COVID-19 mortality paradox(United States vs Africa):Mass vaccination vs early treatment

The coronavirus disease 2019(COVID-19)mortality rate in 55 African countries is almost 4.5 times lower than in the coronavirus disease 2019(COVID-19)despite Africa having over 4.2 times more people.This mortality paradox is also evident when comparing Nigeria,a heavily populated,poorly vaccinated and weakly mandated country to Israel,a small,highly vaccinated and strictly mandated country.Nigeria has almost 4 times lower COVID mortality than Israel.In this Field of Vision perspective,I explain how this paradox has evolved drawing upon my academic,clinical and social experience.Since April 2020,I’ve developed and been using the Egyptian immune-modulatory Kelleni’s protocol to manage COVID-19 patients including pediatric,geriatric,pregnant,immune-compromised and other individuals suffering from multiple comorbidities.It’s unfortunate that severe acute respiratory syndrome coronavirus 2 is still evolving accompanied by more deaths.However in Africa,we’ve been able to live without anxiety or mandates throughout the pandemic because we trust science and adopted early treatment using safe,and effective repurposed drugs that have saved the majority of COVID-19 patients.This article represents an African and Egyptian tale of honor.

Variations in quantifying patient reported outcome measures to estimate treatment effect

In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.

Late effects of the treatment of childhood cancer

Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer treatment.Research has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during adulthood.Therefore,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.

A Review of Abiraterone Acetate for the Treatment of Metastatic Castration-Resistant Prostate Cancer

Prostate cancer is a common malignant tumor of the urinary system in men,and the incidence and detection rate of prostate cancer have been rising significantly in recent years.Androgens play an important role in the occurrence and development of prostate cancer,so hormone deprivation therapy has become an essential means of prostate cancer treatment.Abiraterone acetate is a therapeutic agent for prostate cancer by inhibiting the enzyme activity of CYP17,thereby blocking androgen biosynthesis.In this paper,we present a review of the current mechanism of action of abiraterone acetate for prostate cancer treatment,research progress,and its side effects and limitations.It is expected to provide help for further research on the treatment of prostate cancer.

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer:Identification,prognosis and survival,genetic and epigenetic factors

Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Controversies around the treatment of peritoneal metastases of colorectal cancer

In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology.Surgical resection for peritoneal metastases from colorectal cancer(CRC)has been gradually accepted in the medical oncology community.A randomized trial(PRODIGE 7)on cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin.Nevertheless,isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver.Another tool is required in those patients to achieve more local control of the disease.Surgical groups in peritoneal surgery continue to use HIPEC in their procedures,using other agents than oxaliplatin for peritoneal cavity infusion,such as mitomycin C.These patients present with complex surgical issues to manage,and consequently a large burden of complications has to be anticipated.Therefore,identifying patients who will benefit from CRS with or without HIPEC would be of great interest.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Efficacy,safety and treatment satisfaction of transition to a regimen of insulin degludec/aspart:A pilot study

BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Current Controversies and the State of the Art in Endovascular Treatment of Vascular Malformations

Vascular anomalies constitute some of the most difficult diagnostic and therapeutic enigmas that can be encountered in the practice of medicine. The clinical presentations are extremely protean and can range from an asymptomatic birthmark to fulminant。

Impact of diabetes mellitus on risk of cardiovascular disease and all-cause mortality: Evidence on health outcomes and antidiabetic treatment in United States adults

AIMTo examine the epidemic of diabetes mellitus (DM) and its impact on mortality from all-cause and cardiovascular disease (CVD), and to test the effect of antidiabetic therapy on the mortality in United States adults. METHODS The analysis included a randomized population sample of 272149 subjects ages ≥ 18 years who participated in the National Health Interview Surveys (NHIS) in2000-2009. Chronic conditions (hypertension, DM and CVD) were classified by participants’ self-reports of physician diagnosis. NHIS-Mortality Linked Files, and NHIS-Medical Expenditure Panel Survey Linkage Fileson prescribed medicines for patients with DM were used to test the research questions. χ 2, Poisson and Cox’s regression models were applied in data analysis.RESULTS Of all participants, 22305 (8.2%) had DM. The prevalence of DM significantly increased from 2000 to 2009 in all age groups (P < 0.001). Within an average 7.39 (SD= 3) years of follow-up, male DM patients had 1.56 times higher risk of death from all-cause (HR = 1.56, 95%CI:1.49-1.64), 1.72 times higher from heart disease [1.72 (1.53-1.93)], 1.48 times higher from cerebrovascular disease [1.48 (1.18-1.85)], and 1.67 times higher from CVD [1.67 (1.51-1.86)] than subjects without DM,respectively. Similar results were observed in females. In males, 10% of DM patients did not use any antidiabetic medications, 38.1% used antidiabetic monotherapy, and 51.9% used ≥ 2 antidiabetic medications. These corresponding values were 10.3%, 40.4% and 49.4% in females. A significant protective effect of metformin monotherapy or combination therapy (except for insulin) on all-cause mortality and a protective but non-significant effect on CVD mortality were observed. CONCLUSION This is the first study using data from multiple linkage files to confirm a significant increased prevalence of DM in the last decade in the United States. Patients with DM have significantly higher risk of death from all-cause and CVD than those without DM. Antidiabetic mediations,specifically for metformin use, show a protective effect against all-cause and CVD mortalities.

Effects of high-pressure heat treatment on the solid-state phase transformation and microstructures of Cu_(61.13)Zn_(33.94)Al_(4.93) alloys

The phase transformation activation energy of the Cu61.13Zn33.94A14.93 alloys, which were treated at 4 GPa and 700 ℃ for 15 minutes, was calculated by means of differential scanning calorimetry curves obtained at various heating and cooling rates. Then, the effects of high-pressure heat treatments on the solid-state phase transformation and the microstructures of Cu61.13Zn33.94A14.93 alloys were investigated. The results show that high-pressure heat treatments can refine the grains and can change the preferred orientation from （111） to （200） of α phase. Compared with the as-cast alloy, the sample with high-pressure heat treatment has finer grains, lower β＇→β and/β→β＇ transformation temperature and activation energy. Furthermore, we found that high cooling rate favours the formation of fine needle-like α phase in the range of 5-20℃/min.

Evolving landscape and novel treatments in, metastatic castrate-resistant prostate cancer

Treatment options for castrate-resistant prostate cancer （CRPC） have advanced in recent years and significantly improved the Outlook for patients with this aggressive and lethal disease. Further understanding of the biology＇of CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor （AR） directed therapy. The treatment landscape is rapidly changing and further biologically rationale, biomarker-based ongoing clinical trials are needed. We review the recent results of major clinical trials in CRPC. New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis, microtubules, chaperones, AR and intracellular kinases, as well as immunotherapy, radiopharmaceuticals and bone-targeted agents. The recent improvement in prognosis for CRPC brings continued optimism for further improvements. Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

Chinese guidelines for diagnosis and treatment of prostate cancer 2018 (English version)

Contents1. Overview2. Risk factors of prostate cancer2.1 Age and genetic factors2.2 Exogenous factors3. Pathological classification and grading system4. Diagnostic evaluation4.1 Monitoring and screening for population with high-risk prostate cancer4.2 Genetic testing4.3 Digital rectal examination (DRE)4.4 Magnetic resonance examination4.5 Bone scan examination.

Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

Suppression of gonadal testosterone synthesis represents the standard first line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer （CRPC）, it is possible to detect persistent activation of the androgen receptor （AR） through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17（^-hydroxylase and 17,20-1yase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a significant improvement in overall survival （OS） with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone （ACTH）, providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-1yase （orteronel, galeterone and VT-464） that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors; recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents; and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone benefit or restore abiraterone activity.

Endoclipping treatment of life-threatening rectal bleeding after prostate biopsy

Rectal bleeding is frequently seen in patients undergoing transrectal ultrasound(TRUS)-guided multiple biopsy of the prostate,but is usually mild and stops spontaneously.We report what is believed to be the first case of life-threatening rectal bleeding following this procedure,which was successfully treated by endoscopic intervention through placement of three clips on the sites of bleeding.This case emphasizes endoscopic intervention associated with endoclipping as a safe and effective method to achieve hemostasis in massive rectal bleeding after prostate biopsy.Additionally,current data on the complications of the TRUS-guided multiple biopsy of the prostate and the options for treating fulminant rectal bleeding, a consequence of this procedure,are described.

National guidelines for diagnosis and treatment of prostate cancer 2022 in China(English version)

Contents 1.Overview 2.Etiology 2.1 Age and genetic factors 2.2 Exogenous factors 3.Pathological classification and grading system 3.1 Pathological grading and grouping of prostate cancer 3.2 Staging of prostate cancer 3.3 Risk grouping for patients with local or locally advanced prostate cancer 4.Diagnostic evaluation 4.1 Monitoring,screening and early diagnosis 4.2 Genetic testing。

Multicomponent Assessment of the Geometrical Uncertainty and Consequent Margins in Prostate Cancer Radiotherapy Treatment Using Fiducial Markers

The aim is to compute all sources of geometrical uncertainty in prostate radiotherapy using fiducial markers and determine the safety treatment margins. Based on the markers position, correlations between prostate rotation/deformation and rectal and bladder fillings as well as changes in prostate volume during the treatment course are analyzed. The study includes 375 pre-treatment CBCT images from 15 prostate cancer patients treated with hypofractionated radiotherapy. The position coordinates of the markers were obtained from each image acquisition. In addition, rectum and bladder were outlined on CBCTs. The intrafractional error was estimated by an additional post-treatment CBCT acquired on alternate days. Tau-Kendall analysis was performed to correlate organ fillings with prostate rotation/deformation. Delineation uncertainty was assessed from contours of 10 patients performed by two radiation oncologists and repeated twice. The CT contouring was assisted by a multiparametric MR approach combining a T2-weighted with diffusion-weighted imaging, and a gradient recalled echo for fiducial marker identification. Uncertainty associated to treatment unit was estimated from phantom measurements. The obtained clinical margins were 4.4, 7.3, 5.1 mm in the Left-Right, Superior-Inferior, and Anterior-Posterior directions, respectively, being the contouring the most important contribution. The mechanical limitations of the beam delivery system and the associated imaging device entailed errors of the same order as prostate motion, rotation or deformation. Weak correlations between variation of the rectal volume and the presence of rotations/deformations were found (correlation coefficient 0.182, p = 0.001 for rotations around lateral axis;correlation coefficients 0.1, p < 0.05 for deformations). The distance between markers decreased with session number, becoming more pronounced from fraction 13 and reaching 1 - 1.8 mm at the end of the treatment. In summary we have determined the optimal treatment margins based on geometrical uncertainty assessment using van Herk formalism. An appropriate preparation of rectum and bladder involves minimizing the effect of prostate rotations/deformations. The prostate tends to decrease in size during the treatment which could influence treatment re-planning strategies.

Comments on National guidelines for diagnosis and treatment of prostate cancer 2022 in China (English version)

National guidelines for diagnosis and treatment of prostate cancer 2022 in China (English version)(1) was organized by the National Health Commission of the People’s Republic of China, led by the Cancer Hospital of the Chinese Academy of Medical Sciences, and jointly compiled by well-known experts across China. On the basis of the 2018version, the 2022 version of the guideline not only absorbs the updated content of the latest international guidelines.