Prolongation of the QT interval is associated with adverse cardiac events specifically Torsades de pointes(TdP).There are multiple mediations that have a known,possible,or conditional risk for prolonged QT interval,bu...Prolongation of the QT interval is associated with adverse cardiac events specifically Torsades de pointes(TdP).There are multiple mediations that have a known,possible,or conditional risk for prolonged QT interval,but general practitioners’knowledge of these medications is unknown.We conducted a survey to assess internal medicine(IM)providers’knowledge of risk factors and medications associated with prolonged QT as well as provider experience and comfort when treating patients with prolonged QT.A 17-question,anonymous survey was constructed in 2019 and distributed to IM providers and residents at a tertiary care center.Questions included demographic information,6 Likert-scale questions gauging provider experience with prolonged QT,and 10 multiple choice clinical vignettes to assess clinical knowledge.Data was analyzed descriptively.Knowledge was assessed via clinical vignettes and compared by level of training.Forty-one responses were received out of a total of 87 possible respondents(47.1%response rate).About 70%of respondents see patients with acquired prolonged QT once monthly or more.95%rarely see congenital prolonged QT.When presented with QTc drug issues,73%of providers seldom or sometimes consulted pharmacy,but about half used online resources.The average correct score on the clinical vignettes was 5.59/10,with the highest scores seen in attending physicians in their first five years of practice(6.96/10).Our survey suggests that IM providers commonly encounter QT prolonging drugs.Educational efforts to improve knowledge of drug and patient risk factors for TdP may be needed.展开更多
Surgical repair has been the standard therapy for severe mitral regurgitation causing symptoms or left ventricular dysfunction.Percutaneous mitral valve repair has become an appealing alternative approach for patients...Surgical repair has been the standard therapy for severe mitral regurgitation causing symptoms or left ventricular dysfunction.Percutaneous mitral valve repair has become an appealing alternative approach for patients who are not suitable for surgery.However,clinical trial data are not available on the institutional impact of a percutaneous mitral valve repair program on mitral valve surgery.The current study retrospectively evaluated the impact of the MitraClip program on the mitral valve surgery volume and outcomes.Patient data were retrieved from the 2 years before and the 2 years after initiation of the MitraClip program.The volume of MitraClip procedures increased from eight cases in 2015 to 91 cases in 2017.Since the initiation of the MitraClip program in 2015,the volume of both mitral valve replacement and mitral valve repair also increased(43 vs.60 and 110 vs.154,respectively).Importantly,we observed improved surgical outcomes,including fewer perioperative complications and lower operative mortality and in-hospital mortality.Data from our single-institution experience indicate that the introduction of the MitraClip program is associated with increased mitral valve surgery volume and improved outcomes.The establishment of the MitraClip program enables the hospital to provide higher quality of care and potentially become a referring center for structural heart patients.展开更多
Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficienc...Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset,progression,and worsening of diabetic neuropathy(DNP)as well as its im-provement with supplementation in cases of deficiency.Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measu-rement and supplementation,and some guidelines do not address it at all.Given that vitamin B12 therapy is an economical,safe,and widely available treatment in most countries and supported by emerging evidence of its potential benefits,greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency.Vitamin B12 deficiency should be treated in all affected patients,and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable.Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.展开更多
BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic form of diabetes often misdiagnosed as type 1 or type 2.The MODY7 subtype,attributed to variants in the Kruppel-like factor 11(KLF11)gene,is exceedin...BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic form of diabetes often misdiagnosed as type 1 or type 2.The MODY7 subtype,attributed to variants in the Kruppel-like factor 11(KLF11)gene,is exceedingly rare,and its clinical spectrum is not fully characterized.Precise genetic diagnosis is essential for appropriate management but is challenging due to phenotypic overlap with other diabetes types.This case report describes a patient with a novel KLF11 variant,contributing to the understanding of this rare condition and its clinical implications.CASE SUMMARY A 50-year-old female with a family history of MODY in her son was initially diagnosed with type 2 diabetes.Due to the family history and a non-obese phenotype,a comprehensive genetic panel for monogenic diabetes was performed.The analysis identified a novel heterozygous missense variant,p.Cys105Phe,in the KLF11 gene,establishing a definitive diagnosis of MODY7.Following this diagnosis,the patient’s treatment was adjusted to include lifestyle modifications,resulting in adequate glycemic control.The patient has since maintained target glycated hemoglobin levels.CONCLUSION Monogenic diabetes type MODY7,caused by a mutation in the KLF11 gene,is extremely rare.Although some studies question its existence,compatible cases continue to be diagnosed,given its inclusion in genetic panels for MODY.展开更多
Sickle cell anemia (SCA) is a prevalent genetic disorder primarily affecting individuals of African descent and populations in malaria-endemic regions, with significant global public health implications. Sickle cell c...Sickle cell anemia (SCA) is a prevalent genetic disorder primarily affecting individuals of African descent and populations in malaria-endemic regions, with significant global public health implications. Sickle cell crises are their most common acute complication, characterized by episodes of intense pain and systemic manifestations that impair quality of life and impose a high healthcare burden. We present the case of a 19-year-old male diagnosed with SCA since the age of two, who developed a sickle cell crisis precipitated by right basal pneumonia. The patient exhibited sudden-onset, cyclic lumbar pain with progressive dyspnea. Initial management included multimodal pain control, volume optimization, and targeted antimicrobial therapy to achieve clinical stabilization. This case underscores the importance of a comprehensive approach to managing sickle cell crises, addressing both symptomatic relief and the prevention and treatment of complications. It also highlights the need for public health strategies promoting early diagnosis, access to disease-modifying therapies such as hydroxyurea, and interdisciplinary follow-up to mitigate the socioeconomic and clinical impact of SCA.展开更多
BACKGROUND Gastric antral vascular ectasia(GAVE)accounts for up to 4%of nonvariceal upper gastrointestinal bleeding.Argon plasma coagulation and radiofrequency ablation have been primary treatment modalities for patie...BACKGROUND Gastric antral vascular ectasia(GAVE)accounts for up to 4%of nonvariceal upper gastrointestinal bleeding.Argon plasma coagulation and radiofrequency ablation have been primary treatment modalities for patients with linear and punctate subtypes,with a newer trend of utilization of endoscopic band ligation(EBL).This study evaluates the outcomes of patients undergoing treatment for nodular GAVE.We hypothesize that patients treated initially with EBL will achieve higher rates of clinical remission with fewer endoscopic treatments and a shorter treatment interval.AIM To investigate the effects of EBL as an initial treatment therapy on outcomes associated with nodular GAVE.METHODS A total of 37 patients at a tertiary medical center with nodular GAVE were included in this retrospective study.The study population was divided between those treated initially with EBL(initial EBL)and initial endoscopic thermal therapy.Pretreatment and post-treatment hemoglobin values,the model for end-stage liver disease scores,hospitalization rates,and other outcomes.Additionally,endoscopic treatment modality type and frequency were recorded,including radiofrequency ablation,argon plasma coagulation,and EBL.Continuous variables were compared using a t-test,while categorical variables were compared using Fisher’s exact.RESULTS Linear regression analysis displayed a positive relationship between the time interval from initial therapeutic esophagogastroduodenoscopy to first EBL treatment and overall treatment interval(t=7.39,P<0.001),as well as between the number of endoscopic treatments(t=8.09,P<0.001).Hemoglobin levels increased in both the initial EBL group(8.7 vs 11.4,P<0.001)and the initial endoscopic thermal therapy group(8.6 vs 10.4,P=0.042).Clinical remission rates were higher in the initial EBL group(90%vs 69%P=0.041),with a non-significant trend of higher endoscopic remission rates(57.1%vs 37.5%,P=0.270).CONCLUSION The observed trend favoring EBL,combined with its association with improved clinical remission and reduced treatment burden,supports its consideration as a preferred initial treatment approach.展开更多
BACKGROUND There is increasing incidence of alcohol-associated liver disease in females.Despite this recent increased incidence,there is a paucity of research on the clinical course and outcomes of alcohol-associated ...BACKGROUND There is increasing incidence of alcohol-associated liver disease in females.Despite this recent increased incidence,there is a paucity of research on the clinical course and outcomes of alcohol-associated hepatitis(AH)in females compared to males.AIM To assess if there may be sex differences in severity,outcomes,and healthcare utilization for patients hospitalized for AH.METHODS This study used ICD-9-CM and ICD-10-CM codes to retrospectively identify inpatient encounters for AH at the University of Kentucky from 2012-2021 and obtained data on patient demographics and clinical outcomes.Encounters were cohorted by patient sex and differences in patient demographics and clinical outcomes were assessed.Multivariate logistic regression models were constructed to assess risk of mortality,sepsis,and mechanical ventilation during the encounter.RESULTS Of 1386 subjects,511(36.9%)were female and 875(63.1%)were male.Both sexes had similar baseline characteristics of race/ethnicity,discriminant function score,model of end-stage liver disease score,and length of hospital stay.However,the incidence of urinary tract infection,sepsis,and norepinephrine administration was significantly higher for females.Males had a significantly higher incidence of esophageal variceal bleed.On multivariate logistic regression analysis,females had higher odds of encounter sepsis(OR 1.41;95%CI:1.064-1.869)and mechanical ventilation(OR 1.352;95%CI:1.006-1.816).Odds of encounter mortality were significantly increased in encounters with sepsis(OR 2.309;95%CI:1.419-3.757)and mechanical ventilation(OR 9.301;95%CI:5.724-15.114).CONCLUSION This study shows sex-based differences in AH outcomes at the University of Kentucky.Future studies are warranted to assess whether tailoring treatments will improve clinical outcomes in females with AH.展开更多
BACKGROUND Liver imaging and transient elastography(TE)are both tools used to assess liver fibrosis and steatosis among people with hepatitis C virus(HCV)infection.However,the diagnostic accuracy of conventional imagi...BACKGROUND Liver imaging and transient elastography(TE)are both tools used to assess liver fibrosis and steatosis among people with hepatitis C virus(HCV)infection.However,the diagnostic accuracy of conventional imaging in detecting fibrosis and steatosis in this patient population remains unclear.AIM To investigate the correlation between steatosis and fibrosis and abnormal findings on liver imaging in patients with HCV.METHODS We conducted a retrospective cross-sectional analysis of patients with HCV at Grady Liver Clinic who had TE exams between 2018-2019.We analyzed the correlation of controlled attenuation parameter and liver stiffness measurement on TE and abnormal findings on liver imaging.Liver imaging findings(hepatic steatosis,increased echogenicity,cirrhosis,and chronic liver disease)were further evaluated for their diagnostic performance in detecting fibrosis(≥F2,≥F3,≥F4)and steatosis(≥S1,≥S2,≥S3).RESULTS Of 959 HCV patients who underwent TE,651 had liver imaging.Higher controlled attenuation parameter scores were observed in patients with abnormal liver findings(P=0.0050),hepatic steatosis(P<0.0001),and increased echogenicity(P<0.0001).Higher liver stiffness measurement values were also noted in those with abnormal liver(P<0.0001)and increased echogenicity(P=0.0026).Steatosis severity correlated with hepatic steatosis(r=0.195,P<0.001)and increased echogenicity(r=0.209,P<0.001).For fibrosis detection,abnormal liver imaging had moderate sensitivity(81.7%)and specificity(70.4%)for cirrhosis(≥F4),while cirrhosis on imaging had high specificity(99.2%)but low sensitivity(18.3%).Increased echogenicity showed high specificity(92.8%)but low sensitivity(20.9%)for steatosis detection.CONCLUSION Liver imaging detects advanced fibrosis and steatosis but lacks early-stage sensitivity.Integrating TE with imaging may improve evaluation in patients with HCV.展开更多
Hepatocellular carcinoma(HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with...Hepatocellular carcinoma(HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with 80%-90% of new cases occurring in the background of cirrhosis. Studies have shown that early diagnosis of HCC through surveillance programs improve prognosis and availability of curative therapies. All patients with cirrhosis and high-risk hepatitis B patients are at risk for HCC and should undergo surveillance. The recommended surveillance modality is abdominal ultrasound(US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with non-alcoholic fatty liver disease(NAFLD). With the current obesity epidemic and rise in the prevalence of NAFLD, abdominal computed tomography or magnetic resonance imaging may be indicated as the primary screening modality in these patients. The addition of alpha-fetoprotein to a surveillance regimen is thought to improve the sensitivity of HCC detection.Further investigation of serum biomarkers is needed. Semiannual screening is the suggested surveillance interval. Surveillance for HCC is underutilized and low adherence disproportionately affects certain demographics such as nonCaucasian race and low socioeconomic status.展开更多
Primary sclerosing cholangitis(PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra-and/or extrahepatic biliary ducts. While its features and disease course ...Primary sclerosing cholangitis(PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra-and/or extrahepatic biliary ducts. While its features and disease course can be variable,most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly,PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma,hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.展开更多
Inflammatory fibroid polyp(IFP) is a rare,idiopathic pseudotumorous lesion of the gastrointestinal tract.While mostly reported as solitary gastric lesions,multiple cases of small bowel IFPs are also reported.It is a d...Inflammatory fibroid polyp(IFP) is a rare,idiopathic pseudotumorous lesion of the gastrointestinal tract.While mostly reported as solitary gastric lesions,multiple cases of small bowel IFPs are also reported.It is a documented cause of intussusception in adults.In the case reports of ileal inflammatory fibroid polyps with intussusception,an emergent presentation with small bowel obstruction has been most often described.Here we depict a case of ileal inflammatory fibroid polyp presenting with chronic intermittent ileocolic intussusception,anemia and weight loss with an endoscopic appearance mimicking necrotic cecal carcinoma.展开更多
Background Frailty is a multidimensional syndrome that reflects the physiological reserve of elderly.It is related to unfavorable outcomes in various cardiovascular conditions.We conducted a systematic review and meta...Background Frailty is a multidimensional syndrome that reflects the physiological reserve of elderly.It is related to unfavorable outcomes in various cardiovascular conditions.We conducted a systematic review and meta-analysis of the association of frailty with all-cause mortality and bleeding after acute myocardial infarction(AMI)in the elderly.Methods We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019.The studies that reported mortality and bleeding in AMI patients who were evaluated and classified by frailty status were included.Data from each study were combined using the random-effects,generic inverse variance method of Der Simonian and Laird to calculate hazard ratio(HR),and 95%confidence interval(CI).Results Twenty-one studies from 2011 to 2019 were included in this meta-analysis involving 143,301 subjects(mean age 75.33-year-old,60.0%male).Frailty status was evaluated using different methods such as Fried Frailty Index.Frailty was statistically associated with increased early mortality in nine studies(pooled HR=2.07,95%CI:1.67-2.56,P<0.001,I^2=41.2%)and late mortality in 11 studies(pooled HR=2.30,95%CI:1.70-3.11,P<0.001,I^2=65.8%).Moreover,frailty was also statistically associated with higher bleeding in 7 studies(pooled HR=1.34,95%CI:1.12-1.59,P<0.001,I^2=4.7%).Conclusion Frailty is strongly and independently associated with bleeding,early and late mortality in elderly with AMI.Frailty assessment should be considered as an additional risk factor and used to guide toward personalized treatment strategies.展开更多
BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulat...BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulation treatment have an associated increase rate.GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants(DOAC),especially with active cancer therapies.AIM To evaluate patient risk factors,effectiveness(VTE)and safety(MB)of DOACs and low molecular weight heparin(LMWH)in patients with active GICA-VTE.METHODS A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed.Inclusion criteria included active GI cancer diagnosed at any stage or treatment+/-6 mo of VTE diagnosis,whom were prescribed 6 mo or more of DOACs or LMWH.The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events.Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTS A total of 144 patients were prescribed anticoagulation,in which 106 fulfilled inclusion criteria apixaban(27.3%),rivaroxaban(34.9%)and enoxaparin(37.7%),and 38 were excluded.Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event,with 62%males,80%Caucasian,70%stage IV,pancreatic cancer(40.5%),30%Khorana Score(≥3 points),and 43.5%on active chemotherapy.Sixty-four percent of patients completed anticoagulation therapy(range 1 to 43 mo).Recurrent VTE at 6 mo was noted in 7.5%(n=3),6.8%(n=2)and 2.7%(n=1)of patients on enoxaparin,apixaban and rivaroxaban,respectively(all P=NS).MB at 6 mo were 5%(n=2)for enoxaparin,6.8%(n=2)for apixaban and 21.6%(n=8)for rivaroxaban(overall P=0.048;vs LMWH P=0.0423;all other P=NS).Significant predictors of a primary or secondary outcome for all anticoagulation therapies included:Active systemic treatment(OR=5.1,95%CI:1.3-19.3),high Khorana Score[≥3 points](OR=5.5,95%CI:1.7-17.1),active smoker(OR=6.7,95%CI:2.1-21.0),pancreatic cancer(OR=6.8,95%CI:1.9-23.2),and stage IV disease(OR=9.9,95%CI:1.2-79.1).CONCLUSION Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.展开更多
AIM To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus(HCV)/human immunodeficiency virus(HIV) co-infection in an urban HIV clinic.METHODS A retro...AIM To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus(HCV)/human immunodeficiency virus(HIV) co-infection in an urban HIV clinic.METHODS A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016.All patients included were receiving antiretroviral therapy(ART) with HIV RNA values of 100 copies/m L or fewer regardless of baseline HCV RNA level.The primary end point was a sustained virologic response of HCV at 12 wk(SVR12) after the end of therapy.RESULTS Of the 40 patients enrolled,55% were black,22.5% had been previously treated for HCV,and 25% hadcirrhosis.The patients were on a wide range of ART.Overall,39 patients(97.5%) had a SVR 12 after the end of therapy,including rates of 97.1% in patients with HCV genotype 1 a and 100% in those with HCV genotype 1 b.One patient with HCV genotype 3 a was included and achieved SVR12.Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis.Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn't reveal any resistance associated mutation in the NS5A or NS5B region.Interestingly,7(17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen.Two(5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy,which resolved after resuming the same ART regimen.No severe adverse events were observed and no patient discontinued treatment because of adverse events.The most common adverse events included headache(12.5%),fatigue(10%),and diarrhea(2.5%).CONCLUSION This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV,regardless of HCV baseline levels,HCV treatment history or cirrhosis condition.The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART.Occasional HIV virologic rebound occurred but later resolved without the need to change ART.展开更多
Foreign body ingestion encompasses both foreign object ingestion(FOI) and esophageal food impaction(EFI) and represents a common and clinically significant scenario among patients of all ages. The immediate risk to th...Foreign body ingestion encompasses both foreign object ingestion(FOI) and esophageal food impaction(EFI) and represents a common and clinically significant scenario among patients of all ages. The immediate risk to the patient ranges from negligible to life-threatening, depending on the ingested substance,its location, patient fitness, and time to appropriate therapy. This article reviews the FOI and EFI literature and highlights important considerations and implications for pediatric and adult patients as well as their providers. Where published literature is insufficient to provide evidence-based guidance, expert opinion is included to supplement the content of this comprehensive review.展开更多
Cardiovascular diseases(CVDs)remain the leading cause of death in the world and in most developed countries.Patients with type 2 diabetes mellitus(T2DM)suffer from both microvascular and macrovascular diseases and the...Cardiovascular diseases(CVDs)remain the leading cause of death in the world and in most developed countries.Patients with type 2 diabetes mellitus(T2DM)suffer from both microvascular and macrovascular diseases and therefore have higher rates of morbidity and mortality compared to those without T2DM.If current trends continue,the Center for Disease Control and Prevention estimates that 1 in 3 Americans will have T2DM by year 2050.As a consequence of the controversy surrounding rosiglitazone and the increasing prevalence of diabetes and CVDs,in 2008 the Food and Drug Administration(FDA)established new expectations for the evaluation of new antidiabetic agents,advising for pre and,in some cases,post-marketing data on major cardiovascular events.As a direct consequence,there has been a paradigm shift in new antidiabetic agents that has given birth to the recently published American Diabetes Association/European Association for the Study of Diabetes consensus statement recommending sodium-glucose cotransporter-2 inhibitors(SGLT2i)and glucagon like peptide-1 receptor agonists(GLP-1RA)in patients with T2DM and established CVD.As a result of over a decade of randomized placebo controlled cardiovascular outcome trials,the aforementioned drugs have received FDA approval for risk reduction of cardiovascular(CV)events in patients with T2DM and established CV disease.SGLT2i have been shown to have a stronger benefit in patients with congestiveheart failure and diabetic kidney disease when compared to their GLP-1RA counterparts.These benefits are not withstanding additional considerations such as cost and the multiple FDA Black Box warnings.This topic is currently an emerging research area and this mini-review paper examines the role of these two novel classes of drugs in patients with T2DM with both confirmed,and at risk for,CVD.展开更多
Background: Immune checkpoint inhibitors produce prolonged responses in select non-small cell lung cancer (NSCLC) patients, however the identification of patients most likely to benefit is difficult. Pretreatment deri...Background: Immune checkpoint inhibitors produce prolonged responses in select non-small cell lung cancer (NSCLC) patients, however the identification of patients most likely to benefit is difficult. Pretreatment derived neutrophil-to-lymphocyte ratio (dNLR) is an easily calculated marker available in routine clinical care that has shown prognostic value in many cancer treatment settings, but its association with survival in NSCLC patients treated with immune-checkpoint inhibitors is less understood. Patients and Methods: We retrospectively reviewed 72 NSCLC patients receiving either nivolumab or pembrolizumab between 3/1/15 and 3/1/17 with a median follow-up time of 5.1 months. Patients were compared using Cox proportional hazards models to detect an association between pretreatment dNLR 3 vs ≥3 on overall survival (OS), progression-free survival (PFS) and overall response rate. Results: Median age was 65 (range: 41 - 86), 65% were male, 40% received ≥ 2 prior systemic therapies and 14% had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2. Pretreatment dNLR ≥ 3 was independently associated with shortened OS (median 3.6 vs 8.5 months;HR: 5.4;95% CI: 2.0 - 14.6;p = 0.001) and PFS (median 2.1 vs 3.4;HR: 2.3;95% CI: 1.1 - 4.8;p = 0.027). Conclusion: Pretreatment dNLR ≥ 3 was independently associated with inferior survival in NSCLC treated with immune checkpoint inhibitors in routine practice. Prospective verification of this marker is warranted as it could serve as an inexpensive and widely-available marker for identifying NSCLC patients most likely to benefit from PD-1 inhibitors.展开更多
Shoulder pain is a common musculoskeletal complaint,and rotator cuff(RC)pathologies are one of the main causes.The RC undergoes various tendinopathic and avascular changes during the aging process.Other degenerative c...Shoulder pain is a common musculoskeletal complaint,and rotator cuff(RC)pathologies are one of the main causes.The RC undergoes various tendinopathic and avascular changes during the aging process.Other degenerative changes affecting its healing potential make it an appealing target for biological agents.Platelet-rich plasma(PRP)has demonstrated the potential to deliver a high concentration of several growth factors and anti-inflammatory mediators,and its clinical use is mainly supported by experiments that demonstrated its positive effect on muscle,ligaments,and tendinous cells.This review aimed to specify the role of PRP and its future applications in RC tendinopathies based on the current clinical evidence.Due to the different characteristics and conflicting outcomes,clinicians should use PRP with moderate expectations until more consistent evidence is available.However,it is reasonable to consider PRP in patients with contraindications to corticosteroid injections or those with risk factors for inadequate healing.Its autologous origin makes it a safe treatment,and its characteristics make it a promising option for treating RC tendinopathy,but the efficacy has yet to be established.展开更多
Objective:To identify the relationship between interleukin(IL)-15 levels and sarcopenia in human immunodeficiency virus(HIV)-infected patients who have received antiretroviral therapy.Methods:This study was a cross-se...Objective:To identify the relationship between interleukin(IL)-15 levels and sarcopenia in human immunodeficiency virus(HIV)-infected patients who have received antiretroviral therapy.Methods:This study was a cross-sectional design with 70 participants conducted from January to March 2021.All the participants were assessed for sarcopenia and the IL-15 levels.Sarcopenia was established based on the the Asian Working Group for Sarcopenia(AWGS)2019 criteria.Plasma IL-15 was determined.This analysis was carried out by means of 2×2 tabulation and the statistical test used is Chi-square.Results:Seventy patients received antiretroviral therapy>6 months and showed a good clinical response.Among them,36(51.4%)took zidovudine-based antiretroviral therapy with a median duration of illness of 5 years.The proportion of sarcopenia in patients with HIV infection was 32.9%.The median CD4 cell count was 395.5 cells/L(range:203-937 cells/L).Logistic regression analysis revealed that age>50 years(aOR 8.3,95%CI 1.6-44.5),underweight(aOR 7.7,95%CI 1.5-40.5),IL-15≥150.5 ng/L(aOR 4.9,95%CI 1.3-19.0)and female(aOR 4.8,95%CI 1.2-18.3 were significant and independent adverse predictors of sarcopenia in subjects with HIV infection.Conclusions:There is an association between high levels of IL-15 and sarcopenia in HIV-infected patients on antiretroviral therapy for more than 6 months with good clinical response.展开更多
文摘Prolongation of the QT interval is associated with adverse cardiac events specifically Torsades de pointes(TdP).There are multiple mediations that have a known,possible,or conditional risk for prolonged QT interval,but general practitioners’knowledge of these medications is unknown.We conducted a survey to assess internal medicine(IM)providers’knowledge of risk factors and medications associated with prolonged QT as well as provider experience and comfort when treating patients with prolonged QT.A 17-question,anonymous survey was constructed in 2019 and distributed to IM providers and residents at a tertiary care center.Questions included demographic information,6 Likert-scale questions gauging provider experience with prolonged QT,and 10 multiple choice clinical vignettes to assess clinical knowledge.Data was analyzed descriptively.Knowledge was assessed via clinical vignettes and compared by level of training.Forty-one responses were received out of a total of 87 possible respondents(47.1%response rate).About 70%of respondents see patients with acquired prolonged QT once monthly or more.95%rarely see congenital prolonged QT.When presented with QTc drug issues,73%of providers seldom or sometimes consulted pharmacy,but about half used online resources.The average correct score on the clinical vignettes was 5.59/10,with the highest scores seen in attending physicians in their first five years of practice(6.96/10).Our survey suggests that IM providers commonly encounter QT prolonging drugs.Educational efforts to improve knowledge of drug and patient risk factors for TdP may be needed.
文摘Surgical repair has been the standard therapy for severe mitral regurgitation causing symptoms or left ventricular dysfunction.Percutaneous mitral valve repair has become an appealing alternative approach for patients who are not suitable for surgery.However,clinical trial data are not available on the institutional impact of a percutaneous mitral valve repair program on mitral valve surgery.The current study retrospectively evaluated the impact of the MitraClip program on the mitral valve surgery volume and outcomes.Patient data were retrieved from the 2 years before and the 2 years after initiation of the MitraClip program.The volume of MitraClip procedures increased from eight cases in 2015 to 91 cases in 2017.Since the initiation of the MitraClip program in 2015,the volume of both mitral valve replacement and mitral valve repair also increased(43 vs.60 and 110 vs.154,respectively).Importantly,we observed improved surgical outcomes,including fewer perioperative complications and lower operative mortality and in-hospital mortality.Data from our single-institution experience indicate that the introduction of the MitraClip program is associated with increased mitral valve surgery volume and improved outcomes.The establishment of the MitraClip program enables the hospital to provide higher quality of care and potentially become a referring center for structural heart patients.
文摘Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset,progression,and worsening of diabetic neuropathy(DNP)as well as its im-provement with supplementation in cases of deficiency.Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measu-rement and supplementation,and some guidelines do not address it at all.Given that vitamin B12 therapy is an economical,safe,and widely available treatment in most countries and supported by emerging evidence of its potential benefits,greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency.Vitamin B12 deficiency should be treated in all affected patients,and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable.Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.
文摘BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic form of diabetes often misdiagnosed as type 1 or type 2.The MODY7 subtype,attributed to variants in the Kruppel-like factor 11(KLF11)gene,is exceedingly rare,and its clinical spectrum is not fully characterized.Precise genetic diagnosis is essential for appropriate management but is challenging due to phenotypic overlap with other diabetes types.This case report describes a patient with a novel KLF11 variant,contributing to the understanding of this rare condition and its clinical implications.CASE SUMMARY A 50-year-old female with a family history of MODY in her son was initially diagnosed with type 2 diabetes.Due to the family history and a non-obese phenotype,a comprehensive genetic panel for monogenic diabetes was performed.The analysis identified a novel heterozygous missense variant,p.Cys105Phe,in the KLF11 gene,establishing a definitive diagnosis of MODY7.Following this diagnosis,the patient’s treatment was adjusted to include lifestyle modifications,resulting in adequate glycemic control.The patient has since maintained target glycated hemoglobin levels.CONCLUSION Monogenic diabetes type MODY7,caused by a mutation in the KLF11 gene,is extremely rare.Although some studies question its existence,compatible cases continue to be diagnosed,given its inclusion in genetic panels for MODY.
文摘Sickle cell anemia (SCA) is a prevalent genetic disorder primarily affecting individuals of African descent and populations in malaria-endemic regions, with significant global public health implications. Sickle cell crises are their most common acute complication, characterized by episodes of intense pain and systemic manifestations that impair quality of life and impose a high healthcare burden. We present the case of a 19-year-old male diagnosed with SCA since the age of two, who developed a sickle cell crisis precipitated by right basal pneumonia. The patient exhibited sudden-onset, cyclic lumbar pain with progressive dyspnea. Initial management included multimodal pain control, volume optimization, and targeted antimicrobial therapy to achieve clinical stabilization. This case underscores the importance of a comprehensive approach to managing sickle cell crises, addressing both symptomatic relief and the prevention and treatment of complications. It also highlights the need for public health strategies promoting early diagnosis, access to disease-modifying therapies such as hydroxyurea, and interdisciplinary follow-up to mitigate the socioeconomic and clinical impact of SCA.
文摘BACKGROUND Gastric antral vascular ectasia(GAVE)accounts for up to 4%of nonvariceal upper gastrointestinal bleeding.Argon plasma coagulation and radiofrequency ablation have been primary treatment modalities for patients with linear and punctate subtypes,with a newer trend of utilization of endoscopic band ligation(EBL).This study evaluates the outcomes of patients undergoing treatment for nodular GAVE.We hypothesize that patients treated initially with EBL will achieve higher rates of clinical remission with fewer endoscopic treatments and a shorter treatment interval.AIM To investigate the effects of EBL as an initial treatment therapy on outcomes associated with nodular GAVE.METHODS A total of 37 patients at a tertiary medical center with nodular GAVE were included in this retrospective study.The study population was divided between those treated initially with EBL(initial EBL)and initial endoscopic thermal therapy.Pretreatment and post-treatment hemoglobin values,the model for end-stage liver disease scores,hospitalization rates,and other outcomes.Additionally,endoscopic treatment modality type and frequency were recorded,including radiofrequency ablation,argon plasma coagulation,and EBL.Continuous variables were compared using a t-test,while categorical variables were compared using Fisher’s exact.RESULTS Linear regression analysis displayed a positive relationship between the time interval from initial therapeutic esophagogastroduodenoscopy to first EBL treatment and overall treatment interval(t=7.39,P<0.001),as well as between the number of endoscopic treatments(t=8.09,P<0.001).Hemoglobin levels increased in both the initial EBL group(8.7 vs 11.4,P<0.001)and the initial endoscopic thermal therapy group(8.6 vs 10.4,P=0.042).Clinical remission rates were higher in the initial EBL group(90%vs 69%P=0.041),with a non-significant trend of higher endoscopic remission rates(57.1%vs 37.5%,P=0.270).CONCLUSION The observed trend favoring EBL,combined with its association with improved clinical remission and reduced treatment burden,supports its consideration as a preferred initial treatment approach.
文摘BACKGROUND There is increasing incidence of alcohol-associated liver disease in females.Despite this recent increased incidence,there is a paucity of research on the clinical course and outcomes of alcohol-associated hepatitis(AH)in females compared to males.AIM To assess if there may be sex differences in severity,outcomes,and healthcare utilization for patients hospitalized for AH.METHODS This study used ICD-9-CM and ICD-10-CM codes to retrospectively identify inpatient encounters for AH at the University of Kentucky from 2012-2021 and obtained data on patient demographics and clinical outcomes.Encounters were cohorted by patient sex and differences in patient demographics and clinical outcomes were assessed.Multivariate logistic regression models were constructed to assess risk of mortality,sepsis,and mechanical ventilation during the encounter.RESULTS Of 1386 subjects,511(36.9%)were female and 875(63.1%)were male.Both sexes had similar baseline characteristics of race/ethnicity,discriminant function score,model of end-stage liver disease score,and length of hospital stay.However,the incidence of urinary tract infection,sepsis,and norepinephrine administration was significantly higher for females.Males had a significantly higher incidence of esophageal variceal bleed.On multivariate logistic regression analysis,females had higher odds of encounter sepsis(OR 1.41;95%CI:1.064-1.869)and mechanical ventilation(OR 1.352;95%CI:1.006-1.816).Odds of encounter mortality were significantly increased in encounters with sepsis(OR 2.309;95%CI:1.419-3.757)and mechanical ventilation(OR 9.301;95%CI:5.724-15.114).CONCLUSION This study shows sex-based differences in AH outcomes at the University of Kentucky.Future studies are warranted to assess whether tailoring treatments will improve clinical outcomes in females with AH.
文摘BACKGROUND Liver imaging and transient elastography(TE)are both tools used to assess liver fibrosis and steatosis among people with hepatitis C virus(HCV)infection.However,the diagnostic accuracy of conventional imaging in detecting fibrosis and steatosis in this patient population remains unclear.AIM To investigate the correlation between steatosis and fibrosis and abnormal findings on liver imaging in patients with HCV.METHODS We conducted a retrospective cross-sectional analysis of patients with HCV at Grady Liver Clinic who had TE exams between 2018-2019.We analyzed the correlation of controlled attenuation parameter and liver stiffness measurement on TE and abnormal findings on liver imaging.Liver imaging findings(hepatic steatosis,increased echogenicity,cirrhosis,and chronic liver disease)were further evaluated for their diagnostic performance in detecting fibrosis(≥F2,≥F3,≥F4)and steatosis(≥S1,≥S2,≥S3).RESULTS Of 959 HCV patients who underwent TE,651 had liver imaging.Higher controlled attenuation parameter scores were observed in patients with abnormal liver findings(P=0.0050),hepatic steatosis(P<0.0001),and increased echogenicity(P<0.0001).Higher liver stiffness measurement values were also noted in those with abnormal liver(P<0.0001)and increased echogenicity(P=0.0026).Steatosis severity correlated with hepatic steatosis(r=0.195,P<0.001)and increased echogenicity(r=0.209,P<0.001).For fibrosis detection,abnormal liver imaging had moderate sensitivity(81.7%)and specificity(70.4%)for cirrhosis(≥F4),while cirrhosis on imaging had high specificity(99.2%)but low sensitivity(18.3%).Increased echogenicity showed high specificity(92.8%)but low sensitivity(20.9%)for steatosis detection.CONCLUSION Liver imaging detects advanced fibrosis and steatosis but lacks early-stage sensitivity.Integrating TE with imaging may improve evaluation in patients with HCV.
文摘Hepatocellular carcinoma(HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with 80%-90% of new cases occurring in the background of cirrhosis. Studies have shown that early diagnosis of HCC through surveillance programs improve prognosis and availability of curative therapies. All patients with cirrhosis and high-risk hepatitis B patients are at risk for HCC and should undergo surveillance. The recommended surveillance modality is abdominal ultrasound(US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with non-alcoholic fatty liver disease(NAFLD). With the current obesity epidemic and rise in the prevalence of NAFLD, abdominal computed tomography or magnetic resonance imaging may be indicated as the primary screening modality in these patients. The addition of alpha-fetoprotein to a surveillance regimen is thought to improve the sensitivity of HCC detection.Further investigation of serum biomarkers is needed. Semiannual screening is the suggested surveillance interval. Surveillance for HCC is underutilized and low adherence disproportionately affects certain demographics such as nonCaucasian race and low socioeconomic status.
文摘Primary sclerosing cholangitis(PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra-and/or extrahepatic biliary ducts. While its features and disease course can be variable,most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly,PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma,hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.
文摘Inflammatory fibroid polyp(IFP) is a rare,idiopathic pseudotumorous lesion of the gastrointestinal tract.While mostly reported as solitary gastric lesions,multiple cases of small bowel IFPs are also reported.It is a documented cause of intussusception in adults.In the case reports of ileal inflammatory fibroid polyps with intussusception,an emergent presentation with small bowel obstruction has been most often described.Here we depict a case of ileal inflammatory fibroid polyp presenting with chronic intermittent ileocolic intussusception,anemia and weight loss with an endoscopic appearance mimicking necrotic cecal carcinoma.
文摘Background Frailty is a multidimensional syndrome that reflects the physiological reserve of elderly.It is related to unfavorable outcomes in various cardiovascular conditions.We conducted a systematic review and meta-analysis of the association of frailty with all-cause mortality and bleeding after acute myocardial infarction(AMI)in the elderly.Methods We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019.The studies that reported mortality and bleeding in AMI patients who were evaluated and classified by frailty status were included.Data from each study were combined using the random-effects,generic inverse variance method of Der Simonian and Laird to calculate hazard ratio(HR),and 95%confidence interval(CI).Results Twenty-one studies from 2011 to 2019 were included in this meta-analysis involving 143,301 subjects(mean age 75.33-year-old,60.0%male).Frailty status was evaluated using different methods such as Fried Frailty Index.Frailty was statistically associated with increased early mortality in nine studies(pooled HR=2.07,95%CI:1.67-2.56,P<0.001,I^2=41.2%)and late mortality in 11 studies(pooled HR=2.30,95%CI:1.70-3.11,P<0.001,I^2=65.8%).Moreover,frailty was also statistically associated with higher bleeding in 7 studies(pooled HR=1.34,95%CI:1.12-1.59,P<0.001,I^2=4.7%).Conclusion Frailty is strongly and independently associated with bleeding,early and late mortality in elderly with AMI.Frailty assessment should be considered as an additional risk factor and used to guide toward personalized treatment strategies.
基金The University of Arizona Hematology and Medical Oncology Fellowship program
文摘BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulation treatment have an associated increase rate.GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants(DOAC),especially with active cancer therapies.AIM To evaluate patient risk factors,effectiveness(VTE)and safety(MB)of DOACs and low molecular weight heparin(LMWH)in patients with active GICA-VTE.METHODS A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed.Inclusion criteria included active GI cancer diagnosed at any stage or treatment+/-6 mo of VTE diagnosis,whom were prescribed 6 mo or more of DOACs or LMWH.The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events.Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTS A total of 144 patients were prescribed anticoagulation,in which 106 fulfilled inclusion criteria apixaban(27.3%),rivaroxaban(34.9%)and enoxaparin(37.7%),and 38 were excluded.Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event,with 62%males,80%Caucasian,70%stage IV,pancreatic cancer(40.5%),30%Khorana Score(≥3 points),and 43.5%on active chemotherapy.Sixty-four percent of patients completed anticoagulation therapy(range 1 to 43 mo).Recurrent VTE at 6 mo was noted in 7.5%(n=3),6.8%(n=2)and 2.7%(n=1)of patients on enoxaparin,apixaban and rivaroxaban,respectively(all P=NS).MB at 6 mo were 5%(n=2)for enoxaparin,6.8%(n=2)for apixaban and 21.6%(n=8)for rivaroxaban(overall P=0.048;vs LMWH P=0.0423;all other P=NS).Significant predictors of a primary or secondary outcome for all anticoagulation therapies included:Active systemic treatment(OR=5.1,95%CI:1.3-19.3),high Khorana Score[≥3 points](OR=5.5,95%CI:1.7-17.1),active smoker(OR=6.7,95%CI:2.1-21.0),pancreatic cancer(OR=6.8,95%CI:1.9-23.2),and stage IV disease(OR=9.9,95%CI:1.2-79.1).CONCLUSION Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.
文摘AIM To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus(HCV)/human immunodeficiency virus(HIV) co-infection in an urban HIV clinic.METHODS A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016.All patients included were receiving antiretroviral therapy(ART) with HIV RNA values of 100 copies/m L or fewer regardless of baseline HCV RNA level.The primary end point was a sustained virologic response of HCV at 12 wk(SVR12) after the end of therapy.RESULTS Of the 40 patients enrolled,55% were black,22.5% had been previously treated for HCV,and 25% hadcirrhosis.The patients were on a wide range of ART.Overall,39 patients(97.5%) had a SVR 12 after the end of therapy,including rates of 97.1% in patients with HCV genotype 1 a and 100% in those with HCV genotype 1 b.One patient with HCV genotype 3 a was included and achieved SVR12.Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis.Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn't reveal any resistance associated mutation in the NS5A or NS5B region.Interestingly,7(17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen.Two(5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy,which resolved after resuming the same ART regimen.No severe adverse events were observed and no patient discontinued treatment because of adverse events.The most common adverse events included headache(12.5%),fatigue(10%),and diarrhea(2.5%).CONCLUSION This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV,regardless of HCV baseline levels,HCV treatment history or cirrhosis condition.The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART.Occasional HIV virologic rebound occurred but later resolved without the need to change ART.
文摘Foreign body ingestion encompasses both foreign object ingestion(FOI) and esophageal food impaction(EFI) and represents a common and clinically significant scenario among patients of all ages. The immediate risk to the patient ranges from negligible to life-threatening, depending on the ingested substance,its location, patient fitness, and time to appropriate therapy. This article reviews the FOI and EFI literature and highlights important considerations and implications for pediatric and adult patients as well as their providers. Where published literature is insufficient to provide evidence-based guidance, expert opinion is included to supplement the content of this comprehensive review.
文摘Cardiovascular diseases(CVDs)remain the leading cause of death in the world and in most developed countries.Patients with type 2 diabetes mellitus(T2DM)suffer from both microvascular and macrovascular diseases and therefore have higher rates of morbidity and mortality compared to those without T2DM.If current trends continue,the Center for Disease Control and Prevention estimates that 1 in 3 Americans will have T2DM by year 2050.As a consequence of the controversy surrounding rosiglitazone and the increasing prevalence of diabetes and CVDs,in 2008 the Food and Drug Administration(FDA)established new expectations for the evaluation of new antidiabetic agents,advising for pre and,in some cases,post-marketing data on major cardiovascular events.As a direct consequence,there has been a paradigm shift in new antidiabetic agents that has given birth to the recently published American Diabetes Association/European Association for the Study of Diabetes consensus statement recommending sodium-glucose cotransporter-2 inhibitors(SGLT2i)and glucagon like peptide-1 receptor agonists(GLP-1RA)in patients with T2DM and established CVD.As a result of over a decade of randomized placebo controlled cardiovascular outcome trials,the aforementioned drugs have received FDA approval for risk reduction of cardiovascular(CV)events in patients with T2DM and established CV disease.SGLT2i have been shown to have a stronger benefit in patients with congestiveheart failure and diabetic kidney disease when compared to their GLP-1RA counterparts.These benefits are not withstanding additional considerations such as cost and the multiple FDA Black Box warnings.This topic is currently an emerging research area and this mini-review paper examines the role of these two novel classes of drugs in patients with T2DM with both confirmed,and at risk for,CVD.
文摘Background: Immune checkpoint inhibitors produce prolonged responses in select non-small cell lung cancer (NSCLC) patients, however the identification of patients most likely to benefit is difficult. Pretreatment derived neutrophil-to-lymphocyte ratio (dNLR) is an easily calculated marker available in routine clinical care that has shown prognostic value in many cancer treatment settings, but its association with survival in NSCLC patients treated with immune-checkpoint inhibitors is less understood. Patients and Methods: We retrospectively reviewed 72 NSCLC patients receiving either nivolumab or pembrolizumab between 3/1/15 and 3/1/17 with a median follow-up time of 5.1 months. Patients were compared using Cox proportional hazards models to detect an association between pretreatment dNLR 3 vs ≥3 on overall survival (OS), progression-free survival (PFS) and overall response rate. Results: Median age was 65 (range: 41 - 86), 65% were male, 40% received ≥ 2 prior systemic therapies and 14% had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2. Pretreatment dNLR ≥ 3 was independently associated with shortened OS (median 3.6 vs 8.5 months;HR: 5.4;95% CI: 2.0 - 14.6;p = 0.001) and PFS (median 2.1 vs 3.4;HR: 2.3;95% CI: 1.1 - 4.8;p = 0.027). Conclusion: Pretreatment dNLR ≥ 3 was independently associated with inferior survival in NSCLC treated with immune checkpoint inhibitors in routine practice. Prospective verification of this marker is warranted as it could serve as an inexpensive and widely-available marker for identifying NSCLC patients most likely to benefit from PD-1 inhibitors.
文摘Shoulder pain is a common musculoskeletal complaint,and rotator cuff(RC)pathologies are one of the main causes.The RC undergoes various tendinopathic and avascular changes during the aging process.Other degenerative changes affecting its healing potential make it an appealing target for biological agents.Platelet-rich plasma(PRP)has demonstrated the potential to deliver a high concentration of several growth factors and anti-inflammatory mediators,and its clinical use is mainly supported by experiments that demonstrated its positive effect on muscle,ligaments,and tendinous cells.This review aimed to specify the role of PRP and its future applications in RC tendinopathies based on the current clinical evidence.Due to the different characteristics and conflicting outcomes,clinicians should use PRP with moderate expectations until more consistent evidence is available.However,it is reasonable to consider PRP in patients with contraindications to corticosteroid injections or those with risk factors for inadequate healing.Its autologous origin makes it a safe treatment,and its characteristics make it a promising option for treating RC tendinopathy,but the efficacy has yet to be established.
文摘Objective:To identify the relationship between interleukin(IL)-15 levels and sarcopenia in human immunodeficiency virus(HIV)-infected patients who have received antiretroviral therapy.Methods:This study was a cross-sectional design with 70 participants conducted from January to March 2021.All the participants were assessed for sarcopenia and the IL-15 levels.Sarcopenia was established based on the the Asian Working Group for Sarcopenia(AWGS)2019 criteria.Plasma IL-15 was determined.This analysis was carried out by means of 2×2 tabulation and the statistical test used is Chi-square.Results:Seventy patients received antiretroviral therapy>6 months and showed a good clinical response.Among them,36(51.4%)took zidovudine-based antiretroviral therapy with a median duration of illness of 5 years.The proportion of sarcopenia in patients with HIV infection was 32.9%.The median CD4 cell count was 395.5 cells/L(range:203-937 cells/L).Logistic regression analysis revealed that age>50 years(aOR 8.3,95%CI 1.6-44.5),underweight(aOR 7.7,95%CI 1.5-40.5),IL-15≥150.5 ng/L(aOR 4.9,95%CI 1.3-19.0)and female(aOR 4.8,95%CI 1.2-18.3 were significant and independent adverse predictors of sarcopenia in subjects with HIV infection.Conclusions:There is an association between high levels of IL-15 and sarcopenia in HIV-infected patients on antiretroviral therapy for more than 6 months with good clinical response.
