Activity limitations, use of assistive devices, and mortality and clinical events in 25 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: The focus of most epidemiological studies has been mortality or clinical events, with less information on activity limitations related to basic daily functions and their consequences. Standardised data from multiple countries at different economic levels in different regions of the world on activity limitations and their associations with clinical outcomes are sparse. We aimed to quantify the prevalence of activity limitations and use of assistive devices and the association of limitations with adverse outcomes in 25 countries grouped by different economic levels. METHODS: In this analysis, we obtained data from individuals in 25 high-income, middle-income, and low-income countries from the Prospective Urban Rural Epidemiological (PURE) study (175 660 participants). In the PURE study, individuals aged 35-70 years who intended to continue living in their current home for a further 4 years were invited to complete a questionnaire on activity limitations. Participant follow-up was planned once every 3 years either by telephone or in person. The activity limitation screen consisted of questions on self-reported difficulty with walking, grasping, bending, seeing close, seeing far, speaking, hearing, and use of assistive devices (gait, vision, and hearing aids). We estimated crude prevalence of self-reported activity limitations and use of assistive devices, and prevalence standardised by age and sex. We used logistic regression to additionally adjust prevalence for education and socioeconomic factors and to estimate the probability of activity limitations and assistive devices by age, sex, and country income. We used Cox frailty models to evaluate the association between each activity limitation with mortality and clinical events (cardiovascular disease, heart failure, pneumonia, falls, and cancer). The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: Between Jan 12, 2001, and May 6, 2019, 175 584 individuals completed at least one question on the activity limitation questionnaire (mean age 50·6 years [SD 9·8]; 103 625 [59%] women). Of the individuals who completed all questions, mean follow-up was 10·7 years (SD 4·4). The most common self-reported activity limitations were difficulty with bending (23 921 [13·6%] of 175 515 participants), seeing close (22 532 [13·4%] of 167 801 participants), and walking (22 805 [13·0%] of 175 554 participants); prevalence of limitations was higher with older age and among women. The prevalence of all limitations standardised by age and sex, with the exception of hearing, was highest in low-income countries and middle-income countries, and this remained consistent after adjustment for socioeconomic factors. The use of gait, visual, and hearing aids was lowest in low-income countries and middle-income countries, particularly among women. The prevalence of seeing close limitation was four times higher (6257 [16·5%] of 37 926 participants vs 717 [4·0%] of 18 039 participants) and the prevalence of seeing far limitation was five times higher (4003 [10·6%] of 37 923 participants vs 391 [2·2%] of 18 038 participants) in low-income countries than in high-income countries, but the prevalence of glasses use in low-income countries was half that in high-income countries. Walking limitation was most strongly associated with mortality (adjusted hazard ratio 1·32 [95% CI 1·25-1·39]) and most consistently associated with other clinical events, with other notable associations observed between seeing far limitation and mortality, grasping limitation and cardiovascular disease, bending limitation and falls, and between speaking limitation and stroke. INTERPRETATION: The global prevalence of activity limitations is substantially higher in women than men and in low-income countries and middle-income countries compared with high-income countries, coupled with a much lower use of gait, visual, and hearing aids. Strategies are needed to prevent and mitigate activity limitations globally, with particular emphasis on low-income countries and women. FUNDING: Funding sources are listed at the end of the Article.

Long-term clinical outcomes of male breast cancer patients treated with curative intent by trimodality therapy at an academic university hospital in India.

INTRODUCTION: Male breast cancer is rare and accounts for less than 1% of all breast cancer cases worldwide. METHODS: This retrospective cohort study included all patients of invasive male breast cancer treated with curative intent by a trimodality approach via a multidisciplinary team at an academic university hospital in India between 2009 and 2023. Records were identified from a prospectively maintained database. Clinicopathological parameters, treatment details and survival were recorded and analysed. RESULTS: Thirty-four patients were included. The median (IQR) age was 55(44-63) years. Most patients were overall stage III (74%) and node positive (79%) with Scarff-Bloom-Richardson grade II (50%). Twenty-five patients (73%) were oestrogen receptor (ER) positive. Lymphovascular space invasion (LVSI) and perineural invasion (PNI) were present in 62% and 21% of patients, respectively. The most common chemotherapy timing was adjuvant (53%) followed by neoadjuvant (41%), and the most commonly used regimen consisted of a combination of doxorubicin-cyclophosphamide followed by a taxane (53%). Most (85%) patients underwent a mastectomy, five patients underwent breast conservation. All patients received radiotherapy to a dose of 42.6 Gy in 16 fractions, followed by a tumour bed boost for those undergoing breast conservation. At a median follow-up of 70 months (range 10-159 months), the five and ten-year overall survival was 91% and 58%, and the five-year disease-free survival (DFS) was 67%. The median DFS was 72 months. On univariate analysis, the tumour sub-type (Luminal versus TNBC) significantly predicted DFS (P = 0.03 log-rank). CONCLUSION: Breast cancer in males has a high incidence of node positivity, ER positivity and LVSI. Even with advanced stages at presentation, trimodality therapy in a multidisciplinary setting offers good long-term outcomes.

Genome-wide methylation landscape during somatic embryogenesis in Medicago truncatula reveals correlation between Tnt1 retrotransposition and hyperactive methylation regions.

Medicago truncatula is a model legume for fundamental research on legume biology and symbiotic nitrogen fixation. Tnt1, a retrotransposon from tobacco, was used to generate insertion mutants in M. truncatula R108. Approximately 21 000 insertion lines have been generated and publicly available. Tnt1 retro-transposition event occurs during somatic embryogenesis (SE), a pivotal process that triggers massive methylation changes. We studied the SE of M. truncatula R108 using leaf explants and explored the dynamic shifts in the methylation landscape from leaf explants to callus formation and finally embryogenesis. Higher cytosine methylation in all three contexts of CG, CHG, and CHH patterns was observed during SE compared to the controls. Higher methylation patterns were observed in assumed promoter regions (~2-kb upstream regions of transcription start site) of the genes, while lowest was recorded in the untranslated regions. Differentially methylated promoter region analysis showed a higher CHH methylation in embryogenesis tissue samples when compared to CG and CHG methylation. Strong correlation (89.71%) was identified between the differentially methylated regions (DMRs) and the site of Tnt1 insertions in M. truncatula R108 and stronger hypermethylation of genes correlated with higher number of Tnt1 insertions in all contexts of CG, CHG, and CHH methylation. Gene ontology enrichment and KEGG pathway enrichment analysis identified genes and pathways enriched in the signal peptide processing, ATP hydrolysis, RNA polymerase activity, transport, secondary metabolites, and nitrogen metabolism pathways. Combined gene expression analysis and methylation profiling showed an inverse relationship between methylation in the DMRs (regions spanning genes) and the expression of genes. Our results show that a dynamic shift in methylation happens during the SE process in the context of CG, CHH and CHG methylation, and the Tnt1 retrotransposition correlates with the hyperactive methylation regions.

Cancer stem cell biomarkers SOX2 and Oct4 in cervical cancer patients undergoing chemoradiotherapy.

BACKGROUND: Cancer stem cell biomarkers SRY (sex-determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory. METHODS: In this prospective cohort study, we recruited patients with FIGO IB2-IVA CSCC treated with primary chemoradiotherapy on regular follow-up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores. RESULTS: A total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p = 0.005, odds ratio (95% CI) - 1.23 (1.004-1.520)). At a median follow-up of 36 months, the 3-year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p = 0.856), and 54% and 100% for low and high Oct4 expression (p = 0.114). The 3-year disease-frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p = 0.259), and 59% and 75% for low and high Oct4 expression (p = 0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis. CONCLUSION: Our study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.

Low body mass index is associated with adverse cardiovascular outcomes following PCI in India: ACC-NCDR registry.

Objective: Registry-based prospective study was conducted to evaluate association of body mass index (BMI) with major adverse coronary events (MACE) following percutaneous coronary intervention (PCI). Methods: Successive patients undergoing PCI were enrolled from April'19 to March'22 and classified into five BMI categories (<23.0,23.0-24.9,25.0-26.9,27.0-29.9, and ≥30.0 kg/m2). Clinical, angiographic features, interventions and outcomes were obtained by in-person or telephonic follow-up. Primary endpoints were (a) MACE(cardiovascular deaths, acute coronary syndrome or stroke, revascularization, hospitalization and all-cause deaths) and (b)cardiovascular deaths. Cox-proportionate hazard ratios(HR) and 95 % confidence intervals(CI) were calculated. Results: The cohort included 4045 patients. Mean age was 60.3 ± 11y, 3233(79.7 %) were men. There was high prevalence of cardiometabolic risk factors. 90 % patients had acute coronary syndrome(STEMI 39.6 %, NSTEMI/unstable angina 60.3 %), 60.0 % had impaired ejection fraction(EF) and multivessel CAD. Lower BMI groups (<23.0 kg/m2) had higher prevalence of tobacco use, reduced ejection fraction(EF), multivessel CAD, stents, and less primary PCI for STEMI. There was no difference in discharge medications and in-hospital deaths. Median follow-up was 24 months (IQR 12-36), available in 3602(89.0 %). In increasing BMI categories, respectively, MACE was in 10.9,8.9,9.5,9.1 and 6.8 % (R2 = 0.73) and CVD deaths in 5.1,4.5,4.4,5.1 and 3.5 % (R2 = 0.39). Compared to lowest BMI category, age-sex adjusted HR in successive groups for MACE were 0.89,0.87,0.79,0.69 and CVD deaths 0.98,0.87,0.95,0.75 with overlapping CI. HR attenuated following multivariate adjustments. Conclusions: Low BMI patients have higher incidence of major adverse cardiovascular events following PCI in India. These patients are older, with greater tobacco use, lower EF, multivessel CAD, delayed STEMI-PCI, and longer hospitalization.

Outcomes of cardiac arrest hospitalizations in patients with obesity with versus without prior bariatric surgery status:A nationwide propensity-matched analysis.

Introduction: Prior bariatric surgery (PBS) status in obese patients is thought to curtail the risk of cardiovascular events, but its role in change of outcomes of patients with obesity developing new acute cardiac events such as cardiac arrests (CA) remains largely unknown. Methods: Hospitalizations among adult patients with obesity and CA were identified retrospectively using the National Inpatient Sample (2015 October-2017 December). Propensity-matched analysis (1:1) was performed for sociodemographic/hospital characteristics to identify two cohorts, with (PBS+) or without (PBS-) status. The primary endpoint was in-hospital mortality, and the secondary endpoint was healthcare resource utilization. Results: Both cohorts (n = 1275 each), had patients with comparable age (mean 58 years), with a higher frequency of white (>70 %), females (>60 %), and Medicare enrollees (>40 %). PBS + cohort had lower rates of diabetes (27.8 % vs 36.1 %), hyperlipidemia (33.7 % vs 48.6 %), renal failure (17.3 % vs 22.0 %), chronic pulmonary disease (11.8 % vs 21.2 %) and higher rates of anemias (18.4 % vs 12.2 %), liver disease (5.1 % vs 2.4 %) and alcohol abuse (6.7 % vs 2.4 %) than PBS- cohort (p < 0.05). All-cause mortality (46.3 % vs 45.1 %, p = 0.551) was comparable between the two cohorts. The PBS + cohort was less often transferred routinely (p<0.001) but had a shorter hospital stay (p<0.001) with equivalent hospital charges compared to the PBS- cohort. Conclusions: The PBS status (regardless of chronology) did not increase survival in CA admissions among patients with obesity. Preventive measures are necessary to manage enduring cardiovascular disease risk factors that may limit the advantages of surgery for patients with obesity and aggravate the worse outcomes of future cardiac events.

Clinical and clonal characteristics of monoclonal immunoglobulin M-associated type I cryoglobulinaemia.

Monoclonal immunoglobulin M-associated type I cryoglobulinaemia is poorly characterised. We screened 534 patients with monoclonal IgM disorders over a 9-year period and identified 134 patients with IgM type I cryoglobulins. Of these, 76% had Waldenström macroglobulinaemia (WM), 5% had other non-Hodgkin lymphoma (NHL) and 19% had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinically relevant IgM-associated disorders (including cold agglutinin disease [CAD], anti-MAG antibodies, amyloidosis and Schnitzler syndrome) coexisted in 31%, more frequently in MGUS versus WM/NHL (72% vs. 22%/29%, p < 0.001). The majority of those with cryoglobulins and coexistent CAD/syndrome had the molecular characteristics of a CAD clone (wild-type MYD88 in 80%). A half of all patients had active manifestations at cryoglobulin detection: vasomotor (22%), cutaneous (16%), peripheral neuropathy (22%) and hyperviscosity (9%). 16/134 required treatment for cryoglobulin-related symptoms alone at a median of 38 days (range: 6-239) from cryoglobulin detection. At a median follow-up of 3 years (range: 0-10), 3-year cryoglobulinaemia-treatment-free survival was 77% (95% CI: 68%-84%). Age was the only predictor of overall survival. Predictors of cryoglobulinaemia-related treatment/death were hyperviscosity (HR: 73.01; 95% CI: 15.62-341.36, p < 0.0001) and cutaneous involvement (HR: 2.95; 95% CI: 1.13-7.71, p = 0.028). Type I IgM cryoglobulinaemia is more prevalent than previously described in IgM gammopathy and should be actively sought.

Comparative Study of Dysphagia-optimized Intensity Modulated Radiotherapy (Do-IMRT) and Standard Intensity Modulated Radiotherapy (S-IMRT) and Its Clinical Correlation in Head and Neck Cancer Patients.

OBJECTIVE: Dosimetric sparing of critical swallowing structures like constrictor muscles and larynx can lead to improved functional outcomes in head and neck cancer patients treated by chemoradiation. METHODS: A total of 50 Patients with newly diagnosed, biopsy proven AJCC stage II-IV head and neck squamous cell cancers (HNSCC) were prospectively studied. 25 patients were randomized in each arm of Dysphagia-optimized Intensity Modulated Radiotherapy (Do-IMRT) arm and Standard Intensity Modulated Radiotherapy (SIMRT) arm. Additional dose constraints were applied to the dysphagia/aspiration at risk structures (DARS) in Do-IMRT arm. The impact of using Do-IMRT was assessed by the difference in mean scores of MD Anderson Dysphagia Inventory (MDADI), University of Washington-Quality of Life (UW-QOL), and 100 ml Water Swallow Test (WST). RESULTS: Patients in both arms showed significant (P <0.01 or P < 0.001) improvement in MDADI (global and composite), UW-QOL and Water Swallow Test scores. However, the improvements were found significantly higher in Do-IMRT as compared to S-IMRT. Significant improvements i.e. mean change from baseline to 12 months (P <0.05 or P <0.01 or P <0.001) were 19. 2, 8.6, 14.3, 7.4, 18.6 and 22.0%  higher respectively in Do-IMRT as compared to S-IMRT  in MDADI global and composite scores, UW-QOL swallowing scores, and 100 ml Water Swallow  (swallowing volume, swallowing capacity and swallowing speed)  test scores. CONCLUSION: The Do-IMRT improves swallowing functions compared to S-IMRT in HNSCC patients treated with radical chemoradiation.

Tyrosine kinase inhibitors induced thyroid dysfunction: myth or reality?

Background: Chronic myelogenous leukemia (CML) is a hematopoietic stem cell disorder. It is associated with acquired genetic changes in the hematopoietic stem cells in the form of BCR-ABL fusion gene also known as Philadelphia chromosome. Materials and methods: We prospectively studied thyroid function at baseline and at 6 months of imatinib treatment in 26 newly diagnosed BCR-ABL positive CML patients. Result: The thyroid-stimulating hormone (TSH) levels increased significantly from baseline (3.20 ± 0.978 mIU/L vs. 3.724 ± 1.726 mIU/L, p < 0.05) after 6 months of treatment, 88.4% of the patients remained euthyroid. Only 2 patients had subclinical hypothyroidism, 1 had hypothyroidism after 6 months of tyrosine kinase inhibitors (TKI) therapy. Conclusion: Imatinib did not have any significant effect on thyroid function in CML patients in this study.

External Beam Radiotherapy Interdigitated with High Dose Rate(HDR) Intracavitary Brachytherapy versus External Beam Radiotherapy followed by Sequential HDR Intracavitary Brachytherapy for Locally Advanced Carcinoma Cervix-Randomized Control Study.

BACKGROUND: In cervical cancer treatment, overall treatment time (OTT) is an important prognostic factor. This study compares the clinical outcomes when High-Dose-Rate Intracavitary-Brachytherapy(HDR-ICRT) is interdigitated with external beam radiotherapy(EBRT) versus sequential HDR-ICRT after EBRT in the treatment of locally advanced carcinoma cervix. METHODS: Histologically confirmed carcinoma cervix patients [FIGO Stage IIB-IVA (except IIIC-2)] were included and randomized into two groups. The study group received EBRT 50Gy in 25 fractions with interdigitated HDR-ICRT 7Gy per fraction weekly for three fractions starting after completion of 3 weeks of EBRT or as soon as cervical os became negotiable thereafter. Patients in the control group received EBRT 50Gy in 25 fractions with sequential HDR-ICRT 7Gy per fraction weekly for three fractions starting one week after completion of EBRT. All patients were regularly followed up during and after radiotherapy for local toxicity and disease control. RESULTS: This study enrolled 102 patients; 51 in each arm. Median OTT in study and control arm were 46 and 60 days, respectively. Median follow-up duration was 24 months (two years). Loco-regional control after two years of follow-up was 84.31 % and 72.54% of patients in study arm control arm respectively (p-value 0.148). Two (3.92%) patients from study arm and eight (15.68%) from control arm had residual disease. Two patients in study arm and one from control arm had local recurrence. Two patients from study arm three patients from control arm developed distant metastases. RTOG mucosal grade III acute mucosal toxicity in either arm. Cervical-os negotiability was limiting factor for interdigitated HDR-ICRT. CONCLUSIONS: Interdigitated HDR-ICRT with EBRT may give local control with manageable toxicities as compared to sequential HDR-ICRT, with the advantage of significant reduction in OTT.
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Off-pump CABG surgery in left main coronary artery disease: a single-center prospective registry.

Background and objective: The treatment of left main (LM) coronary artery disease (CAD) requires complex decision-making. Patients with left main multi-vessel coronary artery disease (LM CAD) have concerns regarding incomplete revascularization and reduced survival with off-pump (OPCAB) when compared with on-pump (ONCAB) coronary bypass surgery. To evaluate outcomes among high-risk LM CAD patients undergoing OPCAB, we performed a registry-based prospective study. Methods: We performed 4868 coronary artery bypass graft (CABG) surgeries from Jan 2013 to Jun 2019 with 4662 (95.8%) OPCAB. In OPCAB cohort, we had 1323 patients (28.4%) with significant LM (> 50%) triple vessel CAD. Data regarding clinical features, extent of CAD, operative details, in-hospital outcomes, and 3-year follow-up were obtained. Descriptive statistics are reported. Results: The study cohort (n = 1323) was aged 63 ± 9 years with men 88.4%. Tobacco use was in 328 (24.8%), diabetes 598 (45.2%), previous myocardial infarction 463 (35.0%), previous coronary intervention 40 (3.0%), and congestive heart failure in 54 (4.1%). All patients had LM (100.0%) with triple vessel disease in 99.4% (LAD, left anterior descending 100.0%; LCX, left circumflex 99.4%; RCA, right coronary artery 78.7%). Vessels bypassed/patient were 2.7 ± 0.4 with 3.2 ± 0.7 total grafts and 2.1 ± 0.8 venous grafts. In total, 1278 (96.5%) patients received left internal mammary artery (LIMA), 63(4.7%) bilateral internal mammary artery (BIMA), and 74 (5.6%) radial artery grafts. There was no patient with conversion from OPCAB to ONCAB. In-hospital major adverse cardiovascular events (MACE: all-cause deaths, myocardial infarction, and stroke) were in 21 (1.6%). At 3-year follow-up (n = 1041), MACE rates were in 84 (8.1%) and cardiovascular deaths in 28 (2.7%). Conclusions: This study shows that off-pump CABG surgery is safe in patients with LM CAD. There is low in-hospital mortality and MACE and 3-year outcomes are similar to the published data of LM CAD patients who undergo on-pump CABG. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01526-3.

Loss of TET2 in human hematopoietic stem cells alters the development and function of neutrophils.

Somatic mutations commonly occur in hematopoietic stem cells (HSCs). Some mutant clones outgrow through clonal hematopoiesis (CH) and produce mutated immune progenies shaping host immunity. Individuals with CH are asymptomatic but have an increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Using genetic engineering of human HSCs (hHSCs) and transplantation in immunodeficient mice, we describe how a commonly mutated gene in CH, TET2, affects human neutrophil development and function. TET2 loss in hHSCs produce a distinct neutrophil heterogeneity in bone marrow and peripheral tissues by increasing the repopulating capacity of neutrophil progenitors and giving rise to low-granule neutrophils. Human neutrophils that inherited TET2 mutations mount exacerbated inflammatory responses and have more condensed chromatin, which correlates with compact neutrophil extracellular trap (NET) production. We expose here physiological abnormalities that may inform future strategies to detect TET2-CH and prevent NET-mediated pathologies associated with CH.

A Survey on the Machine Learning Techniques for Automated Diagnosis from Ultrasound Images.

Medical diagnostic systems has recently been very popular and reliable because of possible automatic detections. The machine learning algorithm is evolved as a core tool of computer-aided diagnosis (CAD) for automatic early and accurate disease detections. The algorithm follows region of interest (ROI) selection followed by specific feature extractions and selection from medical images. The selected features are then fed to suitable classifiers for disease identification. The machine learning algorithm's performance depends on the features selected and the classifiers employed for the job. This paper reviews different feature extraction selection and classification techniques for CAD from ultrasound images. Ultrasonography (USG), due to its portability and its non-invasive nature, is the prime choice of doctors for prescribing as an imaging test. A survey on the USG imaging based on four major diseases is performed in this paper, whose diagnosis followed by automatic detection. Various techniques applied for feature extraction, selection, and classification by different authors to achieve improved accuracy are tabulated. For medical images, we found texture based gray-level extracted features and SVM (support vector machine) classifiers to be more significant in improving classification accuracy, even achieving 100% accuracy in many research articles. However, many research articles also suggest the importance of student's t-test in improving classification accuracy by selecting significant features from extracted features. The proposed algorithm's accuracy also depends on the quality of medical images, which are frequently degraded by the introduction of noise and artifacts while imaging acquisition. So, challenges in denoising are added in this paper as a separate topic to highlight the role of the machine learning algorithm in removing noise and artifacts from the USG images.

Association of type 2 diabetes with coronary risk factors, clinical presentation, angiography, coronary interventions and follow-up outcomes: A single centre prospective registry.

BACKGROUND & AIMS: To determine variations in coronary artery disease (CAD) clinical presentation, interventions, and outcomes in patients with diabetes vs without, a prospective study was performed. METHODS: Successive patients with predominantly acute coronary syndromes who underwent percutaneous coronary intervention (PCI) were enrolled from January 2018 to March 2021. Patients with diabetes were compared to those without diabetes to determine differences in clinical and angiographic features and outcomes. In-person and telephonic follow-up were performed. Primary outcome was cardiovascular death and co-primary were major adverse cardiovascular events (cardiovascular death, myocardial infarction, revascularization, stroke). Cox-proportional hazard ratios (HR) and 95% confidence intervals (CI) were calculated. RESULTS: 5181 patients (men 4139,women 1042) were enrolled. Acute coronary syndrome(ACS) was in 4917 (94.9%) and diabetes in 1987 (38.4%). Patients with diabetes were older (61.1 ± 9.6 vs 59.7 ± 11.5years), with more hypertension (71.1 vs 45.5%), chronic kidney disease (3.0 vs 1.7%), previous PCI (13.5 vs 11.0%), past coronary artery bypass graft surgery (4.9 vs 2.4%), non ST-elevation myocardial infarction (59.6 vs 51.6%) and triple vessel disease (20.3 vs 17.2%) (p < 0.01). Duration of hospitalization was more in diabetes (4.2 ± 2.6 vs 4.0 ± 2.1 days, p = 0.023) with no difference in in-hospital deaths (1.4 vs 1.0%, p = 0.197). Follow up was performed in 1202 patients (diabetes 499,41.5%) enrolled from April 2020 to March 2021 (median 16.4 months). In diabetes there were more cardiovascular deaths (multivariate adjusted HR 2.38, CI 1.13-5.02) and all-cause deaths (HR 1.85, CI 1.06-3.22). CONCLUSIONS: CAD patients with diabetes undergoing PCI have more hypertension, chronic kidney disease, non ST-elevation myocardial infarction and triple vessel disease. At medium-term follow-up the incidence of cardiovascular and all-cause deaths is significantly more in these patients.

Bortezomib-based therapy is effective and well tolerated in frontline and multiply pre-treated Waldenström macroglobulinaemia including BTKi failures: A real-world analysis.

Waldenström macroglobulinemia (WM) is a rare, incurable low grade lymphoma following a relapsing trajectory. Management strategies have evolved with the introduction of targeted therapy including new classes of Bruton tyrosine kinase inhibitor (BTKi). Treatment may however be limited particularly at relapse by a lack of drug availability and tolerability. We assessed the real-world efficacy and tolerability of bortezomib-containing regimens in patients with WM at frontline and relapse including those with prior BTKi resistance. Forty-one patients were identified with 44 bortezomib-containing regimens administered (n = 12 frontline, n = 32 relapse). Of patients treated at relapse, the median prior lines of therapy was 3 (range 1-7). 24% (10/41) of the cohort were refractory or intolerant to BTKi prior to bortezomib delivery. The median follow-up after bortezomib administration was 34 months (range 0-131). Overall response rate was 88%; 2-year overall survival and progression-free survival were 90% (95% confidence interval [CI] 73-96) and 76% (95% CI 55-87), respectively. Median time-to-next-treatment was 66 months. Neuropathy (grade 1-2) occurred in 24% (8/34) and did not result in treatment cessation in any case. Gastrointestinal disturbance occurred in 7% (3/41). Treatment discontinuations were rare (1/44; 2%), suggesting a manageable safety profile. Major response rate was comparable in those with prior BTKi compared with those without (75% [6/8] vs 84% [27/32], p = 0.61). Bortezomib should be considered as a treatment modality particularly in those who are refractory to BTKi.

Revisiting secondary prevention in coronary heart disease.

Secondary prevention in coronary heart disease is the prevention of occurrence of recurrent coronary events after clinical diagnosis. High level of adherence to secondary prevention interventions, especially aggressive lifestyle changes and pharmacotherapy can lead to significant decline in recurrent coronary events. Both international and Indian studies have reported low adherence to such therapies. Evidence-based useful interventions include regular physical activity, yoga, intake of healthy diet, smoking and tobacco use cessation and weight management. Pharmacotherapeutic interventions useful are anti-platelet therapy, target oriented lipid lowering therapy with statins, beta blockers and angiotensin converting enzyme inhibitors in patients with impaired left ventricular function. Hypertension and diabetes management with control to targets is important. Novel strategies include use of anticoagulants, anti-inflammatory drugs, and triglyceride lowering for residual risk. Physician and patient level interventions using multifaceted educational, socioeconomic and technological innovations are important to promote life-long adherence to these strategies.