Cancer associated fibroblasts modulate the cytotoxicity of anti-cancer drugs in breast cancer: An in vitro study.

BACKGROUND: Tumour microenvironment (TME) contributes to resistance to anti-cancer drugs through multiple mechanisms including secretion of pro-survival factors by cancer associated fibroblasts (CAFs). In this study, we determined the chemotherapy resistance producing potential of CAFs in molecular subtypes of breast cancer. METHODS: The CAFs were isolated from fresh lumpectomy/mastectomy specimens of different molecular subtypes of breast cancer. The CAFs were cultured and secretome was collected from each breast cancer subtype. Breast cancer cell lines MCF-7, SK-BR3, MDA-MB-231, and MDA-MB-468 were treated with different doses of tamoxifen, trastuzumab, cisplatin, and doxorubicin alone respectively and in combination with secretome of CAFs from respective subtypes. MTT assay was done to check cell death after drug treatment. Liquid chromatography-mass spectrometry (LCMS) analysis of CAF secretome was also done. RESULTS: MTT assay showed that anti-cancer drugs alone had growth inhibitory effect on the cancer cells however, presence of CAF secretome reduced the anti-cancer effect of the drugs. Resistant to drugs in the presence of secretome, was determined by increased cell viability i.e., MCF-7, 51.02% to 63.02%; SK-BR-3, 34.22% to 44.88%; MDA-MB-231, 52.59% to 78.63%; and MDA-MB-468, 48.92% to 55.08%. LCMS analysis of the secretome showed the differential abundance of CAFs secreted proteins across breast cancer subtypes. CONCLUSIONS: The treatment of breast cancer cell lines with anti-cancer drugs in combination with secretome isolated from molecular subtype specific CAFs, reduced the cytotoxic effect of the drugs. In addition, LCMS data also highlighted different composition of secreted proteins from different breast cancer associated fibroblasts. Thus, TME has heterogenous population of CAFs across the breast cancer subtypes and in vitro experiments highlight their contribution to chemotherapy resistance which needs further validation.

Cognitive Functional Therapy compared with usual physiotherapy care in people with persistent low back pain: a mixed methods feasibility randomised controlled trial in the United Kingdom National Health Service.

OBJECTIVES: To determine the feasibility of completing a definitive randomised controlled trial (RCT), evaluating the clinical and cost-effectiveness of Cognitive Functional Therapy (CFT) in comparison to usual physiotherapy care (UPC), for people with persistent low back pain (LBP). DESIGN AND SETTING: A two-arm parallel feasibility RCT completed in a United Kingdom (UK) Secondary Care National Health Service (NHS) physiotherapy service. PARTICIPANTS: Sixty adult participants who reported LBP lasting for more than three months, that was not attributable to a serious (e.g. cancer) or specific (e.g. radiculopathy) underlying cause, were invited to participate. Participants were allocated at random to receive CFT or UPC. INTERVENTIONS: Cognitive Functional Therapy and Usual Physiotherapy Care for persistent LBP. MAIN OUTCOME MEASURES: The primary outcome was the feasibility of completing a definitive RCT, defined by recruitment of at least 5 participants per month, delivery of CFT per protocol and securing relevant and acceptable outcome measures. Data concerning study processes, resources, management and participant reported outcome measures were collected at baseline, 3, 6 and 12-month follow-up. RESULTS: Sixty participants (n = 30 CFT and n = 30 UPC) were recruited with 80% (n = 48), 72% (n = 43) and 53% (n = 32) retained at 3, 6 and 12-month follow-up respectively. NHS physiotherapists were trained to competence and delivered CFT with fidelity. CFT was tolerated by participants with no adverse events. Relevant and clinically important outcome data were collected at all time points (0.4%, 3%, 1% and 0.8% of data was missing from the returned outcome measure booklets at baseline and 3, 6 and 12-month follow-up respectively). The Roland-Morris disability questionnaire was considered the most suitable primary outcome measure with a proposed sample size of 540 participants for a definitive cluster RCT. CONCLUSION: It is feasible to conduct a randomised study of CFT in comparison to UPC for NHS patients. A future study should incorporate an internal pilot to address aspects of feasibility further, including participant retention strategies. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN12965286 CONTRIBUTION OF THE PAPER.

Studies on photocatalytic mineralization of organic pesticides by bimetallic Cu-Zn nanoparticles derived from Zingiber officinale Roscoe (ginger) using green chemistry approach.

Compared to monometallic nanoparticles, bimetallic nanoparticle synthesis and characterization have attracted more attention due to their superior environmental protection properties. In this study, we discuss the preparation and characterization of Cu-Zn bimetallic nanoparticles using Zinger extract, as well as their potential role in photocatalytic degradation of carbendazim, chlorpyrifos, monocrotophos, and cypermethrin. Surface properties were assessed with SEM and TEM, while UV-VIS, XRD, FTIR, and fluorescence spectroscopy were used to characterize the materials. It was observed that higher pH conditions were more conducive to the development of stable Cu-Zn BMNPs with diameters ranging from 60 to 100 nm. UV-VIS spectroscopy showed that the Cu-Zn bimetallic nanoparticles photodegraded 53-95% of the pesticides, monocrotophos, chlorpyrifos, and carbendazim during the 24-72-h incubation period. A number of pesticides may be photocatalytically degraded by primary reactive radicals produced by nanoparticles. We propose that the use of bimetallic nanoparticles could be one alternative strategy for pesticide mineralization.

One-pot DTECT enables rapid and efficient capture of genetic signatures for precision genome editing and clinical diagnostics.

The detection of genomic sequences and their alterations is crucial for basic research and clinical diagnostics. However, current methodologies are costly and time-consuming and require outsourcing sample preparation, processing, and analysis to genomic companies. Here, we establish One-pot DTECT, a platform that expedites the detection of genetic signatures, only requiring a short incubation of a PCR product in an optimized one-pot mixture. One-pot DTECT enables qualitative, quantitative, and visual detection of biologically relevant variants, such as cancer mutations, and nucleotide changes introduced by prime editing and base editing into cancer cells and human primary T cells. Notably, One-pot DTECT achieves quantification accuracy for targeted genetic signatures comparable with Sanger and next-generation sequencing. Furthermore, its effectiveness as a diagnostic platform is demonstrated by successfully detecting sickle cell variants in blood and saliva samples. Altogether, One-pot DTECT offers an efficient, versatile, adaptable, and cost-effective alternative to traditional methods for detecting genomic signatures.

Quality by design fostered fabrication of cabazitaxel loaded pH-responsive Improved nanotherapeutics against prostate cancer.

Cabazitaxel has been approved for the treatment of prostate cancer since 2010. However, its poor solubility and permeability pitfalls prevent its accumulation at the target site and promote severe adverse effects. About 90% of prostate cancer (PCa) patients suffer from bone metastasis. This advent reports the development of CBZ-loaded pH-responsive polydopamine nanoparticles (CBZ NP) against metastatic PCa cells. Quality by design (QbD) and multivariate analysis tools were employed for the optimization of CBZ NP. Amorphisation of CBZ along with metastatic microenvironment responsive release was observed thereby imparting spatial release and circumventing solubility pitfalls. CBZ NP retained its cytotoxic potential, with a significant increase in quantitative cellular uptake. Apoptotic markers observed from nuclear staining with elevated reactive oxygen species (ROS) and mitochondrial damage revealed by JC-1 staining demonstrated the efficacy of CBZ NP against PC-3 cells with good serum stability and diminished hemolysis. Cell cycle analysis revealed substantial S and G2/M phase arrest with enhancement in apoptosis was observed. Western blot studies revealed an elevation in caspase-1 and suppression in Bcl-2 indicating enhanced apoptosis compared to the control group. Substantial reduction in the diameter of 3D-Tumoroid and enhanced cell proliferation inhibition indicated the efficacy of CBZ NP in PCa. Thus, we conclude that CBZ NP could be a promising Nanotherapeutic approach for PCa.

Assessment of Pathological Complete Response Using Vacuum-Assisted Biopsy in Breast Cancer Patients Who Have Clinical and Radiological Complete Response After Neo-Adjuvant Chemotherapy.

Background: Any treatment protocol that leads to complete elimination of surgery may lead to a better patient acceptance of breast cancer treatments. Objectives: We conducted this study to assess the feasibility of preoperative vacuum-assisted biopsies in identifying pathological complete response (pCR) and its accuracy in correlation to final histopathology report (HPR), in an Indian setting. Methods: This was a prospective study conducted between October 1, 2019, and March 31, 2021. Patients with early breast cancer, estrogen and progesterone receptors negative and either Her2 positive or negative, and who were fit to undergo marker placement at the centre of the tumour and to receive third-generation chemotherapy (4 cycles of 3 weekly doxorubicin and cyclophosphamide followed by 4 cycles of 3 weekly docetaxel) were included in the study. Following the enrolment, a tissue marker was placed at the centre of the tumour and appropriate chemotherapy was started. Patients who achieved clinical complete response were subjected to ultrasound-guided vacuum-assisted biopsy (VAB) from the tumour bed before surgery. Pathology results of the VAB and resected specimen were then compared. Descriptive statistics were used in the study. Results: Eighteen patients were enrolled in the study, with a mean age of 43.6 ± 9.8 years. However, only 10 were eligible for VAB procedure, and sensitivity and specificity were calculated based on the results of these 10 patients only. Vacuum-assisted biopsy showed sensitivity of 50% and specificity of 100% in identifying pCR. Combination of mammography, ultrasonography, and VAB showed sensitivity of 77.8% and specificity of 66.7% in identifying pCR. Conclusion: Vacuum-assisted biopsy of tumour bed may not be sensitive enough to eliminate surgery even in patients who have had exceptional response to neo-adjuvant chemotherapy.

Peptide Nucleic Acids: Recent Developments in the Synthesis and Backbone Modifications.

Nucleic acid represents the ideal drug candidate for protein targets that are hard to target or against which drug development is not easy. Peptide nucleic acids (PNAs) are synthesized by attaching modified peptide backbones generally derived from repetitive N-2-aminoethyl glycine units in place of the regular phosphodiester backbone and represent synthetic impersonator of nucleic acids that offers an exciting research field due to their fascinating spectrum of biotechnological, diagnostic and potential therapeutic applications. The semi-rigid peptide nucleic acid backbone serves as a nearly-perfect template for attaching complimentary base pairs on DNA or RNA in a sequence-dependent manner as described by Watson-Crick models. PNAs and their analogues are endowed with exceptionally high affinity and specificity for receptor sites, essentially due to their polyamide backbone's uncharged and flexible nature. The present review compiled various strategies to modify the polypeptide backbone for improving the target selectivity and stability of the PNAs in the body. The investigated biological activities carried out on PNAs have also been summarized in the present review.

Systemic Haemophilus parainfluenzae Infection Manifesting With Endocarditis and Membranoproliferative Glomerulonephritis.

Infective endocarditis (IE) is a potentially fatal disease that is primarily caused by Staphylococci and Streptococci. The HACEK group of bacteria (Hemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) account for only 1-3% of reported IE cases. IE has long been known to cause glomerulonephritis. The most common histologic patterns seen are crescentic and diffuse proliferative glomerulonephritis. Notably, membranoproliferative glomerulonephritis (MPGN) is one of the less common patterns seen with IE. We present a rare case of MPGN associated with Haemophilus parainfluenzae endocarditis. A 56-year-old male with no significant past medical history presented to a local hospital with complaints of fever, night sweats, dyspnea, diarrhea, and dark urine for about a month. He was found to have a hemoglobin of 4g/dL, requiring multiple transfusions. He also had bilateral pleural effusions and pulmonary edema. In the following days, he had worsening renal function and was transferred to our hospital for further workup. Initial labs showed anemia, thrombocytopenia, and leukocytosis. He had creatinine elevated at 5.28 mg/dL and a low estimated glomerular filtration rate (eGFR) of 12 mL/min/1.73m2. Urinalysis showed proteinuria, urine hemoglobin, urine white blood cells (WBCs), and red blood cells (RBCs). Blood cultures revealed H. parainfluenzae. Transesophageal echocardiogram (TEE) showed large vegetations with perforation of the mitral valve leaflet. Serology showed low complement levels. Renal biopsy displayed a membranoproliferative pattern of glomerulonephritis on light microscopy. The hepatitis panel was negative, as was the autoimmune workup. The patient was diagnosed with MPGN associated with H. parainfluenzae endocarditis. His complex clinical course required mitral valve replacement and aortic valve repair. He completed the course of antibiotics, with improvement in renal and cardiac function.

Biopsychosocial approach to understanding predictors of depressive symptoms among men who have sex with men living with HIV in Selangor, Malaysia: A mixed methods study protocol.

BACKGROUND: Depression is the most common psychiatric disorder reported among patients living with Human Immunodeficiency Virus (HIV), resulting from the intricate combination of biological, psychological, and social factors. Biopsychosocial factors can significantly impact the psychological well-being of men who have sex with men (MSM) living with HIV through social stigma, access and compliance to care, economic insecurity, relationship difficulties, and risky behavior. Compared to MSM without HIV, MSM living with HIV were more likely to be depressed. Despite specific vulnerabilities and health needs, MSM living with HIV remain understudied and underserved in Malaysia owing to legal, ethical, and social challenges. OBJECTIVE: This is merely a published protocol, not the findings of a future study. This study aims to determine and explain the predictors of depressive symptoms among MSM living with HIV. Specifically, this study wants to determine the association between depressive symptoms among MSM living with HIV and biological, psychosocial, and social factors. Finally, the mixed methods will answer to what extent the qualitative results confirm the quantitative results of the predictors of depressive symptoms among MSM living with HIV. METHODS: The study has ethical approval from the Medical Research Ethics Committee (MREC) of the Ministry of Health (MOH) NMRR ID-21-02210-MIT. This study will apply an explanatory sequential mixed methods study design. It comprised two distinct phases: quantitative and qualitative study design for answering the research questions and hypothesis. This study will randomly recruit 941 MSM living with HIV in the quantitative phase, and at least 20 MSM living with HIV purposively will be selected in the qualitative phase. The study will be conducted in ten public Primary Care Clinics in Selangor, Malaysia. A self-administered questionnaire will gather the MSM's background and social, psychological, and biological factors that could be associated with depressive symptoms. For the quantitative study, descriptive analysis and simple logistic regression will be used for data analysis. Then, variables with a P value < 0.25 will be included in multiple logistic regression to measure the predictors of depressive symptoms. In the qualitative data collection, in-depth interviews will be conducted among those with moderate to severe depressive symptoms from the quantitative phase. The thematic analysis will be used for data analysis in the qualitative phase. Integration occurs at study design, method level, and later during interpretation and report writing. RESULT: The quantitative phase was conducted between March 2022 to February 2023, while qualitative data collection is from March 2023 to April 2023, with baseline results anticipated in June 2023. CONCLUSION: In combination, qualitative and quantitative research provides a better understanding of depressive symptoms among MSM living with HIV. The result could guide us to provide a comprehensive mental healthcare program toward Ending the AIDS epidemic by 2030.

Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer.

Breast cancer is a heterogenous disease at the molecular level thus, it can be hypothesized that different molecular subtypes differ in their tumor microenvironment (TME) also. Understanding the TME heterogeneity may provide new prognostic biomarkers and new targets for cancer therapy. For deciphering heterogeneity in the TME, immunohistochemistry for immune markers (CD3, CD4, CD8, CD68, CD163, and programmed death-ligand 1), Cancer-associated fibroblast markers [anti-fibroblast activating protein α (FAP-α), platelet-derived growth factor receptor α (PDGFR-α), S100A4, Neuron-glial antigen 2, and Caveolin-1], and angiogenesis (CD31) was performed on tissue microarrays of different molecular subtypes of breast cancer. High CD3 + T cells were noted in the Luminal B subtype ( P =0.002) of which the majority were CD8 + cytotoxic T cells. Programmed death-ligand 1 expression in immune cells was highest in the human epidermal growth factor receptor 2 (Her-2)-positive and Luminal B subtypes compared with the triple-negative breast cancer (TNBC) subtype ( P =0.003). Her-2 subtype is rich in M2 tumor-associated macrophages ( P =0.000) compared with TNBC and Luminal B subtypes. M2 immune microenvironment correlated with high tumor grade and high Ki-67. Her-2 and TNBC subtypes are rich in extracellular matrix remodeling (FAP-α, P =0.003), angiogenesis-promoting (PDGFR-α; P =0.000) and invasion markers (Neuron-glial antigen 2, P =0.000; S100A4, P =0.07) compared with Luminal subtypes. Mean Microvessel density showed an increasing trend: Luminal A>Luminal B>Her-2 positive>TNBC; however, this difference was not statistically significant. The cancer-associated fibroblasts (FAP-α, PDGFR-α, and Neuron-glial antigen 2) showed a positive correlation with lymph node metastasis in specific subtypes. Immune cells, tumor-associated macrophage, and cancer-associated fibroblast-related s tromal markers showed higher expression in Luminal B, Her-2 positive, and TNBC respectively. This differential expression of different components of TME indicates heterogeneity of the TME across molecular subtypes of breast cancer.

Paraneoplastic syndrome of arthropathies as presenting sign for non-small cell lung cancer.

The aim of this study is to showcase an example of paraneoplastic syndrome, so other healthcare providers can be aware of early NSCLC manifestations. This is also important so providers do not dismiss review of symptoms that may not seem pertinent.

A Rare Case of Lower Limb Sarcoma With BCOR-CCNB3 Mutation: Diagnosis and Treatment.

In the past, BCOR-CCNB3 sarcoma was believed to be comparable to Ewing's sarcoma; however, current research has proven that it is, in reality, a distinct type of the illness, now classified as a distinct entity under undifferentiated round cell sarcomas. This tumour most frequently affects teenagers and young adults, and it is more prevalent in men. It can form in both bone and soft tissue, and it appears most frequently in the pelvis, lower extremities, and paraspinal region. Here, we describe a case of a soft tissue tumour in the proximal posterior portion of the right thigh of a 12-year-old male that was subsequently shown to be a BCOR-CCNB3 fusion using genetic analysis.

Correlation of oral mucosa dose and volume parameters with Grade 3 mucositis, in patients treated with volumetric modulated arc radiotherapy for oropharyngeal cancer?

BACKGROUND: Oral mucositis is the dose-limiting toxicity of chemoradiation in oropharyngeal cancer patients, which can be minimized by giving constraints to oral mucosa. However, the constraints defined in literature are extrapolated from chemoradiation in head and neck cancers as a whole. This study aims to determine oral mucosa dose-volume parameters that can predict grade ≥ 3 acute oral mucositis in oropharyngeal cancer patients treated with volumetric modulated arc radiotherapy. METHODS: This prospective study was done in 52 patients of locally advanced oropharyngeal cancer treated with Volumetric modulated arc radiotherapy. Dose-volume histogram data were extracted and then acute oral mucosa toxicity was analysed. Receiver operating characteristic analysis and logistic regression were carried out to determine predictive factors for grade ≥ 3 mucositis. RESULTS: Grade ≥ 3 acute oral mucositis occurred in 57.6% (30/52) patients in the study. V30Gy > 53.35% (P = 0.005) was an independent dosimetric factor related to grade ≥ 3 acute toxicity. In the receiver operating characteristic curve, the area under V30Gy was 0.770 (P = 0.001); the cut-off value of V30 was 46.23% (sensitivity, 0.80; specificity, 0.91). CONCLUSIONS: Dose-volume histogram analysis predicts V30 > 53.35% as independent factors for grade ≥ 3 acute oral mucositis in patients with oropharyngeal cancers treated with Volumetric modulated arc radiotherapy. Studies in future with more patient number can further validate the above results.

The clinical effect of radiotherapy on pulpal microvasculature: a systematic review.

Introduction/objectives Radiotherapy (RT) has a detrimental effect on the histomorphology of oral tissues. Patients undergoing RT are at risk of developing macrovascular and microvascular changes, which can lead to significant clinical consequences. Despite advances in RT delivery systems, radiation injury remains a modern-day clinical problem. The aim of this systematic review is to investigate the available evidence regarding the impact of RT to the dental pulp and the clinical manifestations of these effects.Data and sources A multi-database search (PubMed, Medline, Embase and CINAHL) was performed to identify related papers published from inception until November 2021. An additional manual search was performed to identify further articles. The data extracted from relevant papers were analysed according to the outcomes selected in this review.Study selection The search generated seven articles eligible for analysis with a total of 2,709 teeth included. RT dose exposure ranged from 30-71.2 Gray with a common finding that RT decreases the number of teeth responding to pulp sensibility testing.Conclusions Knowledge related to the impact of RT on dental pulp is limited and based on weak evidence and a low-level quality of studies. Future studies should incorporate exact RT doses to the teeth and use replicable pulpal testing methods. Understanding the pulpal status post-RT remains an important consideration as dental extractions should be avoided in this cohort due to the risk of osteoradionecrosis.

Geospatial epidemiology of hypertension and its risk factors in India: Findings from National Family Health Survey (2015-2016).

Background: The fourth round of National Family Health Survey (2015-2016) measured blood pressure for the first time and provided a unique opportunity of exploring trends in hypertension prevalence across states and districts for the first time. Aim: This study will be the first in India to estimate the geospatial variation of hypertension among those in the 15-49 years age group in India. Materials and Methods: Out of a total of 616,346 selected occupied households, 601,509 were successfully interviewed, giving a response rate of 98%. We adjusted the proportion of hypertension obtained by using national sample weights. We built a multivariable logistic regression model to assess the determinants of hypertension. Results: The overall weighted prevalence of hypertension was 11.7%, and the prevalence was 11.1% in females and 11.0% in males. Urban areas had a higher prevalence (13.0%) compared to rural areas (11.0%). Those with no education (14.4%) and those who reported smoking (16.5%) had hypertension. Consumption of alcohol, fruits, and eggs was also found to be significantly related to hypertension. Conclusion: Hypertension epidemic is spreading alarmingly in India across rural and urban populations. Disturbingly, the hypertension prevalence is now becoming more concentrated among the poor. This phenomenon has serious implications for the country's social and economic well-being. Urgent preventive measures need to be taken at a multidisciplinary level.

Insilico screening and pharmacokinetic properties of phytoconstituents from Ferula asafoetida H.Karst. (Heeng) as potential inhibitors of α-amylase and α-glucosidase for Type 2 Diabetes Mellitus.

Purpose: Ferula asafoetida H.Karst. commonly known as Heeng in India belong to family Umbelliferae (Apiaceae) and has been known for neuroprotective, antioxidant, antispasmodic, hypotensive, hepatoprotective anthelmintic and antagonistic activities. This study was designed to elucidate the key compounds of asafoetida as potential anti alpha amylase and alpha glucosidase inhibitory role in curing the Type 2 Diabetes Mellites. Materials: Based upon the literature survey various compounds of the asafoetida was deduced from the Pubchem and protein structure was deduced from protein data bank. Virtual screening was performed using Pyrx with α- amylase and α- glucosidase. Compounds with highest binding affinity score and 3-d interaction analysis was used to identify the potential inhibitors among various compounds. Pharmacokinetic studies for Drug likeliness and toxicity properties were characterized using SWISS ADME and ADMETSAR webservers. Results: The docking scores, bindging affinity and 3d structure studies showed that Kamolonol, Gummosin, Picealactone B, Farnesiferol A are showing potential anti α- amylase whereas Epi-conferdione, Conferol, Feselol, and Farnesiferol C shows α- glucosidase inhibitory properties. The qualitative structural activity relationship for drug-likeness, pharmacokinetics and carcinogenicity analysis indicates that they are safe as drug molecules as these compounds follows the various parameters such as Lipinski's rule of 5, anti-carcinogenicity etc. Conclusions: This study shows that phytochemicals of F. asafoetida have the potential antidiabetic properties which could be further used to develop into effective antidiabetic drug from a natural resource.

Natural history and outcomes of patients with liver cirrhosis complicated by hepatic hydrothorax.

BACKGROUND: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis with limited treatment options. AIM: To define the clinical outcomes of patients presenting with HH managed with current standards-of-care and to identify factors associated with mortality. METHODS: Cirrhotic patients with HH presenting to 3 tertiary centres from 2010 to 2018 were retrospectively identified. HH was defined as pleural effusion in the absence of cardiopulmonary disease. The primary outcomes were overall and transplant-free survival at 12-mo after the index admission. Cox proportional hazards analysis was used to determine factors associated with the primary outcomes. RESULTS: Overall, 84 patients were included (mean age, 58 years) with a mean model for end-stage liver disease score of 29. Management with diuretics alone achieved long-term resolution of HH in only 12% patients. At least one thoracocentesis was performed in 73.8% patients, transjugular intrahepatic portosystemic shunt insertion in 11.9% patients and 33% patients received liver transplantation within 12-mo of index admission. Overall patient survival and transplant-free survival at 12 mo were 68% and 41% respectively. At multivariable analysis, current smoking [hazard ratio (HR) = 8.65, 95% confidence interval (CI): 3.43-21.9, P < 0.001) and acute kidney injury (AKI) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were associated with a significantly increased risk of mortality. CONCLUSION: Cirrhotic patients with HH are a challenging population with a poor 12-mo survival despite current treatments. Current smoking and episodes of AKI are potential modifiable factors affecting survival. HH is often refractory of diuretic therapy and transplant assessment should be considered in all cases.

In situ Hydrogels for Effective Treatment of Cancer: Strategies and Polymers Used.

Cancer is a worldwide health ailment with no known boundaries in terms of mortality and occurrence rates, thus is one of the biggest threats to humankind. Hence, there is an absolute need to develop novel therapeutics to bridge the infirmities associated with chemotherapy and conventional surgical methodologies including impairment of normal tissue, compromised drug efficiency and an escalation in side effects. In lieu of this, there's been a surge in curiosity towards development of injectable hydrogels for cancer therapy because local administration of the active pharmaceutical agent offers encouraging advantages such as providing higher effective dose at target site, prolonged retention time of drug, ease of administration, mitigation of dose in vivo ,improved patient compliance. Furthermore, due to its biocompatible nature such systems can significantly reduce the side effects that occur on long-term exposure to chemotherapy. The present review details the most recent advancements in in-situ gel forming polymers (natural and synthetic), polymeric cross-linking methodologies and in-situ gelling mechanisms, focusing on their clinical benefits in cancer therapy.

Efficacy of serratus anterior plane block versus thoracic paravertebral block for postoperative analgesia after breast cancer surgery - a randomized trial

Abstract Background Breast cancer surgery is associated with considerable acute post-surgical pain and restricted mobility. Various regional and neuraxial anesthesia techniques have been used to alleviate post-mastectomy pain. Ultrasound-guided serratus anterior plane block (SAPB) has been considered a simple and safe technique. This randomized control study was performed to compare the efficacy of SAPB with the thoracic paravertebral block (TPVB) for postoperative analgesia after breast cancer surgery. Methods A total of 40 adult ASA physical status I - II female patients undergoing radical mastectomy were randomly allocated into two groups to receive either ultrasound-guided TPVB or SAPB with 0.4 mL.kg-1 0.5% ropivacaine, 30 min before surgery. All patients received standardized general anesthesia for surgery. Injection diclofenac and tramadol were used for postoperative rescue analgesia. The time to first rescue analgesia, total analgesic consumption in the first 24 hours, postoperative pain scores, and any adverse effects were recorded. Results The time to first rescue analgesia was significantly longer in the SAPB group (255.3 ± 47.8 min) as compared with the TPVB group (146.8 ± 30.4 min) (p< 0.001). Total diclofenac consumption in 24 hours was also less in the SAPB group (138.8 ± 44.0 mg vs 210.0 ± 39.2 mg in SAPB and TPVB group respectively, p< 0.001). Postoperative pain scores were significantly lower in the SAPB group as compared with TPVB group (p< 0.05). The incidence of PONV was also less in the SAPB group (p= 0.028). No block-related adverse effects were reported. Conclusion We found that the serratus anterior plane block was more effective than the thoracic paravertebral block for postoperative analgesia after breast cancer surgery.