Shared Decision-making Lowers Medical Expenditures and the Effect Is Amplified in Racially-Ethnically Concordant Relationships.

BACKGROUND: Racial-ethnic disparities are pervasive in health care. One mechanism that may underlie disparities is variation in shared decision-making (SDM), which encompasses high-quality clinician-patient communication, including deliberative discussions about treatment options. OBJECTIVES: To determine whether SDM has causal effects on outcomes and whether these effects are stronger within racial-ethnic concordant clinician-patient relationships. RESEARCH DESIGN: We use instrumental variables to estimate the causal effect of SDM on outcomes. SUBJECTS: A total of 60,584 patients from the 2003-2017 Integrated Public Use Microdata Series Medical Expenditure Panel Survey. Years 2018 and 2019 were excluded due to changes in the Medical Expenditure Panel Survey that omitted essential parts of the SDM index. MEASURES: Our key variable of interest is the SDM index. Outcomes included total, outpatient, and drug expenditures; physical and mental health; and the utilization of inpatient and emergency services. RESULTS: SDM lowers annual total health expenditures for all racial-ethnic groups, but this effect is only moderated among Black patients seen by Black clinicians, more than doubling in size relative to Whites. A similar SDM moderation effect also occurs for both Black patients seen by Black clinicians and Hispanic patients seen by Hispanic clinicians with regard to annual outpatient expenditures. There was no significant effect of SDM on self-reported physical or mental health. CONCLUSIONS: High-quality SDM can reduce health expenditures without negatively impacting overall physical or mental health, supporting a business case for health care organizations and systems to improve racial-ethnic clinician-patient concordance for Black and Hispanic patients.

Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study.

BACKGROUND: Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT. METHODS: PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphoma and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician, and met at least one prespecified transplantation not intended criterion. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 days) followed 2-7 days later by two sequential lisocabtagene maraleucel infusions (equal target doses of CD8+ and CD4+ CAR+ T cells for a total target dose of 100 × 106 CAR+ T cells). The primary endpoint was the overall response rate and was assessed in all patients who received lisocabtagene maraleucel and had confirmed PET-positive disease before lisocabtagene maraleucel administration based on an independent review committee according to the Lugano 2014 criteria. Safety was assessed in all patients who received lisocabtagene maraleucel. Patient follow-up is ongoing. This study is registered with ClinicalTrials.gov, NCT03483103. FINDINGS: Between July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70-78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR 6·1-18·0). 49 (80% [95% CI 68-89]; p<0·0001) patients had an overall response. The most common grade 3 or worse treatment-emergent adverse events were neutropenia (29 [48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths. INTERPRETATION: These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended. FUNDING: Juno Therapeutics, a Bristol-Myers Squibb company.

AIDS-Related Kaposi Sarcoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.

Cancer in People Living With HIV, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer.

Shoulder Instability in the Overhead Athlete.

Shoulder instability encompasses a spectrum of disease ranging from subluxation to dislocation, and is typically associated with collision athletes such as wrestlers and football players. Instability, however, also can be the result of repetitive microtrauma, as seen in overhead athletes (baseball, tennis, volleyball, swimming). The presentation of instability can be subtle, and difficult to diagnose in the absence of an acute traumatic event without the proper suspicion, physical examination, and diagnostic evaluation. Overhead athletes present the unique challenge of requiring the glenohumeral joint to exceed its physiologic limits during competition; therefore, injury in this population can be devastating. Additionally, athletes who experience instability, regardless of treatment, require rehabilitation (including periscapular strengthening) to maximize strength of the surrounding musculature. Specifically they will require coordinated throwing programs, and gradual return to play protocols dependent on their sport. This article reviews the specific physiology, diagnosis, and treatment of shoulder instability in this population.

Radiology Case of the Month: Idiopathic CD4 Lymphocytopenia.

A 39 year-old male with a history of diabetes, retinitis pigmentosa, and genital warts presented with intractable occipital headaches accompanied with nausea and vomiting. The patient had markedly depressed CD4 counts. Furthermore the patient tested negative for HIV and HTLV 1/2 and had normal immunoglobulin levels. During hospital course the patient underwent a lumbar puncture and multiple imaging exams, including both CT and MR. Except for occasional nausea and vomiting controlled by therapeutic lumbar punctures, phenergan, and dilaudid the patient's hospital course was uncomplicated.

Comprehensive analysis of gene expression in human retina and supporting tissues.

Understanding the influence of gene expression on the molecular mechanisms underpinning human phenotypic diversity is fundamental to being able to predict health outcomes and treat disease. We have carried out whole transcriptome expression analysis on a series of eight normal human postmortem eyes by RNA sequencing. Here we present data showing that ∼80% of the transcriptome is expressed in the posterior layers of the eye and that there is significant differential expression not only between the layers of the posterior part of the eye but also between locations of a tissue layer. These differences in expression also extend to alternative splicing and splicing factors. Differentially expressed genes are enriched for genes associated with psychiatric, immune and cardiovascular disorders. Enrichment categories for gene ontology included ion transport, synaptic transmission and visual and sensory perception. Lastly, allele-specific expression was found to be significant for CFH, C3 and CFB, which are known risk genes for age-related macular degeneration. These expression differences should be useful in determining the underlying biology of associations with common diseases of the human retina, retinal pigment epithelium and choroid and in guiding the analysis of the genomic regions involved in the control of normal gene expression.

Radiology Case of the Month: Persistent Lateral Foot Pain.

A 33-year-old female presents with persistent lateral foot pain. Patient does not recall prior trauma that may have led to injury. Symptoms are significantly improved with rest and nonsteroidal anti-inflammatory medications.

How I treat CNS lymphomas.

The pathogenesis of primary and secondary central nervous system (CNS) lymphoma poses a unique set of diagnostic, prognostic, and therapeutic challenges. During the past 10 years, there has been significant progress in the elucidation of the molecular properties of CNS lymphomas and their microenvironment, as well as evolution in the development of novel treatment strategies. Although a CNS lymphoma diagnosis was once assumed to be uniformly associated with a dismal prognosis, it is now reasonable to anticipate long-term survival, and possibly a cure, for a significant fraction of CNS lymphoma patients. The pathogenesis of CNS lymphomas affects multiple compartments within the neuroaxis, and proper treatment of the CNS lymphoma patient requires a multidisciplinary team with expertise not only in hematology/oncology but also in neurology, neuroradiology, neurosurgery, clinical neuropsychology, ophthalmology, pathology, and radiation oncology. Given the evolving principles of management and the evidence for improvements in survival, our goal is to provide an overview of current knowledge regarding the pathogenesis of CNS lymphomas and to highlight promising strategies that we believe to be most effective in establishing diagnosis, staging, and therapeutic management.

New meets old: a case study and review of novel therapeutics for the treatment of CLL in older patients.

The treatment of older or medically frail patients with chronic lymphocytic leukemia (CLL) presents unique challenges to clinicians attempting to maximize efficacy while avoiding significant toxicity. This case report presents a 75-year-old man with Rai stage II CLL complicated by massive splenomegaly, high-risk cytogenetics, and intolerance to first-line therapy recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas. A brief summary of his disease and treatment course accompanies a discussion of the special challenges associated with treating this patient population. In addition, emerging novel and targeted therapies, including next-generation monoclonal antibodies and small molecule inhibitors, are reviewed in the broader context of evolving standards of care and the NCCN Guidelines.

The use of multislice CT angiography preoperative study for supraclavicular artery island flap harvesting.

BACKGROUND: The vascular anatomy of the supraclavicular artery island (SAI) flap has been investigated using both cadaveric anatomic dissections and angiographic studies. Accurate preoperative evaluation and localization of its vascular pedicle confirms its location, course, anatomic variation, and improves flap success. The objective of this report is to demonstrate the utility of multislice computed tomography (CT) angiography for confirming the presence of the vascular pedicle of the SAI flap when planning head and neck reconstruction. METHODS: Patients were studied using 64-multislice CT angiography (CTA) to localize the supraclavicular artery, including its origin and destination. Axial images, multiplanar reconstructions, and 3D volume-rendered images were analyzed on a Philips workstation. Radiologic image findings and clinical experience will be described. RESULTS: SAI CT angiography was successfully performed in 15 patients (30 shoulders) ranging from ages 22 to 81 years. Accurate identification of the main vascular pedicle was achieved in 14/15 patients. Location, course, pedicle length, and anatomic variations were reported for 23 of 30 arteries. Mean vessel diameter was found to be 1.49 mm (range, 0.8-2.0 mm) on the right and 1.51 mm (range, 1.0-2.1 mm) on the left. The mean length of the artery was 38.3 mm on the right (range, 26.6-59.6 mm) and 38.4 mm on the left (range, 24.3-67.0 mm). In all patients, the supraclavicular artery originated off the transverse cervical artery-a branch of the thyrocervical trunk. Positioning of the patient's upper extremities at the side was helpful in the identification of the supraclavicular artery and its distribution. Contrast injection site should be contralateral to the side needed for the flap if sidedness is of importance, secondary to contrast bolus artifact. CONCLUSIONS: Preoperative evaluation of the SAI flap with multislice computed tomography angiography is feasible in patients. A radiologic study protocol has been developed which improves the ability to detect this vessel. This technique provides a noninvasive approach to the identification of the vascular anatomy and is easily standardized/reproducible. The identification of the vascular pedicle and its anatomy can be a benefit to the surgical team during preoperative design of the SAI flap; however, clinical experience confirming these radiologic findings will be needed to optimize surgical outcome.

Clinical and radiographic assessment of post-treatment endodontic disease by primary healthcare professionals: A hospital-based 1-year follow-up.

Background: The comprehensive healthcare approach including prophylactic guidance and motivation by the primary healthcare professionals towards oral and maxillofacial diseases such as post-treatment endodontic disease (PTED) plays a significant role in diagnosing and managing the condition. Especially in the developing countries like India where the hygiene practices are severely compromised, the primary healthcare professional plays an upfront role. Objectives: The present study was conducted to assess the clinical and radiographic characteristics of PTED by primary healthcare professional. Materials and Methods: The cross-sectional study was conducted in a dental hospital in Kutch, Gujarat, India. In the present study, out of a total of 755, 96 patients were diagnosed with PTED, met the inclusion criteria, and were enrolled for the study. After performing intraoral and extraoral examination, intraoral periapical radiographs were taken of the concerned teeth. Under dark room conditions, radiographs were examined using dentsply light box and magnifying glass by healthcare professionals. Results: Out of 755 patients, 96 (12.71%) patients were enrolled in the study with 98 concerned teeth. The most common teeth diagnosed with PTED were maxillary molars with 25.51% (21) individuals. Well-defined radiolucent lesions were seen in 62.24% (61) individuals. Voids in both coronal and apical region were seen in majority (38.77%) of patients. The length of root-end fillings with respect to the radiographic apex was satisfactory in 44.89% (44) individuals. The present study showed strong correlation between sinus formation and presence of periapical lesion with P value of 0.0219*. Conclusion: The proper guidance and preventive care by primary healthcare professionals leads to the relatively less prevalence of post-treatment endodontic disease in Indian population. The present study further suggests the higher substandard quality of root-end fillings of endodontically treated teeth.

Diagnostic Accuracy of Ultrasound in Predicting Extrathyroidal Extension and Its Relation to Body Mass Index in a North American Population.

Detection of extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) influences treatment plan and surgical aggressiveness. Ultrasound (US) is the long-standing preoperative imaging method of choice. Recent literature from Asia suggests US accuracy to be influenced by patient characteristics, such as body mass index (BMI). Here, we examine the effect of BMI on the accuracy of US at a North American tertiary referral center. A total of 204 PTC-confirmed patients were retrospectively read by a radiologist blinded to surgical pathology findings. The radiologist recorded multiple sonographic features, including ETE, loss of echogenic capsule, nodule vascularity, capsular abutment, and bulging of contour. When considering all patients, the ultrasonographic feature with the best overall performance was loss of echogenic capsule (diagnostic odds ratio (DOR) = 4.48, 95% confidence interval (CI) = 1.86-10.78). Sub-group analysis by patient BMI found that area under the curve (AUC) for sonographic features was greater in non-obese BMI patients (0.71 ± 0.06) when compared with obese patients (0.43 ± 0.05; p = 0.001). Overall, US diagnostic performance was significantly better in non-obese (DOR = 3.70, 95%CI = 1.53-8.94) patients when compared to those who were obese (DOR = 1.12, 95%CI = 0.62-2.03; p = 0.03). Loss of the echogenic capsule did not differ between the two cohorts with respect to DOR (p = 0.51), specificity (p = 0.52), or sensitivity (p = 0.09). Our work suggests that the diagnostic value of ETE detection by US is impaired in obese patients. Considering that loss of the echogenic capsule did not differ with respect to diagnostic performance, specificity, nor sensitivity between non-obese and obese patients, it could be considered the most important predictor of US-determined ETE.

CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity.

To obtain a deeper understanding of poor responses to COVID-19 vaccination in patients with lymphoma, we assessed blocking antibodies, total anti-spike IgG, and spike-specific memory B cells in the peripheral blood of 126 patients with lymphoma and 20 age-matched healthy controls 1 and 4 months after COVID-19 vaccination. Fifty-five percent of patients developed blocking antibodies postvaccination, compared with 100% of controls. When evaluating patients last treated from days to nearly 18 years prior to vaccination, time since last anti-CD20 was a significant independent predictor of vaccine response. None of 31 patients who had received anti-CD20 treatment within 6 months prior to vaccination developed blocking antibodies. In contrast, patients who initiated anti-CD20 treatment shortly after achieving a vaccine-induced antibody response tended to retain that response during treatment, suggesting a policy of immunizing prior to treatment whenever possible. SIGNIFICANCE: In a large cohort of patients with B-cell lymphoma, time since anti-CD20 treatment was an independent predictor of neutralizing antibody response to COVID-19 vaccination. Comparing patients who received anti-CD20 treatment before or after vaccination, we demonstrate that vaccinating first can generate an antibody response that endures through anti-CD20-containing treatment. This article is highlighted in the In This Issue feature, p. 85.

Radiology case of the month. An unusual case of hemorrhage with rapid deterioation. Posterior reversible encephalopathy syndrome (PRES).

A 42-year-old female presented to the emergency room with altered mental status and visual disturbances. Patient has a known history of recent liver transplant and currently takes cyclosporine. Patient underwent multimodality imaging, including CT and MRI and suffered rapid deterioration within 24 hours.

Stage I-II diffuse large B-cell lymphoma treated with rituximab and chemotherapy with or without radiotherapy.

We set to identify prognostic factors in a retrospective cohort of consecutive patients with stage I-II diffuse large B-cell lymphoma treated with rituximab-chemotherapy with or without radiotherapy from 2001 through 2017 at our institution. We identified 143 patients with median follow-up of 7.7 years. The majority were male (59.4%), had stage II (53.1%), had stage-modified IPI 0-1 (smIPI, 58.1%), and had non-bulky disease (<7 cm, 68.5%). 99 patients (69.2%) received rituximab-chemotherapy followed by radiotherapy, and 44 patients (30.8%) received rituximab-chemotherapy alone. The 5-year progression-free survival (PFS) and overall survival (OS) were 81.2% and 88.9%, respectively. The 5-year PFS for those with smIPI 0-1 versus 2-4 was 89.5% versus 69.7%, respectively (P = 0.005). Bulky disease (≥7 cm) was associated with worse PFS and OS on univariable and multivariable analyses (P < 0.05). Patients with smIPI 0-1 without bulky disease have excellent outcomes. However, patients with smIPI 2-4 or bulky disease have a high risk of progression.

Role of FNA with core biopsy or cell block in patients with nodular lymphocyte-predominant Hodgkin lymphoma.

BACKGROUND: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents a diagnostic challenge on surgical excisional or incisional biopsy. Classification is further challenging on fine needle aspiration (FNA) material accompanied by needle core and/or cell block biopsy (FNA+core/CB). METHODS: The authors studied all FNA+core/CB and surgical excisional or incisional biopsies to evaluate for lymphoma in patients who had a prior history of NLPHL or subsequent diagnosis of NLPHL over a 5-year period from 2012 through 2016. RESULTS: Patients who ultimately were diagnosed with NLPHL represented <0.5% of those who underwent FNA+core/CB for an initial suspicion of lymphoma. FNA+core/CB resulted in a definitive diagnosis in 7 of 13 cases, and surgical excisional or incisional biopsy specimens resulted in a definitive diagnosis in 13 of 13 cases (chi-square statistic, 9.6; P = .002). At initial diagnosis, FNA+core/CB was negative in 2 cases and atypical or suspicious in 3 cases; all 5 of those patients required surgical excisional or incisional biopsy for a definitive lymphoma diagnosis. By contrast, patients who underwent FNA+core/CB for recurrent lymphoma required surgical excisional or incisional biopsy in only 1 of 8 cases (chi-square statistic, 9.5; P = .002). Flow cytometry was positive for a light-chain-restricted B-cell population in only 1 of 11 biopsies that were involved by lymphoma. CONCLUSIONS: Surgical excisional or incisional biopsy remains the gold standard for NLPHL diagnosis and for distinguishing progression to a T-cell/histiocyte-rich large B-cell lymphoma pattern. At a tertiary cancer center with routine collaborative diagnosis of lymphoma on FNA+core/CB by cytopathologists and hematopathologists, FNA+core/CB performs well to assess for recurrent or transformed NLPHL, rarely requiring subsequent surgical excisional or incisional biopsy. FNA+core/CB has limited sensitivity in the initial diagnosis setting.

Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial.

Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of ≥1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe.