Poor Treatment Efficacy Research Articles

Effects of Transjugular Intrahepatic Portosystemic Shunt on Renal and Pulmonary Function in Hepatic Decompensation with and without Hepatorenal and Hepatopulmonary Syndromes: A Review.

Cirrhosis is often characterized by decreased liver function, ranging from a compensated, typically asymptomatic phase to a decompensated phase characterized by the appearance of ascites or variceal bleeding, and ultimately hepatorenal syndrome (HRS) or hepatopulmonary syndrome (HPS). The latter two complications are associated with a poor prognosis and limited treatment efficacy. In cases of ascites or variceal bleeding resistant to medical therapy, transjugular intrahepatic portosystemic shunt (TIPS) is effective and safe. Shunting blood by TIPS diverts portal blood to the systemic circulation, potentially increasing systemic blood volume and benefiting renal function. However, TIPS could also divert nitric oxide to the systemic circulation, potentially worsening systemic hypotension and perfusion, which could be detrimental to renal function. Available evidence indicates that TIPS often improves renal function in patients with portal hypertension, with or without HRS. No studies have shown persistently decreased renal function after TIPS. However, these data are insufficient to support a recommendation for the use of TIPS specifically for HRS. In patients without pre-existing HPS, TIPS does not appear to significantly affect pulmonary gas exchange. Results of TIPS in HPS have been inconsistent; some studies have shown improvement, but effects were transient. No studies have shown a persistent decline in pulmonary function after TIPS. The evidence supports the need for large randomized controlled trials to investigate the beneficial effects of TIPS for HRS. Similar pulmonary function data are less clear regarding TIPS for HPS. The aim of the current report was to review the literature regarding the effects of TIPS on renal and pulmonary function in hepatic decompensation, with or without the development of HRS or HPS.

Polypharmacy and Deprescription: Role of Internists.

Polypharmacy is the concurrent use of five or more drugs per day. It is common in old age because of multimorbidity. The prevalence of polypharmacy is increasing as the number of old people is increasing worldwide. The proliferation of clinical guidelines and wider availability of preventive and curative medicines are important causes of polypharmacy. Appropriate polypharmacy is beneficial to the patients. However, polypharmacy may be inappropriate, causing adverse effects, drug interactions (DI), poor treatment efficacy, hospitalizations, and high healthcare costs. Prescribing cascade and legacy prescribing add to the burden of inappropriate polypharmacy. Inappropriate polypharmacy can be prevented or managed by medication optimization through medication review, deprescription, ensuring adherence, and patient education. Deprescription includes the removal of risky, unnecessary, and duplicate drugs, replacement with efficacious drugs, and relaxation of tight control as per life expectancy. Several deprescription tools (both explicit and implicit) exist for helping physicians to decide when to deprescribe or to add medicines, especially in old age. Care should be taken during deprescription to prevent unjustified omission, reduction to subtherapeutic dose, and onset of withdrawal features. Age and disease-related changes in pharmacokinetics and pharmacodynamics of drugs should be considered during the optimization of pharmacotherapy.

Germline AIP variants in sporadic young acromegaly and pituitary gigantism: clinical and genetic insights from a Han Chinese cohort.

Variants in the Aryl hydrocarbon receptor-interacting protein (AIP) gene have been identified in sporadic acromegaly and pituitary gigantism, especially in young patients, with a predisposition to aggressive clinical phenotype and poor treatment efficacy. The clinical characteristics of patients with sporadic acromegaly and pituitary gigantism as well as AIP variants in Han Chinese have been rarely reported. We aimed to identify AIP gene variants and analyze the clinical characteristics of patients with sporadic acromegaly and pituitary gigantism in Han Chinese. The study included 181 sporadic acromegaly (N = 163) and pituitary gigantism (N = 18) patients with an onset age of no more than 45 years old, who were diagnosed, treated, and followed up in Huashan Hospital. All 6 exons and their flanking regions of the AIP gene were analyzed with Sanger sequencing or NGS. The clinical characteristics were compared between groups with and without AIP variants. Germline AIP variants were found in 15/181 (8.29%) cases. In patients with an onset age ≤30 years old, AIP variants were identified in 12/133 (9.02%). Overall, 13 variants were detected. The pathogenic (P) variants p.R304X and p.R81X were identified in four cases, with two instances of each variant. Six exon variants (p.C254R, p.K103fs, p.Q228fs, p.Y38X, p.Q213*, and p.1115 fs) have not been reported before, which were likely pathogenic (LP). Patients with P/LP variants had younger onset ages, a higher prevalence of pituitary gigantism, larger tumor volumes, and a higher percentage of Ki-67-positive cells in tumors. In addition, the group with P/LP variants showed a less significant reduction of GH levels in an acute octreotide suppression test (OST) [17.7% (0, 65.0%) vs. 80.5% (63.9%, 90.2%), P = 0.001], and a trend of less GH decrease after the 3-month treatment with long-acting somatostatin analogs (SSAs). Germline AIP variants existed in sporadic Chinese Han acromegaly and pituitary gigantism patients and were more likely to be detected in young patients. AIP variants were associated with more aggressive tumor phenotypes and less response to SSA treatment.

Systemic treatments with monoclonal antibodies in mycosis fungoides and Sézary syndrome.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most prevalent non-Hodgkin lymphomas that comprise cutaneous T-cell lymphomas (CTCL), accounting for more than 70% of cases. Following the Tumor Lymph nodes Metastasis Blood system, disease staging is carried out, and within ten years, about thirty percent of patients in the early stages will have advanced disease. Plaques, folliculotropism, and age over 60 are risk factors for progression. A 5-year survival rate of less than 20% is associated with LCT in MF. Treatment requires an interdisciplinary approach; skin-directed therapies are available for early stages of the disease, but there are no curative options for advanced stages of the disease other than allogeneic stem cell transplantation. Because of their severe symptoms and poor treatment efficacy, patients in advanced stages have a lower quality of life and a lower chance of survival. In patients with CD30-expressing CTCL, Brentuximab Vedotin has demonstrated better response rates and progression-free survival (PFS); in advanced SS, mogamulizumab has significantly increased PFS. These findings emphasize the need to standardize prognostic factors and improve CTCL treatment.

A MiR181/Sirtuin1 regulatory circuit modulates drug response in biliary cancers

Despite recent advances, biliary tract cancer (BTC) remains one of the most lethal tumor worldwide due to late diagnosis, limited therapeutic strategies and resistance to conventional therapies. In recent years, high-throughput technologies have enabled extensive genome, and transcriptome sequencing unveiling, among others, the regulatory potential of microRNAs (miRNAs). Compelling evidence shown that miRNA are attractive therapeutic targets and promising candidates as biomarkers for various therapy-resistant tumors. The analysis of miRNA profile successfully identified miR-181c and -181d as significantly downregulated in BTC patients. Low miR-181c and -181d expression levels were correlated with worse prognosis and poor treatment efficacy. In fact, progression-free survival analysis indicated poor survival rates in miR-181c and -181d low expressing patients. The expression profile of miR-181c and -181d in BTC cell lines revealed that both miRNAs were dysregulated. Functional in vitro experiments in BTC cell lines showed that overexpression of miR-181c and -181d affected cell viability and increased sensitivity to chemotherapy compared to controls. In addition, by using bioinformatic tools we showed that the miR-181c/d functional role is determined by binding to their target SIRT1 (Sirtuin 1). Moreover, BTC patients expressing high levels of miR-181 and low SIRT1 shown an improved survival and treatment response. An integrative network analysis demonstrated that, miR-181/SIRT1 circuit had a regulatory effect on several important metabolic tumor-related processes. Our study demonstrated that miR-181c and -181d act as tumor suppressor miRNA in BTC, suggesting the potential use as therapeutic strategy in resistant cancers and as predictive biomarker in the precision medicine of BTC.

Cornea-SELEX for aptamers targeting the surface of eyes and liposomal drug delivery.

Cornea is the major barrier to drug delivery to the eye, which results in low bioavailability and poor efficacy of topical eye treatment. In this work, we first select cornea-binding aptamers using tissue-SELEX on pig cornea. The top two abundant aptamers, Cornea-S1 and Cornea-S2, could bind to pig cornea, and their K d values to human corneal epithelial cells (HCECs) were 361 and 174 nм, respectively. Aptamer-functionalized liposomes loaded with cyclosporine A (CsA) were developed as a treatment for dry eye diseases. The K d of Cornea-S1- or Cornea-S2-functionalized liposomes reduces to 1.2 and 15.1 nм, respectively, due to polyvalent binding. In HCECs, Cornea-S1 or Cornea-S2 enhanced liposome uptake within 15 min and extended retention to 24h. Aptamer CsA liposomes achieved similar anti-inflammatory and tight junction modulation effects with ten times less CsA than a free drug. In a rabbit dry eye disease model, Cornea-S1 CsA liposomes demonstrated equivalence in sustaining corneal integrity and tear break-up time when compared to commercial CsA eye drops while utilizing a lower dosage of CsA. The aptamers obtained from cornea-SELEX can serve as a general ligand for ocular drug delivery, suggesting a promising avenue for the treatment of various eye diseases and even other diseases.

Poor efficacy of immune checkpoint inhibitor treatment in advanced thymic carcinoma patients with liver metastases.

Although immune checkpoint inhibitor treatment for advanced thymic carcinoma exhibits promising efficacy, factors that affect the efficacy and prognosis, including metastases sites, remain uncertain. Our study aimed to investigate the determinants of survival among patients with advanced thymic carcinoma who underwent immunotherapy in real-world settings, with implications for clinical practice. Different therapy regimens of immunotherapy were produced to analyze the influence of liver metastases on survival and prognosis for advanced thymic carcinoma patients. Data for advanced thymic carcinoma patients receiving immunotherapy and their metastases sites were collected for analysis from seven different hospitals between January 2015 and January 2023. Progression-free survival (PFS) and overall survival (OS) analyses were performed using the Kaplan-Meier method. Cox analysis was used to evaluate factors influencing survival. The present study analyzed 136 advanced thymic carcinoma patients from seven different hospitals.The PFS for all patients receiving immunotherapy was 6.4 months, while the OS was 24.0 months. The objective response rate was different for patients with liver and non-liver metastases (11.9% versus 37.2%, p = 0.003). The disease control rate values were also different between the two groups (47.6% versus 80.9%, p = 0.037). The PFS for patients with liver metastases demonstrated poor immunotherapy efficacy compared to patients with non-liver metastases (3.0 versus 8.0 months, p < 0.0001). The OS was also significantly different between these two patient groups (16.1 versus 29.1 months, p = 0.009). Immunotherapy had poor efficacy in advanced thymic carcinoma patients with liver metastases.

An oncolytic system produces oxygen selectively in pancreatic tumor cells to alleviate hypoxia and improve immune activation

IntroductionHypoxia is one of the important reasons for the poor therapeutic efficacy of current pancreatic cancer treatment, and the dense stroma of pancreatic cancer restricts the diffusion of oxygen within the tumor. MethodsA responsive oxygen-self-supplying adv-miRT-CAT-KR (adv-MCK) cascade reaction system to improve hypoxia in pancreatic cancer is constructed. We utilized various experiments at multiple levels (cells, organoids, in vivo) to investigate its effect on pancreatic cancer and analyzed the role of immune microenvironment changes in it through high-throughput sequencing. ResultsThe adv-MCK system is an oncolytic adenovirus system expressing three special components of genes. The microRNA (miRNA) targets (miRTs) enable adv-MCK to selectively replicate in pancreatic cancer cells. Catalase catalyzes the overexpressed hydrogen peroxide in pancreatic cancer cells to generate endogenous oxygen, which is catalyzed by killerRed to generate singlet oxygen (1O2) and further to enhance the oncolytic effect. Meanwhile, the adv-MCK system can specifically improve hypoxia in pancreatic cancer, exert antitumor effects in combination with photodynamic therapy, and activate antitumor immunity, especially by increasing the level of γδ T cells in the tumor microenvironment. ConclusionThe responsive oxygen-self-supplying adv-MCK cascade reaction system combined with photodynamic therapy can improve the hypoxic microenvironment of pancreatic cancer and enhance antitumor immunity, which provides a promising alternative treatment strategy for pancreatic cancer.

The novel subtype of major depressive disorder characterized by somatic symptoms is associated with poor treatment efficacy and prognosis: A data-driven cluster analysis of a prospective cohort in China

BackgroundThere is not yet a valid and evidence-based system to classify patients with MDD into more homogeneous subtypes based on their clinical features. This study aims to identify symptom-based subtypes of MDD and investigate whether the treatment outcomes of those subtypes would be different. MethodThe cohort was established at 12 densely populated cities of China. A total of 1487 patients were enrolled. All participants were 18–65 years old and diagnosed with MDD. Participants were followed up at baseline, weeks 4, 8, and 12, and months 4 and 6. K-means algorithm was used to cluster patients with MDD according to clinical symptoms. The network analysis was adopted to characterize and compare the symptom patterns in the clusters. We also examined the associations between the clusters and the clinical outcomes. ResultsThe optimal number of the clusters was determined to be 2. Each cluster's maximum Jaccard Co-efficient was calculated to be >0.5 (cluster1 = 0.53, cluster 2 = 0.67). The symptom “depressed mood” and some other affective symptoms were the most prominent in cluster 1. Somatic symptoms, such as weight loss and general somatic symptoms, had the greatest expected influence in cluster 2. Compared with the response rates of the patients in the “somatic cluster”, those of the patients in the “affective cluster” were significantly higher (P < 0.05). ConclusionsPatients with MDD might be classified into two symptom-based subtypes featured with affective symptoms or somatic symptoms. The treatment efficacy and prognosis of the subtype featured with somatic symptoms may be worse.

Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) has impacted approximately 390 million people worldwide and the morbidity is increasing every year. However, due to the poor treatment efficacy of COPD, exploring novel treatment has become the hotpot of study on COPD. Endothelial progenitor cells (EPCs) aging is a possible molecular way for COPD development. We aimed to explore the effector whether intravenous administration of EPCs has therapeutic effects in COPD mice.MethodsCOPD mice model was induced by cigarette smoke exposure and EPCs were injected intravenously to investigate their effects on COPD mice. At day 127, heart, liver, spleen, lung and kidney tissues of mice were harvested. The histological effects of EPCs intervention on multiple organs of COPD mice were detected by morphology assay. Quantitative real-time PCR and Western blotting were used to detect the effect of EPCs intervention on the expression of multi-organ senescence-related indicators. And we explored the effect of EPCs systematically intervening on senescence-related USP7/p300 pathway.ResultsCompared with COPD group, senescence-associated β-galactosidase activity was decreased, protein and mRNA expression of p16 was down-regulated, while protein and mRNA expression of cyclin D1 and TERT were up-regulated of multiple organs, including lung, heart, liver, spleen and kidney in COPD mice after EPCs system intervention. But the morphological alterations of the tissues described above in COPD mice failed to be reversed. Mechanistically, EPCs systemic administration inhibited the expression of mRNA and protein of USP7 and p300 in multiple organs of COPD mice, exerting therapeutic effects.ConclusionsEPCs administration significantly inhibited the senescence of multiple organs in COPD mice via down-regulating USP7/p300 pathway, which presents a possibility of EPCs therapy for COPD.

Controllable Adaptive Molybdate-Oligosaccharide Nanoparticles Regulate M2 Macrophage Mitochondrial Function and Promote Angiogenesis via PI3K/HIF-1α/VEGF Pathway to Accelerate Diabetic Wound Healing.

The complex wound environment of diabetic wounds leads to poor treatment efficacy, and the inflammatory disorders and vascular injury are the primary causes of death in such patients. Herein, a sprayable, controllable adaptive, pH-responsive nanosystem of molybdate and oligosaccharide (CMO) is specially developed as an immunomodulatory and angiogenesis-promotion material for diabetic wound healing. CMO exhibited pH-responsive release of Mo2+ and oligosaccharide (COS), specifically in response to the alkalescent environment observed in diabetic wounds. CMO provide an anti-inflammatory environment by promoting M2 polarization through significantly stimulating macrophage mitochondrial function. Specifically, CMO with a certain concentration reduce reactive oxygen species (ROS) and tumor necrosis factor α (TNF-α) expression, and upregulated mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and interleukin 10 (IL-10) expression in macrophages. Moreover, CMO facilitate angiogenesis via upregulating the PI3K/HIF-1α/VEGF pathway-a critical process for the formation of new blood vessels that supply nutrients and oxygen to the healing tissue. Remarkably, CMO promote cell viability and migration of endothelial cells, and enhance the expression of angiogenic genes. In vitro and in vivo studies suggest this simple but powerful nanosystem targeting mitochondrial function has the potential to become an effective treatment for diabetic wound healing.

SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination.

Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKKα/β, subsequently leading to IRF3 and NF-κB phosphorylation. However, the specific E3 ubiquitin ligase for MDA5 K63-polyubiquitination has not been well characterized. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral immune agents indicates that SARS-CoV-2 escapes from antiviral immune responses via several unknown mechanisms. Here, we report that SARS-CoV-2 nonstructural protein 8 (nsp8) acts as a suppressor of antiviral innate immune and inflammatory responses to promote infection of SARS-CoV-2. It downregulates the expression of type I interferon, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and TRIM4 and impairing TRIM4-mediated MDA5 K63-linked polyubiquitination. Our findings reveal that nsp8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.

Patterns of alopecia among patients attended in dermatology clinic of Dhaka city: role of socio-demographic and clinical profiles on treatment process

The treatment of alopecia is widely available, and numerous studies have been conducted for its improvement. However, research focusing on the Bangladeshi population is extremely rare. A number of dermatology clinics in Bangladesh are providing advanced treatment; therefore, the efficacy of those treatments needs to be assessed. The aim of this study was to determine the pattern of alopecia in Bangladesh and identify the factors that are associated with poor treatment responses to administered therapies. We conducted a cross-sectional study among alopecia patients who were getting treatment at Aurora Skin and Aesthetics and completed at least six sessions under an experienced physician. Interviews run by experienced physicians collected demographic, clinical, treatment, and comorbidity-related information from patients aged between 18 and 65 years. The collected data were analyzed using STATA (version 16.0). Among our participants, male pattern baldness (stage-2) was most common (43.6%), followed by male pattern baldness (stage-3) (18.8%) and female pattern hair loss (FPHL), stage-2 (13.9%). The treatment efficacy was good for 46.5% of patients, medium for another 42.56%, and only 10.9% showed poor efficacy. The oily hair of participants showed a statistically significant negative association with treatment efficacy (P=0.018). The presence of chronic disease and stress among alopecia patients also negatively impacts the treatment process (P&lt;0.05). Smoking among alopecia patients also hampers the treatment process and is significantly associated with poor treatment efficacy. From this study, it is clear that the ongoing treatment has overall excellent efficacy; however, attention should be given to the comorbidities and habits of patients to improve the treatment outcome. The findings of this study would help skin specialists make decisions during alopecia treatment. Asian J. Med. Biol. Res. 2023, 9 (4), 106-113

Пропіонова кислота відновлює секрецію муцину у шлунку при експериментальному цукровому діабеті

Type 2 diabetes mellitus (T2DM) is associated with a number of complications, in particular, gastrointestinal tract dysfunction. Impaired mucin secretion by the gastric mucosa in rats with T2DM may affect the absorption of drugs in the stomach and may explain the poor efficacy of treatment and correction of the condition. The aim of our work was to study changes in mucin secretion by the mucous membrane of the gastric fundus in rats with T2DM and the administration of metformin in combination with propionate. T2DM was modelled in rats by a high-fat diet for 3 months with a single administration of streptozotocin (25 mg/kg). Pharmacological correction was performed by intragastric administration of metformin (60 mg/ kg), propionate (60 mg/kg), and combined administration of the mentioned drugs for 14 days. Structural changes in the gastric mucosa and mucopolysaccharide secretion activity were assessed by histochemistry. Western blot analysis of MUC5AC expression was performed. A significant decrease in mucin production was observed in the lower stomach of rats, which was associated with a decrease in the density of cells actively producing acidic mucopolysaccharides. Metformin administration to animals with T2DM did not restore mucin production in the gastric fundus, whereas propionate administration increased acid mucopolysaccharide secretion. An increase in the neutral component of mucus and MUC5AC was found in T2DM. The combined administration of metformin and propionate helped to reduce the content of this mucin. The identified morphofunctional changes in the gastric fundus require further research and should be taken into account when using oral hypoglycaemic drugs because the loss of the mucin barrier layer may affect the state of the gastric mucosa and the absorption of drugs.

Recent Advancements and Strategies for Overcoming the Blood-Brain Barrier Using Albumin-Based Drug Delivery Systems to Treat Brain Cancer, with a Focus on Glioblastoma.

Glioblastoma multiforme (GBM) is a highly aggressive malignant tumor, and the most prevalent primary malignant tumor affecting the brain and central nervous system. Recent research indicates that the genetic profile of GBM makes it resistant to drugs and radiation. However, the main obstacle in treating GBM is transporting drugs through the blood-brain barrier (BBB). Albumin is a versatile biomaterial for the synthesis of nanoparticles. The efficiency of albumin-based delivery systems is determined by their ability to improve tumor targeting and accumulation. In this review, we will discuss the prevalence of human glioblastoma and the currently adopted treatment, as well as the structure and some essential functions of the BBB, to transport drugs through this barrier. We will also mention some aspects related to the blood-tumor brain barrier (BTBB) that lead to poor treatment efficacy. The properties and structure of serum albumin were highlighted, such as its role in targeting brain tumors, as well as the progress made until now regarding the techniques for obtaining albumin nanoparticles and their functionalization, in order to overcome the BBB and treat cancer, especially human glioblastoma. The albumin drug delivery nanosystems mentioned in this paper have improved properties and can overcome the BBB to target brain tumors.

Efficacy and safety of pan retinal photocoagulation combined with intravitreal anti-VEGF agents for high-risk proliferative diabetic retinopathy: A systematic review and meta-analysis.

High-risk proliferative diabetic retinopathy (HR-PDR) is the advanced stage of diabetic retinopathy progression with poor prior treatment efficacy and high rates of blindness. This meta-analysis aims to compare the efficacy and safety of pan retinal photocoagulation (PRP) combined with intravitreal anti-vascular endothelial growth factor (aVEGF) (PRP + aVEGF) versus PRP monotherapy in HR-PDR patients. A thorough search was performed through PubMed, Web of Science, EMBASE, and the Cochran Library from inception to December 18, 2022. Outcome measures included change in central macular thickness, best-corrected visual acuity, fluorescein angiography, incidence of undergoing vitrectomy, and adverse events during the follow-up period. Eight studies (6 randomized controlled trials and 2 retrospective studies) with 375 eyes were included in this meta-analysis. There were no obvious differences in the changes of best-corrected visual acuity and fluorescein angiography between the PRP + aVEGF and PRP monotherapy groups. However, PRP + aVEGF group had a significant reduction in the change of central macula thickness (standard mean deviations = -1.44, 95%CI = -2.55 to -0.32, P = .01) and the rate of undergoing vitrectomy (odds ratio = 0.20, 95%CI = 0.05-0.83, P = .01). Additionally, the risks of vitreous hemorrhage and other complications were not significantly different between the 2 groups. Our meta-analysis indicated that PRP + aVEGF might have potential benefits in the treatment of HR-PDR patients. However, given several limitations of this study, more research is needed to confirm our findings.

Modern Technologies in Diagnosis of Fungal Keratitis (Review).

Traumas and infectious diseases of the eye play a leading role in the development of corneal blindness responsible for 1.5-2 million cases of vision loss per year. To date, the issue of reducing the incidence of fungal keratitis is acute and needs to be solved worldwide. Trauma as a risk factor for corneal fungal disease is thought to be prevalent in developing countries due to agricultural involvement, while in developed countries the onset of the disease is predisposed by medical advances such as contact vision correction and modern ophthalmic surgery. Thorough analysis of the pathogenesis gives the possibility to describe the action of fungal enzymes, biofilm formation, and the resistance mechanism, which on the one hand explains the aggressive course of the disease and difficulties in its diagnosis, and on the other hand, it encourages searching for new methods of diagnosis and treatment. The non-specific clinical picture of fungal keratitis, the variety and availability of antibiotics nowadays become an obstacle for rapid detection of this pathology. Low public awareness and late visit to an ophthalmologist are also a barrier to successful combating the increasing incidence of fungal keratitis. Belated diagnosis, increasing resistance of fungi to antibiotics, and lack of registered antifungal ophthalmic drugs justify poor treatment efficacy resulting in decreased visual acuity or vision loss. Existing diagnostic methods need systematization and detailed comparison, identifying the advantages and disadvantages of each. This review considers causative agents and their influence on pathogenesis of the disease, describes difficulties of fungal keratitis diagnosis and possible ways of overcoming these problems using new developments, and also outlines further prospects of research in this direction.

Is reconstructing anterior sternoclavicular joint dislocation by a high-strength tape suture a good choice?

Objectives: Sternoclavicular joint (SCJ) dislocation is uncommon but dangerous. Redislocation frequently occurs after manual reduction due to the torn ligaments of the joint with a high-energy injury, which is often the case. Reconstruction of the SCJ is recommended to avoid poor efficacy of conservative treatment and decreasing quality of life in the patient due to progressive pain limiting the movement of the shoulder girdle. Our study aimed to evaluate the efficacy, safety, and patient satisfaction using a high-strength non-absorbable tape suture to reconstruct the anterior SCJ dislocation. Methods: This study included ten patients (Nine males and one female) who presented with acute anterior dislocation of the SCJ (six on the right and four on the left side). Our patients’ average age was 40.1 years (18–52 years), with 12 months on average follow-up (9–18 months). Four patients had isolated anterior SCJ dislocation, while the others had associated injuries. Results: All patients had excellent functional and satisfactory outcomes and returned to the pre-injury activity level. No intraoperative or major post-operative complications were recorded, and no injuries to near structures or wound problems were noted. The mean improvement of physical function measured by the American shoulder and elbow score was 24.59, which increased from 68.11 ± 3.72 preoperatively to 92.70 ± 3.54 postoperatively. Conclusion: The technique of open reconstruction of anterior SCJ dislocation using high-strength nonabsorbable tape sutures is recommended because it gave us excellent results regarding the safety, functional outcome, patient satisfaction, and avoidance of other surgical site morbidities.

Soluble interleukin-2 receptor as a predictive biomarker for poor efficacy of combination treatment with anti-PD-1/PD-L1 antibodies and chemotherapy in non-small cell lung cancer patients.

Soluble interleukin-2 receptor (sIL-2R) suppresses effector T-cells. Few studies have assessed serum sIL-2R in patients receiving immunotherapy. We evaluated the association between serum sIL-2R levels and the efficacy of anti-programmed cell death 1/ programmed death-ligand 1 (anti-PD-1/PD-L1) antibody combined with chemotherapy in non-small cell lung cancer (NSCLC) patients. We prospectively enrolled NSCLC patients who received anti-PD-1/PD-L1 antibody combined with platinum-based chemotherapy between 8/2019 and 8/2020 and measured their serum sIL-2R. The patients were divided into high and low sIL-2R groups based on the median of sIL-2R levels at pretreatment. Progression-free survival (PFS) and overall survival (OS) of patients in the high and low sIL-2R groups were compared. The Kaplan-Meier curves of PFS and OS were evaluated using the log-rank test. The multivariate analysis of PFS and OS was performed using the Cox proportional hazard models. Among 54 patients (median age 65, range 34-84), 39 were male and 43 had non-squamous cell carcinoma. The sIL-2R cut-off value was 533 U/mL. Median PFS was 5.1 months (95% CI, 1.8-7.5 months) and 10.1 months (95% CI, 8.3-not reached [NR] months) in the high and low sIL-2R groups (P = 0.007), respectively. Median OS was 10.3 months (95% CI, 4.0-NR months) and NR (95% CI, 10.3-NR months) in the high and low sIL-2R groups (P = 0.005), respectively. Multivariate Cox regression analysis showed that high sIL-2R was significantly associated with shorter PFS and OS. SIL-2R may be a biomarker for the poor efficacy of anti-PD-1/PD-L1 antibody combined with chemotherapy.

Sharing is in fact about caring: Care concerns feature prominently in subreddits devoted to self-injurious thoughts and behaviors

ObjectiveGiven poor treatment efficacy and utilization for self-injurious thoughts and behaviors (SITBs) and the pervasive SITB-stigma present in many treatment settings, research that identifies values and experiences that resonate with individuals engaged in SITBs is urgently needed to improve current treatment offerings. The present study uses Moral Foundations Theory, a leading framework for conceptualizing values and behavior, to identify responses to SITBs most likely to resonate with those who have lived SITB experience. MethodsNatural language processing methods (topic modeling, neural network-based classifier) were used to extract latent conversation topics and moral concerns from 1.68 M messages on the two largest SITB forums on Reddit. Once conversation topics and moral concerns were extracted, a linear regression model was fit to describe the relationship between likes on Reddit, moral concerns, and latent conversation topics. ResultsFindings revealed several types of messages most likely to resonate with individuals engaged in SITBs: 1) Specific situational narratives compared to general messages of sadness (p < .01); 2) messages that expressed care (p < .001); and 3) specific messages that expressed care, fairness, loyalty, and purity. ConclusionsSpecific, care-focused content (kind, nurturing content that discusses avoidance of emotional/physical harm to others) resonates most with individuals engaged in SITBs, providing insight to the real-time needs and experiences of those engaged in SITBs and suggesting the importance of framing SITB interventions in care language rather than success/failure language. Study findings may inform one-on-one clinical interactions, the development of SITB-specific interventions, and SITB training for clinicians.