Sickle cell crisis presenting as livedo racemosa.

Sickle cell disease is a monogenic hemoglobinopathy that results in the abnormal production of hemoglobin S, which yields the characteristic sickle-shaped red blood cells. Sickle cell vaso-occlusive crisis is a painful complication of sickle cell disease caused by red blood cell entrapment within the microcirculation. The resulting tissue ischemia triggers a secondary inflammatory process involved in the pathogenesis of varying inflammatory skin conditions. Chronic leg ulcers are the most common skin presentation in sickle cell disease. A 58-year-old woman with sickle cell disease presented with systemic edematous plaques with the most notable involvement of her bilateral legs, which exhibited reticulated purpuric patches with central pallor. We report a case highlighting an unusual presentation of livedo racemosa as the presenting sign in a patient with sickle cell disease in vaso-occlusive crisis.

Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial.

Importance: Selecting effective antidepressants for the treatment of major depressive disorder (MDD) is an imprecise practice, with remission rates of about 30% at the initial treatment. Objective: To determine whether pharmacogenomic testing affects antidepressant medication selection and whether such testing leads to better clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized clinical trial that compared treatment guided by pharmacogenomic testing vs usual care. Participants included 676 clinicians and 1944 patients. Participants were enrolled from 22 Department of Veterans Affairs medical centers from July 2017 through February 2021, with follow-up ending November 2021. Eligible patients were those with MDD who were initiating or switching treatment with a single antidepressant. Exclusion criteria included an active substance use disorder, mania, psychosis, or concurrent treatment with a specified list of medications. Interventions: Results from a commercial pharmacogenomic test were given to clinicians in the pharmacogenomic-guided group (n = 966). The comparison group received usual care and access to pharmacogenomic results after 24 weeks (n = 978). Main Outcomes and Measures: The co-primary outcomes were the proportion of prescriptions with a predicted drug-gene interaction written in the 30 days after randomization and remission of depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) (remission was defined as PHQ-9 ≤ 5). Remission was analyzed as a repeated measure across 24 weeks by blinded raters. Results: Among 1944 patients who were randomized (mean age, 48 years; 491 women [25%]), 1541 (79%) completed the 24-week assessment. The estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59.3%, 30.0%, and 10.7% compared with 25.7%, 54.6%, and 19.7% in the usual care group. The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction for no drug-gene vs moderate/substantial interaction (odds ratio [OR], 4.32 [95% CI, 3.47 to 5.39]; P < .001) and no/moderate vs substantial interaction (OR, 2.08 [95% CI, 1.52 to 2.84]; P = .005) (P < .001 for overall comparison). Remission rates over 24 weeks were higher among patients whose care was guided by pharmacogenomic testing than those in usual care (OR, 1.28 [95% CI, 1.05 to 1.57]; P = .02; risk difference, 2.8% [95% CI, 0.6% to 5.1%]) but were not significantly higher at week 24 when 130 patients in the pharmacogenomic-guided group and 126 patients in the usual care group were in remission (estimated risk difference, 1.5% [95% CI, -2.4% to 5.3%]; P = .45). Conclusions and Relevance: Among patients with MDD, provision of pharmacogenomic testing for drug-gene interactions reduced prescription of medications with predicted drug-gene interactions compared with usual care. Provision of test results had small nonpersistent effects on symptom remission. Trial Registration: ClinicalTrials.gov Identifier: NCT03170362.

Squamous cell carcinoma or squamous proliferation associated with nivolumab treatment for metastatic melanoma.

Nivolumab is a programmed death-1 (PD1) immune checkpoint inhibitor that treats various types of cancers including non-small cell lung carcinoma and melanoma, among others. Although it serves as an effective immunotherapy, there are many associated immune-related adverse events. Even years after the introduction of nivolumab, the breadth of its side effect profile continues to expand. We present a case of squamous cell carcinoma associated with nivolumab treatment for metastatic melanoma.

Primary care and mental health providers' perceptions of implementation of pharmacogenetics testing for depression prescribing.

BACKGROUND: Pharmacogenetic testing (PGx) has the potential to improve the quality of psychiatric prescribing by considering patients' genetic profile. However, there is limited scientific evidence supporting its efficacy or guiding its implementation. The Precision Medicine in Mental Health (PRIME) Care study is a pragmatic randomized controlled trial evaluating the effectiveness of a specific commercially-available pharmacogenetic (PGx) test to inform antidepressant prescribing at 22 sites across the U.S. Simultaneous implementation science methods using the Consolidated Framework for Implementation Research (CFIR) are integrated throughout the trial to identify contextual factors likely to be important in future implementation of PGx. The goal of this study was to understand providers' perceptions of PGx for antidepressant prescribing and implications for future implementation. METHODS: Qualitative focus groups (n = 10) were conducted at the beginning of the trial with Primary Care and Mental Health providers (n = 31) from six PRIME Care sites. Focus groups were audio-recorded and transcribed and data were analyzed using rapid analytic procedures organized by CFIR domains. RESULTS: Analysis revealed themes in the CFIR Intervention Characteristics domain constructs of Evidence, Relative Advantage, Adaptability, Trialability, Complexity, and Design that are important for understanding providers' perceptions of PGx testing. Results indicate: 1) providers had limited experience and knowledge of PGx testing and its evidence base, particularly for psychiatric medications; 2) providers were hopeful that PGx could increase their precision in depression prescribing and improve patient engagement, but were uncertain about how results would influence treatment; 3) providers were concerned about potential misinterpretation of PGx results and how to incorporate testing into their workflow; 4) primary care providers were less familiar and comfortable with application of PGx testing to antidepressant prescribing than psychiatric providers. CONCLUSIONS: Provider perceptions may serve as facilitators or barriers to implementation of PGx for psychiatric prescribing. Incorporating implementation science into the conduct of the RCT adds value by uncovering factors to be addressed in preparing for future implementation, should the practice prove effective. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03170362 ; Registered 31 May 2017.

Providers' Use of Pharmacogenetic Testing to Inform Antidepressant Prescribing: Results of Qualitative Interviews.

OBJECTIVE: Pharmacogenetic testing (PGx) for patients experiencing depression has been associated with modest improvements in symptoms. However, little is known about providers' use of PGx, including how and for whom providers use the test results in clinical decision making. In this article, results from qualitative interviews on the experience of providers participating in a pragmatic trial of PGx are described; implications of the providers' experiences are highlighted to inform future implementation of PGx. METHODS: Interviews were conducted with providers participating in the trial (N=61) who treated veterans who had depression. Questions were informed by the Consolidated Framework for Implementation Research. A rapid analytic approach was used. RESULTS: Two main themes were identified: perceptions regarding which patients would likely benefit from PGx and approaches to using the test results in prescribing. Providers generally expressed positive experiences with using PGx results. However, the providers varied in application of the test results to clinical decision making regarding medications, were uncertain about how much to rely on the results, and differed in perceptions about which patients would benefit from PGx. CONCLUSIONS: To support future implementation, policies and procedures are needed, as well as mechanisms to support ongoing provider education on PGx.

Homeopathic and integrative treatment for feline hyperthyroidism--four cases (2006-2010).

Hyperthyroidism is a frequent veterinary problem, particularly in elderly cats. Homeopathic treatment and other integrative modalities were provided for four hyperthyroid cats whose owners did not want conventional treatment. Symptomatic homeopathic treatment with Thyroidinum was helpful in one cat. All cats were prescribed an appropriate individualized homeopathic remedy. All four cats showed resolution of clinical signs; three attained normal thyroid hormone levels. Three cats later received acupuncture and/or herbal medicines; two cats later received symptomatic homeopathic remedies. Two cats are thriving after over 3.5 and 4.25 years of treatment; two were euthanized for unrelated problems after 3 and 4 years of treatment. Homeopathic and complementary therapies avoid the potential side effects of methimazole and surgical thyroidectomy, they are less costly than radioactive iodine treatment, and they provide an option for clients who decline conventional therapies.

Femorotibial joint kinematics in nine dogs treated with lateral suture stabilization for complete cranial cruciate ligament rupture.

OBJECTIVE: To quantify 3-D femorotibial joint kinematics during ambulation in dogs with cranial cruciate ligament (CCL) rupture treated with lateral fabellotibial suture stabilization (LFTS). ANIMALS: 9 adult dogs (body weight, 15 to 35 kg [33 to 77 lb]) with unilateral complete CCL rupture. PROCEDURES: Digital 3-D bone models of the femur and fabellae and tibia and fibula were created from CT scans. Lateral fluoroscopic images of stifle joints were collected during treadmill walking before surgery and 6 months after LFTS. The LFTS was performed with nylon leader material secured with knots. Gait cycles were analyzed with a 3-D to 2-D image registration process. Femorotibial joint kinematics (craniocaudal translation, internal-external rotation, and flexion and extension angles) were compared among CCL-deficient stifle joints before LFTS, CCL-deficient stifle joints 6 months after LFTS, and unaffected contralateral (control) stifle joints. Owners and veterinarians subjectively assessed lameness by use of a visual analog scale and gait examination, respectively, at each time point. RESULTS: At midstance phase, medial cranial tibial translation decreased from 9.3 mm before LFTS to 7.6 mm after LFTS but remained increased when compared with control stifle joint values. Following LFTS, axial rotation and stifle joint flexion and extension angles were not significantly different from control stifle joints. On the owner survey, the median walking lameness score improved from 9.3 of 10 before surgery to 0.3 after surgery. On gait examination, median walking lameness score improved from 2 of 4 before surgery to 0 after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Stifle joint instability was only slightly mitigated at 6 months following LFTS performed with knotted nylon leader material in medium to large dogs with CCL rupture, despite improvement in lameness.

Study design and implementation of the PRecision Medicine In MEntal health Care (PRIME Care) Trial.

Genomic testing has the potential to improve patient outcomes and reduce patient care costs by personalizing medication selection. Commercial pharmacogenetic (PGx) testing for psychotropic and other medications is widely available and promoted as a means to implement "precision medicine." Despite evidence that genetic variation affects the metabolism of psychotropic medications, the clinical utility of these test results has not been established. Moreover, implementing such testing in routine clinical care is complex, requiring informatics support and a systematic approach to patient and provider education. The PRIME Care program is designed to bridge this gap, applying both clinical trials and implementation science methods to conduct a program of research. It is centered on a large, pragmatic randomized clinical trial (RCT) in which 2000 Veterans with a major depressive disorder (MDD) and their health care providers are randomized together to receive PGx test results at the beginning of an episode of care or 6 months later. We hypothesize that providers who receive the PGx test results will prescribe an antidepressant guided by the PGx findings and Veterans whose care is guided by PGx testing will experience higher rates of remission from MDD. If the results of the trial replicate those of prior PGx studies, which provided preliminary evidence of the utility of PGx guided prescribing, it would strongly support using a precision medicine approach to treat MDD. This program of research is also evaluating dissemination influencers, other biomarkers (e.g., genetic variation associated with depression response), and the health care cost implications of PGx testing. ClinicalTrials.gov Identifier: NCT03170362.

A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process.

Pseudomyxoma peritonei (PMP) is a complex disease with unique biological behavior that usually arises from appendiceal mucinous neoplasia. The classification of PMP and its primary appendiceal neoplasia is contentious, and an international modified Delphi consensus process was instigated to address terminology and definitions. A classification of mucinous appendiceal neoplasia was developed, and it was agreed that "mucinous adenocarcinoma" should be reserved for lesions with infiltrative invasion. The term "low-grade appendiceal mucinous neoplasm" was supported and it was agreed that "cystadenoma" should no longer be recommended. A new term of "high-grade appendiceal mucinous neoplasm" was proposed for lesions without infiltrative invasion but with high-grade cytologic atypia. Serrated polyp with or without dysplasia was preferred for tumors with serrated features confined to the mucosa with an intact muscularis mucosae. Consensus was achieved on the pathologic classification of PMP, defined as the intraperitoneal accumulation of mucus due to mucinous neoplasia characterized by the redistribution phenomenon. Three categories of PMP were agreed-low grade, high grade, and high grade with signet ring cells. Acellular mucin should be classified separately. It was agreed that low-grade and high-grade mucinous carcinoma peritonei should be considered synonymous with disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, respectively. A checklist for the pathologic reporting of PMP and appendiceal mucinous neoplasms was also developed. By adopting the classifications and definitions that were agreed, different centers will be able to use uniform terminology that will allow meaningful comparison of their results.

Endoscopic fenestration of middle cranial fossa arachnoid cysts: does size matter?

The middle cranial fossa (MCF) is the commonest location for intracranial arachnoid cysts and there has long been controversy regarding the optimal surgical management. Over the last 10 years there has been an increased interest in the potential of endoscopic techniques to treat these. In a review of the literature we identified 91 patients with MCF cysts treated with endoscopic techniques. Clinical improvement was seen in 95% of patients and radiological improvement was seen in 74%. The most common complications reported are subdural hygromas (9%) and subdural haematomas (5%). There does not appear to be an undue increased risk of complications compared to open surgical techniques. Reported methods of endoscopic fenestration advocate making as wide an opening as possible without damage to the surrounding neurovascular structures. We consider the possibility that smaller cystocisternostomy may be effective in achieving therapeutic goals while reducing potential risks to the patient.