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AIM: Automated insulin delivery (AID) systems have demonstrated improved glycaemic outcomes in people with type 1 diabetes (T1D), yet limited data exist on these systems in very young children and their impact on caregivers. We evaluated psychosocial outcomes following use of the tubeless Omnipod® 5 AID System in caregivers of very young children. MATERIALS AND METHODS: This 3-month single-arm, multicentre, pivotal clinical trial enrolled 80 children aged 2.0-5.9 years with T1D to use the Omnipod 5 AID System. Caregivers completed questionnaires assessing psychosocial outcomes-diabetes distress (Problem Areas in Diabetes), hypoglycaemia confidence (Hypoglycemia Confidence Scale), well-being (World Health Organization 5 Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), insulin delivery satisfaction (Insulin Delivery Satisfaction Survey) and system usability (System Usability Scale) at baseline with standard therapy and after 3 months of AID use. RESULTS: Following 3 months of Omnipod 5 use, caregivers experienced significant improvements across all measures, including diabetes-related psychosocial outcomes (Problem Areas in Diabetes; p < 0.0001, Hypoglycemia Confidence Scale; p < 0.01), well-being (World Health Organization 5 Well-Being Index; p < 0.0001) and perceived system usability (System Usability Scale; p < 0.0001). Significant improvements were seen in the Pittsburgh Sleep Quality Index total score and the overall sleep quality, sleep duration and efficiency subscales (all p < 0.05). Insulin Delivery Satisfaction Survey scores improved on all subscales (greater satisfaction, reduced burden and reduced inconvenience; all p < 0.0001). CONCLUSIONS: Caregivers face unique challenges when managing T1D in very young children. While glycaemic metrics have unquestioned importance, these results evaluating psychosocial outcomes reveal additional meaningful benefits and suggest that the Omnipod 5 AID System alleviates some of the burdens caregivers face with diabetes management.

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Smartphones, with embedded accelerometers, may be a viable method to monitor gait variability in the free-living environment. However, measurements estimated using smartphones must first be compared to known quantities to ensure validity. This study assessed the validity and reliability of smartphone-derived gait measures compared to a gold-standard footswitch system during overground walking. Seventeen adults completed three 8-minute overground walking trials during 3 separate visits. The stride time series was calculated as the time difference between consecutive right heel contact events within the footswitch and smartphone-accelerometry signals. Linear (average stride time, stride time standard deviation, and stride time coefficient of variation) and nonlinear (fractal scaling index, approximate entropy, and sample entropy) measures were calculated for each stride time series. Bland-Altman plots with 95% limits of agreement assessed agreement between systems. Intraclass correlation coefficients assessed reliability across visits. Bland-Altman plots revealed acceptable limits of agreement for all measures. Intraclass correlation coefficients revealed good-to-excellent reliability for both systems, except for fractal scaling index, which was moderate. The smartphone system is a valid method and performs similarly to gold-standard research equipment. These findings suggest the development and implementation of an inexpensive, easy-to-use, and ubiquitous telehealth instrument that may replace traditional laboratory equipment for use in the free-living environment.

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PREMISE: Seed dispersal is a critical process impacting individual plants and their communities. Plants have evolved numerous strategies and structures to disperse their seeds, but the evolutionary drivers of this diversity remain poorly understood in most lineages. We tested the hypothesis that the evolution of wind dispersal traits within the melicgrasses (Poaceae: Meliceae Link ex Endl.) was correlated with occupation of open and disturbed habitats. METHODS: To evaluate wind dispersal potential, we collected seed dispersal structures (diaspores) from 24 melicgrass species and measured falling velocity and estimated dispersal distances. Species' affinity for open and disturbed habitats were recorded using georeferenced occurrence records and land cover maps. To test whether habitat preference and dispersal traits were correlated, we used phylogenetically informed multilevel models. RESULTS: Melicgrasses display several distinct morphologies associated with wind dispersal, suggesting likely convergence. Open habitat taxa had slower-falling diaspores, consistent with increased wind dispersal potential. However, their shorter stature meant that dispersal distances, at a given wind speed, were not higher than those of their forest-occupying relatives. Species with affinities for disturbed sites had slower-falling diaspores and greater wind dispersal distances, largely explained by lighter diaspores. CONCLUSIONS: Our results are consistent with the hypothesized evolutionary relationship between habitat preference and dispersal strategy. However, phylogenetic inertia and other plant functions (e.g., water conservation) likely shaped dispersal trait evolution in melicgrasses. It remains unclear if dispersal trait changes were precipitated by or predated changing habitat preferences. Nevertheless, our study provides promising results and a framework for disentangling dispersal strategy evolution.

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Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors. Methods: Demographic, clinical and dosimetric data were retrospectively obtained for a clinical observational cohort of 1129 patients with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. ORNJ was diagnosed in 198 patients (18%). A multivariable logistic regression analysis with forward stepwise variable selection identified significant predictors for ORNJ. These predictors were then used to train a Weibull Accelerated Failure Time (AFT) model, which was externally validated using an independent cohort of 265 patients (92 ORNJ cases and 173 controls) treated at Guy's and St. Thomas' Hospitals. Findings: Our model identified that each unit increase in D25% is significantly associated with a 12% shorter time to ORNJ (Adjusted Time Ratio [ATR] 0·88, p<0·005); pre-RT dental extractions was associated to a 27% faster (ATR 0·73, p=0·13) onset of ORNJ; male patients experienced a 38% shorter time to ORNJ (ATR 0·62, p = 0·11). The model demonstrated strong internal calibration (integrated Brier score of 0·133, D-calibration p-value 0.998) and optimal discrimination at 72 months (Harrell's C-index of 0·72). The model also showed good generalization to the independent cohort, despite a slight drop in performance. Interpretation: This study is the first to demonstrate a direct relationship between radiation dose and the time to ORNJ onset, providing a novel characterization of the impact of delivered dose not only on the probability of a late effect (ORNJ), but the conditional risk during survivorship. Funding: This work was supported by various funding sources including NIH, NIDCR, NCI, NAPT, NASA, BCM, Affirmed Pharma, CRUK, KWF Dutch Cancer Society, NWO ZonMw, and the Apache Corporation.

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To estimate a watershed's response to climate change, it is crucial to understand how human activities and climatic extremes have interacted over time. Over the last century, the Zarivar Lake watershed, Iran, has been subjected to various anthropogenic activates, including deforestation and inappropriate land-management practices alongside the implementation of conservation measures like check dams. To understand the effects of these changes on the magnitude of sediment, organic carbon (OC), and phosphorus supplies in a small sub-watershed connected to the lake over the last century, a lake sediment core was dated using 210Pbex and 137Cs as geochronometers. The average mass accumulation rate (MAR), organic carbon accumulation rates (OCAR), and particulate phosphorus accumulation rates (PPAR) of the sediment core were determined to be 6498 ± 2475, 205 ± 85, and 8.9 ± 3.3 g m-2 year-1, respectively. Between the late 1970s and early 1980s, accumulation rates were significantly higher than their averages at 7940 ± 3120, 220 ± 60, and 12.0 ± 2.8 g m-2 year-1 respectively. During this period, the watershed underwent extensive deforestation (12%) on steep slopes, coinciding with higher mean annual precipitations (more than double). Conversely, after 2009, when check dams were installed in the sub-watershed, the sediment load to the lake became negligible. The results of this research indicate that anthropogenic activities had a pronounced effect on MAR, OCAR, and PPAR, causing them to fluctuate from negligible amounts to values twice the averages over the last century, amplified by climatic factors. These results imply that implementing climate-smart watershed management strategies, such as constructing additional check dams and terraces, reinforcing restrictions on deforestation, and minimum tillage practices, can facilitate protection of lacustrine ecosystems under accelerating climate change conditions.

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BACKGROUND: In the United States, community overdose education and naloxone distribution (OEND) programs have demonstrated efficacy in reducing opioid-related mortality. OEND programs have expanded across San Diego County, California, but differential naloxone accessibility among people who use drugs (PWUD) has not been assessed. We examined factors that shape individual naloxone accessibility in San Diego. METHODS: We employed a convergent parallel mixed methods design using surveys (n = 194) and qualitative interviews (n = 20). Ordinal logistic regression examined factors associated with individual naloxone accessibility (i.e., the frequency with which participants could access naloxone within five minutes, categorized as never, sometimes, or always). Qualitative interviews explored participant perceptions of naloxone accessibility and whether and how they maintained naloxone. We organized multilevel findings into a modified social-ecological model. RESULTS: In quantitative and qualitative samples, participants were majority male (72 % and 70 % respectively), non-White race/ethnicity (55 % and 75 %), with an average age around 42 years. In the quantitative sample, 24 % never had personally accessible naloxone, 52 % sometimes did, and 24 % always did. Factors independently associated with individual naloxone accessibility were female gender (Adjusted Odds Ratio [AdjOR]: 2.51, 95 % Confidence Interval [CI]: 1.31-4.85), monthly income <$500 (AdjOR: 0.42, 95 %CI:0.19, 0.90), witnessing an overdose (AdjOR: 3.51, 95 %CI:1.67-7.55), and knowing where to get free naloxone (AdjOR: 3.44, 95 %CI: 1.79-6.75). Qualitative data suggested that naloxone was generally easy to acquire in San Diego due to community harm reduction outreach and mutual aid among peers, albeit community barriers including distance to harm reduction providers and frequent relocation/displacement for those experiencing homelessness. Individual attitudes toward overdose risk, naloxone, and community responsibility contributed to varied individual naloxone accessibility. CONCLUSIONS: This study highlights multilevel factors influencing individual naloxone accessibility among people who use drugs in San Diego, emphasizing the importance of harm reduction outreach and peer-to-peer support. We identified opportunities for interventions that address both individual attitudes and community-level barriers to improve naloxone accessibility.

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Chronic wasting disease (CWD) is a fatal neurodegenerative disease of cervids caused by an infectious misfolded protein (prion). Several members of the Cervidae, including Rocky Mountain elk (Cervus canadensis nelsoni), are susceptible to CWD. There is no evidence of complete genetic resistance to CWD; the M132L polymorphism in the elk prion protein gene influences the incubation period: longest in 132LL, intermediate in 132ML, and shortest in 132MM elk. We retrospectively analyzed six female 132LL elk housed in an environment heavily contaminated with prions to 1) document clinical outcomes and incubation periods, 2) describe PrPSc distribution and extent in tissues, and 3) characterize their histologic lesions. In five of six elk, PrPSc was detected postmortem, with a distribution pattern distinct from that of 132MM and 132ML elk; time to clinical CWD onset CWD ranged from 73 to 117 mo (6.1-9.8 yr). Although the remaining animal was observed for 220 mo (18.3 yr), PrPSc was not detected in its tissues postmortem. This study suggests that 132LL elk infected via natural exposure may live even longer with CWD than previously thought, but ultimately remain susceptible. We also report a distinct distribution of PrPSc in 132LL genotypes and highlight unusual histologic findings. Understanding the relationship between cervid genetics and CWD is of increasing importance, especially given the growing interest in leveraging genetics that delay disease onset despite not preventing infection.

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In order to understand how prefrontal cortex provides the benefits of working memory (WM) for visual processing we examined the influence of WM on the representation of visual signals in V4 neurons in two macaque monkeys. We found that WM induces strong ß oscillations in V4 and that the timing of action potentials relative to this oscillation reflects sensory information- i.e., a phase coding of visual information. Pharmacologically inactivating the Frontal Eye Field part of prefrontal cortex, we confirmed the necessity of prefrontal signals for the WM-driven boost in phase coding of visual information. Indeed, changes in the average firing rate of V4 neurons could be accounted for by WM-induced oscillatory changes. We present a network model to describe how WM signals can recruit sensory areas primarily by inducing oscillations within these areas and discuss the implications of these findings for a sensory recruitment theory of WM through coherence.

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Decades of research have been dedicated to the study and prevention of sexual aggression (SA) perpetration. Despite robust evidence linking acute intoxication and SA perpetration, few studies have examined this association in naturalistic contexts like drinking settings. Field studies are needed to inform etiological models and interventions that generalize to the naturalist environment. OBJECTIVE: The goal of this paper is to provide guidance to researchers on the logistical and ethical considerations involved in conducting an alcohol field study by detailing the methodology employed in a field study on alcohol and sexual misperception. METHOD: This article presents a field study protocol for measuring sexual misperception, a precursor to SA, in patrons exiting bars. One hundred forty-three participants completed study procedures. In-depth information on procedures for site selection, recruitment, screening, measure selection, consent, and capacity assessment is provided. CONCLUSIONS: Field studies can evaluate proximal causes of alcohol-involved sexual aggression and intermediary processes like sexual misperception in naturalistic settings. Greater implementation of field studies is required for a comprehensive understanding of alcohol-involved SA perpetration and for generalizable interventions.

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BACKGROUND AND OBJECTIVES: Exposure of the root entry zone (REZ) of the trigeminal nerve (TN) for microvascular decompression is commonly obtained with a retrosigmoid approach, with or without endoscopic assistance. We hypothesized that adequate exposure of the TN REZ could be obtained through an endoscopic retrolabyrinthine (RL) approach. We aim to quantify exposure of the REZ of the TN using endoscopic RL approach, with and without drilling of the suprameatal tubercle of the internal auditory canal. METHODS: Surgical dissection was performed bilaterally on 3 embalmed cadaveric human heads at the anatomy laboratory of the House Institute. Heads were scanned for volumetric analysis using 3D Slicer software both before and after dissection. Extent of exposure was quantified in 2 ways: first, by assessment of the surgeon's ability to visualize 16 predetermined anatomic landmarks with the endoscope and second, we estimated the "working" area by placing fiducials under the fully endoscopic view and calculating the resultant 3D volume. RESULTS: Using the standard endoscopic RL approach, an average of 13.8 landmarks (range 12-16) was visualized. The estimated working volume exposed by the RL on each side of each head varied from 189.28 to 527.85 mm3. Drilling of the suprameatal tubercle provided both increases in landmark visualization and, on average, an additional 55 mm3 of working volume. CONCLUSION: The endoscopic RL approach is a viable alternative to the standard retrosigmoid approach. Potential advantages of the RL include a more lateral trajectory that minimizes the need for cerebellar retraction and a shorter working distance and shallower angle to the cerebellopontine angle. Potential disadvantages include longer surgery time, increased technical difficulty of exposure, and potential for cerebrospinal fluid leak and or hearing loss.

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Advances in medical technology have begun to blur the lines between life and death as well as the lines between appropriate and inappropriate therapy. This review addresses the charged issue of the management of cardiac devices at or near the end of a patient's life, provides a summary of prior and current opinion with some historical context, and attempts to provide some modest guidance as to how to approach the various options to the patient's best advantage. Modalities to be addressed include indwelling electronic devices, the left ventricular assistance device, and extracorporeal mechanical oxygenation, and includes available outcome data as well as ethical analysis from a number of commentators. The expected further increase in technical sophistication of these devices is expected to render the various aspects of device deactivation more and more complex over the course of the next few years such that careful attention to and knowledge about this issue will continue to be more and more necessary.

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Twin lamb mortality is a significant economic problem impacting the Australian sheep industry. Maternal betaine supplementation improved lamb vigour and early post-natal survival when ewes and lambs were housed indoors, suggesting that betaine may be beneficial to feed under extensive pasture systems. This study investigated whether maternal betaine supplementation during late gestation would improve Merino twin lamb live weight, thermoregulation, vigour and survival to weaning under field conditions. Ewes received dietary betaine at either 0 g/day (CTL; n = 115) or 4 g/day from day 110 of gestation (dG 110) until ~49 days post-partum (pp) (BET; n = 115). Measures indicative of lamb viability and survival were collected within 4-24 h of birth and at ~49 days pp and ~93 days pp. BET ewes had higher creatine and creatinine concentrations at dG 130 than CTL ewes (p < 0.05). BET lambs had a higher rectal temperature within 4-24 h following birth than CTL lambs (p < 0.05). CTL lambs were heavier at ~49 days pp and grew faster from birth to ~49 days pp than BET lambs (both p < 0.05). The time taken after release from the researcher to first suckling was quicker in the CTL lambs than BET lambs (p < 0.05). This study demonstrated that supplementing betaine increased creatine concentration in twin-bearing ewes and thermoregulatory capacity in neonatal lambs under extensive grazing systems.

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Protein kinases are key signaling nodes that regulate fundamental biological and disease processes. Illuminating kinase signaling from multiple angles can provide deeper insights into disease mechanisms and improve therapeutic targeting. While fluorescent biosensors are powerful tools for visualizing live-cell kinase activity dynamics in real time, new molecular tools are needed that enable recording of transient signaling activities for post hoc analysis and targeted manipulation. Here, we develop a light-gated kinase activity coupled transcriptional integrator (KINACT) that converts dynamic kinase signals into "permanent" fluorescent marks. KINACT enables robust monitoring of kinase activity across scales, accurately recording subcellular PKA activity, highlighting PKA activity distribution in 3D cultures, and identifying PKA activators and inhibitors in high-throughput screens. We further leverage the ability of KINACT to drive signaling effector expression to allow feedback manipulation of the balance of GαsR201C-induced PKA and ERK activation and dissect the mechanisms of oncogenic G protein signaling.

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BACKGROUND: Evidence from clinical trials of early pulsed field ablation (PFA) systems in treating atrial fibrillation has demonstrated their promising potential to reduce complications associated with conventional thermal modalities while maintaining efficacy. However, the lack of a fully integrated mapping system, a staple technology of most modern electrophysiology procedures, poses limitations in lesion creation and workflow options. A novel variable-loop PFA catheter integrated with an electroanatomic mapping system has been developed that allows for real-time nonfluoroscopic procedural guidance and lesion indexing as well as feedback of tissue-to-catheter proximity. ADMIRE (Assessment of Safety and Effectiveness in Treatment Management of Atrial Fibrillation With the Bosense-Webster Irreversible Electroporation Ablation System), a multicenter, single-arm, Food and Drug Administration investigational device exemption study, evaluated the long-term safety and effectiveness of this integrated PFA system in a large United States-based drug-refractory symptomatic paroxysmal atrial fibrillation patient population. METHODS: Using the PFA catheter with a compatible electroanatomic mapping system, patients with drug-refractory symptomatic paroxysmal atrial fibrillation underwent pulmonary vein isolation. The primary safety end point was primary adverse event within 7 days of ablation. The primary effectiveness end point was a composite end point that included 12-month freedom from documented atrial tachyarrhythmia (ie, atrial fibrillation, atrial tachycardia, atrial flutter) episodes, failure to achieve pulmonary vein isolation, use of a nonstudy catheter for pulmonary vein isolation, repeat procedure (except for one redo during blanking), taking a new or previously failed class I or III antiarrhythmic drug at higher dose after blanking, or direct current cardioversion after blanking. RESULTS: At 30 centers, 277 patients with paroxysmal atrial fibrillation (61.5±10.3 years of age; 64.3% male) in the pivotal cohort underwent PFA. More than 25% of the procedures were performed without fluoroscopy. Median (Q1, Q3) pulmonary vein isolation procedure, fluoroscopy, and transpired PFA application times were 81.0 (61.0, 112.0), 7.1 (0.00, 14.3), and 31.0 (24.8, 40.9) minutes, respectively. The primary adverse event rate was 2.9% (8 of 272), with the most common complication being pericardial tamponade. The 12-month primary effectiveness end point was 74.6%. The 1-year freedom from atrial fibrillation, atrial tachycardia, or atrial flutter recurrence rate after blanking was 75.4%. Substantial improvements in quality of life were observed as early as 3 months after the procedure, concurrent with a reduction in multiple health care use measures. CONCLUSIONS: ADMIRE confirmed the safety and effectiveness of the variable-loop PFA catheter, with short procedure and PFA application times and low fluoroscopy exposure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05293639.

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PURPOSE: Meningiomas are the most common type of primary brain tumour. Hyperostosis is commonly associated but remains incompletely understood. This study aimed to evaluate the relationship between meningioma-associated hyperostosis and other tumour variables. MATERIALS AND METHODS: We retrospectively analysed 245 patients with 263 cranial meningiomas (202 CNS WHO grade 1, 53 grade 2, and 8 grade 3) who underwent surgery over a three-year period. Meningiomas adjacent to the skull were included. Demographic, radiological, and tumour characteristics were analysed using standard statistical methods. RESULTS: Hyperostosis was evident in 99 (38%) of meningiomas. The most common subtypes were meningothelial, transitional, fibrous, atypical, and anaplastic. There were no statistically significant relationships between hyperostosis and bone invasion, and CNS WHO grade and histological subtype. Hyperostosis was more common in skull base meningiomas than in convexity meningiomas (p = 0.001). Ki-67 index was significantly related to CNS WHO grade but not histological subtype when grade was considered. Mean Ki-67 index was higher in meningiomas without hyperostosis (p = 0.03). There was no such relationship with bone invasion (p = 0.29). Univariate and multivariate analysis revealed that Ki-67 index was negatively correlated with hyperostosis (p = 0.03), while bone invasion (p < 0.001) and skull base location (p = 0.03) were positively correlated with hyperostosis. CONCLUSIONS: Hyperostosis did not appear to be related to CNS WHO grade or histological subtype. Proliferative activity appeared to be higher in meningiomas without hyperostosis and hyperostosis was associated with evidence of bone invasion and skull base location.

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Rheumatoid arthritis (RA) is a potentially devastating autoimmune disease. The great majority of patients with RA are seropositive for anti-citrullinated protein antibodies (ACPAs), rheumatoid factors, or other autoantibodies. The onset of clinically apparent inflammatory arthritis meeting classification criteria (clinical RA) is preceded by ACPA seropositivity for an average of 3-5 years, a period that is designated as 'at-risk' of RA for ACPA-positive individuals who do not display signs of arthritis, or 'pre-RA' for individuals who are known to have progressed to developing clinical RA. Prior studies of individuals at-risk of RA have associated pulmonary mucosal inflammation with local production of ACPAs and rheumatoid factors, leading to development of the 'mucosal origins hypothesis'. Recent work now suggests the presence of multiple distinct mucosal site-specific mechanisms that drive RA evolution. Indicatively, subsets of individuals at-risk of RA and patients with RA harbour a faecal bacterial strain that has exhibited arthritogenic activity in animal models and that favours T helper 17 (TH17) cell responses in patients. Periodontal inflammation and oral microbiota have also been suggested to promote the development of arthritis through breaches in the mucosal barrier. Herein, we argue that mucosal sites and their associated microbial strains can contribute to RA evolution via distinct pathogenic mechanisms, which can be considered causal mucosal endotypes. Future therapies instituted for prevention in the at-risk period, or, perhaps, during clinical RA as therapeutics for active arthritis, will possibly have to address these individual mechanisms as part of precision medicine approaches.

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Transcatheter aortic valve replacement (TAVR) has emerged as a pivotal intervention for patients with severe aortic stenosis who are at high or prohibitive surgical risk. Although TAVR is a minimally invasive procedure, it is linked to serious hematological problems, most notably thrombosis and bleeding. Numerous factors, such as procedural features, patient comorbidities, and anticoagulation management techniques, contribute to these complications. Bleeding complications can be major, minor, or life-threatening. They can be caused by problems with the vascular access site, anticoagulation medication, or coexisting conditions like renal dysfunction and frailty. Hemoglobin drop, overt bleeding, and hematoma signs must all be closely watched to identify bleeding. Careful selection and modification of anticoagulation medication, the use of vascular closure devices, and timely attention to bleeding sites are examples of management techniques. Thrombotic consequences, which include cerebrovascular accidents and valve thrombosis, are caused by endothelial injury, stent implantation, and patient hypercoagulability. Imaging modalities such as computed tomography and transesophageal echocardiography are used in the crucial process of detection. The goal of preventive care is to maximize anticoagulation regimens that are customized to each patient's risk profile, frequently striking a balance between the risk of thrombosis and bleeding. A multidisciplinary strategy that integrates surgical, hematological, and cardiology expertise is necessary for the effective management of these hematological complications. To improve patient outcomes, ongoing research attempts to improve risk stratification and create safer anticoagulation protocols. This review emphasizes how critical it is to identify bleeding and thrombotic events as soon as possible and treat them promptly to reduce the risk of negative outcomes for TAVR patients.

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Pulmonary arterial hypertension (PAH) is a severe condition characterized by increased pulmonary vascular resistance and right ventricular failure. This review examines the intersection of PAH and pregnancy, highlighting the significant physiological, hemodynamic, and hormonal changes that exacerbate PAH during gestation. Pregnancy is contraindicated in PAH patients due to high maternal and fetal morbidity and mortality rates. However, some patients choose to continue their pregnancies, necessitating a comprehensive understanding of the implications and management strategies. Effective management of PAH in pregnant patients involves individualized treatment plans. Prepartum management focuses on optimizing therapy and monitoring hemodynamic status. Prostacyclin analogs and phosphodiesterase inhibitors are commonly used, though their safety profiles require further investigation. Intrapartum management prioritizes preventing right ventricular failure, utilizing therapies such as intravenous epoprostenol, inhaled iloprost, and inhaled nitric oxide. Managing PAH in pregnancy requires careful planning, continuous monitoring, and tailored therapeutic strategies to navigate the complex interplay of physiological changes and mitigate risks. Future research should focus on elucidating the pathophysiology of PAH during pregnancy and developing safer, more effective treatments to improve maternal and fetal outcomes.

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Multiple myeloma (MM) arises in plasma cells, a type of white blood cell. The cancerous plasma cells produce monoclonal immunoglobulins in the bone marrow. The extent of proliferation in the malignant state can manifest in many complications including osteopenia, osteolytic lesions, pathologic fractures, hypercalcemia, anemia, and kidney dysfunction. As is the case with the treatment of other malignancies, the research relating to the management of MM is dynamic and evolving. In this review, we aim to succinctly summarize and categorize the major treatment options of MM, including both new treatments and also older treatments that are now less frequently utilized, with a specific focus on the cardiotoxicity of these agents.

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T-Cell Prolymphocytic Leukaemia (T-PLL) is an aggressive disease with a poor prognosis and only curable by allogeneic stem cell transplantation. We describe the case of a male suffering from T-PLL. Therapy was alemtuzumab followed by an allograft from an unrelated donor. T-PLL relapsed after allogeneic stem cell transplantation. Discontinuation of immunosuppression had no effected and three increasing doses of donor lymphocytes were given within one month. The patient developed acute GvHD of the lover (grade III). GvHD was successfully treated by steroids and ruxolitinib and graft-versus-leukaemia effects induced a complete remission of T-PLL. 18,5 months after transplantation the patient is well and alive without GvHD under immunosuppression with ruxolitinib. Flow cytometry of peripheral blood was negative for residual leukemic cells.