Lymphoma: Diagnosis and Treatment.

Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma. Approximately 82,000 new U.S. patients are diagnosed with lymphoma annually. Any tobacco use and obesity are major modifiable risk factors, with genetic, infectious, and inflammatory etiologies also contributing. Lymphoma typically presents as painless adenopathy, with systemic symptoms of fever, unexplained weight loss, and night sweats occurring in more advanced stages of the disease. An open lymph node biopsy is preferred for diagnosis. The Lugano classification system incorporates symptoms and the extent of the disease as shown on positron emission tomography/computed tomography to stage lymphoma, which is then used to determine treatment. Chemotherapy treatment plans differ between the main subtypes of lymphoma. Non-Hodgkin lymphoma is treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (R-CHOP), bendamustine, and lenalidomide. Hodgkin lymphoma is treated with combined chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), Stanford V (a chemotherapy regimen consisting of mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone), or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) with radiotherapy. Subsequent chemotherapy toxicities include neuropathy, cardiotoxicity, and secondary cancers such as lung and breast, and should be considered in the shared decision-making process to select a treatment regimen. Once remission is achieved, patients need routine surveillance to monitor for complications and relapse, in addition to age-appropriate screenings recommended by the U.S. Preventive Services Task Force. Patients should receive a 13-valent pneumococcal conjugate vaccine followed by a 23-valent pneumococcal polysaccharide vaccine at least eight weeks later with additional age-appropriate vaccinations because lymphoma is an immunosuppressive condition. Household contacts should also be current with their immunizations.

Four-year longitudinal culinary and lifestyle medicine track for undergraduate medical students: development and implementation.

The importance of culinary and lifestyle medicine education to combat the growing burden of chronic disease is gaining recognition in the United States. However, few medical schools offer in-depth training with a 4-year longitudinal track. The Culinary and Lifestyle Medicine Track (CLMT) is a 4-year curriculum thread created at West Virginia University School of Medicine to address the need for comprehensive culinary and lifestyle medicine education. CLMT teaches concepts of healthy nutrition, physical activity, stress management, and restorative sleep. CLMT students complete approximately 300 h of in-person and virtual culinary and lifestyle medicine education, including hands-on teaching kitchens, distributed over the preclinical and clinical years. Students are selected into the track prior to matriculation after an application and interview process. The students have exceeded expectations for scholarly and community activity. Track graduates have entered into primary care as well as specialty and surgical residencies, demonstrating that lifestyle education plays a role for students interested in a wide range of careers. Exit survey responses from learners reflected tangible and intangible benefits of participation and offered constructive feedback for improvement. Presented here are the components of the curricular design, implementation, and initial outcomes.

Pertussis: a reemerging infection.

Pertussis, also known as whooping cough, is an acute respiratory tract infection that has increased in incidence in recent years. The initial catarrhal stage presents with nonspecific symptoms of malaise, rhinorrhea, sneezing, lacrimation, and mild cough. During the paroxysmal stage, severe outbreaks of coughing often lead to the classic high-pitched whooping sound patients make when gasping for breath. The paroxysmal stage is followed by the convalescent stage and resolution of symptoms. Complications vary by age, with infants more likely to experience severe complications such as apnea, pneumonia, seizures, or death. In adolescents and adults, complications are the result of chronic cough. The diagnosis depends on clinical signs and laboratory testing. Both culture and polymerase chain reaction testing can be used to confirm the diagnosis; serologic testing is not standardized or routinely recommended. Although antibiotics have not shown clear effectiveness in the treatment of pertussis, they eradicate nasal bacterial carriage and may reduce transmission rates. Macrolide antibiotics such as azithromycin are first-line treatments to prevent transmission; trimethoprim/sulfamethoxazole is an alternative in cases of allergy or intolerance to macrolides. Immunization against pertussis is essential for disease prevention. Current recommendations in the United States consist of administering five doses of the diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine to children before seven years of age, and administering a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) booster between 11 and 18 years of age. Recent efforts have focused on the vaccination of adolescents and adults, with new recommendations for a single dose of the Tdap booster if it has not been previously administered.

The Appalachia Mind Health Initiative (AMHI): a pragmatic randomized clinical trial of adjunctive internet-based cognitive behavior therapy for treating major depressive disorder among primary care patients.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disease morbidity. Combined treatment with antidepressant medication (ADM) plus psychotherapy yields a much higher MDD remission rate than ADM only. But 77% of US MDD patients are nonetheless treated with ADM only despite strong patient preferences for psychotherapy. This mismatch is due at least in part to a combination of cost considerations and limited availability of psychotherapists, although stigma and reluctance of PCPs to refer patients for psychotherapy are also involved. Internet-based cognitive behaviorial therapy (i-CBT) addresses all of these problems. METHODS: Enrolled patients (n = 3360) will be those who are beginning ADM-only treatment of MDD in primary care facilities throughout West Virginia, one of the poorest and most rural states in the country. Participating treatment providers and study staff at West Virginia University School of Medicine (WVU) will recruit patients and, after obtaining informed consent, administer a baseline self-report questionnaire (SRQ) and then randomize patients to 1 of 3 treatment arms with equal allocation: ADM only, ADM + self-guided i-CBT, and ADM + guided i-CBT. Follow-up SRQs will be administered 2, 4, 8, 13, 16, 26, 39, and 52 weeks after randomization. The trial has two primary objectives: to evaluate aggregate comparative treatment effects across the 3 arms and to estimate heterogeneity of treatment effects (HTE). The primary outcome will be episode remission based on a modified version of the patient-centered Remission from Depression Questionnaire (RDQ). The sample was powered to detect predictors of HTE that would increase the proportional remission rate by 20% by optimally assigning individuals as opposed to randomly assigning them into three treatment groups of equal size. Aggregate comparative treatment effects will be estimated using intent-to-treat analysis methods. Cumulative inverse probability weights will be used to deal with loss to follow-up. A wide range of self-report predictors of MDD heterogeneity of treatment effects based on previous studies will be included in the baseline SRQ. A state-of-the-art ensemble machine learning method will be used to estimate HTE. DISCUSSION: The study is innovative in using a rich baseline assessment and in having a sample large enough to carry out a well-powered analysis of heterogeneity of treatment effects. We anticipate finding that self-guided and guided i-CBT will both improve outcomes compared to ADM only. We also anticipate finding that the comparative advantages of adding i-CBT to ADM will vary significantly across patients. We hope to develop a stable individualized treatment rule that will allow patients and treatment providers to improve aggregate treatment outcomes by deciding collaboratively when ADM treatment should be augmented with i-CBT. TRIAL REGISTRATION: ClinicalTrials.gov NCT04120285 . Registered on October 19, 2019.

The ACS National Surgical Quality Improvement Program-Inflammatory Bowel Disease Collaborative: Design, Implementation, and Validation of a Disease-specific Module.

BACKGROUND: Surgery for inflammatory bowel disease (IBD) involves a complex interplay between disease, surgery, and medications, exposing patients to increased risk of postoperative complications. Surgical best practices have been largely based on single-institution results and meta-analyses, with multicenter clinical data lacking. The American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) has revolutionized the way in which large-volume surgical outcomes data have been collected. Our aim was to employ the ACS-NSQIP to collect disease-specific variables relevant to surgical outcomes in IBD. STUDY DESIGN: A collaborative of 13 high-volume IBD surgery centers was convened to collect 5 IBD-specific variables in NSQIP. Variables included biologic and immunomodulator medications usage, ileostomy utilization, ileal pouch anastomotic technique, and colonic dysplasia/neoplasia. A sample of the Surgical Clinical Reviewer collected data was validated by a colorectal surgeon at each institution, and kappa's agreement statistics generated. RESULTS: Over 1 year, data were collected on a total of 956 cases. Overall, 41.4% of patients had taken a biologic agent in the 60 days before surgery. The 2 most commonly performed procedures were laparoscopic ileocolic resections (159 cases) and subtotal colectomies (151 cases). Overall, 56.8% of cases employed an ileostomy, and 134 ileal pouches were constructed, of which 92.4% used stapled technique. A sample of 214 (22.4%) consecutive cases was validated from 8 institutions. All 5 novel variables were shown to be reliably collected, with excellent agreement for 4 variables (kappa ≥ 0.70) and very good agreement for the presence of colonic dysplasia (kappa = 0.68). CONCLUSION: We report the results of the initial year of implementation of the first disease-specific collaborative within NSQIP. The selected variables were demonstrated to be reliably collected, and this collaborative will facilitate high-quality, large case-volume research specific to the IBD patient population.

[64Cu]XYIMSR-06: A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma.

Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1 - 8.9 GBq/µmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.

Leukocyte profiles for western fence lizards, Sceloporus occidentalis, naturally infected by the malaria parasite Plasmodium mexicanum.

Plasmodium mexicanum is a malaria parasite that naturally infects the western fence lizard, Sceloporus occidentalis , in northern California. We set out to determine whether lizards naturally infected with this malaria parasite have different leukocyte profiles, indicating an immune response to infection. We used 29 naturally infected western fence lizards paired with uninfected lizards based on sex, snout-to-vent length, tail status, and the presence-absence of ectoparasites such as ticks and mites, as well as the presence-absence of another hemoparasite, Schellackia occidentalis. Complete white blood cell (WBC) counts were conducted on blood smears stained with Giemsa, and the proportion of granulocytes per microliter of blood was estimated using the Avian Leukopet method. The abundance of each WBC class (lymphocytes, monocytes, heterophils, eosinophils, and basophils) in infected and uninfected lizards was compared to determine whether leukocyte densities varied with infection status. We found that the numbers of WBCs and lymphocytes per microliter of blood significantly differed (P < 0.05) between the 2 groups for females but not for males, whereas parasitemia was significantly correlated with lymphocyte counts for males, but not for females. This study supports the theory that infection with P. mexicanum stimulates the lizard's immune response to increase the levels of circulating WBCs, but what effect this has on the biology of the parasite remains unclear.

Multiple myeloma: diagnosis and treatment.

Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons. Typical symptoms are bone pain, malaise, anemia, renal insufficiency, and hypercalcemia. Incidental discovery on comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression. Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma. The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated. Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible. Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue lenalidomide have been used successfully. It is important that family physicians recognize and appropriately treat multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty, or kyphoplasty; nephrotoxic nonsteroidal anti-inflammatory drugs should be avoided. Hypercalcemia is treated with isotonic saline infusions, steroids, furosemide, or bisphosphonates. Because of susceptibility to infections, patients require broad-spectrum antibiotics for febrile illness and immunization against influenza, pneumococcus, and Haemophilus influenzae B. Five-year survival rates approach 33 percent, and the median survival rate is 33 months.

Hepatic hemorrhage caused by percutaneous tumor ablation: radiofrequency ablation versus cryoablation in a porcine model.

PURPOSE: To determine the extent of hepatic hemorrhage caused by percutaneous cryoablation performed with a small-diameter cryoablation probe compared with that caused by percutaneous radiofrequency (RF) ablation in a porcine model. MATERIALS AND METHODS: The study was pre-approved by the institutional research animal care and use committee, and husbandry and experiments complied with National Institutes of Health standards for care and use of laboratory animals. Percutaneous hepatic ablation was performed in 18 domestic pigs (mean weight, 45 kg) by using a 17-gauge (1.5-mm-diameter) RF electrode (n = 6), a cluster of three RF electrodes (n = 6), or a 13-gauge (2.4 mm-diameter) cryoprobe (n = 6). Ablation was performed in four sites per liver. Total blood loss, minimum lesion diameter, maximum lesion diameter, and lesion volume were determined for each group and compared by using analysis of variance. RESULTS: Mean blood loss was 11.11 mL +/- 11.47 (standard deviation), 105.29 mL +/- 175.58, and 28.06 mL +/- 30.97 with the single RF electrode, RF electrode cluster, and cryoablation probe, respectively. Mean minimum and maximum lesion diameters were largest with the RF electrode cluster (2.40 and 3.98 cm, respectively), followed by the cryoablation probe (2.38 and 3.94 cm) and single RF electrode (1.49 and 2.63 cm). Mean minimum and maximum lesion diameters were significantly different between the single RF electrode and the RF electrode cluster, as well as between the single RF electrode and the cryoablation probe (P < .001). Mean lesion volume was largest for the RF electrode cluster (24.03 cm3), followed by those for the cryoablation probe (17.46 cm3) and single RF electrode (9.05 cm3) (single RF electrode vs cryoablation probe, P < .05). Lesion volumes were not significantly different with the RF electrode cluster versus the single RF electrode (P = .052) or with the RF electrode cluster versus the cryoablation probe (P = .381). CONCLUSION: Mean blood loss from percutaneous cryoablation in this model was between that for RF ablation with the single electrode and that for RF ablation with the electrode cluster.