default in these people with newly diagnosed tuberculosis and is associated with poor treatment outcome despite successful tuberculosis treatment. This could be happened because of long period time that needed to consume the treatment and complexity of the drug regimen.

The liquid-liquid phase separation signature predicts the prognosis and immunotherapy response in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common and fatal malignancy characterized by poor patient prognosis and treatment outcome. The process of liquid-liquid phase separation in tumour cells alters the dysfunction of biomolecular condensation in tumour cells, which affects tumour progression and treatment. We downloaded the data of HCC samples from TCGA database and GEO database, and used a machine learning method to build a new liquid-liquid phase separation index (LLPSI) by liquid-liquid phase separation related genes. The LLPSI-related column line Figure was constructed to provide a quantitative tool for clinical practice. HCC patients were divided into high and low LLPSI groups based on LLPSI, and clinical features, tumour immune microenvironment, chemotherapeutic response, and immunotherapeutic response were systematically analysed. LLPSI, which consists of five liquid-liquid phase separation-associated genes (MAPT, WDR62, PLK1, CDCA8 and TOP2A), is a reliable predictor of survival in patients with HCC and has been validated in multiple external datasets. We found that the high LLPSI group showed higher levels of immune cell infiltration and better response to immunotherapy compared to the low LLPSI group, and LLPSI can also be used for prognostic prediction in various cancers other than HCC. Invitro experiments verified that knockdown of MAPT could inhibit the proliferation and migration of HCC. The LLPSI identified in this study can accurately assess the prognosis of patients with HCC and identify patient populations that will benefit from immunotherapy, providing valuable insights into the clinical management of HCC.

Oral health in young adults with a mild intellectual disability and multiple problems

More than 1.1 million people in the Netherlands have a mild intellectual disability (MID). They are relatively more likely to have poor oral health. The aim of this study was to investigate the oral health of MID young adults with multiple problems (such as addiction). A questionnaire was administered orally to 76 inpatient clients of the Salvation Army in Amsterdam and intraoral examinations were also performed. The research group consisted of young adults with MID and additional multi-problems. The collected data was compared with a reference group (Dutch young adults with a low socio-economic status). The results suggest that oral hygiene is poor in this population, and that a more internal locus of control is associated with a higher caries index. The findings of this study emphasize the importance of professional oral care in young adults with MID given poor oral hygiene and treatment delays. A tailor-made approach with more flexibility in treatment is essential to provide young adults with MID the right oral care.

Mapping the complexity and diversity of tertiary lymphoid structures in primary and peritoneal metastatic gastric cancer

BackgroundTertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric cancers (GCs), however, TLSs are predominantly found in...

Mapping spatially resolved transcriptomes in human and mouse pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. Here we generated spatially resolved transcriptome maps of human IPF (n = 4) and bleomycin-induced mouse pulmonary fibrosis (n = 6) to address these limitations. We uncovered distinct fibrotic niches in the IPF lung, characterized by aberrant alveolar epithelial cells in a microenvironment dominated by transforming growth factor beta signaling alongside predicted regulators, such as TP53 and APOE. We also identified a clear divergence between the arrested alveolar regeneration in the IPF fibrotic niches and the active tissue repair in the acutely fibrotic mouse lung. Our study offers in-depth insights into the IPF transcriptional landscape and proposes alveolar regeneration as a promising therapeutic strategy for IPF.

PREVALENCE AND MANAGEMENT OF MALNUTRITION IN CHILDREN WITH CONGENITAL HEART DISEASE : A COMPREHENSIVE SYSTEMATIC REVIEW

Background: Congenital heart disease is a congenital abnormality that affects the structure of the heart walls and vessels. Malnutrition has a significant impact on the likelihood of infection in children with congenital heart disease, which leads to poor treatment outcomes. The aim: The aim of this study to show about prevalence and management of malnutrition in children with congenital heart disease. Methods: By the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. This search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed, SagePub, and Sciencedirect were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: Five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: Nutrition is crucial in the treatment of chronic illness. It’s one of the most important factors affecting patients’ recovery after surgery and lowering the risk of infection in children with congenital heart disease.

Towards a sustainable supply chain: contribution to hospital waste management in an Algerian hospital

The object of research is medical waste management. Healthcare activities protect health, cure patients and save lives. However, they generate waste that is harmful to public health and the environment. As a result, the management of this healthcare waste is becoming increasingly important in the field of public health and the environment. One of the most problematic places is, poor management of these issues that can put healthcare workers, medical waste workers, patients and their families, and the entire population at risk. On the other hand, poor treatment or inadequate disposal of this waste can also cause risks. From now on, the rational elimination of this pollution is one of the essential conditions for respecting hygiene rules, not only inside establishments, but also in the general environment. In this unfavorable context, we are trying through this contribution to achieve adequate management using reverse logistics practices with the main objective of resolving healthcare waste management problems while taking into account the reality of things in situ. For this purpose, an approach guided by data, carried out directly in the field, by direct contact with the different categories of health personnel interviewed, through findings, observations, audits, questionnaire and knowledge of the causes was used. This approach is based on the audit of compliance with the supply chain in the management of hospital waste in the different departments of the Constantine University Hospital (Algeria). As a result of the research it is shown that the situation is very poor given that the logistics chain is completely faulty or no step is respected. Thus, the least respected stage is storage, where no service exceeds 25 %, this is due to the fact that no clinic has an intermediate waste storage area. And the most respected is treatment stage that does not exceed 75 %. This allowed to detect the inadequacies recorded at the level of the study establishment, and even improvements are suggested for sustainable management of healthcare waste at the level of Algerian health establishments.

Analysis of the Technical and Tactical Characteristics of Li Shifeng in 2023

Objective: To explore and understand the skills and tactics used by the world's top badminton players in the competition, so that ordinary badminton lovers can understand and use the skills and tactics of badminton, improve the level of skills and combat, and expect to provide reference for improving the skills and tactics of the athlete Li Shifeng. Methods: Using the literature method, video observation method and mathematical statistics method, we analyzed the serve, reception, front court ball processing, midfield ball processing, back court ball processing and gain and loss in the competition, and summarized the characteristics of his skills and tactics in the competition. Conclusion: 1) Li Shifeng's serve is mainly backhand ball, and the serve is concentrated in areas 1 and 5 in front court; other areas are involved but not frequently. At present, there is a tendency of men's singles in badminton. 2) Li Shifeng's use of receiving service skills and tactics is mainly to rub and put the net and pick the ball, while the use of other technical balls is involved but not much. He has a high sense of defense, but also actively attack, trying to break free of the control of the opponent, actively strive for the initiative of the game, so the net in the return stage is also particularly important. 3) The use of forward ball skills often requires more energy into dealing with the opponent's return to gain the chance to dominate the game. Li Shifeng's front court attack is more active, like to rub the ball and pick the ball skills and tactics, so as to win the advantage in front of the net. 4) There is no obvious technical and tactical gap in the performance of Li Shifeng and his opponents in the midfield, and all the ball techniques are used. The straight line technology before the net is the most used, followed by the diagonal and pick the ball, and the flat ball is the lowest frequency. 5) Li Shifeng in the back using the ball and kill the ball tactical ability is better, the back is Li Shifeng in the back of the highest utilization technology, using the ball back, facilitate the best time to use the ball, and consciously and accurately control the point and Li Shifeng in the back is given priority to with the ball score, steady, fast, drop ball point precision, to the field of control consciousness is strong, control the rhythm of the tactical intention.6) Li Shifeng loses too much points actively, which is in a phenomenon that he wants to actively grab the advantage but loses points due to poor technical treatment.

A nurse-led coaching intervention with home telemonitoring for patients with heart failure: Protocol for a feasibility randomized clinical trial

Poor treatment adherence and lack of self-care behaviors are significant contributors to hospital readmissions of people with heart failure (HF). A transitional program with non-invasive telemonitoring may help sustain patients and their caregivers to timely recognize signs and symptoms of exacerbation.We will conduct a Randomized Clinical Trial (RCT) to evaluate the feasibility and acceptability of a 6-month supportive intervention for patients discharged home after cardiac decompensation. Forty-five people aged 65 years and over will be randomized to either receive a supportive intervention in addition to standard care, which combines nurse-led telephone coaching and a home-based self-monitoring vital signs program, or standard care alone. Four aspects of the feasibility will be assessed using a mixed-methods approach: process outcomes (e.g., recruitment rate), resources required (e.g., adherence to the intervention), management data (e.g., completeness of data collection), and scientific value (e.g. 90- and 180-day all-cause and HF-related readmissions, self-care capacity, quality of life, psychological well-being, mortality, etc.). Participants will be interviewed to explore preferences and satisfaction with the intervention. The study is expected to provide valuable insight into the design of a definitive RCT.

Therapeutic efficiency and safety assessment of intradermal platelet-rich plasma combined with oral tranexamic acid in patients with facial melasma.

Melasma is a chronic, acquired hypermelanosis that primarily affects the face. Platelet-rich plasma (PRP) and tranexamic acid (TXA) are promising treatments for melasma. However, only a few randomized clinical trials have examined the efficacy and safety of combining these therapies for melasma. We aimed to compare the efficacy and safety of combining PRP and oral TXA with those of PRP alone in the treatment of facial melasma. A randomized controlled trial was conducted at Walailak University Hospital, Nakhon Si Thammarat, Thailand, between March and September 2023. Participants with mixed-type melasma were randomly allocated in a 1:1 ratio to either group A (PRP injection alone without placebo) or group B (PRP injection with oral TXA). Therapeutic efficacy and safety assessments were performed over a 12-week follow-up period. The study included 26 participants (mean age: 45.9 years, standard deviation (±SD): 5.0) who were predominantly female (84.6%). In group A, the modified Melasma Area and Severity Index (mMASI) scores significantly decreased from a median of 4.30 interquartile range (IQR): 4.10) to 3.60 (IQR: 3.10) between week 0 and week 12, respectively. In group B, the median mMASI decreased from 6.40 (IQR: 7.80) to 3.60 (IQR: 3.70) over the same period. The median change in mMASI scores in group B (2.90, IQR: 2.40) was significantly larger than in group A (0.90, IQR: 0.60) (p < 0.001, U = 160.50). However, there were no significant differences in the physicians' global assessment (PGA), melasma quality of life scale (MelasQoL) or patient satisfaction during follow-up. Four patients (15.4%) experienced transient erythema and swelling. In group B, 1 participant (7.7%) experienced transient mild gastrointestinal discomfort after receiving oral TXA. The combination of intradermal PRP injection and oral TXA is effective for melasma, even in patients with poor prognostic treatment response factors. No serious adverse reactions were observed in either group.

Brachial Plexus Injury Influences Efferent Transmission on More than Just the Symptomatic Side, as Verified with Clinical Neurophysiology Methods Using Magnetic and Electrical Stimulation.

The variety of sources of brachial plexus injuries (BPIs) and the severity and similarity of their clinical symptoms with those of other injuries make their differential diagnosis difficult. Enriching their diagnosis with objective high-sensitivity diagnostics such as clinical neurophysiology may lead to satisfactory treatment results, and magnetic stimulation (MEP) might be an advantageous addition to the diagnostic standard of electrical stimulation used in electroneurography (ENG). The asymptomatic side in BPI cases sometimes shows only subclinical neurological deficits; this study aimed to clarify the validity and utility of using MEP vs. ENG to detect neural conduction abnormalities. Twenty patients with a BPI and twenty healthy volunteers with matching demographic and anthropometric characteristics were stimulated at their Erb's point in order to record the potentials evoked using magnetic and electrical stimuli to evaluate their peripheral motor neural transmission in their axillar, musculocutaneous, radial, and ulnar nerves. MEP was also used to verify the neural transmission in participants' cervical roots following transvertebral stimulations, checking the compatibility and repeatability of the evoked potential recordings. The clinical assessment resulted in an average muscle strength of 3-1 (with a mean of 2.2), analgesia that mainly manifested in the C5-C7 spinal dermatomes, and a pain evaluation of 6-4 (mean of 5.4) on the symptomatic side using the Visual Analog Scale, with no pathological symptoms on the contralateral side. A comparison of the recorded potentials evoked with magnetic versus electrical stimuli revealed that the MEP amplitudes were usually higher, at p = 0.04-0.03, in most of the healthy volunteers' recorded muscles than in those of the group of BPI patients, whose recordings showed that their CMAP and MEP amplitude values were lower on their more symptomatic than asymptomatic sides, at p = 0.04-0.009. In recordings following musculocutaneous and radial nerve electrical stimulation and ulnar nerve magnetic stimulation at Erb's point, the values of the latencies were also longer on the patient's asymptomatic side compared to those in the control group. The above outcomes prove the mixed axonal and demyelination natures of brachial plexus injuries. They indicate that different types of traumatic BPIs also involve the clinically asymptomatic side. Cases with predominantly median nerve lesions were detected in sensory nerve conduction studies (SNCSs). In 16 patients, electromyography revealed neurogenic damage to the deltoid and biceps muscles, with an active denervation process at work. The predominance of C5 and C6 brachial plexus injuries in the cervical root and upper/middle trunk of patients with BPI has been confirmed. A probable explanation for the bilateral symptoms of dysfunction detected via clinical neurophysiology methods in the examined BPI patients, who showed primarily unilateral damage, maybe the reaction of their internal neural spinal center's organization. Even when subclinical, this may explain the poor BPI treatment outcomes that sometimes occur following long-term physical therapy or surgical treatment.

تقدير الكفاءة الاقتصادية والفنية لمشاريع تسمين العجول في محافظة واسط للعام 2022

Calf breeding and fattening projects in general are considered the main source of meat production in Iraq. This vital and widespread sector is considered the largest in Wasit Governorate. There are a significant number of fields specialized in raising and fattening calves. Despite the increase in production that the owners of these fields have experienced, these Owners face difficulties in obtaining expensive feed and poor vaccines, veterinary services and treatments imported and controlled by the private sector, which has led to high economic costs. Calf fattening projects have similar social and economic advantages. Calf fattening, which is a sub-sector of the livestock sector, has an important role in transforming... Calves turn into high-quality and efficient beef through economic use. Increased live weight, feed intake, feed efficiency and capacity, and the relationship between profitability are direct factors on calf breeding and fattening projects. The results showed that the total costs (fixed and variable) for the average projects in the sample amounted to approximately (136,779) one hundred and thirty-six million, seven hundred and seventy-nine thousand Iraqi dinars. Through the results, it was shown that the variable costs have a greater relative importance in the calf rearing and fattening projects in the study area than the fixed costs, and the other costs are due to the prices of the calves upon purchase (before the start of the fattening cycle), so their percentage reached (61.46%) of the total total costs, while the cost amounted to (61.46%). Net sale of one calf after fattening (2009000) is two million and nine thousand dinars The economic efficiency and its components for the calf rearing and fattening projects in the study sample were estimated using the DEAP data envelopment analysis method and according to the cost function variables in light of the resources used and their prices assuming changing returns to scale. The economic efficiency and its components, both the technical and Allocative efficiency of the calf breeders in the study sample, were estimated using the data envelopment analysis method (DEAP), and the results of the estimates of economic (EE), technical (TE), and Allocative (AE) efficiency were confirmed. By reviewing these results, it was found that the level of technical efficiency of the study sample ranged Between a minimum of about 72.4%) and a maximum of 100%), with an average of (97.5%). As for the number of fields that achieved full efficiency (100%), it reached 30 fields, and a percentage of (60%) was formed. As for the fields that achieved efficiency between (%80-100%) reached (49) fields, and as for the fields that achieved technical efficiency (72.4%), it was one field.

Real-world use patterns, effectiveness, and tolerability of sacituzumab govitecan for second-line and later-line treatment of metastatic triple-negative breast cancer in the United States

PurposePatients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and limited treatment options. Sacituzumab govitecan (SG), a Trop-2–directed antibody–drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies (≥ 1 in the metastatic setting) based on the ASCENT study (NCT02574455). The current study describes real-world SG use and outcomes in patients with mTNBC in the United States.MethodsThis retrospective, observational study included adult patients with mTNBC from the ConcertAI Patient360™ database who received SG in the second line (2L) and later from April 2020 to May 2022. SG use patterns, effectiveness, and tolerability are described.ResultsThis analysis included 230 patients (median age 60 years, 26% Black, 17% with ECOG performance status ≥ 2, 66% in community settings; median of 2 prior lines of treatment in the metastatic setting); median follow-up was 7.2 months. Median (95% CI) real-world overall survival was 10.0 (8.3–11.1) months for all patients and 13.9 (9.8-not estimable) months in the 2L subgroup (n = 77). Granulocyte-colony stimulating factor (G-CSF) was administered concomitantly with SG in 134 (58%) patients; 35 (15%) received G-CSF for the first time. Median (IQR) time from SG start to G-CSF use was 8.5 (8.0–29.0) days. Seventeen (7%) patients discontinued SG due to toxicity.ConclusionsUsing a real-world, ethnically diverse population of patients with mTNBC presenting with poor prognosis, these data reinforced the findings from ASCENT. In routine clinical practice, SG is an effective treatment in the 2L setting, consistent with treatment guidelines.

The impact of COVID-19 on non-communicable disease patients in sub-Saharan African countries: A systematic review.

COVID-19 and its prevention measures have had a significant impact on patients with non-communicable diseases (NCDs) by disrupting routine healthcare service and increasing risk factors. These challenges were expected to be more severe in sub-Saharan Africa due to the lack of physical infrastructure and inadequate resources. The quantity of studies conducted was limited, and there was a lack of published systematic reviews in the specified region. This systematic review aimed to assess the indirect impacts of the COVID-19 pandemic and associated lockdown measures on individuals with non-communicable diseases (NCDs) in sub-Saharan African countries. This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and is registered with PROSPERO (ID CRD42023387755). Extensive searches were conducted in MEDLINE, EMBASE, and CINAHL databases in December 2023, supplemented by a manual search of references, grey literature, and the WHO COVID-19 database. Inclusion criteria encompassed studies that reported on the impact of COVID-19 on NCD patients in sub-Saharan African countries, focusing on access to care, health outcomes, and factors related to NCDs. Critical appraisal of study quality was performed using the Joanna Briggs Institute (JBI) analytical cross-sectional studies critical appraisal tool. Data were extracted and synthesized, highlighting the main findings and relevant limitations. This review included 30 primary studies with a cumulative sample size of 25634 participants, conducted in seven sub-Saharan African countries. These studies demonstrated that the COVID-19 pandemic significantly disrupted regular NCD patient care provision, with regional variations. The studies also identified a reduction in patient health-seeking behavior and reduced medication adherence, leading to poor treatment outcome. Furthermore, the pandemic and related lockdowns have been implicated in the increased prevalence of substance use, decreased physical exercise, and increased mental health problems. This systematic review identified the complex challenges faced by NCD patients in sub-Saharan Africa during the COVID-19 pandemic. It also underlines the need to consider the indirect impact on vulnerable populations while developing pandemic prevention and control strategies for the future. The current NCD management strategies should prioritize the restoration of access to essential healthcare services while considering the multifaceted risks posed by decreased physical activity, poor dietary practices, and increased substance use. The main limitation of this review was the study design and setting. All of the studies included in this review employed a cross-sectional design, which may result in a low quality of evidence. This study identified research conducted in only seven countries among the 46 UN-classified sub-Saharan nations, which may impair the generalizability of the result.

Cancer/testis antigen expression and co-expression patterns in Gastroesophageal Adenocarcinoma.

Gastroesophageal adenocarcinoma (GEAC) poses a significant challenge due to its poor prognosis and limited treatment options. Recently, Cancer/testis antigens (CTAs) have emerged as potential therapy targets due to their high expression in tumor cells and their immunogenic nature. We aimed to explore the expression and co-expression of CTAs in GEAC. We analyzed 63 GEAC patients initially and validated our findings in 329 patients from The Cancer Genome Atlas (TCGA) database. CTA expression was measured after RNA sequencing, while clinical information, including survival outcomes and treatment details, was collected from an institutional database. Co-expression patterns among CTAs were determined using Pearson correlation analysis. The majority of the study cohort were male (87%), Caucasian (94%), and had stage IV disease (64%). CTAs were highly prevalent, ranging from 58-19%. The MAGE gene family showed the highest expression, consistent across both cohorts. The correlation matrix revealed a distinct cluster of significantly co-expressed genes, including MAGEA3, NY-ESO-1, and others (0.27 ≤ r ≤ 0.73). Survival analysis revealed that individual CTAs were associated with poorer survival outcomes in patients not receiving immunotherapy while showing potential for improved survival in those undergoing immunotherapy, although these findings lacked robust reliability. Our study provides a comprehensive characterization of CTA expression and co-expression in GEAC. The strong correlation among CTAs like MAGE, NY-ESO-1, and GAGE suggests a potential for therapies targeting multiple CTAs simultaneously. Further research, including prospective trials, is warranted to assess the prognostic value of CTAs and their suitability as therapeutic targets.

Treatment approaches for older Hodgkin lymphoma patients.

Hodgkin lymphoma (HL) occurs at two age peaks around 25 and 60 years of age. Due to varying fitness and co-morbidities older patients are a heterogeneous group that has relatively poor treatment outcomes. The evolving therapeutic landscape for older HL is summarized herein. Due to lack of data from larger trials and approval of novel drugs, first-line treatment of limited-stage HL (i.e. early-stage favourable and unfavourable) remains largely A(B)VD and radiotherapy based. For patients with advanced-stage HL, the anti-CD30 antibody-drug conjugate brentuximab vedotin is approved in combination with AVD chemotherapy (BV-AVD). Due to toxicities such as febrile neutropenia or polyneuropathy and lack of improvement in progression-free and overall survival in the older subgroup, fully concomitant BV-AVD is however not used widely. More recently, promising early data was reported with the combination of nivolumab and AVD (N-AVD) in patients >60 years with advanced-stage HL. Second-line treatment depends on fitness and might include high-dose chemotherapy and autologous stem-cell transplantation for selected patients. For unfit or multiply relapsed patients, anti-PD1 antibodies are the preferred treatment option. The increasing number of older HL patients constitutes a therapeutic challenge despite recent advances and the increased usage of targeted agents.