Advanced Comorbidities Research Articles

Effect of Physical Function on Access to Repeat Kidney Transplantation.

Background: The long-term success rate of kidney transplantation is disappointing, with repeat transplantation necessary for more than half of recipients. When a repeat kidney transplantation is needed, patients are often elderly and suffer from underlying advanced kidney disease, comorbidities, and adverse effects of immunosuppressants, leading to physical function limitations. Limited physical function is known to hinder access to an initial kidney transplantation, but there is no information about its impact on repeat transplantations. Objective: This study aimed to determine the effect of physical function on access to wait-listing for repeat transplantation. Methods: Data from the national registry was utilized to analyze 28,884 kidney transplant recipients. Physical function was assessed with Karnofsky scores, and patients were categorized into three strata: total assistance, some assistance, and no assistance. Logistic regression and multivariate Cox proportional hazard models were used to assess the impact of physical function on waiting list access and duration until wait-listing, respectively. Results: Patients with greater physical independence were more likely to be wait-listed for repeat kidney transplantation. Highly sensitized patients, those with diabetes, Black patients, and elderly individuals had a lower likelihood of access to wait-listing after kidney failure. Interestingly, those with limited physical function, provided they remained in the work-up process, experienced a relatively shorter duration to wait-listing after graft failure.Conclusions: These findings highlight the need to promote and support physical function throughout the kidney transplant journey to improve access to repeat transplantation and subsequent patient outcomes.

Assessing the Risk of QT Prolongation in a Psychiatric Inpatient Cohort: A Retrospective Cross-Sectional Study.

QT prolongation is a potential serious adverse drug reaction, and assessing the risk of QT-prolonging drugs is routinely included in psychotropic medication reviews. However, the actual clinical benefits of such assessments are unknown. We investigate whether QT prolongation (QTc value > 480 ms) manifests in psychiatric inpatients at risk of QT prolongation as identified by assessing drug regimens. Secondly, we test the predictive value of well-known risk factors for QT prolongation. The median patient age was 49 years (IQR 34-64) for patients treated with a median of nine drugs (IQR 6-12) and a median QT-prolonging drug sum of three daily defined dosages (IQR 1.88-4.76). We extracted 290 ECGs for patients where pharmacist-led-medication reviews (PMRs) identified an increased risk of QT prolongation and 190 ECGs for patients with no such risk, identifying 33 cases of verified QT prolongation equally distributed between groups. Unadjusted regression analysis revealed that advanced age (OR 3.27 CI 95% 1.60-6.84) and cardiovascular comorbidity (OR 3.53 CI 95% 1.71-7.29) were associated with manifest QT prolongation, while the QT-prolonging drug load was not. We reviewed electronic health records (EHRs) of 799 psychiatric inpatients exposed to PMRs made from 1 September 2016 to 31 December 2018 in Region Zealand Denmark. Patients at risk of QT prolongation as identified by drug reviews rarely manifests with actual QT prolongation. Non-pharmacological risk factors seem to be better predictors for identifying patients with QT prolongation.

Contrast-Enhanced Digital Mammography for the Diagnosis and Determination of Extent of Disease in Invasive Lobular Carcinoma: Our Experience and Literature Review.

Contrast-enhanced imaging, including magnetic resonance imaging and, more recently, contrast-enhanced digital mammography (CEM), is indicated for the precise diagnosis of invasive lobular carcinoma (ILC). The aim of our study was to further validate the use of CEM for evaluation of extent of disease in ILC cases, with digital breast tomosynthesis (DBT) as an adjunct. A retrospective, institutional review board approved study was conducted in a tertiary medical center. All CEM examinations performed on ILC patients between 2017 and 2023 were reread by 2 dedicated breast radiologists. Clinical data and pathology reports were retrieved from electronic medical records. The longest diameter of the enhancing lesion was correlated to pathology findings. In addition, for each case, the readers provided brief commentary on the added value of DBT. Twenty-four CEM examinations were evaluated. The subjects in the study cohort were on average older than expected for ILC patients (74 vs 63 years) and were unable to undergo breast magnetic resonance imaging due to advanced age and comorbidities. Three subjects were treated with neoadjuvant therapy and thus were excluded from the correlation to pathology analysis. Enhancing lesions, ranging from 4-75 mm, strongly correlated to pathology results, with statistical significance. This was demonstrated for mass and nonmass lesions (r = 0.94, P < 0.001 and r = 0.99, P = 0.002, respectively). For most lesions (17/24, 71%), readers remarked that the addition of DBT allowed for improved characterization of lesion margins, mainly detecting architectural distortion. When compared with the pathology findings, ILC was accurately diagnosed and assessed using CEM. The addition of DBT was reported by the interpreting radiologists as a valuable adjunct for margin analysis.

A clinical case of extremely severe COVID-19 with a favourable outcome

COVID-19 is an infectious disease that can progress from carrier and mild symptoms of acute respiratory infections to bilateral pneumonia, severe respiratory failure, acute respiratory distress syndrome (ARDS), multiorgan failure, sepsis and shock. One of the predictors of severe course of infection is advanced age and comorbidities. In this work we considered a clinical case of COVID-19 patient S., 86 years old, who was admitted to the hospital, to the intensive care unit on the 10th day of the disease, in an extremely severe condition. A diagnosis of bilateral polisegmental pneumonia with 70% lung involvement caused by SARS-CoV-2 virus was made. In addition to antiviral therapy with remdesivir and symptomatic therapy, pathogenetic therapy with tocilizumab was applied. On admission, the patient had leukopenia, thrombocytopenia, elevated values of COE, urea, significant elevation of inflammatory markers CRP and D-dimer, as well as pCo2. During inpatient treatment, positive dynamics of the condition and laboratory parameters were observed. The patient was discharged in satisfactory condition, all laboratory parameters were normalised, except for a slight increase in CRP and pCO2 levels. Despite the age of the patient and the severity of COVID-19 course, the combined use of drugs with multidirectional action, including tocilizumab, may improve the outcome of the disease.

Postoperative Outcomes of the Awake Colorectal Surgery with Neuraxial Anaesthesia.

To determine the outcome of awake surgery with combined spinal epidural in geriatric colon cancer patients with advanced comorbidity. Quasi-experimental study. Place and Duration of the Study: Department of Anaesthesiology and Reanimation, Ankara Bilkent City Hospital, Ankara, Turkiye, from April 2022 to 2023. Twenty-four American Society of Anaesthesiologists (ASA) I-II patients, aged 25-65 years and scheduled for colon cancer surgery were included in this research. All patients were observed preoperatively, at the operation room and at the postoperative surgery service. Spinal anaesthesia was planned for Group I and general anaesthesia for Group II. Ketofol (1:1) was administered to the combined spinal-epidural group, with a Ramsay sedation score of 3 after the spinal block. Epidural analgesia was planned for all patients. Patients' age, gender, weight, comorbidities, ASA risk scores, intraoperative haemodynamic parameters, bleeding amounts, colloid, crystalloid, and blood products were collected. There was no significant difference between the demographic characteristics of both anaesthesia groups (p >0.05). The amount of bleeding was statistically lower in Group I than in the general anaesthesia group (p = 0.004). Oral intake, drain withdrawal, mobilisation, discharge times, and costs were similar in all groups (p >0.05). The regional anaesthesia applications facilitate compliance with routine mobilisation, discharge procedures and prevent complications in abdominal surgery and its positive perioperative effects in patients with poor respiratory parameters, poor general condition, and high comorbidity in advanced age. Regional anaesthesia, Spinal-epidural, Mobilisation, Pain, Colon cancer.

Serum Anti-SARS-CoV-2 IgG in Chronic Hepatitis B Virus Positive Patients

Background: Advanced age and comorbidities such as diabetes mellitus, hypertension, chronic obstructive pulmonary disease or cardiovascular diseases are proven risk factors in COVID-19. In COVID-19, pre-existing liver illnesses could be a substantial risk factor for hospitalization and severity. Infection with the hepatitis B virus (HBV) is one of the most significant and common health disorders. Objective: To estimate serum anti-SARS-CoV-2 IgG in chronic Hepatitis B virus positive patients. Methodology: This cross-sectional analytical study was conducted in the Department of Biochemistry, Dhaka Medical College, Dhaka, during the period of January 2021 to December 2021. A total of 63 subjects were selected from Hepatology Department of DMCH and BSMMU as per selection criteria. Among them, 23 were chronic HBV positive patients (3 with COVID-19 and 20 without COVID-19) (group A) and the rest 40 were non HBV cases (20 with COVID-19 and 20 without COVID-19) (group B). Blood sample was collected for the measurement of anti-SARS-CoV-2 IgG. Biochemical analysis was performed by chemiluminescent microparticle immunoassay (CMIA) in the Department of Biochemistry, BSMMU, Dhaka. Result: In this study, the mean age of group A was 47.26 ± 11.24 years and group B was 44.53 ± 10.17 years. Males were predominant in both the groups. In group A, male was 65.2% &amp; female was 34.8% and in group B, male was 60% &amp; female was 40%. The median value of serum anti-SARS-CoV-2 IgG level was 1110.70 in group A and 417.85 in group B (p&gt;0.05). The study showed frequency of positivity of serum anti-SARS-CoV-2 IgG level in COVID-19 positive cases was 95.7% and in COVID-19 negative cases it was 90%. In this study, the median value of serum anti-SARS-CoV-2 IgG level significantly higher in COVID-19 positive (1063.20) than in COVID-19 negative (119.00) in non-HBV cases. Conclusion: Serum anti-SARS-CoV-2 IgG level was non-significantly higher in chronic HBV positive patients than non-HBV patients. J Com Med Col Teachers Asso Jan 2024; 28(1): 19-23

Clinical features of COVID-19 infection in patients with myasthenia gravis: a real-world retrospective study.

We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

In-Hospital Mortality in Patients With Acute Myocardial Infarction: A Literature Overview.

Acute myocardial infarction (AMI) continues to be a predominant cause of global morbidity and mortality, with in-hospital mortality (IHM) serving as a pivotal metric for patient outcomes. This review explores the influence of several clinical variables on IHM in individuals with AMI. Factors such as age, gender, body mass index (BMI), smoking habits, existing comorbidities, prior coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), and biomarkers, including high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase MB (CK-MB), significantly affect the prognosis of the patient. Advanced age and comorbid conditions such as diabetes and hypertension exacerbate myocardial damage and systemic impacts, thus increasing IHM. Gender and BMI are also critical, and women and patients with obesity face different risks. Smoking increases both the risk of AMI and IHM, underscoring the importance of cessation interventions. ST-elevation myocardial infarctionis associated with elevated IHM and requires immediate reperfusion therapy, while non-ST-elevation myocardial infarctionrequires customized management for risk assessment. Previous CABG and PCI add complexity to AMI treatment and elevate IHM due to pre-existing coronary pathology and the intricacies of the procedures involved. The application of biomarker-centered techniques facilitates the swift identification of individuals at elevated risk, improves therapeutic planning, and reduces IHM for patients with AMI. Understanding and incorporating these clinical determinants are essential to optimize the management of AMI, minimize IHM, and improve patient outcomes. This all-encompassing strategy requires ongoing research, quality improvement efforts, and personalized care approaches.

Presentation, care, coronary intervention and outcomes of patients with NSTEMI according to age: insights from the international prospective ACVC-EAPCI EORP NSTEMI registry.

Older people less frequently receive invasive coronary angiography (ICA) for NSTEMI than younger patients. We describe care, ICA data, and in-hospital and 30-day outcomes of NSTEMI by age in a contemporary and geographically diverse cohort. Prospective cohort study including 2947 patients with NSTEMI from 287 centres in 59 countries, stratified by age (≥75years, n = 761). Quality of care was evaluated based on 12 guideline-recommended care interventions, and data collected on ICA. Outcomes included in hospital acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding and death, as well as 30-day mortality. Patients aged ≥75years, compared with younger patients, at presentation had a higher prevalence of comorbidities and oral anticoagulation prescription (22.4% vs 7.6%, p< 0.001). Older patients less frequently received ICA than younger patients (78.6% vs 90.6%, p< 0.001) with the recorded reason more often being advanced age, comorbidities or frailty. Of those who underwent ICA, older patients more frequently demonstrated 3-vessel, 4-vessel and/or left main stem coronary artery disease compared to younger patients (49.7% vs 34.1%, p< 0.001) but less frequently received revascularisation (63.6% vs 76.9%, p< 0.001). Older patients experienced higher rates of in-hospital acute heart failure (15.0% vs 8.4%, p< 0.001) and bleeding (2.8% vs 1.3%, p= 0.006), as well as in-hospital and 30-day mortality (3.4% vs 1.3%, p< 0.001; 4.8% vs 1.7%, p< 0.001; respectively), than younger patients. Patients aged ≥75years with NSTEMI, compared with younger patients, less frequently received ICA and guideline-recommended care, and had worse short-term outcomes.

Retrospective Analysis of Efficacy and Toxicity of Stereotactic Body Radiotherapy and Surgical Resection of Adrenal Metastases from Solid Tumors.

This single-center retrospective study aimed to evaluate the efficacy and toxicity profiles of stereotactic body radiotherapy (SBRT) and surgical resection in patients with adrenal metastases originating from solid tumors. Patients with advanced tumor conditions or comorbidities typically received SBRT, whereas those considered physically fit underwent standard surgical treatment. Endpoints included local control (LC), progression free survival (PFS), overall survival (OS), and complication rates (CR). 41 patients with 48 adrenal metastases were included, with 27 (65.9%) patients receiving SBRT and 14 (34.1%) patients undergoing adrenalectomy. One- and two-year LC values were 100% for both periods after adrenalectomy, and 70.0% and 52.5% after SBRT (p = 0.001). PFS showed values of 40.2% and 32.1% at one and two years after adrenalectomy and of 10.6% for both periods after SBRT (p = 0.223). OS was 83.3% both one and two years after surgery and 67.0% and 40.2% after SBRT (p = 0.031). There was no statistically significant difference between the two groups regarding acute complications (p = 0.123). Despite potential confounders, adrenalectomy exhibited statistically significant superior LC and OS compared to SBRT in managing adrenal metastases, while both treatment methods displayed acceptable toxicity profiles. However, patient selection bias must be taken into account when directly comparing the two therapy modalities. Nevertheless, the study provides new and important results for the scientific and medical communities regarding oncological outcomes after SBRT or surgical resection of adrenal metastases.

Concentration of High-Cost Head and Neck Cancer Surgical Patients.

Health care costs are disproportionately concentrated among a small number of patients. We sought to identify variables associated with high-cost patients and high hospital concentration of high-cost patients and to examine associations with short-term outcomes in head and neck cancer (HNCA) surgery. The Nationwide Inpatient Sample was used to identify 170,577 patients who underwent HNCA surgery in 2001-2011. High-cost patients were defined as patients whose costs of care were in the top decile, and high-concentration hospitals were defined as those whose percentage of high-cost patients was in the top decile. Multivariable regression was used to evaluate associations between cost and patient and hospital variables, postoperative complications, and in-hospital mortality. Costs associated with high-cost patients were 4.47-fold greater than the remaining 90% of patients. High-concentration hospitals treated 36% of all high-cost patients. High-cost patients were more likely to be non-white (OR = 2.08 [1.45-2.97]), have oral cavity cancer (OR = 1.21 [1.05-1.39]), advanced comorbidity (OR = 1.53 [1.31-1.77]), Medicaid (OR = 1.93 [1.62-2.31]) or self-pay payor status (OR = 1.72 [1.38-2.14]), income>50th percentile (OR = 1.25 [1.05-1.51]), undergo major procedures (OR = 3.52 [3.07-4.05]) and have non-routine discharge (OR = 7.50 [6.01-9.35]). High-concentration hospitals were more likely to be teaching hospitals (OR = 3.14 [1.64-6.05]) and less likely to be urban (OR = 0.20 [0.04-0.93]). After controlling for all other variables, high-cost patients were associated with an increased odds of mortality (OR = 8.00 [5.89-10.85]) and postoperative complications (OR = 5.88 [5.18-6.68]). High-concentration hospitals were associated with an increased odds of postoperative complications (OR = 1.31 [1.08-1.61]) but were not associated with increased mortality (OR = 0.98 [0.67-1.44]). High-cost HNCA surgical patients are associated with increased postoperative morbidity and mortality, and are disproportionately concentrated at teaching hospitals. 4 Laryngoscope, 2024.

Infections in residents of long- term care facilities in southern Poland, 12-month surveillance preliminary results

Long-Term Care Facility (LTCF) residents are particularly vulnerable to infections due to factors such as advanced age, co-morbidities, and regular medication use. Data from American and European sources indicate an anticipated occurrence rate of 2 to 11 infections per 1000 patient-days (pds) in LTCFs. The incidence rate of Clostridioides difficile infections (CDI) is reported at 0.52 per 10,000 resident days. The research objectives aimed to assess infection epidemiology in Polish LTCFs. An observational prospective study was conducted on residents from five LTCFs (2 residential homes and 3 nursing homes) in southern Poland between September 2022 and September 2023, utilizing the definition from the pan-European HALT study. The study received approval from the Bioethics Committee of the JU (1072.6120.73.2022) and was funded by the Polish NCN grant No.2021/41/B/NZ6/00749. CDI was defined by positive toxins A and B enzyme immunoassays (EIA) and positive glutamate dehydrogenase (DHA) EIA. Results from the study, involving 250 residents, revealed 157 cases of Healthcare-Associated Infections (HAIs) excluding gastrointestinal and CDI, with an incidence rate of 1.97/1000 pds. Lower respiratory tract infections dominated with 77 cases, including 36 pneumonia cases (47%). Additionally, 25 cases of gastrointestinal infections were reported, including only 7 CDI cases, resulting in an incidence rate of 0.88 CDI per 10,000 pds. Norovirus was detected in only one case, while the microbiological results were negative in the remaining cases. The incidence rate among Polish LTCF residents was lower than expected, contrasting with the CDI incidence that aligned with other research findings. Notably, the etiology of diarrhea remained undetermined in 68% of cases.

Outcomes in patients with definite and possible infective endocarditis related to a cardiac implantable electronic device.

Diagnosing lead‑related infective endocarditis (LRIE) often poses a substantial challenge. Current diagnostic criteria include definite and possible LRIE. The aim of this study was to compare the outcomes of patients with definite and possible LRIE undergoing transvenous lead extraction (TLE) procedures. A retrospective analysis of data from 3782 patients undergoing TLE between 2006 and 2023 was performed. The study included 838 patients with definite and possible LRIE, whose clinical data on short- and long‑term survival were evaluated. The comparison of clinical data showed more frequent occurrences of vegetations (81.58% vs 37.21%; P <0.001), positive blood cultures (66.12% vs 51.64%; P <0.001), and septic pulmonary embolism (40.14% vs 13.78%; P <0.001) in the patients with definite LRIE. Long‑term mortality of patients with definite and possible LRIE (median [interquartile range] follow-up, 4.61 [1.04-9.4] and 5.06 [2.07-8.75] years, respectively) was 61.14% and 49.29% (P <0.001). Predictors of mortality in patients with definite LRIE included: advanced age, low left ventricular ejection fraction (LVEF), comorbidities, septic pulmonary embolism, positive blood culture, and presence of an abandoned lead. In possible LRIE, only the influence of advanced age, low LVEF, and comorbidities was demonstrated. There was no documented evidence of a direct impact of a delayed diagnosis on the long‑term survival of patients after TLE. The study showed better survival in patients with possible LRIE than with definite LRIE, which confirms the need to extend the diagnostic criteria. Introducing appropriate treatment at an early stage of infection improves the prognosis.

Venetoclax combined with hypomethylating agents for favorable risk acute myeloid leukemia: A single center experience.

e18514 Background: Favorable risk acute myeloid leukemia (FR-AML) is typically treated with intensive induction chemotherapy followed by high dose consolidative cytarabine. However, a subgroup of FR-AML are not candidates for high intensity induction because of advanced age, comorbidities, or poor performance status. For these patients, hypomethylating agents (HMA) combined with venetoclax (HMA-Ven) is inferred as the standard of care based upon results of the VIALE-A trial; however, that trial enrolled only intermediate or poor risk AML. The efficacy of HMA-Ven in FR-AML is unclear. Here we present a single center experience of this regimen in FR-AML. Methods: In this retrospective single center case series, we collected data from all patients &gt;18 years old with newly diagnosed FR-AML between January 2018 to December 2022 at AdventHealth Orlando who were treated with HMA-Ven. Patient with relapsed/refractory disease or a diagnosis of acute promyelocytic leukemia were excluded. FR-AML was defined using ELN 2022 guidelines based on the results of genomic testing of the initial bone marrow aspirate. The primary endpoints were the complete remission (CR) rate and 1-year overall survival (OS). Statistical analyses were performed using the R survminer package. Results: Newly diagnosed FR-AML who received HMA-Ven were identified (n=12). The median age was 67.5 years. 3 (25%) cases had inversion of chromosome 16 and 9 (75%) had NPM1 mutations without FLT3-ITD mutations. 11 (92%) patients received decitabine and venetoclax. Patients received a median of 2.5 cycles of HMA-Ven, and all 12 patients achieved CR after one cycle of treatment. 6 (50%) patients were consolidated with intermediate-dose cytarabine (IDAC), 3 (25%) continued HMA-Ven, 2 (17%) underwent allogeneic stem cell transplant, and 1 (8%) received enasidenib. The 1-year OS was 80% (CI 0.59-1), and the median OS was not reached. 1 patient died due to chemotherapy toxicity with IDAC, and 1 patient died due to heart complications. 2 patients relapsed, 1 after IDAC and 1 after intolerance to further treatment after 6 cycles of HMA-Ven. Conclusions: Our findings suggest that HMA-Ven is an effective treatment for newly diagnosed favorable risk AML. All patients achieved CR with one cycle of treatment with most surviving more than one year. Large multicenter studies are needed to further validate these promising results.

Clinical characteristics and outcomes among hospitalised COVID-19 patients across epidemic waves in Spain: An unCoVer analysis

Background and objectivesThe COVID-19 pandemic had a significant impact in population health worldwide, and particularly in people with pre-existing chronic diseases. Early risk identification and stratification is essential to reduce the impact of future outbreaks of pandemic potential. This study aimed to comprehensively examine factors associated with COVID-19 mortality across the pandemic waves in Spain. MethodsA retrospective study analyzed the characteristics of 13,974 patients admitted to Spanish hospitals due to SARS-CoV-2 infection from 2020-01-28 to 2022-12-31. The demographic and clinical features of patients during hospitalization on each pandemic waves were analyzed. Main findingsThe findings highlight the heterogeneity of patient characteristics, comorbidities and outcomes, across the waves. The high prevalence of cardiometabolic diseases (53.9%) among COVID-19 patients emphasizes the importance of controlling these risk factors to prevent severe COVID-19 outcomes. ConclusionsIn summary, the study associate hospital mortality with factors such as advanced age and comorbidities. The decline in mortality after the 4th wave indicates potential influences like vaccination, viral adaptation, or improved treatments. Notably, dementia and cancer metastases emerge as critical factors linked to higher mortality, highlighting the importance of addressing these conditions in COVID-19 management and preparing for future challenges.

Long-term follow-up of patients with hairy cell leukemia treated with different modalities at a single institution: Real-life experience over 25 years.

e19023 Background: Hairy cell leukemia (HCL) is an uncommon and indolent leukemia of mature B cells, accounting for 2% of all lymphoid neoplasms. We analyzed characteristics, treatment modalities, response rates, and survival of HCL patients followed at our institution. Methods: We retrospectively reviewed data from the medical records of 56 consecutive HCL patients evaluated in our Hematology/Oncology clinic between 1998 and 2023. Results: The median age at diagnosis was 59 years (range, 37-94). Forty-nine patients (87%) were male. First-line therapy was cladribine in 30 patients (54%), cladribine + rituximab in 6 patients (11%), observation in 5 patients (9%), and another modality (fludarabine, pentostatin, single agent-rituximab, and other) in the rest of patients. The median follow-up was 122 months (1-291). The overall response rate was 96%. CR and PR rates were 68% and 28%, respectively. Relapses were observed in 44% of patients. The median OS was not reached, and the median PFS was 181 months (95% CI, 128-252). The 5-year and 10-year PFS were 78% and 29%, respectively. Only 3 patients (5%) died as a result of HCL, either indirectly from immune suppression (pneumonia, 2 patients) or directly (cachexia in 1 patient, untreated because of advanced age and comorbidities). Conclusions: Treatment with purine analogues such as cladribine, plus or minus rituximab, achieves deep and durable responses in most HCL patients. Although relapses were commonly observed, the vast majority of HCL patients did not die as a result of HLC.

Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study.

Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes. The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm3, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm3 at any time during 48-week analysis periods through week 192. Through a median of 258 weeks (range, 0.14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm3, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm3 at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm3 at any time vs those sustaining <200 cells/mm3. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm3. Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment. NCT02362503, https://clinicaltrials.gov/study/NCT02362503.

Barriers to cancer treatment for people experiencing socioeconomic disadvantage in high-income countries: a scoping review

BackgroundDespite advances in cancer research and treatment, the burden of cancer is not evenly distributed. People experiencing socioeconomic disadvantage have higher rates of cancer, later stage at diagnoses, and are dying of cancers that are preventable and screen-detectable. However, less is known about barriers to accessing cancer treatment.MethodsWe conducted a scoping review of studies examining barriers to accessing cancer treatment for populations experiencing socioeconomic disadvantage in high-income countries, searched across four biomedical databases. Studies published in English between 2008 and 2021 in high-income countries, as defined by the World Bank, and reporting on barriers to cancer treatment were included.ResultsA total of 20 studies were identified. Most (n = 16) reported data from the United States, and the remaining included publications were from Canada (n = 1), Ireland (n = 1), United Kingdom (n = 1), and a scoping review (n = 1). The majority of studies (n = 9) focused on barriers to breast cancer treatment. The most common barriers included: inadequate insurance and financial constraints (n = 16); unstable housing (n = 5); geographical distribution of services and transportation challenges (n = 4); limited resources for social care needs (n = 7); communication challenges (n = 9); system disintegration (n = 5); implicit bias (n = 4); advanced diagnosis and comorbidities (n = 8); psychosocial dimensions and contexts (n = 6); and limited social support networks (n = 3). The compounding effect of multiple barriers exacerbated poor access to cancer treatment, with relevance across many social locations.ConclusionThis review highlights barriers to cancer treatment across multiple levels, and underscores the importance of identifying patients at risk for socioeconomic disadvantage to improve access to treatment and cancer outcomes. Findings provide an understanding of barriers that can inform future, equity-oriented policy, practice, and service innovation.

Comparison of Volumetric Modulated Arc Therapy (VMAT) and Conventional Intensity-Modulated Radiotherapy (IMRT) for Locally Advanced Head and Neck Squamous Cell Carcinoma: A Retrospective Cohort Study.

Purpose This study examines the outcomes of locally advanced head and neck squamous cell carcinoma (HNSCC) following the adoption of conventional intensity-modulated radiotherapy (cIMRT) and volumetric-modulated arc therapy (VMAT) over a decade. The region under study has higher comorbidities associated with increased HNSCC incidence and poorer prognosis. Materials and methods A 10-year retrospective review of electronic medical records included 296 patients with stage III, IVA, and IVB HNSCC (American Joint Committee on Cancer, Seventh edition). Survival outcomes were compared between VMAT and cIMRT using Kaplan-Meier survival curves and adjusted for relevant demographic factors using Cox's proportional hazards model. Analysis was performed using R software(R Foundation, Vienna, Austria). Results The median age of the cohort was 63 years, comprising of 80% males. The oropharynx was the most common primary tumor site. 264 (89%) received 50Gy or higher dose radiation by either cIMRT (22%) or VMAT (67%). At five years, locoregional control (LC) and overall survival (OS) rates were 79.5% and 56.7%, respectively. VMAT showed a significant improvement in five-year OS (63.4% versus 43.8% for cIMRT, p=0.0023)but no significant difference in five-year LC (81% VMAT versus 74.5% cIMRT, p=0.17). Grade 3-4 acute toxicity was observed in 22% of patients. Conclusions VMAT and cIMRT demonstrated excellent LC in locally advanced HNSCCdespite high comorbidity rates. Notably, VMAT was associated with significantly better OS compared to cIMRT. These outcomes surpass historical data, suggesting that VMAT technology may lead to improved patient outcomes. However, larger randomized controlled trials and dosimetric studies are needed to confirm these findings.

Postoperative atrial fibrillation is associated with late mortality independently of patient comorbidities: a systematic review and reconstructed individual patient data meta-analysis

Abstract Background Early postoperative atrial fibrillation (POAF) is the most common complication within the first days after cardiac surgery. It is hypothesized to result from perioperative stressors such as inflammation, oxidative stress, and increased adrenergic tone, along with an advanced arrhythmogenic substrate resulting from advanced age and cardiovascular comorbidities including hypertension, heart failure, or chronic obstructive pulmonary disease (COPD).[1, 2] Although prior studies have demonstrated an association between in-hospital POAF and late mortality or stroke, it is questionable whether these long-term adverse events result from the occurrence of early-POAF or, rather, from the advanced cardiovascular risk profile that partly underlies the development of early-POAF.[3] Purpose To investigate the association of early-POAF with late mortality (primary outcome) and stroke (secondary outcome) in patients undergoing cardiac surgery after adjustment for age and the cardiovascular risk profile. Methods A systematic search, covering PubMed, EMBASE, and the Cochrane Library, was conducted to identify studies reporting on late mortality after cardiac surgery in patients with and without new-onset POAF during hospitalization. Articles meeting the criteria, which included Kaplan-Meier (KM) curves along with risk tables, were included for a pooled analysis of late mortality and stroke. Individual time-to-event data were reconstructed from the KM curves and incorporated into a multivariable frailty Cox model. The model included adjustments for age, sex, preoperative cardiovascular comorbidity profile (hypertension, diabetes mellitus [DM], peripheral artery disease [PAD], history of stroke, heart failure, and COPD), type of surgery, and a frailty term (study variable). Results In total, 28 studies were included in the analysis for late mortality (N=112931), and 9 studies in the analysis for late stroke (N=35004). Overall, 31039 patients had early-POAF with a pooled incidence of 29.7% (95% CI: 25.7-34.1%). Patients developing POAF were older (68.5 vs. 64.1 years old, p&amp;lt;0.001), had a more frequent history of PAD (9.5% vs. 7.8%, p=0.026), a history of stroke (9.3% vs. 7.6%, p&amp;lt;0.001), heart failure (17.2% vs. 15.1%, p&amp;lt;0.001), and COPD (12.5% vs. 9.7%, p&amp;lt;0.001). Unadjusted analysis showed that POAF was strongly associated with increased late mortality (Hazard Ratio [HR]=1.64, 95% CI: 1.59 to 1.69, p&amp;lt;0.001) and late stroke (HR=1.46, 95% CI: 1.36 to 1.58, p&amp;lt;0.001) (Figure 1). POAF was an independent predictor for late mortality (HR=1.46, 95% CI: 1.36 to 1.58, p&amp;lt;0.001) but not for late stroke (HR=1.10, 95% CI: 0.85 to 1.43, p=0.48) after adjustment for age, cardiovascular comorbidity profile, type of surgery, and frailty (study term). Conclusion Early-POAF after cardiac surgery is an independent predictor of mortality in the years following discharge after cardiac surgery, regardless of age, cardiovascular comorbidity profile, and type of surgery.Figure 1