Associations between remote patient monitoring programme responsiveness and clinical outcomes for patients with COVID-19

ObjectiveTo assess whether engagement in a COVID-19 remote patient monitoring (RPM) programme or telemedicine programme improves patient outcomes.MethodsThis is a retrospective cohort study analysing patient responsiveness to our RPM survey or telemedicine visits and outcomes during the COVID-19 pandemic. Daily text message surveys and telemedicine consultations were offered to all patients who tested positive for SARS-CoV-2 at our institutional screening centres. Survey respondents with alarm responses were contacted by a nurse. We assessed the relationship between virtual engagement (telemedicine or RPM survey response) and clinical outcomes using multivariable logistic regression.ResultsBetween 10 July 2020 and 2 January 2021, 6822 patients tested positive, with 1230 (18%) responding to at least one survey. Compared with non-responders, responders were younger (49 vs 53 years) and more likely to be white (40% vs 33%) and female (65% vs 55%) and had fewer comorbidities. After adjustment, individuals who engaged virtually were less likely to experience an emergency department visit, hospital admission or intensive care unit–level care.ConclusionTelemedicine and RPM programme engagement (vs no engagement) were associated with better outcomes, but this was likely due to differences in groups at baseline rather than the efficacy of our intervention alone.

Molecular correlates of immune cytolytic subgroups in colorectal cancer by integrated genomics analysis

Although immune checkpoint inhibition (ICI) has shown promising results in metastatic dMMR/MSI-H colorectal cancer (CRC), the majority of pMMR/MSS patients do not respond to such therapies. To systematically evaluate the determinants of immune response in CRC, we explored whether patients with diverse levels of immune cytolytic activity (CYT) have different patterns of chromothripsis and kataegis. Analysis of CRC genomic data from the TCGA, indicated an excess of chromothriptic clusters among CYT-low colon adenocarcinomas, affecting known cancer drivers (APC, KRAS, BRAF, TP53 and FBXW7), immune checkpoints (CD274, PDCD1LG2, IDO1/2 and LAG3) and immune-related genes (ENTPD1, PRF1, NKG7, FAS, GZMA/B/H/K and CD73). CYT-high tumors were characterized by hypermutation, enrichment in APOBEC-associated mutations and kataegis events, as well as APOBEC activation. We also assessed differences in the most prevalent mutational signatures (SBS15, SBS20, SBS54 and DBS2) across cytolytic subgroups. Regarding the composition of immune cells in the tumor milieu, we found enrichment of M1 macrophages, CD8+ T cells and Tregs, as well as higher CD8+ T-cells/Tregs ratio among CYT-high tumors. CYT-high patients had higher immunophenoscores, which is predictive of their responsiveness if they were to be treated with anti-PD-1 alone or in combination with anti-CTLA-4 drugs. These results could have implications for patient responsiveness to immune checkpoint inhibitors.

Tingkat Ketanggapan Pelayanan Kesehatan Rawat Inap di Indonesia

Responsiveness of the health system in in-patient services is closely related to patient's reasonable expectations of non-clinical aspects for inpatient care. A comfortable patient can straight influence level of responsiveness. This study aimed to determine level of in-patient responsiveness and significance of respondent characteristics on eight responsiveness domains. It was a further analysis of the Responsiveness Survey of 2017. A Cross-Sectional design with a quantitative approach and has performed in 34 provinces in Indonesia. Most mean responsiveness scores were in range of good scores. Moreover, Lowest score was quality basic amenities domain, while highest score was confidentiality domain. Level of in-patient responsiveness was good category (8,05). Each characteristic has significantly correlated with one or more responsiveness domains. We can increase in-patient responsiveness value that less than 8,0 through improving three responsiveness domains, i.e., dignity, access to social network, and provider choice. Abstrak Ketanggapan rawat inap sistem kesehatan berkaitan dengan harapan logis pasien terhadap aspek non medis. Level Ketanggapan dapat secara langsung mempengaruhi kenyamanan pasien. Penelitian bertujuan mengetahui level Ketanggapan rawat inap dan signifikansi karakteristik responden terhadap 8 domain Ketanggapan. Penelitian ini merupakan analisa lanjut data survei Ketanggapan tahun 2017. Metode penelitian adalah cross-sectional dengan pendekatan kuantitatif. Survei ini dilakukan di 34 provinsi di Indonesia. Semua rerata skor Ketanggapan berada pada rentang skor baik. Nilai skor yang paling rendah adalah domain quality basic amenities. Sedangkan nilai skor yang paling tinggi adalah domain confidentiality. Level Ketanggapan rawat inap adalah 8,05 dan masuk kategori baik. Setiap karakteristik mempunyai hubungan signifikan dengan satu atau lebih domain Ketanggapan. Nilai Ketanggapan rawat inap bisa ditingkatkan dengan memperbaiki 3 domain Responsiveness, yaitu Dignity, Acces to social network, Choice of provider.

Renal Cell Tumors: Uncovering the Biomarker Potential of ncRNAs

Renal cell tumors (RCT) remain as one of the most common and lethal urological tumors worldwide. Discrimination between (1) benign and malignant disease, (2) indolent and aggressive tumors, and (3) patient responsiveness to a specific therapy is of major clinical importance, allowing for a more efficient patient management. Nonetheless, currently available tools provide limited information and novel strategies are needed. Over the years, a putative role of non-coding RNAs (ncRNAs) as disease biomarkers has gained relevance and is now one of the most prolific fields in biological sciences. Herein, we extensively sought the most significant reports on ncRNAs as potential RCTs’ diagnostic, prognostic, predictive, and monitoring biomarkers. We could conclude that ncRNAs, either alone or in combination with currently used clinical and pathological parameters, might represent key elements to improve patient management, potentiating the implementation of precision medicine. Nevertheless, most ncRNA biomarkers require large-scale validation studies, prior to clinical implementation.

Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding

Mechanisms of resistance to cancer immunotherapy remain poorly understood. Lymphocyte activation gene–3 (LAG3) signaling is regulated by a disintegrin and metalloprotease domain-containing protein–10 (ADAM10)– and ADAM17-mediated cell surface shedding. Here, we show that mice expressing a metalloprotease-resistant, noncleavable LAG3 mutant (LAG3NC) are resistant to PD1 blockade and fail to mount an effective antitumor immune response. Expression of LAG3NC intrinsically perturbs CD4+ T conventional cells (Tconvs), limiting their capacity to provide CD8+ T cell help. Furthermore, the translational relevance for these observations is highlighted with an inverse correlation between high LAG3 and low ADAM10 expression on CD4+ Tconvs in the peripheral blood of patients with head and neck squamous cell carcinoma, which corresponded with poor prognosis. This correlation was also observed in a cohort of patients with skin cancers and was associated with increased disease progression after standard-of-care immunotherapy. These data suggest that subtle changes in LAG3 inhibitory receptor signaling can act as a resistance mechanism with a substantive effect on patient responsiveness to immunotherapy.

A patient-centredness improvement study for efficacy of behaviour change for healthy lifestyle and weight loss in a student-run free clinic

Background Primary care is the ideal place to implement behaviour change interventions for weight management. However, most primary care physicians are not managing patient weight as a standard of care due to lack of knowledge, skills and reimbursement. Generating more physicians who are familiar and comfortable with providing weight management is essential in leveraging a global change. In our university free clinic, medical students provide healthy lifestyle counselling using shared decision making to each patient at every clinic visit. Objective Improve the efficacy of behaviour change interventions via increased patient responsiveness and adherence. Methods The needs assessment demonstrated a subpar patient response rate to check-ins regarding behavioural change goals. In the first and second interventions, check-in message structure and contact schedule were varied to maximize patient responsiveness and goal achievement. Results In the needs assessment, 58% of patients responded to follow-ups and 58% of patients accomplished their goal. The first intervention cycle resulted in an improvement of responsiveness to 70% and accomplishment of goals to 59%. The second intervention cycle resulted in an improvement of responsiveness to 78% and accomplishment of goals to 74%. Conclusions Messages that were frequent, unique, succinct and delivered within 4 weeks after the clinic visit resulted in the highest response rate and goal attainment. Other primary care clinics can use these interventions to increase patient completion of implemented behaviour changes for a healthier lifestyle.

Development of a Prediction Model for Short-Term Success of Functional Treatment of Class II Malocclusion

(1) Background: The nature of the changes that contribute to Class II correction with functional appliances is still controversial. A broad variation in treatment responses has been reported. The purpose of this study was to find cephalometric predictors for individual patient responsiveness to twin-block treatment in patients with Class II Division 1 malocclusion; (2) Methods: The study was performed on a sample of 39 pubertal patients (21 females, 18 males) treated with the twin block appliance. Lateral cephalograms were available at the start of the treatment (T1) and at the end of functional therapy (T2). The outcome variable was the T2–T1 change in the sagittal position of the soft tissue pogonion with respect to the vertical line perpendicular to the Frankfort plane and passing through point subnasale. The predictive variables were age, gender at T1, and all the cephalometric parameters measured T1. Forward stepwise linear regression with p value to enter 0.05 and p value to leave 0.10 was applied; (3) Results: The only significant predictive variable that was selected was the Co–Go–Me angle (p = 0.000); (4) Conclusions: A greater advancement of the soft tissue chin on the profile is expected with smaller pretreatment values of Co–Go–Me angle.

Membrane-bound TNF mediates microtubule-targeting chemotherapeutics-induced cancer cytolysis via juxtacrine inter-cancer-cell death signaling

Microtubule-targeting agents (MTAs) are a class of most widely used chemotherapeutics and their mechanism of action has long been assumed to be mitotic arrest of rapidly dividing tumor cells. In contrast to such notion, here we show—in many cancer cell types—MTAs function by triggering membrane TNF (memTNF)-mediated cancer-cell-to-cancer-cell killing, which differs greatly from other non-MTA cell-cycle-arresting agents. The killing is through programmed cell death (PCD), either in way of necroptosis when RIP3 kinase is expressed, or of apoptosis in its absence. Mechanistically, MTAs induce memTNF transcription via the JNK-cJun signaling pathway. With respect to chemotherapy regimens, our results establish that memTNF-mediated killing is significantly augmented by IAP antagonists (Smac mimetics) in a broad spectrum of cancer types, and with their effects most prominently manifested in patient-derived xenograft (PDX) models in which cell–cell contacts are highly reminiscent of human tumors. Therefore, our finding indicates that memTNF can serve as a marker for patient responsiveness, and Smac mimetics will be effective adjuvants for MTA chemotherapeutics. The present study reframes our fundamental biochemical understanding of how MTAs take advantage of the natural tight contact of tumor cells and utilize memTNF-mediated death signaling to induce the entire tumor regression.

Tyrosyl-DNA Phosphodiesterase 1 and Topoisomerase I Activities as Predictive Indicators for Glioblastoma Susceptibility to Genotoxic Agents

Glioblastoma (GBM) patients have an estimated survival of ~15 months with treatment, and the standard of care only modestly enhances patient survival. Identifying biomarkers representing vulnerabilities may allow for the selection of efficacious chemotherapy options to address personalized variations in GBM tumors. Irinotecan targets topoisomerase I (TOP1) by forming a ternary DNA–TOP1 cleavage complex (TOP1cc), inducing apoptosis. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a crucial repair enzyme that may reduce the effectiveness of irinotecan. We treated GBM cell lines with increasing concentrations of irinotecan and compared the IC50 values. We found that the TDP1/TOP1 activity ratio had the strongest correlation (Pearson correlation coefficient R = 0.972, based on the average from three sets of experiments) with IC50 values following irinotecan treatment. Increasing the TDP1/TOP1 activity ratio by the ectopic expression of wild-type TDP1 increased in irinotecan IC50, while the expression of the TDP1 catalytic-null mutant did not alter the susceptibility to irinotecan. The TDP1/TOP1 activity ratio may be a new predictive indicator for GBM vulnerability to irinotecan, allowing for the selection of individual patients for irinotecan treatment based on risk–benefit. Moreover, TDP1 inhibitors may be a novel combination treatment with irinotecan to improve GBM patient responsiveness to genotoxic chemotherapies.