Individual Patient Research Articles

Dermatopathological diagnosis of porphyria cutanea tarda - Two case reports

Porphyria cutanea tarda and its relationship with HIV and Hepatitis C are highlighted in the case reports. Porphyria cutanea tarda arises from a deficiency in the uroporphyrinogen decarboxylase enzyme, where there is an anomaly in the buildup of specific porphyrins, notably in blood vessels, liver, and skin. It can be either hereditary or acquired. In this context, we have discussed two individual patients with HIV and Hepatitis C who were diagnosed with porphyria cutanea tarda through skin biopsy.

Prognostic Value of Complete Resection of the High-Frequency Oscillation Area in Intracranial EEG: A Systematic Review and Meta-Analysis.

High-frequency oscillations (HFOs; ripples 80-250 Hz; fast ripples [FRs] 250-500 Hz) recorded with intracranial electrodes generated excitement and debate about their potential to localize epileptogenic foci. We performed a systematic review and meta-analysis on the prognostic value of complete resection of the HFOs-area (crHFOs-area) for epilepsy surgical outcome in intracranial EEG (iEEG) accessing multiple subgroups. We searched PubMed, Embase, and Web of Science for original research from inception to October 27, 2022. We defined favorable surgical outcome (FSO) as Engel class I, International League Against Epilepsy class 1, or seizure-free status. The prognostic value of crHFOs-area for FSO was assessed by (1) the pooled FSO proportion after crHFOs-area; (2) FSO for crHFOs-area vs without crHFOs-area; and (3) the predictive performance. We defined high combined prognostic value as FSO proportion >80% + FSO crHFOs-area >without crHFOs-area + area under the curve (AUC) >0.75 and examined this for the clinical subgroups (study design, age, diagnostic type, HFOs-identification method, HFOs-rate thresholding, and iEEG state). Temporal lobe epilepsy (TLE) was compared with extra-TLE through dichotomous variable analysis. Individual patient analysis was performed for sex, affected hemisphere, MRI findings, surgery location, and pathology. Of 1,387 studies screened, 31 studies (703 patients) met our eligibility criteria. Twenty-seven studies (602 patients) analyzed FRs and 20 studies (424 patients) ripples. Pooled FSO proportion after crHFOs-area was 81% (95% CI 76%-86%) for FRs and 82% (73%-89%) for ripples. Patients with crHFOs-area achieved more often FSO than those without crHFOs-area (FRs odds ratio [OR] 6.38, 4.03-10.09, p < 0.001; ripples 4.04, 2.32-7.04, p < 0.001). The pooled AUCs were 0.81 (0.77-0.84) for FRs and 0.76 (0.72-0.79) for ripples. Combined prognostic value was high in 10 subgroups: retrospective, children, long-term iEEG, threshold (FRs and ripples) and automated detection and interictal (FRs). FSO after complete resection of FRs-area (crFRs-area) was achieved less often in people with TLE than extra-TLE (OR 0.37, 0.15-0.89, p = 0.006). Individual patient analyses showed that crFRs-area was seen more in patients with FSO with than without MRI lesions (p = 0.02 after multiple correction). Complete resection of the brain area with HFOs is associated with good postsurgical outcome. Its prognostic value holds, especially for FRs, for various subgroups. The use of HFOs for extra-TLE patients requires further evidence.

Antithrombotic Treatment for Cervical Artery Dissection: A Systematic Review and Individual Patient Data Meta-Analysis.

Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients. To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection. PubMed.gov, Cochrane database, Embase, and ClinicalTrials.gov were searched from inception to August 1, 2023. Randomized clinical trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets vs anticoagulation) in patients with cervical artery dissection were included in the meta-analysis. The primary end point was required to include a composite of (1) any stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. Two independent investigators performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and inconsistencies were resolved by a principal investigator. The primary outcome was a composite of (1) ischemic stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative association with the outcome were performed. Logistic regression was performed using the maximum penalized likelihood method including interaction in the subgroup analyses. Two randomized clinical trials, Cervical Artery Dissection in Stroke Study and Cervical Artery Dissection in Stroke Study and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection, were identified, of which all participants were eligible. A total of 444 patients were included in the intention-to-treat population and 370 patients were included in the per-protocol population. Baseline characteristics were balanced. There were fewer primary end points in those randomized to anticoagulation vs antiplatelet therapy (3 of 218 [1.4%] vs 10 of 226 [4.4%]; odds ratio [OR], 0.33 [95% CI, 0.08-1.05]; P = .06), but the finding was not statistically significant. In comparison with aspirin, anticoagulation was associated with fewer strokes (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = .01) and more bleeding events (2 vs 0). This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.

End of Life Outcomes Following Comfort Care Orders: A Single Center Experience.

Background: Few studies have explored the outcomes of patients placed on comfort care with respect to hospice disposition. The objective of this study was to perform a retrospective analysis of patients who transitioned to comfort care. Methods: We conducted a retrospective study of patients placed on the comfort care order set between July 1st, 2021, until June 30th, 2022. Each individual patient chart was then analyzed to collect multiple clinical variables. IRB approval was obtained as per institutional guidelines. Results: 541 patients were included in the analysis. An average of 1.5 patients were placed on comfort care a day. 424 (78.37%) patients died while in the hospital. The median time on comfort care was 1 day. For subspecialty and hospital medicine patients the median time was 2 days. 40% of non-ICU patients were discharged with hospice services. 60% of patients were in the intensive care unit (ICU) and spent a median of 2.33 hours on comfort care. 19% of these patients were on comfort care for over 12 hours. 94% of the patients placed on comfort care in the ICU died in the hospital as compared to 53% of subspecialty and 59% of hospital medicine patients. Conclusions: The majority of patients placed on comfort care died during their hospitalization demonstrating a real need for comprehensive end of life care and immediate hospice services. For those discharged with hospice services, they spent an excessive amount of time in the hospital waiting for services to be arranged.

Population pharmacokinetics and pharmacodynamics of nasal glucagon in patients with type 1 or 2 diabetes.

The objective was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of glucagon after injectable or nasal administration and confirm the appropriate therapeutic dose of nasal glucagon (NG) for adult patients. Six clinical studies with PK and five clinical studies with PD (glucose) data were included in the analysis. Doses ranging from 0.5 to 6 mg NG, and 0.5 to 1 mg injectable glucagon were studied. A total of 6284 glucagon and 7130 glucose concentrations from 265 individuals (patients and healthy participants) were available. Population PK/PD modeling was performed using NONMEM. Glucagon exposure and glucose response were simulated for patients administered various doses of NG to confirm the optimal dose. Glucagon PK was well-described with a single compartment disposition with first-order absorption and elimination processes. Bioavailability of NG relative to injectable glucagon was 16%. Exposure-response modeling revealed that lower baseline glucose was associated with higher maximum drug effect. The carry-over effect from prior insulin administration was incorporated into the model through a time-dependent increase in elimination rate of glucose. Simulations showed that more than 99% of hypoglycemic adult patients would experience treatment success, defined as an increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from nadir within 30 min after administration of NG 3 mg. The population PK/PD model adequately described the PK and PD profiles of glucagon after nasal administration. Modeling and simulations confirmed that NG 3 mg is the most appropriate dose for rescue treatment during hypoglycemia emergencies.

Pooled Population Pharmacokinetic Analysis and Dose Recommendations for Ciprofloxacin in Intensive Care Unit Patients with Obesity.

Recent studies have explored the influence of obesity and critical illness on ciprofloxacin pharmacokinetics. However, variation across the subpopulation of individuals with obesity admitted to the intensive care unit (ICU) with varying renal function remains unexamined. This study aims to characterize ciprofloxacin pharmacokinetics in ICU patients with obesity and provide dose recommendations for this special population. Individual patient data of 34 ICU patients with obesity (BMI >30 kg/m2) from four studies evaluating ciprofloxacin pharmacokinetics in ICU patients were pooled and combined with data from a study involving 10 individuals with obesity undergoing bariatric surgery. All samples were collected after intravenous administration. Non-linear mixed effects modeling and simulation were used to develop a population pharmacokinetic model and describe ciprofloxacin exposure in plasma. Model-based dose evaluations were performed using a pharmacokinetic/pharmacodynamic target of AUC/MIC >125. The data from patients with BMI ranging from 30.2 to 58.1 were best described by a two-compartment model with first-order elimination and a proportional error model. The inclusion of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) as a covariate on clearance reduced inter-individual variability from 57.3% to 38.5% (P <.001). Neither body weight nor ICU admission significantly influenced clearance or volume of distribution. Renal function is a viable predictor for ciprofloxacin clearance in ICU patients with obesity, while critical illness and body weight do not significantly alter clearance. As such, body weight and critical illness do not need to be accounted for when dosing ciprofloxacin in ICU patients with obesity. Individuals with CKD-EPI >60 mL/min/1.73 m2 may require higher dosages for the treatment of pathogens with minimal inhibitory concentration ≥0.25 mg/L.

Algorithm-based modular psychotherapy vs. cognitive-behavioral therapy for patients with depression, psychiatric comorbidities and early trauma: a proof-of-concept randomized controlled trial.

Effect sizes of psychotherapies currently stagnate at a low-to-moderate level. Personalizing psychotherapy by algorithm-based modular procedures promisesimproved outcomes, greater flexibility, and a better fit between research and practice. However, evidence for the feasibility and efficacy of modular-based psychotherapy, using a personalized treatment algorithm, is lacking. This proof-of-concept randomized controlled trial was conducted in 70 adult outpatients with a primary DSM-5 diagnosis of major depressive disorder, a score higher than 18 on the 24-item Hamilton Rating Scale for Depression (HRSD-24), at least one comorbid psychiatric diagnosis according to the Structured Clinical Interview for DSM-5 (SCID-5), a history of at least "moderate to severe" childhood maltreatment on at least one domain of the Childhood Trauma Questionnaire (CTQ), and exceeding the cut-off value on at least one of three measures of early trauma-related transdiagnostic mechanisms: the Rejection Sensitivity Questionnaire (RSQ), the Interpersonal Reactivity Index (IRI), and the Difficulties in Emotion Regulation Scale-16 (DERS-16). Patients were randomized to 20 sessions of either standard cognitive-behavioral therapy alone (CBT) or CBT plus transdiagnostic modules according to a mechanism-based treatment algorithm (MoBa), over 16 weeks. We aimed to assess the feasibility of MoBa, and to compare MoBa vs. CBT with respect to participants' and therapists' overall satisfaction and ratings of therapeutic alliance (using the Working Alliance Inventory - Short Revised, WAI-SR), efficacy, impact on early trauma-related transdiagnostic mechanisms, and safety. The primary outcome for efficacy was the HRSD-24 score at post-treatment. Secondary outcomes included, among others, the rate of response (defined as a reduction of the HRSD-24 score by at least 50% from baseline and a score <16 at post-treatment), the rate of remission (defined as a HRSD-24 score ≤8 at post-treatment), and improvements in early trauma-related mechanisms of social threat response, hyperarousal, and social processes/empathy. We found no difficulties in the selection of the transdiagnostic modules in the individual patients, applying the above-mentioned cut-offs, and in the implementation of MoBa. Both participants and therapists reported higher overall satisfaction and had higher WAI-SR ratings with MoBa than CBT. Both approaches led to major reductions of depressive symptoms at post-treatment, with a non-significant superiority of MoBa over CBT. Patients randomized to MoBa were nearly three times as likely to experience remission at the end of therapy (29.4% vs. 11.4%; odds ratio, OR = 3.2, 95% CI: 0.9-11.6). Among mechanism-based outcomes, MoBa patients showed a significantly higher post-treatment effect on social processes/empathy (p<0.05) compared to CBT patients, who presented an exacerbation on this domain at post-treatment. Substantially less adverse events were reported for MoBa compared to CBT. These results suggest the feasibility and acceptability of an algorithm-based modular psychotherapy complementing CBT in depressed patients with psychiatric comorbidities and early trauma. While initial evidence of efficacy was observed, potential clinical advantages and interindividual heterogeneity in treatment outcomes will have to be investigated in fully powered confirmation trials.

Correlation of microscopic tumor extension with tumor microenvironment in esophageal cancer patients.

In the era of image-guided adaptive radiotherapy, definition of the clinical target volume (CTV) is achallenge in various solid tumors, including esophageal cancer (EC). Many tumor microenvironmental factors, e.g., tumor cell proliferation or cancer stem cells, are hypothesized to be involved in microscopic tumor extension (MTE). Therefore, this study assessed the expression of FAK, ILK, CD44, HIF-1α, and Ki67 in EC patients after neoadjuvant radiochemotherapy followed by tumor resection (NRCHT+R) and correlated these markers with the MTE. Formalin-fixed paraffin-embedded tumor resection specimens of ten EC patients were analyzed using multiplex immunofluorescence staining. Since gold fiducial markers had been endoscopically implanted at the proximal and distal tumor borders prior to NRCHT+R, correlation of the markers with the MTE was feasible. In tumor resection specimens of EC patients, the overall percentages of FAK+, CD44+, HIF-1α+, and Ki67+ cells were higher in tumor nests than in the tumor stroma, with the outcome for Ki67+ cells reaching statistical significance (p < 0.001). Conversely, expression of ILK+ cells was higher in tumor stroma, albeit not statistically significantly. In three patients, MTE beyond the fiducial markers was found, reaching up to 31 mm. Our findings indicate that the overall expression of FAK, HIF-1α, Ki67, and CD44 was higher in tumor nests, whereas that of ILK was higher in tumor stroma. Differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not found. Thus, there is insufficient evidence that the TME influences the required CTV margin on an individual patient basis. BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886 .

Noninvasive Atherosclerotic Phenotyping: The Next Frontier into Understanding the Pathobiology of Coronary Artery Disease.

Despite recent advances, coronary artery disease remains one of the leading causes of mortality worldwide. Noninvasive imaging allows atherosclerotic phenotyping by measurement of plaque burden, morphology, activity and inflammation, which has the potential to refine patient risk stratification and guide personalized therapy. This review describes the current and emerging roles of advanced noninvasive cardiovascular imaging methods for the assessment of coronary artery disease. Cardiac computed tomography enables comprehensive, noninvasive imaging of the coronary vasculature, and is used to assess luminal stenoses, coronary calcifications, and distinct adverse plaque characteristics, helping to identify patients prone to future events. Novel software tools, implementing artificial intelligence solutions, can automatically quantify and characterize atherosclerotic plaque from standard computed tomography datasets. These quantitative imaging biomarkers have been shown to improve patient risk stratification beyond clinical risk scores and current clinical interpretation of cardiac computed tomography. In addition, noninvasive molecular imaging in higher risk patients can be used to assess plaque activity and plaque thrombosis. Noninvasive imaging allows unique insight into the burden, morphology and activity of atherosclerotic coronary plaques. Such phenotyping of atherosclerosis can potentially improve individual patient risk prediction, and in the near future has the potential for clinical implementation.

Re-resection Rates and Disease Recurrence in Crohn's Disease - A Population-Based Study Using Individual-Level Patient Data.

Despite advances in the medical treatment of Crohn's disease (CD), many patients will still need bowel resections and face the subsequent risk of recurrence and re-resection. We describe contemporary re-resection rates and identify disease-modifying factors and risk factors for re-resection. We conducted a retrospective, population-based, individual patient data cohort study covering 47.4% of the Danish population, including all CD patients who underwent a primary resection between 2010 and 2020. Among 631 primary resected patients, 24.5% underwent a second resection, and 5.3% a third. Re-resection rates after one, five, and 10 years were 12.6%, 22.4%, and 32.2%, respectively. Reasons for additional resections were mainly disease activity (57%) and stoma reversal (40%). Disease activity-driven re-resection rates after one, five, and 10 years were 3.6%, 10.1%, and 14.1%, respectively. Most stoma reversals occurred within one year (80%). The median time to recurrence was 11.0 months. Biologics started within one year of the first resection revealed protective effect against re-resection for stenotic and penetrating phenotypes. Prophylactic biologic therapy at primary ileocecal resection reduced disease recurrence and re-resection risk (HR 0.58, 95% CI (0.34-0.99), p=0.047). Risk factors for re-resection were location of resected bowel segments at the primary resection, disease location, disease behavior, smoking, and perianal disease. Re-resection rates, categorized by disease activity, are lower than those reported in other studies and are closely associated with disease phenotype and localization. Biological therapy may be disease-modifying for certain subgroups when initiated within one year of resection.

Current advances and gaps in knowledge on personalizing masks for non-invasive respiratory support: a scoping review.

Non-invasive respiratory support delivered through a face mask has become a cornerstone treatment for adults and children with acute or chronic respiratory failure. However, an imperfect mask fit using commercially available interfaces is frequently encountered, which may result in patient discomfort and treatment inefficiency or failure. To overcome this challenge, over the last decade increasing attention has been given to the development of personalized face masks, which are custom made to address the specific facial dimensions of an individual patient. With this scoping review we aim to provide a comprehensive overview of the current advances and gaps in knowledge regarding the personalization of ventilation masks. We performed a systematic search of the literature, and identified and summarized a total of 23 studies. Most studies included were involved in the development of nasal masks. Studies targeting adult respiratory care mainly focused on chronic (home) ventilation and included some clinical testing in a relevant subject population. In contrast, pediatric studies focused mostly on respiratory support in the acute setting, while testing was limited to bench or case studies only. Most studies were positive regarding the performance (i.e. comfort, level of air leak and mask pressure applied to the skin) of personalized masks in bench testing or in human, healthy or patient, subjects. Advances in the field of 3D scanning and soft material printing were identified, but important gaps in knowledge remain. In particular, more insight into cushion materials, headgear design, clinical feasibility and cost-effectiveness is needed, before definite recommendations can be made regarding implementation of large scale clinical programs that personalize non-invasive respiratory support masks for adults and children.

To the point – the basics of bovine acupuncture

Acupuncture is recognized these days by many institutions as an effective complementary therapeutic technique both in human and veterinary medicine. Acupuncture is only one of several treatment modalities within Traditional Chinese Vet­erinary Medicine (TCVM), but it is the one that shows the fast­est effects. Although most acupuncture treatments require a careful selection of appropriate acupoints for each individual patient, there are several acupoints with such a specific and potent effect on the body that they can be used by themselves, in conjunction with Western therapy to expedite healing. This is the case with GV14 for fever or immunostimulation, GV26 for resuscitation, CV9 for edema, Shan-gen for appetite stimulation, An-shen for sedation, and BL20 and BL21 as a pair for digestive disorders. Their location and function are explained. The in­tention of this clinical skills presentation is to provide Western practitioners with additional tools that can be used along with the customary Western therapeutic approach to help our pa­tients heal faster.

Interstitial cystitis—an imbalance of risk and protective factors?

Interstitial cystitis (IC) presents as a chronic pain condition with variable combinations of symptoms depending on the species and individual patient. It is diagnosed by the presence of lower urinary tract signs and symptoms in combination with a variety of comorbid health problems, a history of life adversities, and the absence of other conditions that could cause the lower urinary tract signs. IC occurs naturally in humans and cats as a dimensional condition, with patients presenting with mild, moderate, and severe symptoms. Most patients appear to recover without specific treatment. A number of rodent models of IC have been used to study its causes and treatments. Unfortunately, current therapies generally fail to ameliorate IC symptoms long-term. The recent classification of IC as a chronic primary pain disorder calls for a rethinking of current clinical and research approaches to it. Beginning when a patient encounters a clinician, precipitating, perpetuating, and palliating risk factors can be addressed until a cause or reliably effective therapy is identified, and identifying predisposing and preventive factors can inform epidemiological studies and health promotion interventions. Predisposing, precipitating, and perpetuating risk factors, including environmental, psychological, and biological, increase the activity of the central threat response system (CTRS), which plays a clinically important role in IC symptoms. Studies in cats and rodent models have revealed that environmental enrichment (EE), in the absence of bladder-directed therapies, leads to amelioration of IC symptoms, implying a central role for the CTRS in symptom precipitation and perpetuation. Conceptually moving the source of IC pain to the brain as a motivational state rather than one resulting from peripheral nociceptive input offers both clinicians and researchers novel opportunities to improve care for patients with IC and for researchers to use more ecologically valid rodent models. It may even be that IC results from an excess of risk to protective factors, making this imbalance a targetable cause rather than a consequence of IC.

Criterion (Concurrent) Validity and Clinical Utility of the Tongueometer Device.

Tongue manometry (i.e., tongue pressure measurement) is a commonly used assessment for patients with suspected oral-motor involvement in swallowing disorders. Availability of lingual manometry has changed in recent years, with the introduction of the Tongueometer device being a more affordable tongue manometry system. The purpose of this study was to test concurrent (criterion) validity of the Tongueometer compared to the current standard reference device, the Iowa Oral Performance Instrument (IOPI). Adults without dysphagia were recruited for participation in this study. Standard lingual measurements (swallowing-related pressures, maximum isometric pressure [MIP], and maximum isometric endurance) were recorded, with the bulb anteriorly placed, with both devices, in a randomized order. The Bland-Altman method was used to determine concurrent (criterion) validity of these measurements compared to the clinical standard IOPI device. A recently available suggested corrective value by Curtis et al. (2023) was also applied, with comparisons made between devices both with and without the Curtis correction. The final sample included 70 adult participants aged 20-89 years (Mage = 52.3 years). Measures with the Tongueometer device were significantly lower when compared with the same measures taken using the IOPI (p < .01) for all measures including MIP, endurance, and swallow pressures. The correction suggested by Curtis and colleagues did not ameliorate these differences. The Tongueometer lingual measurements were consistently lower compared to the IOPI. Clinical use of values taken with the Tongueometer device should be compared to normative data published for each specific device. Available features of each device (e.g., display, bulb texture, technology/application) should be considered when selecting which device to use with an individual patient.

Feasibility of a Telemedicine-Based Principal Illness Navigation (PIN) Service for Complex Populations Following Hospital Discharge After Acute Stroke

Background Principal Illness Navigation (PIN) services may play an important role in helping patients through important transitions in care following acute hospitalization. We evaluated a novel PIN telemedicine approach to understand the feasibility of providing these services to diverse patient cohorts. Methods A single-arm, retrospective observational study of Kandu Health’s post-acute PIN service was conducted in patients experiencing ischemic or hemorrhagic stroke in California and New Jersey. The technology-enabled program offered remote healthcare support led by occupational therapists and licensed clinical social workers that was tailored to individual patient needs to facilitate transition to community settings post-discharge. Barriers to recovery were addressed through patient education, one-on-one guidance, and specialized referrals. Patient outcomes were assessed through in-app assessments and clinician-assessed modified Rankin Scores conducted via video consultation. Readmissions were monitored through both patient reporting and admission/discharge/transfer feeds from health information exchanges. Results A total of 111 patients were enrolled between June 22, 2022 and January 11, 2024. Patients were onboarded an average of 29 ± 40 days (median 18, IQR 8-32) after acute care hospital discharge and spent an average of 81 ± 21 days (median 90, IQR 75-90) in the program. During that time, the average enrollee spent 333 ± 156 minutes (median 350, IQR 205-435) of 1:1 time interacting with their dedicated navigator, and navigators spent an additional 113 ± 87 minutes (median 95, IQR 61-140) per patient on care coordination and curriculum curation. Patients with 5 or more social determinants of health (SDOH) needs required over 50% more navigator time than those without any SDOH needs. Within 6 weeks of hospital discharge, 8.5% experienced an inpatient hospital all-cause readmission that was not associated with race, ethnicity, or SDOH. Conclusions High rates of enrollment and extensive patient engagement in both navigator-facilitated and self-directed program elements can be achieved using the Kandu program. Our findings indicate that telemedicine facilitated, app-supported PIN is feasible to deliver following acute stroke discharge across diverse ages, races, ethnicities, functional status (mRS), and social needs.

PCI Vs. CABG: Battle For Better Outcomes in Pakistani Triple Vessel Disease Patients

Background: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, with Triple Vessel Disease (TVD) representing a severe form that poses significant treatment challenges. In Pakistan, the burden of CVDs is high, exacerbated by genetic and lifestyle factors. Objective: To evaluate and compare the clinical outcomes of Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Grafting (CABG) in patients diagnosed with Triple Vessel Disease (TVD) in a Pakistani cohort. Methods: This prospective cohort study was conducted at Lady Reading Hospital, Peshawar, from January 1, 2020, to December 31, 2021. A total of 400 patients diagnosed with TVD based on angiographic findings were enrolled. Inclusion criteria included age above 18 years, clinical diagnosis of stable angina or non-ST elevation myocardial infarction, and consent to participate. Exclusion criteria were previous revascularization procedures, concomitant valvular or congenital heart disease, and life expectancy less than a year due to non-cardiac conditions. Patients were assigned to either PCI or CABG based on clinical decisions by their managing cardiologists, considering anatomical considerations, comorbid conditions, and patient preferences. Baseline demographic and clinical data, including age, gender, smoking status, presence of diabetes, hypertension, and previous myocardial infarction (MI), were collected through patient interviews and medical record reviews. Clinical outcomes were monitored for 12 months post-procedure. Primary outcome measures included mortality, myocardial infarction, repeat revascularization, and stroke within 12 months. Secondary outcomes were hospital readmission rates and quality of life scores, measured using a standardized 10-point scale. Statistical analyses were performed using SPSS version 25, with continuous variables expressed as means and standard deviations and categorical variables as percentages. The chi-square test or Fisher’s exact test was used for categorical outcomes, and the student’s t-test or Mann-Whitney U test for continuous outcomes, with a p-value of less than 0.05 considered statistically significant. Results: The mean age of the participants was 62.5 ± 7.8 years, with 62 ± 8 years in the PCI group and 63 ± 7 years in the CABG group (p=0.45). Gender distribution was similar, with 255 males and 145 females overall (p=0.55). Smoking status, diabetes, hypertension, and previous MI were comparably distributed between the groups. Mortality was 5% in the PCI group and 3% in the CABG group (p=0.31). Myocardial infarction occurred in 10% of PCI patients compared to 5% of CABG patients (p=0.05). Repeat revascularization was required in 15% of the PCI group versus 7% of the CABG group (p=0.01). Stroke incidence was 2% in the PCI group and 1% in the CABG group (p=0.45). Hospital readmission rates were 20% for PCI and 15% for CABG (p=0.10). Quality of life scores were higher in the CABG group (8.0 ± 1.1) compared to the PCI group (7.5 ± 1.2) (p=0.04). Conclusion: CABG may offer superior outcomes compared to PCI in managing TVD among Pakistani patients, particularly in reducing myocardial infarction rates and repeat revascularization. Despite the invasive nature of CABG, its long-term benefits suggest it should be considered preferentially for patients with complex coronary anatomies. Clinical decisions should, however, be tailored to individual patient factors and preferences.

Population kinetic/pharmacodynamic modelling of the haemodynamic effects of cafedrine/theodrenaline (Akrinor) under general anaesthesia.

The 20:1 combination of cafedrine and theodrenaline (C/T) is widely used in Germany for the treatment of arterial hypotension. Since there is little knowledge about the impact of covariates on the effect, the aim was to develop a kinetic/pharmacodynamic covariate model describing mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) for 30 min after the administration of C/T. Data of patients receiving C/T from the HYPOTENS study (NCT02893241, DRKS00010740) were analysed using nonlinear mixed-effects modelling techniques. Overall, 16 579 measurements from 315 patients were analysed. The combination of two kinetic compartments and a delayed effect model, coupled with distinct Emax models for HR, SBP and DBP, described the data best. The model included age, sex, body mass index (BMI), antihypertensive medication, American Society of Anaesthesiologists (ASA) physical status classification grade, baseline SBP at the time of hypotension and pre-surgery HR as covariates (all P < .001). A higher baseline SBP led to a lower absolute increase in MAP. Patients with higher age, higher BMI and lower ASA grade showed smaller increases in MAP. The initial increase was similar for male and female patients. The long-term effect was higher in women. Concomitant antihypertensive medication caused a delayed effect and a lower maximum MAP. The HR increased only slightly (median increase 2.6bpm, P < .001). Seven covariates with an impact on the effect of C/T could be identified. The results will enable physicians to optimize the dose with respect to individual patients.

Open, endovascular, or hybrid repair of aortic arch disease: narrative review of diverse strategies with diverse options.

The management of aortic arch disease is complex. Open surgical management continues to evolve, and the introduction of endovascular repair is revolutionizing aortic arch surgery. Although these innovative techniques have generated the opportunity for better outcomes in select patients, they have also introduced confusion and uncertainty regarding best practices. In New York, we have developed a collaborative group named the New York Aortic Consortium (NYAC) as a means of crosslinking knowledge and working together to better understand and treat aortic disease. In our meeting in May 2023, regional aortic experts and invited international experts discussed the contemporary management of aortic arch disease, differences in interpretation of the available literature, as well as the integration of endovascular technology into disease management. In this review article, we summarize the current state of aortic arch surgery. Approaches to aortic arch repair have evolved substantially, whether it be methods to reduce cerebral ischaemia, improve hemostasis, simplify future operations, or expand options for high-risk patients with endovascular approaches. However, the transverse aortic arch remains challenging to repair. Amongst our collaborative group of cardiac/aortic surgeons, we discovered a wide disparity in our practice patterns and management strategies of patients with aortic arch disease. It is important to build unique institutional expertise in the context of complex and evolving management of aortic arch disease with open surgery, endovascular repair, and hybrid approaches, tailored to the risk profiles and anatomical specifics of individual patients.

Combining rivaroxaban with aspirin for peripheral artery disease: an in-depth systematic review and meta-analysis

Abstract Funding Acknowledgements None. Introduction Peripheral artery disease (PAD) poses a significant challenge in the realm of cardiovascular medicine, necessitating a multifaceted approach to mitigate its impact and enhance patient outcomes. One treatment approach involves the combined use of rivaroxaban, a direct oral anticoagulant, and aspirin, a commonly used antiplatelet agent in decreasing possible complications that can develop in patients with PAD. Methods An extensive search of randomized controlled trials (RCTs) comparing the efficacy of rivaroxaban in combination with aspirin versus aspirin monotherapy among individuals diagnosed with peripheral artery disease. The assessment of this treatment approach involved evaluating the following primary outcomes: a decrease in major adverse cardiovascular events (MACE) and the need for major amputation. Safety profile was also evaluated by examining the rate of major bleeding, utilizing the scoring tool from International Society of Thrombosis and Hemostasis (ISTH). The analyses were performed using a random effects analysis approach via Review Manager V5.4. Results This meta-analysis encompassed three studies involving a total of 9,352 participants. There was reduction of MACE in rivaroxaban with aspirin therapy (RR 0.83 [95% CI: 0.71-0.97] I2 = 29%, p = 0.02] but there was no significant difference in terms of major amputation rates (RR 0.96 [95% CI: 0.80-1.14] I2 = 0%, p = 0.62). However, there was increased risk of bleeding in rivaroxaban with aspirin therapy (RR 1.46 [95% CI: 1.17-1.82] I2=0, p = 0.0009) compared to aspirin alone. Conclusion Rivaroxaban combined with aspirin therapy demonstrated a 17% reduction in MACE compared with aspirin monotherapy but didn’t reduce major amputation rates. Also, doing this strategy poses a higher risk of bleeding. Therefore, a balance between the risks and benefits of this combined therapy necessitates a thorough assessment of individual patient profiles, considering factors such as overall cardiovascular risk, comorbidities, and bleeding tendencies. Further research and long-term studies are needed to establish comprehensive guidelines for the appropriate utilization of this combination therapy in various patient populations.

Comprehensive molecular analyses of cuproptosis-related genes with regard to prognosis, immune landscape, and response to immune checkpoint blockers in lung adenocarcinoma

BackgroundRecent studies have emphasized the importance of the biological processes of different forms of cell death in tumor heterogeneity and anti-tumor immunity. Nonetheless, the relationship between cuproptosis and lung adenocarcinoma (LUAD) remains largely unexplored.MethodsData for 793 LUAD samples and 59 normal lung tissues obtained from TCGA-LUAD cohort GEO datasets were used in this study. A total of 165 LUAD tissue samples and paired normal lung tissue samples obtained from our hospital were used to verify the prognostic value of dihydrolipoamide S-acetyltransferase (DLAT) and dihydrolipoamide branched chain transacylase E2 (DBT) for LUAD. The cuproptosis-related molecular patterns of LUAD were identified using consensus molecular clustering. Recursive feature elimination with random forest and a tenfold cross-validation method was applied to construct the cuproptosis score (CPS) for LUAD.ResultsBioinformatic and immunohistochemistry (IHC) analyses revealed that 13 core genes of cuproptosis were all significantly elevated in LUAD tissues, among which DBT and DLAT were associated with poor prognosis (DLAT, HR = 6.103; DBT, HR = 4.985). Based on the expression pattern of the 13 genes, two distinct cuproptosis-related patterns have been observed in LUAD: cluster 2 which has a relatively higher level of cuproptosis was characterized by immunological ignorance; conversely, cluster 1 which has a relatively lower level of cuproptosis is characterized by TILs infiltration and anti-tumor response. Finally, a scoring scheme termed the CPS was established to quantify the cuproptosis-related pattern and predict the prognosis and the response to immune checkpoint blockers of each individual patient with LUAD.ConclusionCuproptosis was found to influence tumor microenvironment (TME) characteristics and heterogeneity in LUAD. Patients with a lower CPS had a relatively better prognosis, more abundant immune infiltration in the TME, and an enhanced response to immune checkpoint inhibitors.