Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center:A retrospective analysis

BACKGROUND Follicular lymphoma(FL)is a type of B-cell lymphoma that originates at the germinal center and has a low malignancy rate.FL has become the most common inert lymphoma in Europe and America but has a relatively low incidence in Asia.AIM To explore the clinical features,curative effects,and prognostic factors of FL.METHODS Completed medical records of 49 patients with FL who were admitted to the Ningbo First Hospital from June 2010 to June 2021 were examined.These patients were definitively diagnosed by pathological biopsy or immunohistochemical staining.The diagnostic criteria were based on the 2008 World Health Organization classification of lymphomas.Ann Arbor staging was performed according to the imaging and bone marrow examination results.Risk stratification of all patients was performed based on the International Prognostic Index(IPI),age-adjusted IPI,Follicular Lymphoma International Prognosis Index(FLIPI),and FLIPI2 to compare the efficacy of different treatment regimens and analyze the related prognostic factors.RESULTS The age of onset in patients ranged from 24 to 76 years,with a median age of 51 years.Most patients developed the disease at 40–59 years of age,and the male:female ratio was 1.6:1.No significant difference was noted in the curative effect between the non-chemotherapy,combined chemotherapy,and other chemotherapy regimens(P>0.05).Hemoglobin(Hb)level<120 g/L,Ki-67 value>50%,bone marrow involvement,and clinical stagesⅢ–IV were associated with a poor prognosis of FL(P<0.05).However,the influence of other indicators was not statistically significant.Risk grouping was performed using the FLIPI,and the results showed that 24.5%,40.8%,and 34.7%of patients were in the low-,moderate-,and high-risk groups,respectively.According to the survival analysis results,the survival rate of patients was lower in the high-risk group than in the other low-risk and moderate-risk groups(P<0.05).CONCLUSION FL mainly occurs in middle-aged and elderly men,primarily affecting lymph nodes and bone marrow.Hb level,Ki-67 value,bone marrow involvement,and clinical staging were used to evaluate prognosis.

Effect of T-regulatory cells and interleukin-35, interleukin-10, and transforming growth factor-beta on diffuse large B-cell lymphoma

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is an aggressive non-Hodgkin lymphoma that affects B lymphocytes.It can develop in the lymph nodes and can be localized or generalized.Despite DLBCL being considered potentially curable,little research has been conducted on the relationship between the body's immune response and DLBCL.AIM To study the expression and significance of T-regulatory cells(Tregs)interleukin(IL)-35,IL-10,and transforming growth factor-beta(TGF-β)in DLBCL.METHODS Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University(Zhejiang Province,China)between January 2017 and June 2022 and treated with standard first-line regimens were reviewed.Three patients were lost to follow-up;thus,79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy:Incipient(new-onset and treatment-naïve),effectively treated,and relapsed-refractory.Thirty healthy individuals were included in the control group.The expression of peripheral blood T lymphocytes and their associated factors IL-35,IL-10,and TGF-βin the four groups were observed.RESULTS In contrast to the successfully treated and normal control groups,both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive(+)Tregs(P<0.05),whereas the proportion of CD8+Tregs did not differ substantially between the groups.Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups(P<0.05).There was no statistically significant distinction in the expression level of TGF-βbetween the groups(P>0.05).The correlation between IL-35 and IL-10 concentrations was significantly positive,with a correlation coefficient of 0.531(P<0.05).The correlation between IL-35 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.375(P<0.05).The correlation between IL-10 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.185(P<0.05).The expression concentrations of IL-35,IL-10 and TGF-βwere apparently and positively correlated(P<0.05).CONCLUSION Tregs IL-35,and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.

Monkeypox in humans:Transmission,pathophysiology,diagnosis,treatment,prevention,and all recent updates

The Centers for Disease Control and Prevention(CDC)is monitoring an epidemic of monkeypox infection in the United States.The outbreak is now global and more than 6900 cases have already been reported.There are 83 confirmed cases among children and adolescents,as shown in the report published on November 3,2022,in the USA.However,monkeypox in pediatric patients is still infrequent(<0.3%of total cases).Among cases in the United States,16 cases were in children<5 years,12 in the age group 5-12 years,and 55 cases in adolescents 13-17 years old.In the adolescent age group,89%were male.For children<12 years of age,close physical contact with an adult household with monkeypox was the primary exposure,but for adolescents,male-to-male sexual contact was found more frequently.The CDC advised United States healthcare providers to remain vigilant for patients with a rash resembling monkeypox,even if there is no history of travel to a country with high risk.This article summarizes the history and epidemiology of monkeypox with a specific emphasis on clinical features and management in pediatric patients.

Proton pump inhibitor-associated pneumonia:Not a breath of fresh air after all?

Over the past two decades,proton pump inhibitors (PPIs)have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders.Unfortunately,this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings.While generally well-tolerated,research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired(CAP)and hospital-acquired pneumonias(HAP).The mechanism behind PPI-associated pneumonia may be multifactorial,but is thought to stem from compromising the stomach's"acid mantle"against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated.A secondary postulate is that PPIs,through their inhibition of extra-gastric H+/K+ATPase enzymes,may reduce the acidity of the upper aerodigestive tract,thus resulting in increased bacterial colonization of the larynx,esophagus and lungs.To date,several retrospective case control studies have been published looking at the association between PPI use and CAP.Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia,but only two could define a dose-response re-lationship.Furthermore,other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP,we reviewed two retrospective cohort studies and one prospective study.One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy,while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H2RAs.The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H2RAs.In conclusion,the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H2RAs,but the findings are not consistent across all studies.Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP.Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations.In the interim,it appears prudent to limit the use of PPIs to situations where they are clinically indicated and,in such cases,use them at the lowest effective dose.In the case of prescribing for stress ulcer prophylaxis in ICU patients,perhaps H2RAs should be used as the preferred agents over PPIs.

Peripartum cardiomyopathy: A puzzle closer to solution

Peripartum cardiomyopathy(PPCM) represents new heart failure in a previously heart-healthy peripartum patient. It is necessary to rule out all other known causes of heart failure before accepting a diagnosis of PPCM. The modern era for PPCM in the United States and beyond began with the report of the National In-stitutes of Health PPCM Workshop in 2000, clarifying all then-currently known aspects of the disease. Since then, hundreds of publications have appeared, an indi-cation of how devastating this disease can be to young mothers and their families and the urgent desire to find solutions for its cause and better treatment. The purpose of this review is to highlight the important ad-vances that have brought us nearer to the solution of this puzzle, focusing on what we have learned about PPCM since 2000; and what still remains unanswered. Despite many improvements in outcome, we still do not know the actual triggers that initiate the pathological process; but realize that cardiac angiogenic imbalances resulting from complex pregnancy-related immune sys-tem and hormonal changes play a key role.

Cockcroft-gault revisited: New de-liver-ance on recommendations for use in cirrhosis

The Cockcroft-Gault(CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine(SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the "rounding up" approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance(Cr Cl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure Cr Cl. Furthermore, "rounding up" of SCr values often underestimated Cr Cl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

Down-regulation of Helios Expression in Tregs from Patients with Hypertension

Regulatory T cells（Tregs） play a pivotal role in the pathological development of hypertension.Helios,a transcription factor from the Ikaros family,was recently reported to be a bona fide marker for natural Tregs or activated Tregs with suppression function,however,little has been known about its role in hypertension.This study was aimed to find whether Helios＋ Tregs really play a vital role in hypertension.A total of 60 hypertension patients,and 46 normotension subjects were enrolled in this study.Frequencies of different Tregs subsets in peripheral blood were measured by flow cytometry.Plasma cytokine level was determined by ELISA.The m RNA expression of Foxp3 and Helios in purified CD4＋ T cells was detected by RT-PCR.Proportion of CD4＋Foxp3＋Helios＋ Tregs was decreased significantly in patients with hypertension（62.52%±1.18% vs.71.89%±1.03%,P〈0.01）,and it was correlated with plasma level of IL-10 positively（r=0.505,P〈0.05） and plasma level of IFN-gamma negatively（r=–0.551,P〈0.05）.The m RNA expression of Foxp3（7.23±1.00 vs.10.58±0.54,P〈0.05） and Helios（8.47±0.95 vs.15.52±2.0,P〈0.05） was decreased in CD4＋ T cells from patients with hypertension.Helios＋ Tregs were decreased in patients with hypertension and may play a protective role in hypertension progression.

T-cell immunoglobulin mucin molecule-3, transformation growth factor β, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma

BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) have not been elucidated.AIM To examine the correlation between Tim-3,TGF-β and CXCL12 expression and DLBCL prognosis.METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups,respectively.The expression of Tim-3,TGF-β,and CXCL12 was detected immunohistochemically.Patients were followed up for 3 years,and progression-free survival was recorded.Cox mult-ifactorial analysis was performed to analyze the risk factors for poor prognosis.RESULTS The positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in DLBCL tissues than in non-cancerous(control) tissues(P < 0.05).One-year postsurgery,the positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment(P < 0.05).The 3-year progression-free survival of 97 patients with DLBCL was 67.01%(65/97).Univariate analysis revealed that clinical stage,bone marrow infiltration,International Prognostic Index(IPI) score,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were associated with poor prognosis(P < 0.05).Multivariate Cox regression analysis demonstrated that clinical stage Ⅲ–Ⅳ,bone marrow infiltration,mediate-to-high-risk IPI scores,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were independent risk factors affecting prognosis(P < 0.05).CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3,TGF-β,and CXCL12,and a high expression of all three indicates a poor prognosis.

Pornography use among adolescents and the role of primary care

Given the increase in pornography use among adolescents over the years,we discuss the impact of its use on sexual health development as well as the role of primary care providers(PCPs)in assessing use and providing sexual health education.While pornography use is often viewed negatively,it is important to develop unbiased understanding of the use in order to provide non-judgemental,adolescent-focused and educational care.As PCPs are often the first point of contact when adolescents experience medical and behavioural health concerns,it is essential for them to be equipped to screen for pornography use effectively,create a confidential and comfortable environment to talk about pornography use and sexuality,and be informed of ways to promote open discussion between youth and parents.In addition to PCP involvement,parental collaboration,knowledge and comfortability with discussing pornography use with their child are powerful tools in understanding and navigating pornography use in this population.This special communication seeks to provide an objective view of adolescents’pornography use,guidelines for screening of pornography use and ways to facilitate conversations about the use between adolescents and caregivers.