Initial Treatment Strategy Research Articles

SINGLE-PILL, TRIPLE ANTIHYPERTENSIVE THERAPY IN RURAL SUB-SAHARAN AFRICA: PRELIMINARY EXPERIENCE

Objective: Arterial hypertension is worldwide the leading modifiable cardiovascular risk factor. Beside life-style changes, strong evidence supports the efficacy of pharmacological treatment in reducing the complications of hypertension. International guidelines have recommended single-pill, low-dose combinations as initial treatment strategy. We investigated whether management of hypertension through this approach is feasible and effective in a rural sub-Saharan Africa setting. Design and method: Diagnosis of hypertension was established over three sets of blood pressure measurements: during a community-based, house-to-house screening in 2020 and in 2022, and at the hypertension outpatient clinic. Blood pressure measurements were performed according to the ESH recommendations by trained personnel, using a validated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals diagnosed to have arterial hypertension, once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at a dose suitable to their blood pressure values and clinical characteristics. They were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. Treatment regimen was adjusted, if needed, at each outpatient clinic visit scheduled after 4, 8, 12, and 16 weeks Results: 79 patients (aged 61 [53-70] years; median and interquartile range) strictly adhered to the treatment schedule, while overall 19 individuals dropped-out (aged 70 [65-80] years) because of different reasons. About 20% were tobacco smokers and nearly all consumed alcohol. Blood pressure was <140/90 mm Hg after 4 weeks in 44 (56%), after 8 weeks in 62 (78%), after 12 weeks in 69 (87%), and after 16 weeks in 74 (94%) participants. Excellent tolerance was widely reported. Conclusions: Management of hypertension with once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide as initial treatment was feasible and effective also in a rural sub-Saharan setting, with very high rate of hypertension control in patients adherent to treatment. Our results provide real life evidence in favor of extensive implementation of single-pill combination therapy also in low- and middle-income countries where local Health Care Systems should include recommendation on their usage in national guidelines and should make them available also in rural and remote areas at low or no cost as reliable first-line treatment strategy

Focal brain oxygen, blood flow, and intracranial pressure measurements in relation to optimal cerebral perfusion pressure.

Different paradigms for neurocritical care of traumatic brain injury (TBI) have emerged in conjunction with advanced neuromonitoring technologies and derived metrics. The priority for optimizing these metrics is not currently clear. The goal of this study was to determine whether achieving cerebral perfusion pressure (CPPopt) also improves other metrics like brain oxygenation and brain blood flow. The authors performed a retrospective analysis of high-frequency data from patients with TBI who were treated at a single center and who had partial pressure of brain oxygen (PbtO2) measurements and/or brain blood flow measurements, while also undergoing intracranial pressure (ICP) monitoring. CPPopt was not calculated or targeted during patient care, but was retrospectively computed, as was the difference between the observed CPP and CPPopt. A total of 22 patients with ICP, PbtO2, and/or brain blood flow monitoring were included in the analysis, and 245.7 days of measurements obtained every second were analyzed including 6,748,866 PbtO2 measurements, 3,296,405 blood flow measurements, and 10,264,770 ICP measurements. The data obtained every second were averaged by minute for analysis. In summative data, PbtO2 measurements peaked near CPPopt and were not improved above CPPopt. Blood flow measurements remained stable near CPPopt, decreased below it, and increased when CPP exceeded CPPopt. ICP decreased linearly with CPP without a specific relationship with CPPopt. In an inverse analysis, the percentage of CPP values at CPPopt, although significantly higher on the favorable side of contemporary treatment thresholds of PbtO2, ICP, and blood flow, was not found to be strongly correlated with the mean values of the physiological measurements obtained every minute (r = 0.27, r = 0.11, and r = 0.47 for ICP, PbtO2, and blood flow, respectively; p < 0.0001). Although CPPopt was not targeted in the patients in this study, CPPopt was a physiologically significant value based on concurrent measurements of PbtO2 and blood flow. In summative data, achievement of CPPopt was associated with optimized PbtO2 and blood flow. Conversely, the correlation between achievement of CPPopt and the mean measurement value was not strong, strengthening the significance of CPPopt. In individual patients, achieving CPPopt is not always associated with optimal PbtO2 or blood flow. Further research should explore these relationships in treatment paradigms that specifically target CPPopt. These data do not support the premise that targeting and achieving CPPopt obviates the need for concurrent PbtO2 and blood flow monitoring. Although these data suggest that targeting CPPopt may be an appropriate initial treatment strategy, they do not provide evidence that CPPopt should be targeted with highest priority.

Autologous Hematopoietic Cell Transplantation Consolidation for First Response is Associated With Longer Survival Among Patients With Nodal Peripheral T Cell Lymphoma

Nodal peripheral T cell lymphomas (PTCLs) are challenging subsets of non-Hodgkin lymphomas characterized by their heterogeneity and aggressive clinical behavior. Given the mixed outcomes reported in previous studies, the efficacy of autologous hematopoietic cell transplantation (auto-HCT) as a consolidation strategy following initial chemotherapy response remains uncertain. This study aims to evaluate the impact of upfront auto-HCT consolidation on overall survival (OS) and event-free survival (EFS) among patients with nodal PTCL who achieved a complete or partial response to initial chemotherapy. A retrospective cohort study was conducted at Moffitt Cancer Center, involving 123 patients with nodal PTCL treated between February 2005 and February 2021. Patients were stratified into 2 groups based on whether they received auto-HCT as part of their initial treatment strategy. Kaplan-Meier method and Cox proportional hazard models were used for statistical analysis to compare OS and EFS between groups. Patients undergoing auto-HCT after first response demonstrated significantly longer median OS (12.3 versus 4.3 yr; P = .035) and EFS (6.2 versus 2.2 yr; P = .003) compared to those who did not. Multivariate analyses indicated that auto-HCT at first response and younger age at diagnosis were favorable prognostic factors. The findings suggest that upfront auto-HCT consolidation can significantly improve long-term outcomes in patients with nodal PTCL, supporting the strategy of early auto-HCT consideration and referral following initial chemotherapy response. These results underscore the importance of integrating upfront auto-HCT into the treatment paradigm for nodal PTCL, emphasizing early referral to transplantation services to optimize patient outcomes.

OA20 Serious infections hospital admissions and mortality in patients with early inflammatory arthritis: results from the National Early Inflammatory Arthritis Audit

Abstract Background/Aims To identify the risk of serious infections (SI) according to initial treatment strategy, using conventional synthetic disease modifying anti-rheumatic drugs (csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods An observational cohort study design was used. The population included adults in England with a new onset rheumatoid arthritis (RA), fulfilling ACR/EULAR 2010 criteria, between April 2018-March 2021. Outcomes studied were SI, defined by infections requiring hospitalisation (primary admission diagnosis/nosocomial acquisition) or death (SI stated on death certificate), identified using NHS Digital linkage. Patients' characteristics were tabulated by treatment strategies. Hazard ratios (HR) were calculated using single failure Cox proportional-hazards models, with confounders-adjusted models (age, gender, smoking status, comorbidities, social deprivation) and fully-adjusted models including disease factors (seropositivity, DAS28). Individuals were considered at risk from the date of RA diagnosis, and censored at SI event, death, or March 2021 (whichever was earliest). Results 20,060 patients with RA were included. Initial DMARD therapy was known for 19,572 patients, of whom 11,966 were on methotrexate/MTX based strategies (mono or combo), 5,059 on csDMARD combination strategies (other than MTX) and 2,547 on no DMARD strategy. 15,319 patients were on corticosteroids at baseline. Mean age 59.5 years (+/-15); 63% female; smoking status (20% current; 30% ex-smokers); comorbidities (21% hypertension; 10% diabetes; and 12% lung disease). Rheumatoid Factor/CCP antibodies were positive in 68%. At presentation, median disease scores were 5.1 (interquartile range [IQR]: 4.0-5.9) for DAS28, 1.1 (IQR: 0.6-1.7) for health assessment questionnaire (HAQ) and 24 (IQR: 16.0-33.0) for musculoskeletal health questionnaire (MSKHQ).There were 519 SI admissions and 17 SI deaths, corresponding to incidence rates per 100 person-years for admissions: 3.19 (95% CI: 2.93-3.48) and deaths: 0.10 (95% CI: 0.06-0.16). In fully-adjusted models, increasing age predicted both SI admissions and deaths. Being a smoker, having a comorbidity, higher disease activity (DAS28), symptom burden (MSKHQ) and disability (HAQ) at presentation associated with more SI admissions. For each 1 unit increase in DAS28, the risk of SI increased by 8% (HR 1.08 [95% CI:1.01-1.16]). Seropositivity did not associate with SI. MTX-based strategies 0.75 (95% CI:0.62-0.91) and csDMARD combination therapy 0.70 (95% CI:0.53-0.94) associated with fewer SI admissions compared to no DMARD. In unadjusted models, corticosteroid associated with more SI admissions 1.29 (95% CI:1.10 -1.62); however, in fully-adjusted models this association was no longer statistically significant. csDMARD strategies did not associated with SI deaths in any of the models. Conclusion Patient and disease factors at diagnosis appear to be important predictors of admissions and mortality for serious infections. Infection risk appears to be greatest in those with higher RA disease activity. An important limitation is that NEIAA does not capture data on treatment changes over time and steroid use beyond baseline. Disclosure M. Adas: None. K. Bechman: None. M. Russell: Honoraria; Lilly and Menarini. Other; upport for attending conferences from Lilly, Pfizer, Janssen, and UCB, and advisory board fees from Biogen.. I. Karafotias: None. D. Nagra: None. S. Patel: None. S. Gallagher: None. E. Price: None. M. Garton: None. A. Rutherford: None. A. Cope: None. S. Norton: None. J. Galloway: Honoraria; from Abbvie, Biovitrum, Bristol Myers Squib (BMS), Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, and UCB.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Crimson Concussa - Initial Treatment of The Polytraumatized Patient in Hemorrhagic Shock

This comprehensive article, titled ‘Crimson Concussa’, delves into the complexities of hemorrhagic shock in the context of polytrauma. It offers an in-depth analysis of the pathophysiological processes, diagnostic challenges, and treatment modalities associated with this critical condition. Emphasizing the importance of the ‘golden hour’ and the Advanced Trauma Life Support (ATLS) protocol, the paper underscores the necessity of a swift, systematic approach and a multidisciplinary team in managing polytraumatized patients. The review explores the nuances of initial treatment strategies, including airway management, breathing and ventilation assessment, circulatory function, and hemorrhage control. Additionally, it addresses the intricate details of pathophysiology, etiology, clinical stages, and treatment options, including fluid therapy, blood transfusions, and coagulopathy management. The article aims to enhance understanding and provide insights into the latest advancements in trauma care, highlighting the importance of ongoing research for improving therapeutic approaches and patient outcomes in the realm of emergency medicine.

Parry-Romberg Syndrome and an Associated Complex Vascular Lesion Managed With Hybrid Strategies: A Case Report

BACKGROUND AND IMPORTANCE: Parry-Romberg syndrome (PRS) is a condition of unknown etiology, most commonly characterized by progressive facial hemi-atrophy due to breakdown of the underlying skin and soft tissues. PRS has been associated with neurologic disease such as intracranial aneurysms and vascular malformations. However, its exact role in the incidence of neurovascular disease remains unknown. CLINICAL PRESENTATION: We present a case of a complex fusiform aneurysm involving the A1 segment of the left anterior cerebral artery in a 21-year-old man with PRS. The patient initially presented with a left giant fusiform/dissecting internal carotid artery aneurysm initially managed with overlapping flow diverters. His post-flow diverter treatment course was confounded by progressive growth of the aneurysm with worsening mass effect on the optic chiasm leading to complete visual loss in the left eye and a right hemifield cut. To manage the aneurysm recurrence, retreatment with surgical bypass-supported carotid occlusion was performed. Thereafter, visual symptoms improved, but complete normalization of vision was not achieved. The patient remained clinically stable for several years until follow-up imaging demonstrated a novel adjacent recurrence involving the ipsilateral A1 segment, previously noted to be angiographically normal. The patient underwent superselective angiography followed by endovascular occlusion of the new fusiform lesion. DISCUSSION: The case presented here illustrates the hybrid roles of endovascular and surgical treatment modalities in treating complex vascular lesions. The recurrence of the lesion following initial treatment strategies introduces questions about how the nature and development of the lesion affected the success of treatment at each stage. Considerations for the efficacy of each stage of treatment in this case include the patients underlying connective tissue disorder, the pediatric etiology of the lesion, and the timing of each treatment option given these factors. CONCLUSION: In addition to understanding the biological behavior of flow diversion for complex intracranial aneurysms, the role of PRS in the incidence of neurovascular disease should also be considered when applicable. More research into the mechanisms of PRS in neurovascular disease is needed.

Ticagrelor vs clopidogrel when coadministered with bivalirudin in patients with acute coronary syndrome undergoing percutaneous coronary intervention

BackgroundThe optimal perioperative antithrombotic strategy for patients with acute coronary syndrome (ACS) during percutaneous coronary intervention (PCI) remains controversial. ObjectivesTo determine the safety and effectiveness of bivalirudin plus ticagrelor vs bivalirudin plus clopidogrel in patients with ACS undergoing PCI in the real world. MethodsBetween March 2016 and March 2019, 7234 patients with ACS who had undergone PCI, received bivalirudin periprocedurally, and were prescribed ticagrelor or clopidogrel were enrolled in a single-center, all-comer, modern, retrospective cohort study. Incidence rates of 12-month ischemia (cardiac death, myocardial infarction, or stroke), all-cause death, Bleeding Academic Research Consortium (BARC) type 2,3,5 bleeding, and BARC type 3,5 bleeding were compared between different groups. ResultsIn total, 4960 patients received bivalirudin plus clopidogrel and 2274 patients received bivalirudin plus ticagrelor. Compared with bivalirudin plus clopidogrel, bivalirudin plus ticagrelor was associated with lower ischemic events (1.74% vs 2.84%; relative risk, 0.61; 95% CI, 0.41-0.91; P = .02) and stroke (0.05% vs 1.01%, P < .001) within 12 months after PCI without excessive risk of bleeding (BARC type 2,3,5 bleeding: 4.49% vs 3.76%, P = .22; BARC type 3,5 bleeding: 2.84% vs 2.02%, P = .08). The beneficial effects of bivalirudin plus ticagrelor were consistent among subgroups. ConclusionAs an initial treatment strategy, bivalirudin plus ticagrelor could reduce the 12-month risk of ischemic events compared with bivalirudin plus clopidogrel significantly without increasing the bleeding risk in ACS patients undergoing PCI.

Single-Pill, Triple Antihypertensive Therapy in Rural Sub-Saharan Africa: Preliminary Experience.

Worldwide, arterial hypertension is the foremost preventable and modifiable cardiovascular risk factor. In addition to lifestyle changes, recent international guidelines recommend single-pill, low-dose combinations as initial treatment strategy. We investigated whether this approach is feasible in a rural sub-Saharan Africa setting. Diagnosis of hypertension was established over three sets of blood pressure measurements, performed according to the European Society of Hypertension recommendations by trained personnel, using a validated, automated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals with arterial hypertension, aonce-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at an appropriate dose. Patients were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. The treatment regimen was adjusted, if needed, at each outpatient clinic scheduled after 4, 8, 12, and 16 weeks. Seventy-nine patients (aged 61 [53-70] years; median and interquartile range) strictly adhered to the treatment schedule, while 19 individuals (70 [65-80] years) dropped out. Blood pressure was < 140/90 mmHg after 4 weeks in 44 (56%), after 8 weeks in 62 (78%), after 12 weeks in 69 (87%), and after 16 weeks in 74 (94%) participants. Excellent tolerance was reported. These results provide real-life evidence that hypertension management with aonce-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide as initial treatment is feasible and effective alsoin a rural sub-Saharan setting. Single-pill combinations should be made available also in rural and remote areas in low- and middle-income countries as a reliable first-line treatment strategy.

Optimal Treatment Strategy for Oligo-Recurrence Lung Cancer Patients with Driver Mutations.

The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. Therefore, we aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. Among 2152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated, focusing on their post-recurrence therapies and prognoses. The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701-2.912; log-rank, p = 0.324) and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459-1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can cure the recurrence and can delay the start of administration of molecular targeted therapies.

Outcomes >30 Years After Initial Nonoperative Treatment of Anterior Cruciate Ligament Injuries

Background: It is unclear how anterior cruciate ligament (ACL) reconstruction (ACLR) affects the development of osteoarthritis (OA). This uncertainty is partly caused by the lack of long-term studies on ACL injuries treated primarily without reconstruction and the underreporting of symptomatic OA. Purpose: To determine (1) the knee function, symptoms, and activity level, as well as the presence of radiographic and symptomatic OA; (2) how these clinical outcomes have changed over time; and (3) the frequency of subsequent knee surgeries after the index ACL injury in a cohort of patients with ACL injuries treated primarily without reconstruction. Study Design: Case series; Level of evidence, 4. Methods: A total of 100 patients underwent initial nonoperative treatment >30 years ago (mean, 33.2 ± 1.4 years). Of these, 81 patients (mean age, 59 ± 8 years) completed the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Scoring Scale, and Tegner Activity Scale. Seventy-three patients underwent radiography to evaluate tibiofemoral and patellofemoral OA in the ACL-injured knee. Patients only underwent late ACLR if they experienced insufficient knee stability. Results: At 33 years after the ACL injury, the KOOS Activities of Daily Living subscore was better than population-based reference values, but scores were similar for the remaining KOOS subscales. Furthermore, 65% of patients had a good or excellent Lysholm score (≥84 points). The Tegner score decreased 4 points from before the injury to 33-year follow-up (P < .001). Most patients (75%) had evidence of radiographic tibiofemoral and/or patellofemoral OA, but only 38% were classified as having symptomatic OA (defined as radiographic OA in combination with a symptomatic knee according to cutoffs on the KOOS). Approximately 50% underwent meniscal surgery, and 29% subsequently underwent ACLR for recurrent instability. There were 2 patients who underwent total knee replacement. Conclusion: Despite a high prevalence of radiographic OA, patients achieved acceptable subjective knee function and had a relatively low prevalence of symptomatic OA at >30 years after an ACL injury when an initial nonoperative treatment strategy was employed.

Tailored risk assessment and forecasting in intermittent claudication.

Guidelines recommend cardiovascular risk reduction and supervised exercise therapy as the first line of treatment in intermittent claudication, but implementation challenges and poor patient compliance lead to significant variation in management and therefore outcomes. The development of a precise risk stratification tool is proposed through a machine-learning algorithm that aims to provide personalized outcome predictions for different management strategies. Feature selection was performed using the least absolute shrinkage and selection operator method. The model was developed using a bootstrapped sample based on patients with intermittent claudication from a vascular centre to predict chronic limb-threatening ischaemia, two or more revascularization procedures, major adverse cardiovascular events, and major adverse limb events. Algorithm performance was evaluated using the area under the receiver operating characteristic curve. Calibration curves were generated to assess the consistency between predicted and actual outcomes. Decision curve analysis was employed to evaluate the clinical utility. Validation was performed using a similar dataset. The bootstrapped sample of 10 000 patients was based on 255 patients. The model was validated using a similar sample of 254 patients. The area under the receiver operating characteristic curves for risk of progression to chronic limb-threatening ischaemia at 2 years (0.892), risk of progression to chronic limb-threatening ischaemia at 5 years (0.866), likelihood of major adverse cardiovascular events within 5 years (0.836), likelihood of major adverse limb events within 5 years (0.891), and likelihood of two or more revascularization procedures within 5 years (0.896) demonstrated excellent discrimination. Calibration curves demonstrated good consistency between predicted and actual outcomes and decision curve analysis confirmed clinical utility. Logistic regression yielded slightly lower area under the receiver operating characteristic curves for these outcomes compared with the least absolute shrinkage and selection operator algorithm (0.728, 0.717, 0.746, 0.756, and 0.733 respectively). External calibration curve and decision curve analysis confirmed the reliability and clinical utility of the model, surpassing traditional logistic regression. The machine-learning algorithm successfully predicts outcomes for patients with intermittent claudication across various initial treatment strategies, offering potential for improved risk stratification and patient outcomes.

Outcomes and risk assessment in pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare and severe subtype of pulmonary arterial hypertension (PAH). Although European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines advise assessing PAH severity at baseline and during follow-up, no existing risk assessment methods have been validated for PVOD. This study aimed to identify prognostic factors, examine the impact of treatment strategies and evaluate risk assessment methods for PVOD patients. The study analysed all incident PVOD patients included in the French Pulmonary Hypertension Registry between 2006 and 2021. Survival was assessed based on initial treatment strategy and risk status and compared to a matched (age, sex, pulmonary vascular resistance) PAH group. Six risk assessment methods (number of four low-risk and three noninvasive low-risk variables, ESC/ERS guidelines three-strata and four-strata models, REVEAL 2.0 and Lite 2) were applied at baseline and early follow-up, and their accuracy was compared using Harrell's c-statistic. Among the 327 included PVOD patients, survival rates at 1, 3 and 5 years were 86%, 50% and 27%, respectively. Multivariate analysis showed that only 6-min walk distance was associated with survival, with no significant difference based on initial treatment strategy. All six risk assessment methods could discriminate mortality risk, and the ESC/ERS four-strata model was the most accurate at both baseline and follow-up (C-index 0.64 and 0.74). PVOD survival rates were consistently lower than PAH when comparing baseline risk status using the ESC/ERS four-strata model. PVOD is associated with poor outcomes, and initial treatment strategies do not significantly affect survival. Risk assessment methods can be useful in predicting survival for PVOD patients.

Characteristics of black bear-related trauma: A retrospective observational study.

Bear-related trauma is a significant concern in Japan. This study identified trauma patterns, outcomes, and therapeutic approaches for bear-related injuries treated. This retrospective observational study used medical records from Akita University Hospital, focusing on patients with bear-related trauma in 2023. Demographic data, injury details, treatment procedures, and outcomes were extracted. The study included 20 patients (median age: 74.5 years, 65% males). Most injuries occurred in human habitats, mainly in autumn, with the face being the most affected area (90%). Three patients required emergency transfusions and tracheal intubation. Emergency surgery was performed in 52.6% of patients, and 42.1% were admitted to the intensive care unit. All patients survived with a median hospital stay of 17 days. However, 15.8% of patients had significant sequelae, such as blindness. Despite prophylactic antibiotics, wound infections occurred in 21.1% of patients, particularly in deep wounds that were not adequately washed under general anesthesia. Bear-related trauma often results in severe upper-body injuries that require prompt medical intervention. These findings highlight the need for improved preventive measures and strategies for initial treatment and long-term care.

Gastroenterology integration in specialized clinics for late complications after colorectal cancer surgery

The integration of gastroenterology expertise in clinics managing late complications of colorectal and anal cancer surgery is an advancement in patient care. This paper explores the multifaceted role of gastroenterologists in such settings, emphasizing diagnostic evaluation, personalized treatment planning, and the management of complex gastrointestinal symptoms. There is an obvious necessity for gastroenterological expertise to address complex issues such as diarrhea, malabsorption, discomfort, pain, bleeding, and incontinence, which are frequently under-treated in routine colorectal surgical outpatient care. In the article, we give recommendations for initial assessment, diagnostic workup, treatment strategies, follow-up, and monitoring of these issues. Highlighting the importance of a multidisciplinary approach, we discuss how gastroenterologists contribute to improved treatment outcomes and patient quality of life after surgery for colorectal and anal cancer.

Managing Constipation in Children: A Comprehensive Approach for Community Nurses

Constipation is a prevalent issue among children, with an estimated 3% of paediatric outpatient visits concerning this problem [1]. This paper presents a comprehensive examination of the strategies for diagnosing, investigating, and managing childhood constipation, with a focus on the role of community nurses. We explore clinical history pointers, examination findings, investigations, and treatments, emphasizing practical interventions that community nurses can implement to support affected children. Constipation is a common yet frequently overlooked paediatric condition, posing significant challenges to healthcare professionals due to its multifactorial aetiology and potential long-term consequences. This article provides a comprehensive review of the diagnostic and therapeutic strategies for managing constipation in children, emphasising the vital role of community nurses. A meticulous clinical history and detailed physical examination form the cornerstone of diagnosis. Investigations are typically reserved for cases with atypical presentations, red flag symptoms, or when initial treatment strategies have failed. Treatment approaches are largely dependent on the severity of constipation, ranging from lifestyle and dietary modifications in mild cases to pharmacological interventions, including polyethylene glycol, lactulose, or Senna, for moderate to severe cases. Home management strategies also play a significant role in symptom control and recurrence prevention. The article underscores the role of community nurses in early detection, education, initiating management, and referral to specialist services. Considering the substantial psychological implications of constipation in children, a holistic approach addressing both physical and emotional aspects is advocated for successful management.

Management of cerebrospinal fluid pseudocysts in the laparoscopic age.

Abdominal CSF pseudocysts are an uncommon but challenging complication of ventriculoperitoneal shunts. Pseudocysts consist of a loculated intraperitoneal compartment that inadequately absorbs CSF and may be infected or sterile at diagnosis. The treatment goal is to clear infection if present, reduce inflammation, and reestablish long-term function in an absorptive (intraperitoneal) space. This aim of this paper was to study the efficacy of primary laparoscopic repositioning of the distal shunt catheter for treatment of sterile abdominal CSF pseudocysts. All patients treated for abdominal CSF pseudocysts at Dallas Children's Health from 1991 to 2021 were retrospectively reviewed. Patient history and pseudocyst characteristics were analyzed, with a primary outcome of pseudocyst recurrence at 1 year. Of 92 primary pseudocysts, 5 initial treatment strategies (groups) were used depending on culture status, clinical history, and surgeon preference: 1) shunt explant/external ventricular drain (EVD) placement (23/92), 2) distal tubing externalization (13/92), 3) laparoscopic repositioning (35/92), 4) open repositioning (4/92), and 5) other methods such as pseudocyst drainage or direct revision to another terminus (17/92). Seventy pseudocysts underwent shunt reimplantation in the peritoneal space. The 1-year peritoneal shunt survival for groups 1 and 2 combined was 90%, and 62% for group 3. In group 3, 1-year survival was better for those with normal systemic inflammatory markers (100%) than for those with high markers (47%) (p = 0.042). In a univariate Cox proportional hazards model, the risk of pseudocyst recurrence was increased if the most recent abdominal procedure was a nonshunt abdominal surgery (p = 0.012), and it approached statistical significance with male sex (p = 0.054) and elevated inflammatory markers (p = 0.056. Multivariate Cox analysis suggested increased recurrence risk with male sex (p = 0.05) and elevated inflammatory markers (p = 0.06), although the statistical significance threshold was not reached. The length of hospital stay was shorter for laparoscopic repositioning (6 days) than for explantation/EVD placement (21 days) (p < 0.0001). Ultimately, 62% of patients had a peritoneal terminus at the last follow-up, 33% (n = 30) had an extraperitoneal terminus (19 pleura, 8 right heart, and 3 gallbladder), and 5 patients were shunt free. Some sterile pseudocysts with normal systemic inflammatory markers can be effectively treated with laparoscopic repositioning, resulting in a significantly shorter hospitalization and modestly higher recurrence rate than shunt explantation.

Lymphoma-Related Quality of Life (QOL) Is Not Impacted By Initial Treatment Choice in Patients with Marginal Zone Lymphoma (MZL): Results from the Prospective Lymphoma Epidemiology of Outcomes (LEO) Cohort

Background: QOL can be affected by disease burden, side effects of treatment, and psychosocial effects of living with cancer. Although MZL is considered incurable, we previously found that patients diagnosed from 2002-2015 had a good QOL both at baseline (BL) and the first decade after diagnosis, regardless of treatment choice (Bommier et al., submitted). Here, we evaluate whether these findings can be extended to the 2015-2020 treatment era and a more diverse US cohort. Methods: Adults with newly diagnosed MZL from 8 academic centers were prospectively enrolled within 6 months of diagnosis from 2015-2020 in the LEO cohort (NCT02736357). Participants were actively followed for disease progression/relapse, retreatment and death. QOL was measured at BL, and at 1, 2, 3 and 5 years after diagnosis using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale (range 0-164), which consists of the FACT-General (FACT-G, range 0-104) plus a lymphoma-specific scale (range 0-60). Total FACT-G measures 4 QOL domains (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being (WB). We also used the Trial Outcome Index (TOI; range 0-112), which consists of FACT-G physical and functional WB plus the lymphoma-specific scale and is commonly used as an endpoint in treatment trials. All MZL patients with both BL and at least one follow-up QOL questionnaire were eligible for analysis. Patients were grouped by initial management: active surveillance (observation), local/antibiotic therapy (radiation, surgery, or anti- H. pylori therapy), or systemic therapy (chemotherapy, targeted agents, or antibody therapy). Change in QOL scores over time was analyzed using mixed models for repeated measurements, and initial treatment groups were compared. Results: Of 384 patients, 60% were female, 91% were White, 6.6% were Black/African American, and 13% were Hispanic (all races). The median age was 64 years (range 19-94). For initial management, 28% (N=106) were observed, 31% (N=118) received local/antibiotic therapy, and 42% (N=160) received systemic therapy. Across treatment groups, there were no significant differences by age, gender, race, or performance status, while there were differences by Hispanic ethnicity (p=0.006), Ann Arbor stage (p&amp;lt;0.001) and MALT-IPI score (p&amp;lt;0.001) (Table). At BL, patients receiving systemic therapy had lower physical WB (p=0.008), emotional WB (p=0.04), functional WB (p=0.03), FACT-G total score (p=0.008), lymphoma subscale (p&amp;lt;0.001), FACT-Lym (p=0.001) and TOI (p&amp;lt;0.001) compared to observation and local/antibiotic therapy (Table). While FACT-G total scores were largely stable through 5 years after diagnosis, social/family WB declined from BL for patients initially receiving either local/antibiotic therapy (mean at 1-year -1.4, p&amp;lt;0.05; 2-year -2.1, p&amp;lt;0.05; 3-year -1.6, p&amp;lt;0.05; 5-year-2.9, p&amp;lt;0.05) or systemic therapy (mean at 2-year -1.2 , p&amp;lt;0.05; 3-year -1.4, p&amp;lt;0.05; and 5-year -1.2, p&amp;lt;0.05), while this was stable for observed patients. In patients receiving initial systemic therapy, there was a transient improvement in the lymphoma-specific scale (mean +1.7, p&amp;lt;0.05) and TOI (mean +3.7, p&amp;lt;0.05). Otherwise, QOL remained stable over time and global QoL (FACT-G, FACT-Lym), TOI, Lymphoma-specific scale (Figure), and the other FACT-G subscales (physical, emotional, or functional WB) did not differ by initial treatment strategy. Conclusions: In the diverse LEO cohort from the recent treatment era, we confirm our prior findings for newly diagnosed MZL patients that QOL is globally stable over the first 5 years after diagnosis; emotional WB is not associated with initial treatment type, providing evidence that being initially observed does not negatively impact emotional health; and there is a decline in social/family WB (support from friends and family, family acceptance of illness, family communication, close to partner), which supports the need to consider interventions for patients to address these unmet needs. In addition, this study extends these findings to the lymphoma-specific scale, FACT-Lym, and TOI, which all showing largely stable trends in the 5 years after diagnosis and suggest that recent MZL treatment strategies, including systemic therapies, neither impair nor improve QOL.

Mortality Risk and the Clinical Outcome of Carbapenem-Resistant Enterobacteriaceae Carriers with Neutropenia: A Matched Case-Control Study

Patients with hematologic diseases are often accompanied by immunodeficiency, treatments as well as the disease itself can lead to granulocyte deficiency. Patients with granulocyte deficiency are under the high risk of infection. In recent years, the rate of Carbapenem-resistant Enterobacteriaceae (CRE) infection has gradually increased. Treatment options of CRE infection is limited, and effective anti-infection treatment is usually delayed, leading to the death of patients due to infection. CRE screening can provide clinical evidence for early detection of CRE by clinicians, thereby formulating antimicrobial treatment strategies. However, whether the initial empirical treatment covering CRE can improve the adverse outcomes of patients still lacks a definitive conclusion. We collected clinical data on patients with neutropenia who also undergoing CRE screening between January 2017 and December 2022. To further analyze the impact of CRE positivity on patient mortality risk and the clinical effectiveness of initial empirical treatment for CRE, we conducted two case-cohort studies with clinical baseline data matching. In total, we performed 3529 fecal CRE screenings from 664 patients. Out of these, 345 screenings from 135 patients tested positive for CRE. We identified 16 different strains, with the most common being Klebsiella pneumoniae (184/345), followed by Escherichia coli (76/345). To determine the influence of CRE positivity on patient mortality rates, we conducted a 1:2 case matching based on age, gender, diagnosis, and medical history of CRE-positive patients (Table 1). The results showed that in the overall analysis, CRE positivity, age over 60, and male gender were adverse factors influencing mortality. However, in the subgroup analysis of CRE-positive patients, no adverse factors affecting mortality were observed. To further assess the impact of CRE positivity on patient infection outcomes, we defined the initial antibiotic treatment strategies for a total of 4,872 infection events in screened patients. We divided them into the following groups: the empirical treatment group without CRE results (n=3,954), the empirical treatment group not covering CRE (n=122), and the CRE based empirical treatment group (n=796). The CRE based empirical treatment group had a higher success rate in initial empirical treatment compared to the group without covering CRE (65.5% vs. 59.0%). To further investigate the differences in initial empirical treatment success rates and 30-day mortality rates between patients in the CRE-based empirical treatment group and empirical treatment group without CRE covering, we performed 1:2 case matching for clinical baseline data on age, sex, diagnosis, past history, and disease status at infection according to the clinical characteristics of the CRE-based anti-infection treatment group. The results indicated that there were no significant differences in initial empirical treatment success rate and 30-day mortality rate between the CRE-based empirical treatment group and case-matched controls. In conclusion, diagnosing and treating patients with CRE infection presents significant challenges. Early screening for CRE and empirical treatment targeting CRE can increase the success rate of initial empirical treatment in CRE-positive patients.

Impact of Frontline Treatment Strategy on Quality of Life in the First Decade after a Diagnosis of Marginal Zone Lymphoma

Background: Marginal Zone Lymphoma (MZL) is considered indolent but incurable, with a variety of initial treatment strategies including observation. Quality of life (QOL) can be affected by disease burden, side effects of treatment, and psychosocial effects of living with an incurable cancer. However, little is known about long-term QOL in patients with MZL. We investigated QOL at baseline (BL), and up to nine years after a diagnosis of MZL. Methods: Newly diagnosed MZL patients aged 18 years and older were prospectively enrolled within 9 months of diagnosis in the Iowa/Mayo Clinic Molecular Epidemiology Resource from 9/2002 - 6/2015. Pathology was reviewed by a hematopathologist. All MZL participants with both BL and at least one follow-up (FU) QOL questionnaire were eligible for this analysis. QOL was measured at BL and years 1-, 2-, 3-, 6- and 9-year FU with the Functional Assessment of Cancer Therapy-General (FACT-G) scale (range 0-108), which measures 4 QOL domains (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being (WB). Clinical data were abstracted according to a standard protocol and patients were systematically followed for events (progression, re-treatment, and death). Patients were grouped into initial management with active surveillance (observation), local/antibiotic therapy (including radiation, surgery, and anti- H. pylori therapy), or systemic therapy (including chemotherapy, targeted agents, or antibody therapy). Change in QOL scores over time was analyzed using mixed models for repeated measurements, and comparisons were made according to initial treatment group. Results: Of 324 participants in the analysis, 59% were female, 98% were White and the median age was 63 years. For initial management, 36% (N=118) were observed, 30% (N=96) received local/antibiotic therapy and 34% (N=110) received systemic therapy. Across the initial treatment groups, there were no statistically significant differences by age, gender, or performance status, while there were differences for Ann Arbor Stage IV (observation 50%, local/antibiotic 27%, systemic 67%, p&amp;lt;0.001) and MALT-IPI score 2+ (observation 23%, local/antibiotic 18%, systemic 28%, p&amp;lt;0.001). At BL, mean FACT-G total score was 85.7 (SD 13.1), and physical, social/family, emotional, and functional WB scores were 20.3 (SD 4.2), 24.4 (SD 3.9), 18.9 (SD 3.5), 22.1 (SD 5.3); these scores were similar across initial treatment groups (all p&amp;gt;0.05). FACT-G total score was largely stable over time by treatment group (Panel 1). However, it declined at years 6 (mean -4.0, p&amp;lt;0.05) and 9 (mean -3.7, p&amp;lt;0.05) in the observation group (Panel 2), driven by a decline in functional WB, although this change was not significantly different from the other treatment groups. Further, in comparison with other treatment groups, local therapy was associated with a short-term 1-year improvement of FACT-G total score (mean +2.8, p=0.04), driven by improvements in both functional and emotional WB. For the subscales, we identified two major trends irrespective of treatment group: an overall improvement from BL of emotional WB at years 1 (mean +0.6, p&amp;lt;0.05), 2 (mean +0.7, p&amp;lt;0.05), 3 (+1.3, p&amp;lt;0.05), 6 (+1, p&amp;lt;0.05), and 9 (+1.3, p&amp;lt;0.05) and an overall decline of social/family WB at years 1 (mean -1.1, p&amp;lt;0.05), 2 (mean -1.7, p&amp;lt;0.05), 3 (-2.1, p&amp;lt;0.05), 6 (-2.7, p&amp;lt;0.05), and 9 (-2.2, p&amp;lt;0.05). There was no notable change from BL for physical or functional WB. Conclusions: This analysis is the first to provide prospective real-world QOL data on a longitudinal cohort of MZL patients with long follow-up. At BL, initial treatment was associated with stage and MALT-IPI score, but not QOL. Except for the transient 1-year QOL improvement in patients under local/antibiotic therapy, initial treatment groups had no impact on QOL over time. Irrespective of treatment group, emotional WB showed improvement over time, suggesting psychosocial adaptation by the patient, as it was found in aggressive lymphomas (Thompson et al., 2018). Further, emotional WB over time did not vary across treatment groups, suggesting that being initially observed did not lead to more emotional stress than being actively treated. Finally, decline in social/family WB (support from friends, family, family acceptance of illness, family communication, close to partner) suggests a need to consider interventions to patients and families to address these needs.