Monkeypox Diagnosis in Clinical Settings: A Comprehensive Review of Best Laboratory Practices.

An outbreak of monkeypox (Mpox) was reported in more than 40 countries in early 2022. Accurate diagnosis of Mpox can be challenging, but history, clinical findings, and laboratory diagnosis can establish the diagnosis. The pre-analytic phase of testing includes collecting, storing, and transporting specimens. It is advised to swab the lesion site with virus transport medium (VTM) containing Dacron or polyester flock swabs from two different sites. Blood, urine, and semen samples may also be used. Timely sampling is necessary to obtain a sufficient amount of virus or antibodies. The analytical phase of infectious disease control involves diagnostic tools to determine the presence of the virus. While polymerase chain reaction (PCR) is the gold standard for detecting Mpox, genome sequencing is for identifying new or modified viruses. As a complement to these methods, isothermal amplification methods have been designed. ELISA assays are also available for the determination of antibodies. Electron microscopy is another effective diagnostic method for tissue identification of the virus. Wastewater fingerprinting provides some of the most effective diagnostic methods for virus identification at the community level. The advantages and disadvantages of these methods are further discussed. Post-analytic phase requires proper interpretation of test results and the preparation of accurate patient reports that include relevant medical history, clinical guidelines, and recommendations for follow-up testing or treatment.

Overcoming Stigma: The Human Side of Monkeypox Virus.

Monkeypox (Mpox) virus is a zoonotic disease that was recently declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). Symptoms of Mpox include fever, headache, muscle pain, and a rash which starts on the face and spreads to the rest of the body. The stigma surrounding the Mpox virus has been one of the greatest challenges in dealing with the disease. People with Mpox have been often shunned by their communities, and many are afraid to seek medical care for fear of ostracism. For those affected by the virus, this stigma can significantly impact their mental health and quality of life. It is further fueled by misinformation and societal norms. Hence, a multifaceted approach that includes education, awareness campaigns, and community engagement is needed to overcome the stigma associated with Mpox. Effective communication strategies are critical to the dispelling of rumors and the reduction of fear. Interventional measures need to be shaped according to the needs of those affected.

The Impact of Tumor Hypoxia Modulation on sIL-2R Levels in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients Undergoing Chemotherapy: A Randomized Clinical Trial.

OBJECTIVE: Tumor hypoxia induces the production of Hypoxia-Inducible Factor (HIF)-1 alpha, which interacts with NF-kB, leading to cancer proliferation and metastasis. This study investigated the effect of tumor hypoxia modulation using carbogen (95% O2 and 5% CO2) and nicotinamide on reducing soluble interleukin-2 receptor (sIL-2R) levels in newly diagnosed DLBCL patients with tissue overexpression of HIF-1α ≥10%. MATERIAL AND METHODS: A prospective randomized controlled clinical trial was conducted at Dr. Kariadi Hospital in Semarang, Indonesia, from 2021 to 2022. Newly diagnosed DLBCL patients with tissue HIF-1α ≥10% were randomized into an intervention group (nicotinamide 2,000 mg + carbogen 10 liters/min during R-CHOP) and a control group (R-CHOP alone) for one cycle. sIL-2R levels were measured in the blood before and after intervention. RESULTS: The intervention group showed a significant reduction in sIL-2R levels after chemotherapy (p=0.026), with 85% of samples exhibiting a decrease. In contrast, only 45% of samples in the control group demonstrated a decrease in sIL-2R levels (p=0.184). The median sIL-2R level decreased from 139.50 pg/mL to 70.50 pg/mL in the intervention group, while the control group exhibited an increase from 182.50 pg/mL to 250.00 pg/mL following one cycle of chemotherapy. CONCLUSION: Tumor hypoxia modulation led to a significant decrease in serum sIL-2R levels, potentially through improvements in the crosstalk between hypoxia and inflammation pathways.

Immune Checkpoint Inhibitor Colitis, a Rising Issue in Targeted Cancer Therapy Era: A Literature Review.

Research advances in the oncology treatment field have led to the widespread use of immunotherapy. The usage of immune checkpoint inhibitor (ICI) has improved the survival of cancer patients with metastases. This has also led to the rapidly expanding indications for ICI use. However, ICI usage may lead to toxicity, which may be immune-related, in different organ-specific targets. The immune-related adverse events (irAEs) of ICI may lead to increased morbidity, decreased quality of life, and early termination of ICI. The clinical manifestations of irAEs in the gastrointestinal system are variable, ranging from self-limited to life-threatening or fatal events. In this review article, we would like to focus on discussing ICI-induced colitis, which is one of the most common ICI irAEs in the gastrointestinal tract.

Systemic Immune-Inflammation Index as a Potential Biomarker for Predicting Acute Pulmonary Embolism: A Systematic Review.

BACKGROUND: Acute pulmonary embolism (APE) is a life-threatening condition with a high mortality rate. The pathophysiology involves various complex processes. The systemic immune-inflammatory index (SII) is a well-known biomarker that reflects the intricate balance between pro-inflammatory and anti-inflammatory immune components. In this systematic review, we aim to determine the significance of SII as a potential biomarker for APE. METHOD: We utilized PubMed, ProQuest, EBSCOHost, and Google Scholar to search for articles. We assessed bias risk using the Newcastle Ottawa Scale (NOS). The outcomes we examined included in-hospital and long-term mortality, the severity of APE, and the sensitivity and specificity of the SII in predicting APE. RESULTS: Four studies, involving 2,038 patients, were included for analysis. These studies discuss the use of SII in predicting APE severity, APE mortality, high-risk APE, and the occurrence of APE. SII demonstrates significant results in predicting each of these variables. Furthermore, each study establishes different SII cut-off values. Specifically, a cut-off of 1161 predicts massive APE events with a sensitivity of 91% and a specificity of 90%. A cut-off of >1235.35 differentiates high-risk APE with a sensitivity of 87.32% and a specificity of 68.85%. A cut-off of >1111x109 predicts overall mortality with a sensitivity of 72% and a specificity of 51%. Finally, a cut-off at 1839.91 predicts APE events with a sensitivity of 75.8% and a specificity of 61.9%. CONCLUSION: The SII can be employed as a potential new biomarker to predict outcomes in APE patients, particularly the occurrence, severity, and mortality of APE.

Colorectal cancer screening guidelines for average-risk and high-risk individuals: A systematic review.

AIMS: This review aims to summarize the different colorectal cancer guidelines for average-risk and high-risk individuals from various countries. METHODS: A comprehensive literature search regarding guidelines, consensus recommendations, or position statements about colorectal cancer screening published within the last 10 years (1st January 2012 to 27th August 2022), was performed at EBSCOhost, JSTOR, PubMed, ProQuest, SAGE, and ScienceDirect. RESULTS: A total of 18 guidelines were included in this review. Most guidelines recommended screening between 45 and 75 years for average-risk individuals. Recommendations regarding colorectal cancer screening in high-risk individuals were more varied and depended on the risk factor. For high-risk individuals with a positive family history of colorectal cancer or advanced colorectal polyp, screening should begin at age 40. Some frequently suggested screening modalities in order of frequency are colonoscopy, FIT, and CTC. Furthermore, several screening intervals were suggested, including colonoscopy every 10 years for average-risk and every 5-10 years for high-risk individuals, FIT annually in average-risk and every 1-2 years in high-risk individuals, and CTC every five years for all individuals. CONCLUSION: All individuals with average-risk should undergo colorectal cancer screening between 45 and 75. Meanwhile, individuals with higher risks, such as those with a positive family history, should begin screening at age 40. Several recommended screening modalities were suggested, including colonoscopy every 10 years in average-risk and every 5-10 years in high-risk, FIT annually in average-risk and every 1-2 years in high-risk, and CTC every five years.

Efficacy and Safety of Ibrutinib for Chronic Graft-Versus-Host Disease: A Systematic Review.

INTRODUCTION: Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management. METHOD: We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies. RESULTS: A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue. CONCLUSION: The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.

Efficacy and safety of medical cannabinoids in children with cerebral palsy: a systematic review.

INTRODUCTION: The increasing popularity of cannabinoids for treating numerous neurological disorders has been reported in various countries. Although it reduces tetrahydrocannabinol psychoactivity, it helps patients tolerate higher doses and complements the anti-spasmodic effects of tetrahydrocannabinol. One of the most important potential of cannabinoids are related to its potential to help children with cerebral palsy, a contributor of lifelong disability. Therefore, this systematic review aimed to assess the efficacy and safety of medical cannabinoids in children with cerebral palsy. METHODS: This review adhered to The Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidelines. Seven databases, namely, Scopus, PubMed, EBSCO Host, ProQuest, Google Scholar, Semantic Scholar, and JSTOR, were used to identify relevant studies. Studies examining pediatric patients with cerebral palsy and reporting the efficacy and safety of medical cannabinoids through clinical trials, observational cross-sectional studies, or cohort designs were included. The outcomes of the studies included the efficacy of medical cannabinoids administered for spasticity, motor components, pain control, sleep difficulties, adverse effects, and seizure control. RESULTS: Of 803 identified articles, only three met the inclusion criteria for data synthesis. One study exhibited a moderate risk-of-bias. A total of 133 respondents, mainly from Europe, were investigated. Overall effectiveness and safety were considered good. However, the results are inconsistent, especially regarding spasticity treatment variables. CONCLUSION: The anti-spasticity, anti-inflammatory, and anti-seizure properties of cannabinoids might be beneficial for patients with cerebral palsy, although their effectiveness has not been widely studied. Further studies with larger sample sizes and various ethnicities are warranted. Prospero database registration: (www.crd.york.ac.uk/prospero) under ID CRD42022358383.

The Impact of Artificial Intelligence in Improving Polyp and Adenoma Detection Rate During Colonoscopy: Systematic-Review and Meta-Analysis.

INTRODUCTION: Colonoscopy may detect colorectal polyp and facilitate its removal in order to prevent colorectal cancer. However, substantial miss rate for colorectal adenomas detection still occurred during screening colonoscopy procedure. Nowadays, artificial intelligence (AI) have been employed in trials to improve polyp detection rate (PDR) and adenoma detection rate (ADR). Therefore, we would like to determine the impact of AI in increasing PDR and ADR. METHODS: The present study adhered to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 (PRISMA 2020) statement. To identify relevant literature, comprehensive searches were conducted on major scientific databases, including Pubmed, EBSCO-host, and Proquest. The search was limited to articles published up to November 30, 2022. Inclusion criteria for the study encompassed full-text accessibility, articles written in the English language, and randomized controlled trials (RCTs) that reported both ADR and PDR values, comparing conventional diagnostic methods with AI-aided approaches. To synthesize the data, we computed the combined pooled odds ratio (OR) using a random-effects model. This model was chosen due to the expectation of considerable heterogeneity among the selected studies. To evaluate potential publication bias, the Begg's funnel diagram was employed. RESULTS: A total of 13 studies were included in this study. Colonoscopy with AI had significantly higher PDR compared to without AI (pooled OR 1.46, 95% CI 1.13-1.89, p = 0.003) and higher ADR (pooled OR 1.58, 95% CI 1.37-1.82, p < 0.00001). PDR analysis showed moderate heterogeneity between included studies (p = 0.004; I2=63%). Furthermore, ADR analysis showed moderate heterogeneity (p < 0.007; I2 = 57%). Additionally, the funnels plot of ADR and PDR analysis showed an asymmetry plot and low publication bias. CONCLUSION: AI may improve colonoscopy result quality through improving PDR and ADR.

The expression of hypoxia inducible factor-1 alpha in diffuse large B-cell lymphoma (DLBCL) patients: a cross-sectional study in Indonesia.

Introduction: Hypoxia fuels cancer growth by supporting blood vessel formation, suppressing immune response, and helping cancer cells adapt to harsh surroundings. This happens when cancer cells react to low oxygen levels by activating hypoxia inducible factor-1 alpha (HIF-1α). High levels of HIF-1α can indicate an aggressive form of cancer and resistance to treatment in diffuse large B-cell lymphoma (DLBCL) patients. This study aimed to identify which factors are linked to HIF-1α distribution using immunohistochemistry in DLBCL patients. Method: This study conducted at a hospital in Indonesia between 2020 and 2022 aimed to investigate factors associated with HIF-1α expression in DLBCL patients. Newly diagnosed DLBCL patients were categorized into two groups based on HIF-1α distribution (<40% and ≥40%). Various factors were analyzed between the two groups using statistical tests such as χ2, Mann-Whitney U, and Spearman correlation tests. Results: In this study, 40 participants diagnosed with DLBCL were divided into two groups based on their HIF-1α distribution. The group with HIF-1α distribution greater than or equal to 40% had a higher incidence of extranodal involvement, including primary extranodal disease, compared to the group with less than 40% distribution. This difference was statistically significant. The authors also found that haemoglobin level statistically significant (P=0.041) in this research. The Spearman test analysis showed negative correlation between haemoglobin (P = <0.05, r = -0.44) and positive correlation of soluble interleukin-2 receptor (sIL-2R) (P = <0.05, r = 0.5) with vascular endothelial growth factor (VEGF), as well as between tumour volume (P = <0.05, r = 0.37) with sIL-2R. Additionally, there was a positive correlation between VEGF and sIL-2R (P = <0.05, r= 0.5). Conclusion: Patients with higher HIF-1α expression (≥40%) had more extranodal involvement and primary extranodal disease in this study of 40 DLBCL patients. Haemoglobin level, sIL-2R, and VEGF were also identified as potential biomarkers.

The effect of multidisciplinary team on survival rates of women with breast cancer: a systematic review and meta-analysis.

Breast cancer is quite frequent all around the world. This disease was responsible for an estimated 2.1 million malignancies in 2022, making it the seventh-highest cause of cancer deaths globally. A multidisciplinary team (MDT) care policy was developed in the United Kingdom (UK) in 1995 to enhance the quality of care for cancer patients. The purpose of this systematic review and meta-analysis study is to assess the effects of MDT on breast cancer survival rates. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. Systematic search was conducted in several international databases including Google Scholar, PubMed, EBSCOhost, and Proquest from 2012 to 2022. The authors used RevMan 5.4 to do the meta-analysis of the pooled hazard ratio. Newcastle-Ottawa Scale to measure the risk of bias. Newcastle-Ottawa Scale evaluated participant selection, comparability, and reporting of results using eight subscale items. Egger's test funnel plot was used to assess the potential publication bias for this study. Results: A total of 1187 studies were identified from research database. The authors found a total of six studies from six different countries (China, the UK, Taiwan, Australia, Africa, and France) included for this study. Based on the meta-analysis of the pooled hazard ratio of the included studies, the authors found that the overall effect size of the study was 0.80 (CI 95%: 0.73-0.88). Conclusions: Breast cancer patients who participated in well-organized MDT discussions had a greater survival rate than those who did not.

Efficacy and safety of medical cannabinoids in children with cerebral palsy: a systematic review

ABSTRACT Introduction The increasing popularity of cannabinoids for treating numerous neurological disorders has been reported in various countries. Although it reduces tetrahydrocannabinol psychoactivity, it helps patients tolerate higher doses and complements the anti-spasmodic effects of tetrahydrocannabinol. One of the most important potential of cannabinoids are related to its potential to help children with cerebral palsy, a contributor of lifelong disability. Therefore, this systematic review aimed to assess the efficacy and safety of medical cannabinoids in children with cerebral palsy. Methods This review adhered to The Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidelines. Seven databases, namely, Scopus, PubMed, EBSCO Host, ProQuest, Google Scholar, Semantic Scholar, and JSTOR, were used to identify relevant studies. Studies examining pediatric patients with cerebral palsy and reporting the efficacy and safety of medical cannabinoids through clinical trials, observational cross-sectional studies, or cohort designs were included. The outcomes of the studies included the efficacy of medical cannabinoids administered for spasticity, motor components, pain control, sleep difficulties, adverse effects, and seizure control. Results Of 803 identified articles, only three met the inclusion criteria for data synthesis. One study exhibited a moderate risk-of-bias. A total of 133 respondents, mainly from Europe, were investigated. Overall effectiveness and safety were considered good. However, the results are inconsistent, especially regarding spasticity treatment variables. Conclusion The anti-spasticity, anti-inflammatory, and anti-seizure properties of cannabinoids might be beneficial for patients with cerebral palsy, although their effectiveness has not been widely studied. Further studies with larger sample sizes and various ethnicities are warranted. Prospero database registration: (www.crd.york.ac.uk/prospero) under ID CRD42022358383.

Bovine Lactoferrin and Current Antifungal Therapy Against Candida Albicans: A Systematic Review and Meta-Analysis.

Candida albicans is an important causative organism of opportunistic fungal infection, and it is a growing medical concern due to the increasing usage of broad-spectrum antibiotics, immunosuppressant agents, and other immunocompromising conditions. Currently, bLf and antifungal drugs have been known to have synergistic effects, increasing the drug's efficacy. This study aims to investigate the efficacy of the synergistic effect of bLf and antifungal drugs. This review addressed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We conducted literature searches to assess the association of lactoferrin and current antifungal therapy against Candida albicans in ProQuest, PubMed, MEDLINE, EBSCOhost, SAGE, JSTOR, GARUDA, and Open Gray with no date restriction (until March 5th, 2021). We used Jeffry's Amazing Statistical Program (JASP) to measure the overall size effect of MIC (minimum inhibitory concentration) between studies. A total of 7 studies retained were experimental in vitro studies. Based on the available data, 4 out of 7 studies were included in the quantitative analysis. This systematic review showed that bovine lactoferrin could help inhibit the development of azole-susceptible and azole-resistant C. albicans. Furthermore, there was synergistic activity between lactoferrin and various antifungals. Our meta-analysis showed that lactoferrin could significantly inhibit the C. albicans growth than the control group. Bovine lactoferrin and its peptide derivatives isolated from bovine milk can significantly inhibit the growth of C. albicans, both susceptible to azoles and those with azole resistance.

The Association of Immune Cell Infiltration with Metastasis Location in De Novo Metastatic Triple Negative Breast Cancer: A Multicenter Cross-Sectional Study in Indonesia.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, with limited treatments and a high metastasis risk. The varying location of metastasis in TNBC patients often leads to in prognosis in breast cancer. Therefore, this study aimed to investigate the potential association between immune cells profiles in the tumor microenvironment and metastatic patterns. METHODS: We conducted a multicenter cross-sectional study in 2022 to examine formalin-fixed paraffin-embedded (FFPE) and medical record data from 2015 to 2020 in de novo metastatic TNBC patients. The medical records provided crucial information about the sites of metastasis. Immunohistochemistry (IHC) analysis was carried out on primary breast tumor tissues to evaluate the expressions of cluster of differentiation (CD)4 T-cells, CD8 T-cells, CD163, FOXP3 Tregs, and programmed death-ligand 1 (PD-L1), along with immune cells ratios showing antitumor-to-protumor activity (CD4/FOXP3, CD8/FOXP3, CD4/CD163, CD8/CD163). Metastatic locations were grouped into bone-only, visceral, lung, liver, and brain metastasis.  Results: A total of 120 metastatic TNBC patients were documented for their metastatic location and IHC report. The clinical and histopathological characteristics showed that the majority of the patients were within the 40-65 years old group, and 34.2% had standard body mass index (BMI). Furthermore, the majority (89.22%) of the patients showed No Special Type (NST), (56.7%) had histopathology grade III, high Ki-67 ≥20% (85.8%), and positive PD-L1 expression (30.8%), with visceral metastasis indicating the highest proportion of 75.8%. Patients with a high CD8/FOXP3 and CD4/FOXP3 ratio were significantly prone to have bone-only metastasis compared to visceral metastasis (p= 0.028 and p=0.024, respectively).  Conclusion: The ratio of antitumor to protumor T-lymphocytes had a significant relevance in the metastatic location patterns in TNBC.