Notes

Lemmel affliction: unheard of problem associated with periampullary duodenal diverticulum.
Patients with primary metastatic/recurrent endometrial cancer have poor prognosis and available therapeutic options are limited. Current treatment is mainly based on platinum-based chemotherapy. Recently, the Food and Drug Administration (FDA) granted approval for the combination of pembrolizumab and lenvatinib for endometrial cancer patients without microsatellite instability (MSS) progressing on a previous line of therapy while European Medicines Agency (EMA) approved the combination for all comers patients failing previous platinum treatment. Anti programmed cell death protein-1 (PD-1) dostarlimab (TSR-042) was approved as monotherapy in patients with advanced, microsatellite instable (MSI) endometrial cancer progressing to platinum treatment. Phase II-III clinical trials in metastatic endometrial cancer are mainly focused on target therapies and immunotherapy as single agents or in combination. Unfortunately, most of these trials are lacking of predictive biomarkers of response to select patients most or at least likely to benefit from those treatments.Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are now a backbone of treatment for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. CDK4/6i plus ET is more effective than ET alone in this setting; however, the risk of grade 3-4 adverse events also increases. Approved agents in this class have similar efficacies, but important differences due to their structural and pharmacological properties. We review biomarkers and discuss determinants to inform a rational approach to therapy choice when selecting the most appropriate ET and CDK4/6i partners. We also identify subgroups that may benefit from specific ET-CDK4/6i combinations and discuss strategies to overcome resistance. This personalized approach aims to minimize treatment-related toxicities that may affect patient QoL and compliance, and ultimately therapy efficacy.
Gastric cancer with peritoneal metastases (GCPM) carries a poor prognosis. Pressurised Intraperitoneal Aerosolised Chemotherapy (PIPAC) offers pharmacokinetic advantages over intravenous therapy, resulting in higher chemotherapy concentrations in peritoneal deposits, and potentially reduced systemic absorption/toxicity. This review evaluates efficacy, tolerability and impact on quality of life (QOL) of PIPAC for GCPM.

Following registration with PROSPERO (CRD42021281500), MEDLINE, EMBASE and The Cochrane Library were searched for PIPAC in patients with peritoneal metastases, in accordance with PRISMA standards RESULTS Across 18 included reports representing 751 patients with GCPM (4 prospective, 11 retrospective, 3 abstracts, no phase III studies), median overall survival (mOS) was 8 - 19.1 months, 1-year OS 49.8-77.9%, complete response (PRGS1) 0-35% and partial response (PRGS2/3) 0-83.3%. Grade 3 and 4 toxicity was 0.7-25% and 0-4.1% respectively. Three studies assessing QOL reported no significant difference.

PIPAC may offer promising survival benefits, toxicity, and QOL for GCPM.
PIPAC may offer promising survival benefits, toxicity, and QOL for GCPM.Merkel cell carcinoma (MCC), advanced cutaneous squamous cell carcinoma (cSCC), and advanced basal cell carcinoma (BCC) are rare, and the often frail patients may require potentially mutilating local treatments. Immune checkpoint inhibitors (ICIs) are effective in melanoma and are moving towards the neoadjuvant setting. This systematic review explores data supporting the transition of ICIs from the metastatic to the (neo)adjuvant setting non-melanoma skin cancer (NMSC) and describes how knowledge from melanoma can be utilized. ICI response rates in advanced NMSC and melanoma are comparable. Five early phase studies show effectivity of neoadjuvant ICIs in melanoma and adjuvant treatment is standard-of-care. Eight adjuvant and 12 neoadjuvant ICI studies are ongoing for NMSC. Encouragingly, data from two small neoadjuvant ICI studies in NMSC, demonstrated complete responses in approximately half of patients. In conclusion, neoadjuvant ICI treatment has potential to avert mutilating treatments in NMSC. Progress can be accelerated by learning from melanoma.The association between colorectal cancer (CRC) and alterations in intestinal microbiota has been demonstrated by several studies, and there is increasing evidence that bacteria are an important component of the tumour microenvironment. Bacteria may contribute to the development of CRC metastasis by signalling through metabolites, promoting epithelial-mesenchymal transition, creating an immunosuppressive microenvironment and through the impairment of the gut-vascular barrier. Host immunity and intestinal microbiome symbiosis play a key role in determining innate and adaptive immune responses at the local and systemic level. How this gut-systemic axis might contribute to the development of CRC metastasis is however unclear. Several clinical trials are investigating the impact of microbiome-targeted interventions on the systemic inflammatory response, treatment-related complications, and side effects. This review examines pre-clinical and clinical studies which have examined the role of microbes in relation to CRC metastasis, the mechanisms which may contribute to tumour dissemination, and directions for future work.Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The current treatment of HCC mainly includes surgery, chemotherapy, and liver transplantation. HCC differentiation therapy aims to restore tumor cells' normal liver characteristics and unlock their phenotypic plasticity. Estradiol Benzoate manufacturer Understanding the molecular and signaling pathways that control HCC differentiation can help identify new targets for inducing differentiation and provide ideas for drug design. Downregulation of liver enriched transcription factors, imbalanced signal pathway, and dysregulated microRNA play essential roles in regulating the differentiation state of HCC. Restoring normal expression levels of these molecules could induce the tumor cells to differentiate into hepatocyte-like cells (HLCs) and suppress the malignant tumor phenotype. The strategies for inducing HLCs from induced pluripotent stem cells, fibroblasts, and other somatic cells provide a reference for the induced differentiation of liver cancer. The differentiation therapy is expected to be a promising and effective treatment for HCC.This article reviews the role of ALK tyrosine kinase inhibitors (TKIs) in the literature and provides expert commentary on local use in Argentina, Brazil, China, Russia, South Korea, and Turkey. We identified 56 articles involving patients with ALK-positive non-small cell lung cancer (NSCLC) and brain metastases (BM) treated with ALK TKIs published between January 2000 and June 2021. In first-line settings, central nervous system response rates in clinical trials with alectinib (86-94%), brigatinib (67-78%), and lorlatinib (42-82%) were generally higher than those reported with crizotinib (16-71%). Median progression-free survival in patients receiving crizotinib (5.6-7.4 months) was lower than alectinib (not reached), brigatinib (24.0 months), and ceritinib (10.7-25.2 months). Across these counties, next-generation TKIs are preferred for patients with progressing BM lesions. Although next-generation ALK TKIs demonstrate significant activity in these patients and following progression on crizotinib, access remains a challenge for personalized therapy.
Anterior cervical discectomy and fusion (ACDF) is commonly performed in patients with radiculopathy and myelopathy. Although the goal of surgery in patients with radiculopathy is to improve function and reduce pain, patients with myelopathy undergo surgery to halt disease progression. Although the expectations between these preoperative diagnoses are generally understood to be disparate by spine surgeons, there is limited literature demonstrating their discordant outcomes.

To compare improvements in patient reported outcome measures (PROMs) for patients undergoing ACDF for myelopathy or radiculopathy. Secondarily, we analyzed the proportion of patients who attain the minimum clinically important difference (MCID) postoperatively using thresholds derived from radiculopathy, myelopathy, and mixed cohort studies.

Single institution retrospective cohort study PATIENT SAMPLE Patients undergoing primary, elective ACDF with a preoperative diagnosis of radiculopathy or myelopathy and a complete set of preoperatinical outcomes. Compared to radiculopathy, patients with myelopathy have better baseline function, decreased improvement in PROMs, and are less likely to reach MCID using general threshold values, but there is no difference in the proportion reaching MCID when using specific threshold values.

IRB.
IRB.Dickkopf-1 (DKK-1) is mostly known as a mature inhibitor of classic Wnt signaling pathways, which plays a critically role in regulating bone formation and bone metastasis. In recent years, the roles of DKK-1 played in bone resorption, bone formation, immune homeostasis and inflammation have been investigated. The role of DKK-1 in the pathogenesis and treatment of autoimmune diseases (ADs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), etc, has attracted widespread attention. Various studies have found that DKK-1 may be used as a biomarker for the occurrence and development of ADs, and as a potential target for the treatment of ADs. In this review, we have briefly summed up the intricate immunological functions and regulatory mechanisms of DKK-1 in ADs, aiming to further learning more about the role of DKK-1 involved in the pathogenesis of ADs and provide an outlook for the potential future researches.The receptor for advanced glycation endproducts (RAGE) is involved in multiple inflammatory processes. RAGE participates in adaptive and innate immune responses but its role in human immune cell responses has not been directly tested in vivo. We treated humanized mice (NSG) with the small molecule antagonist of RAGE, azeliragon, (AZ), and measured effects on xenogeneic (B6) skin graft rejection. AZ delayed the median time to xenograft rejection (22 vs 56 days, P = 0.0001). PD-1 expression on CD4+ and CD8+ T cells was lower following AZ therapy. Transcriptome studies showed inhibition of pathways in splenocytes with AZ including IL-23, IL-17A and IL-1β signaling. The serum levels of IL-1β and IL-17A in AZ treated mice were reduced in mice that did not reject skin grafts. The RAGE antagonist prevented xenograft rejection by human immune cells in a murine model. A RAGE antagonist may be a useful inhibitor of adaptive human immune responses.Municipal wastewater treatment that mainly performed by conventional activated sludge (CAS) process faces the challenge of intensive aeration-associated energy consumption for oxidation of organics and ammonium, contributing to significant directly/indirectly greenhouse gas (GHG) emissions from energy use, which hinders the achievement of carbon neutral, the top priority mission in the coming decades to cope with the global climate change. Therefore, this article aimed to offer a comprehensive analysis of recently developed biological treatment processes with the focus on reducing discharge and CO2 footprint. The biotechnologies including "Zero Carbon", "Low Carbon", "Carbon Capture and Utilization" are discussed, it suggested that, by integrating these processes with energy-saving and carbon recovery, the challenges faced in current wastewater treatment plants can be overcome, and a carbon-neutral even be possible. Future research should investigate the integration of these methods and improve anammox contribution as well as minimize organics lost under different scales.
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