Huntington University

The purpose of the article is to revisit, after a quarter of a century, Professor Keith Hitchins’s two-volume Oxford synthesis of Romanian history from 1774 to 1947. It will summarize his principal premises and conclusions and then assess how well his findings have held up since then.

Approximately 14.7 million US children aged 2 to 19 years are obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution (Vd) for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased owing to increased lean body mass, blood volume, and decreased percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Association recommends that weight-based dosing should be used in patients ages <18 years who weigh <40 kg; weight-based dosing should be used in patients ≥40 kg, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in children diagnosed with overweight and obesity; and research efforts continue to evaluate dosing of medications in children diagnosed with overweight and obesity.

Purpose This study presents the use of dry needling (DN) as an intervention to support functional rehabilitation for an adult diagnosed with lateral epicondylosis. Methods A retrospective, single subject, AB design was implemented. A 50-year-old male with a six-month history of dominant left lateral epicondylosis received traditional interventions for 4 weeks (baseline phase; A) followed by the same interventions with the addition of DN (intervention phase; B). The QuickDASH assessment, numeric rating scale (NRS) for pain, grip strength (elbow flexed and neutral), and Maudsley’s test were used as measures of effectiveness along with patient self-report of ability to perform activities of daily living (ADLS), instrumental ADLs, work, and leisure occupations. Results The patient made minimal progress for the initial 4 weeks of traditional treatment. There were no changes to his initial pain rating of 7/10 on the NRS, left hand grip strength (67 lbs.), or initial QuickDASH score. DN was initiated at week five with a reduction in pain from 7/10 to 2/10 from weeks six to eight. He was discharged at week 12 with no pain, a score of 0/100 on the QuickDASH, non-painful grip of 83 lbs., and a self-report of the ability to perform all ADLs, instrumental ADLs, work, and leisure occupations independently. Conclusions Dry needling appears to have been an effective intervention when integrated with a holistic approach for an individual with chronic lateral epicondylosis. More research is needed to evaluate dry needling as an intervention to support functional rehabilitation with a larger sample size and randomization.

The purpose of this study was to evaluate the effectiveness of custom seating and mobility services provided via an international service learning (ISL) model on the occupational performance of individuals with disabilities in Guatemala. A one-group prospective pretest-posttest design was implemented using the standardized Wheelchair Outcome Measure (WhOM - Spanish) administered on the day of wheelchair fitting, and at 3- and 6-month intervals after receiving seating and mobility services. A two-tailed t-test demonstrated a statistically significant (p < 0.001) improvement in satisfaction for in-home and out-of-home occupations for all participants (n = 71) at 3-months with a huge effect size (d > 2) and this improvement was maintained at the 6-month interval. The results were consistent for various areas of occupational performance (e.g. activities of daily living). The provision of customized seating and mobility services by occupational therapists through an ISL model demonstrated effectiveness at improving satisfaction with occupational performance for individuals with disabilities in Guatemala. Cultural humility, customization of equipment based on personal and environmental factors, inclusion of education and training, and collaboration with in-country partners were identified as contributors to positive outcomes.

e12656 Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, constituting approximately 15-20% of all breast cancer cases. While less than 10% of all breast cancer patients harbor BRCA1/2 mutations, ~20% of TNBC patients carry these mutations. Notably, at least one-third of BRCA1 carriers develop TNBC. This study aimed to investigate the association between BRCA mutation status and pathological response (PR) in early-stage TNBC patients, specifically, the impact of BRCA positivity on achieving pathological complete response (pCR), and identify other potential predictors of PR. Methods: We conducted a retrospective cohort study of patients with early-stage (Stage I-III) triple-negative breast cancer diagnosed and treated at our institution between January 2012 and June 2022, following Institutional Review Board (IRB) approval. Patients were identified from our Institutional Cancer Registry based on complete data availability (including other inclusion criteria) excluding patients who did not receive neoadjuvant chemotherapy. Data on demographics, tumor characteristics, treatment regimens, and pathological response (assessed according to [specified criteria]) were extracted from the charts. Results: Out of 228 patients diagnosed with early-stage triple-negative breast cancer, 54.6% had no genetic mutations, while 7.9%, 4.9%, and 8.4% harbored BRCA1, BRCA2, and other mutations, respectively. Notably, 23.4% did not receive genetic counseling or testing at our institution. Patients with BRCA2 mutations had a 100% pathological response rate, of which 57.14% had pCR, compared to 85.7% for BRCA1, of which 71.43% had pCR. Furthermore, 93.8% of patients with other genetic mutations had pathological response, of which 56.25% had pCR, as compared to 68.42% in non-mutated cases of which 26.7% had pCR ( P=0.038). Analysis of other variables revealed no significant impact of age, BMI, performance status, or neoadjuvant chemotherapy regimen on pathological response. Conclusions: This retrospective study suggests a trend towards higher complete pathological responses in early-stage triple-negative breast cancer patients with BRCA and other genetic mutations compared to those without. These findings were statistically significant, indicating a potential clinical trend that specific genetic mutations may be associated with improved response to neoadjuvant chemotherapy in early-stage triple-negative breast cancer. Further research is needed to confirm these findings and guide the development of personalized treatment strategies based on a patient's genetic profile. Additionally, our findings highlight the importance of genetic testing for all patients with early-stage triple-negative breast cancer, regardless of age or family history.

e12542 Background: Early stage (Stage I-III) human epidermal receptor -2 (HER2) positive and triple negative breast cancers (TNBC) tend to behave more aggressively than hormone positive breast cancers with higher and earlier incidences of recurrences. Oftentimes, testing for receptor subtypes is done only on the primary tumor and not on the synchronous axillary metastasis, with the assumption that the axillary metastasis is congruous to the primary lesion. Current guidelines also do not specify a requisite to do this testing. Information about the receptor expression types is fundamental for the treatment of breast cancer. We aimed to determine if there is significant discordance between the primary and ipsilateral axillary metastasis in early-stage breast cancer. Methods: We conducted a retrospective analysis via electronic medical record review of a large institutional database from 2008 to 2020. Sample for this study included all patients with a diagnosis of early-stage breast cancer (Stage I - III) with triple negative or HER2 positive tumors. Data on demographics, comorbidities, receptor status, staging, and mortality were collected. Results: Electronic charts from 448 patients were reviewed. 140 patients had axillary node positive disease. 40 (29%) of the 140 patients underwent testing for receptors subtypes on both primary and axillary nodal metastasis. 8 (20%) of the 40 patients had discordance in their receptor subtype expressed in their respective axillary nodal metastasis. 32 (80%) of the 40 patients had axillary receptor expression congruous to the primary tumor. At the time of our review, there was no statistically significant mortality between discordant compared to concordant group (13% vs 20%; p=0.54). 2 patients were lost to follow up. Conclusions: Our data suggests that one in every five axillary metastatic breast cancers can have receptor subtypes discordant compared to the receptors expressed on the primary tumor. Knowledge about any such discordance between the primary and respective axillary metastasis has a consequential impact on the treatment approach for early-stage breast cancer. This is especially true if the patient’s nodal metastatic lesions indeed prove HER2 receptor positivity or do not express any receptors (TNBC). Consequently, patients may be being deprived of benefits from advances in treatment of these cancers, such as targeted therapies towards HER2 receptor, hormonal treatments when indicated, or the utilization of neoadjuvant chemotherapy. A strong case can be thus made to revise current standards to include receptor testing on all primary and synchronous axillary metastasis. Further testing is needed to validate our findings.

5518 Background: Patients with recurrent platinum-resistant epithelial ovarian cancer (EOC) have poor clinical outcomes, owing in large part to the presence of therapy-resistant cancer stem cells (CSCs). A randomized clinical trial (NCT03949283) was conducted to determine if chemotherapy regimens guided by the CSCs functional assay (ChemoID) can improve objective response rate (ORR) in patients with recurrent platinum-resistant EOC when compared to empiric treatment selection. Methods: Patients with recurrent platinum-resistant EOC who had failed standard of care (SOC) therapy, were randomly assigned (1:1) to one of two intervention groups and given one of thirteen mono or combination chemotherapies based on the results of a ChemoID assay or physician choice. Fresh biopsy samples obtained from all subjects enrolled in the study were used to determine the sensitivity of CSCs and the bulk of tumor cells to the same panel of chemotherapies. Subjects randomized to the ChemoID-guided arm were treated with chemotherapies predicted by the assay while taking into consideration their health status, whereas treating physicians of subjects enrolled in the physician-choice arm were blinded to the test results. RECIST 1.1 response was assessed on CT scans. Results: The study met its primary endpoint at its first predetermined efficacy analysis by comparing the objective response rate (ORR) between treatment groups. The median ORR (mORR) of subjects treated with chemotherapies guided by the ChemoID assay was 55% (CI 95 39% – 73%), compared to 5% (CI 95 0% – 11%) for subjects treated with physician's choice chemotherapy with a p-value p<0.0001. The secondary endpoint analysis of duration of response (DOR) showed statistically significant differences (p<0.0001) between subjects treated with chemotherapies guided by the ChemoID assay versus subjects treated with physician’s choice chemotherapy with a median duration of response of 8 months vs. 5.5 months, respectively. The median clinical benefit rate (mCBR) of subjects treated with ChemoID-guided chemotherapies was 85% (CI 95 73% – 97%) and the mCBR of subjects treated with chemotherapies empirically chosen by the physicians was 24% (CI 95 11% – 38%) with a p-value <0.0001. No association was found between response and the number of prior platinum-based treatments (p = 0.651), age (p = 0.195), race (p = 0.173), or ECOG status (p = 0.938). The association between treatment groups and response was not modified by CA125 (p = 0.199) nor was CA125 itself associated with response (p = 0.187). Conclusions: These findings suggest that individually screening standard cytotoxic chemotherapy treatments with the ChemoID assay improves objective responses in recurrent platinum-resistant EOC patients. Clinical trial information: NCT03949283 .

Head and neck cancer (HNC), commonly known as oral cancer, is a devastating disease and the 6th most common cancer worldwide. Most HNC patients are diagnosed with advanced-stage disease for which the 5-year survival is below 50%, stressing the need for chemoprevention. Recently, we have reported that the combination of resveratrol and EGCG induces synergistic apoptosis and inhibits xenografted HNC growth by inhibiting the AKT-mTOR pathway. This study investigated the chemopreventive efficacy of resveratrol, EGCG, and their combination using the 4NQO-induced oral carcinogenesis model. C57BL/6 mice were exposed to 4-NQO (50 μg/ml) via drinking water for 10 weeks, followed by treatment with vehicle (50% sweetened condensed milk), resveratrol (30 mg/kg), EGCG (30 mg/kg) and their combination for 8 weeks, 5 days/week. The mice were sacrificed on week 24, and the number of visible and microscopic lesions was counted. Resveratrol alone and in combination with EGCG significantly inhibited the number of visible lesions. In contrast, the number of microscopic lesions and lesion area was significantly inhibited only in the combination group. The expression of Ki-67 was also significantly inhibited in resveratrol and combination groups when compared with untreated control. Furthermore, RNASeq and qPCR analysis using an HNC cell line identified GDF15, ATF3, p21, p27, and Bim as significantly upregulated genes, with GDF15 being the most upregulated one. Expression of GDF15 and ATF3 proteins was confirmed by Western blotting. Taken together, our data strongly demonstrate the chemopreventive potential of the combination of EGCG and resveratrol and pave the way for further clinical developments. (Supported by NIH Grants R15DE032063 and P20GM103434) Citation Format: Adeoluwa A. Adeluola, Lukmon Raji, Saroj Sigdel, ASM Anisuzzaman, A.R.M. Ruhul Amin. The combination of epigallocatechin gallate (EGCG) and resveratrol prevents 4-NQO-induced oral carcinogenesis in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB377.

Purpose For breast cancer survivors (BCS) living with breast cancer-related lymphedema (BCRL), what outcome measures (OMs) are recommended to be used to measure standardized outcome domains to fully assess the burden of the disease and efficacy of interventions? An integral component of a standardized core outcome set (COS) are the OMs used to measure the COS. Methods A supplemental online survey was linked to a Delphi study investigating a COS for BCRL. OMs were limited to a maximum of 10 options for each outcome domain (OD). There were 14 ODs corresponding to the International Classification of Functioning, Disability, and Health (ICF) framework and respondents rated the OMs with a Likert level of recommendation. The feasibility of the listed OMs was also investigated for most outpatient, inpatient, and research settings. Results This study identified 27 standardized OMs with a few ODs having 2–3 highly recommended OMs for proper measurement. A few of the recommended OMs have limitations with reliability due to being semi-quantitative measures requiring the interpretation of the rater. Conclusion Narrowing the choices of OMs to 27 highly recommended by BCRL experts may reduce selective reporting, inconsistency in clinical use, and variability of reporting across interdisciplinary healthcare fields which manage or research BCRL. There is a need for valid, reliable, and feasible OMs that measure tissue consistency. Measures of upper extremity activity and motor control need further research in the BCS with BCRL population.

Gout can potentially be diagnosed clinically and treated, if classical symptoms are present. In some cases, gout and osteomyelitis can have similar presenting signs and symptoms and it may be difficult to differentiate just on clinical presentation, routine laboratory workup and imaging like radiography or ultrasound. Arthrocentesis can be crucial in such scenarios to differentiate the two entities as missed opportunity to treat infectious etiology can have detrimental outcomes. We present a case of patient with ankle pain and swelling treated as recurrent gout, as there were no risk factors for osteomyelitis. Arthrocentesis confirmed the diagnosis of osteomyelitis and patient was treated with intravenous antibiotics, resulting in resolution of symptoms.

Purpose For breast cancer survivors (BCS) living with breast cancer-related lymphedema (BCRL), what outcome domains (OD) should be measured to assess the burden of the disease and efficacy of interventions? A Core Outcome Set (COS) that promotes standardized measurement of outcomes within the constraints of time influenced by work environments is essential for patients and the multidisciplinary professionals that manage and research BCRL. Methods Using Delphi methodology, a multidisciplinary group of BCRL experts (physical and occupational therapists, physicians, researchers, physical therapist assistants, nurses, and massage therapist) completed two waves of online surveys. BCRL expert respondents that completed the first survey (n = 78) had an average of 26.5 years in practice, whereas, respondents who completed the second survey (n = 33) had an average of 24.9 years. ODs were included in the COS when consensus thresholds, ranging from 70% to 80%, were met. Results A total of 12 ODs made up the COS. Reaching a minimum consensus of 70%; volume, tissue consistency, pain, patient-reported upper quadrant function, patient-reported health-related quality of life, and upper extremity activity and motor control were recommended at different phases of the BCRL continuum in a time-constrained environment. Joint function, flexibility, strength, sensation, mobility and balance, and fatigue met an 80% consensus to be added when time and resources were not constrained. Conclusion The COS developed in this study thoroughly captures the burden of BCRL. Using this COS may reduce selective reporting, inconsistency in clinical use, and variability of reporting across interdisciplinary healthcare fields, which manage or research BCRL.

Background Catheter laboratories are high-radiation exposure environments, especially during X-ray procedures like percutaneous transluminal coronary angioplasty and electrophysiological studies. Radiation exposure poses risks of stochastic (e.g., cancer) and deterministic (e.g., skin changes) effects. This study assessed radiation safety and health practices in a cardiac catheterization unit to optimize radiation safety. A cross-sectional study in Cairo University Hospital (March–September 2019) evaluated 700 patients and healthcare workers. Real-time radiation measurements, educational lectures, and radiation protection measures were implemented in three phases. Data on radiation exposure, procedures, and compliance were collected and analyzed. Results The total procedure time and fluoroscopy time per cardiologist did not significantly differ between phases, but there was a statistically significant reduction in the mean total cumulative radiation doses between Phase I and Phase III for cardiologists ( P = 0.013). Among nurses and technicians, there was no significant difference in radiation doses between the two phases. Significant correlations were found between operators' radiation doses, procedure time, and fluoroscopy time. Patients' radiation doses decreased significantly from Phase I to Phase III, with correlations between dose, procedure time, and gender. Compliance with radiation protection measures was suboptimal. Conclusions Compliance with radiation safety standards in the cardiac catheterization unit at the Cairo University Hospital needs improvement. The study highlights the importance of adhering to radiation safety principles and optimizing protective measures to reduce radiation exposure for both patients and healthcare personnel. Despite low compliance, significant reductions in radiation doses were achieved with increased awareness and adherence to specific protection measures. Future efforts should focus on enhancing radiation safety protocols and organ-specific radiation impact assessments.

A 67-year-old man was found to have a pancreatic head mass on abdominal ultrasound. He had compensated liver cirrhosis due to hepatitis C. The fine-needle aspiration (FNA) biopsy of the mass reported an adenocarcinoma of the pancreas, while the subsequent histopathology report of the supraclavicular lymph node showed features of hepatocellular carcinoma (HCC). A second read and additional stains on the FNA specimen confirmed a hepatoid (hepatocellular) carcinoma of the pancreas. He received atezolizumab and bevacizumab and had a good response. Tumors with features of HCC outside of the liver rarely occur and even more rarely in pancreas, with less than 50 cases reported so far. Pure HCC-like morphology is the most common histological form among four subtypes and has a relatively better prognosis. Surgical resection is considered the treatment of choice if amenable and variable outcomes are reported with different chemotherapies. Challenges exist in the diagnosis and the management of this rare and intriguing entity, and the potential misdiagnosis can have grave consequences as the management is completely different for a pancreatic adenocarcinoma and hepatoid carcinoma. We report a case with a challenging diagnosis of metastatic pancreatic hepatoid carcinoma which was treated as unresectable HCC with immunotherapy and the patient had a good response.

Protease activated receptors 1 and 4 (PAR1, PAR4) on platelets mediate thrombin signaling and are vital for thrombus development. Hypercoagulation and thrombin generation are major risk factors for thrombosis. Sustained thrombin signaling through PAR4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single-nucleotide polymorphism (SNP, rs2227376) leads to an amino acid change in extracellular loop 3 (ECL3) of PAR4, which decreases PAR4 activation (PAR4-P310L). This SNP is also associated with a significantly lower risk for venous thromboembolism (VTE) in a GWAS meta-analysis. We aim to determine the mechanism by which PAR4-P310L (rs2227376) impacts platelet function and reduces the risk of VTE using mice with a homologous mutation (PAR4-P322L). Ex vivo platelet function was determined using flow cytometry and aggregometry. Arterial and venous thrombosis was examined using the ferric-chloride induced carotid artery injury and inferior vena cava (IVC) stasis models, respectively. Platelets from heterozygous (PAR4-322P/L) and homozygous (PAR4-322L/L) mice had decreased thrombin-mediated aggregation and decreased PAR4 reactivity compared to wild types. These mice also had a prolonged time to occlusion in arterial thrombosis, with 55% of PAR4-322P/L mice unable to develop stable thrombi within 30 minutes. In venous thrombosis, wild-type mice developed clotted IVCs that averaged 31 mg after 48 hours, while global PAR4-knockout mice averaged 21 mg (p<0.01), PAR4-322P/L 23 mg (p<0.01), and PAR4-322L/L 28 mg. Since platelet procoagulant activity is known to drive venous thrombosis, we used lactadherin to show that PAR4-P322L platelets express less phosphatidylserine in response to thrombin (5 nM) and convulxin (1 nM). Platelet-rich plasma from PAR4-P322L mice also generated less thrombin compared to wild-types, and whole blood from mice lacking PAR4 showed delayed clot formation in rotational thromboelastometry. Altogether, this suggests a direct impact of PAR4 signaling on platelet-mediated thrombin generation. Our new mouse model shows that the polymorphism in ECL3, PAR4-322L, decreases platelet reactivity and thrombosis. We also show PAR4-322L leads to less procoagulant platelets and decreases the endogenous thrombin potential. This decreased ability to generate thrombin offers a mechanism for PAR4's role in VTE. Our findings highlight a key role of PAR4 signaling in platelet activation and procoagulant activity in thrombosis.

Background: Heparin-induced thrombocytopenia (HIT) is a prothrombotic and potentially fatal adverse drug reaction mediated by platelet-activating antibodies against multimolecular complexes of platelet factor 4 (PF4) and heparin. The 4Ts is a pretest scoring system for HIT that was developed to improve and standardize clinical diagnosis. The strength of the 4Ts score lies in the negative predictive value of a low pretest probability score. Those with a 4T score ≥4 is considered to have moderate to high probability of HIT and should undergo confirmatory laboratory test. Delays in treatment are associated with risk of thrombosis. Immediate cessation of heparin and initiation of a non-heparin anticoagulant is therefore standard of care. Method: This is a single institutional retrospective study. We reviewed the charts of 219 patients with thrombocytopenia with suspected HIT to evaluate the appropriateness of ordering the HIT testing based on the pretest probability of the 4Ts scoring system. All patients had enzyme linked immunosorbent assay (ELISA) test for HIT antibodies (the screening test). We studied tests that were sent from 03\16\2021 through 07\03\2023. The serotonin release assay (SRA) which is the confirmatory test for HIT was only sent for patients who had a positive ELISA test. 4T scores were calculated retrospectively using chart's information available to clinicians at the time of the HIT tests were sent. Results: Out of the 219 patients, 80(36.5%), 120(54.7%) and 19(8.6%) patients had a low, intermediate and high pretest probability respectively. The HIT ELISA test was positive in 33 (15.7%) patients and 196 (84.9%) patients had negative results. HIT ELISA had 100% and 93.5% sensitivity and specificity respectively while the positive and negative predicative values were 60% and 100% respectively. A positive SRA test was reported in 23 patients (10.5% of the total study population). Seventy-nine patients (36% of our total sample) scored 4 points which represents intermediate pretest probability. Out of these 79 patients only 6 (11.3%) patients had a positive ELISA test, and 5 (6.3%) patients had a positive SRA test. Aiming to minimize the HIT over testing we examined the increase in the cutoff point of the intermediate pretest probability from 4 points to 5 points which resulted in significant increase in the sensitivity and positive predictive value of the intermediate pretest probability (75.4% and 21% versus 39% and 12.9% respectively). However, the sensitivity dropped from 90% to 65%. The 4th part of 4Ts score gives points based on the probability of HIT versus other pathology as a cause of the thrombocytopenia. Most of the patients with suspected HIT will score one point out of the 4th part of 4Ts score which makes this part of the score is less helpful in distinguishing between patients with suspected HIT and will result in higher overall pretest probability and more testing. We studied the 3Ts score (the 4Ts scoring system after elimination of the 4th part) effect on the intermediate pretest probability. The cutoff points for the 3Ts score are 1-3, 4-5 and 6 for low, intermediate and high pretest probability respectively. The 3Ts score model resulted in significant increase in the specificity and the positive predictive value (76% and 21.7% versus 39.2% and 12.9% respectively) however the sensitivity dropped from 90% to 65%. The average turnaround time for HIT ELISA test and the SRA test was 2.3 days and 4.4 days respectively. Fifteen patients (21% out the patient had low pretest probability on the 4Ts score), 41 patients (59% of the patient who had an intermediate pretest probability on the 4Ts score) and 13 patients (18.8% of the patients who had high pretest probability on the 4Ts score) started on non-heparinoid anticoagulation meanwhile awaiting on the HIT testing result. Conclusion: Over testing of HIT is common secondary to underuse of 4Ts scoring system. Multicomponent educational interventions to increase the awareness and utility of the 4Ts score in addition to implantation of clinical decision support based on HIT computerized score will help to reduce unnecessary diagnostic testing of HIT in patients with low pretest probability. Increasing the cutoff point of the intermediate pretest probability or applying the 3Ts score model resulted in significant increase in the specificity and the positive predictive value of the 4Ts scoring system on expense of the scoring system sensitivity.

Introduction Choreiform movement disorders are characterized by involuntary, rapid, irregular, and unpredictable movements of the limbs, face, neck, and trunk. These movements often initially go unnoticed by the affected individuals and may blend together with seemingly intended, random motions. Choreiform movements can occur both at rest and during voluntary movements. They typically increase in intensity with stress and physical activity and essentially cease during deep sleep stages. In particularly in advanced stages of Huntington disease (HD), choreiform hyperkinesia occurs alongside with dystonic postures of the limbs or trunk before they typically decrease in intensity. Summary or definition of the topic The differential diagnosis of HD can be complex. Here, the authors aim to provide guidance for the diagnostic process. This guidance was prepared for the German Neurological Society (DGN) for German-speaking countries. Recommendations Hereditary (inherited) and non-hereditary (non-inherited) forms of chorea can be distinguished. Therefore, the family history is crucial. However, even in conditions with autosomal-dominant transmission such as HD, unremarkable family histories do not necessarily rule out a hereditary form (e.g., in cases of early deceased or unknown parents, uncertainties in familial relationships, as well as in offspring of parents with CAG repeats in the expandable range (27–35 CAG repeats) which may display expansions into the pathogenic range). Conclusions The differential diagnosis of chorea can be challenging. This guidance prepared for the German Neurological Society (DGN) reflects the state of the art as of 2023.

Introduction Ameliorating symptoms and signs of Huntington’s disease (HD) is essential to care but can be challenging and hard to achieve. The pharmacological treatment of motor signs (e.g. chorea) may favorably or unfavorably impact other facets of the disease phenotype (such as mood and cognition). Similarly, pharmacotherapy for behavioral issues may modify the motor phenotype. Sometimes synergistic effects can be achieved. In patients undergoing pragmatic polypharmacological therapy, emerging complaints may stem from the employed medications' side effects, a possibility that needs to be considered. It is recommended to clearly and precisely delineate the targeted signs and symptoms (e.g., chorea, myoclonus, bradykinesia, Parkinsonism, or dystonia). Evidence from randomized controlled trials (RCTs) is limited. Summary or definition of the topic Therefore, the guidelines prepared for the German Neurological Society (DGN) for German-speaking countries intentionally extend beyond evidence from RCTs and aim to synthesize evidence from RCTs and recommendations of experienced clinicians. Recommendations First-line treatment for chorea is critically discussed, and a preference in prescription practice for using tiapride instead of tetrabenazine is noted. In severe chorea, combining two antidopaminergic drugs with a postsynaptic (e.g., tiapride) and presynaptic mode of action (e.g., tetrabenazine) is discussed as a potentially helpful strategy. Sedative side effects of both classes of compounds can be used to improve sleep if the highest dosage of the day is given at night. Risperidone, in some cases, may ameliorate irritability but also chorea and sleep disorders. Olanzapine can be helpful in the treatment of weight loss and chorea, and quetiapine as a mood stabilizer with an antidepressant effect. Conclusions Since most HD patients simultaneously suffer from distinct motor signs and distinct psychiatric/behavioral symptoms, treatment should be individually adapted.

A total of 60 young adults responded to vignettes presenting moral dilemmas experienced in caregiving interactions with a family member with dementia. Four types of reasons for deceiving (or not deceiving) a family member with dementia emerged: care reasons (improving the welfare of the person with dementia), justice reasons (universal principles), care-for-others reasons (protecting the welfare of others), and relationship reasons (maintaining the relationship). Care reasons and care-for-others reasons positively predicted moral decisions to lie, whereas justice reasons and relationship reasons negatively predicted these decisions. These findings underscore the importance of understanding the motives underlying deception in dementia relationships.