Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement.

Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population.

The effect of combat exposure on sexually transmitted diseases.

Traumatic exposures can affect beliefs and behaviors related to the spread of sexually transmitted diseases (STDs), a persistent public health problem. I leverage a natural experiment created by variation in US military deployment location assignments to estimate how combat exposure changes a surviving deployed male veteran's probability of acquiring a sexually transmitted disease. I analyze longitudinal data from 1994 to 2008 on 485 deployed veterans with information theoretic methods to reduce the sensitivity of estimates to small samples, an infrequently observed outcome, and highly correlated covariates. For veterans assigned to a combat zone, I estimate combat exposure results in a 5.4 percentage point increase in the probability of acquiring an STD. Additional estimations provide evidence suggesting risky behaviors involving substance use or multiple sexual partners may serve as pathways from combat exposure to STDs. My results are relevant to discussions regarding STD screening and care needs for trauma exposed individuals.

Estrogen attenuates left ventricular and cardiomyocyte hypertrophy by an estrogen receptor-dependent pathway that increases calcineurin degradation.

Left ventricular (LV) hypertrophy commonly develops in response to chronic hypertension and is a significant risk factor for heart failure and death. The serine-threonine phosphatase calcineurin (Cn)A plays a critical role in the development of pathological hypertrophy. Previous experimental studies in murine models show that estrogen limits pressure overload-induced hypertrophy; our purpose was to explore further the mechanisms underlying this estrogen effect. Wild-type, ovariectomized female mice were treated with placebo or 17beta-estradiol (E2), followed by transverse aortic constriction (TAC), to induce pressure overload. At 2 weeks, mice underwent physiological evaluation, immediate tissue harvest, or dispersion of cardiomyocytes. E2 replacement limited TAC-induced LV and cardiomyocyte hypertrophy while attenuating deterioration in LV systolic function and contractility. These E2 effects were associated with reduced abundance of CnA. The primary downstream targets of CnA are the nuclear factor of activated T-cell (NFAT) family of transcription factors. In transgenic mice expressing a NFAT-activated promoter/luciferase reporter gene, E2 limited TAC-induced activation of NFAT. Moreover, the inhibitory effects of E2 on LV hypertrophy were absent in CnA knockout mice, supporting the notion that CnA is an important target of E2-mediated inhibition. In cultured rat cardiac myocytes, E2 inhibited agonist-induced hypertrophy while also decreasing CnA abundance and NFAT activation. Agonist stimulation also reduced CnA ubiquitination and degradation that was prevented by E2; all in vitro effects of estrogen were reversed by an estrogen receptor (ER) antagonist. These data support that E2 reduces pressure overload induced hypertrophy by an ER-dependent mechanism that increases CnA degradation, unveiling a novel mechanism by which E2 and ERs regulate pathological LV and cardiomyocyte growth.

Lingual compression for acute macroglossia in a COVID-19 positive patient.

We describe a 40-year-old woman with severe, persistent macroglossia following prone positioning as part of treatment for COVID-19. We used the treatment method of lingual compression with satisfactory results.

Organ donation after trauma: A 30-year review.

BACKGROUND: Over the past 30 years, the demographics, clinical characteristics, and management of trauma patients have changed dramatically. During this same period, the organ donor population has also changed. The interactions between these two demographic shifts have not been examined in a systematic way. We hypothesize that trauma victims continue to be an important source of organs. We set out to systematically examine traumatic donors in an attempt to identify opportunities to increase organ recovery and quality. METHODS: In this retrospective analysis, we compared trauma donors (TDs) and non-TDs (NTDs) in the Scientific Registry of Transplant Recipients standard analysis files, a clinical data set collected by the Organ Procurement Transplant Network on all solid organ transplant candidates, donors, and recipients in the United States since 1987. RESULTS: Scientific Registry of Transplant Recipients contained data on 191,802 deceased donors. The percentage of TDs decreased from 55.3% in 1987 to 35.8% in 2016 (p < 0.001) primarily due to a steady increase in NTDs. Trauma donors are younger and have fewer comorbidities while the percentage of donors who were public health service high risk or who underwent donation after cardiac death were clinically similar. The TDs produce more organs/donor (3.5 vs. 2.4, p < 0.001), are more likely to yield an extrarenal organ, and exhibit lower (better) Kidney Donor Risk Index scores, a predictor of graft longevity. These better outcomes are maintained after stratifying by age. CONCLUSION: Over the past 30 years, the number of NTDs has increased much more than the number of TDs. However, TDs remain a critically important organ donor source, yielding more organs per donor, better quality kidneys, and a higher likelihood of extrarenal organs. Potential causes, such as improved resuscitation protocols, should be examined in the future. LEVEL OF EVIDENCE: Retrospective review, level III.

Association of an Opioid Standard of Practice Intervention With Intravenous Opioid Exposure in Hospitalized Patients.

Importance: Opioids are commonly used to treat pain in hospitalized patients; however, intravenous administration carries an increased risk of adverse effects compared with oral administration. The subcutaneous route is an effective method of opioid delivery with favorable pharmacokinetics. Objective: To assess an intervention to reduce intravenous opioid use, total parenteral opioid exposure, and the rate of patients administered parenteral opioids. Design, Setting, and Participants: A pilot study was conducted in an adult general medical unit in an urban academic medical center. Attending physicians, nurse practitioners, and physician assistants who prescribed drugs were the participants. Use of opioids was compared between a 6-month control period and 3 months following education for the prescribers on opioid routes of administration. Interventions: Adoption of a local opioid standard of practice, preferring the oral and subcutaneous routes over intravenous administration, and education for prescribers and nursing staff on awareness of the subcutaneous route was implemented. Main Outcomes and Measures: The primary outcome was a reduction in intravenous doses administered per patient-day. Secondary measures included total parenteral and overall opioid doses per patient-day, parenteral and overall opioid exposure per patient-day, and daily rate of patients receiving parenteral opioids. Pain scores were measured on a standard 0- to 10-point Likert scale over the first 5 days of hospitalization. Results: The control period included 4500 patient-days, and the intervention period included 2459 patient-days. Of 127 patients in the intervention group, 59 (46.5%) were men; mean (SD) age was 57.6 (18.5) years. Intravenous opioid doses were reduced by 84% (0.06 vs 0.39 doses per patient-day, P < .001), and doses of all parenteral opioids were reduced by 55% (0.18 vs 0.39 doses per patient-day, P < .001). In addition, mean (SD) daily parenteral opioid exposure decreased by 49% (2.88 [0.72] vs 5.67 [1.14] morphine-milligram equivalents [MMEs] per patient-day). The daily rate of patients administered any parenteral opioid decreased by 57% (6% vs 14%; P < .001). Doses of opioids given by oral or parenteral route were reduced by 23% (0.73 vs 0.95 doses per patient-day, P = .02), and mean daily overall opioid exposure decreased by 31% (6.30 [4.12] vs 9.11 [7.34] MMEs per patient-day). For hospital days 1 through 3, there were no significant postintervention vs preintervention differences in mean reported pain score for patients receiving opioid therapy: day 1, -0.19 (95% CI, -0.94 to 0.56); day 2, -0.49 (95% CI, -1.01 to 0.03); and day 3, -0.54 (95% CI, -1.18 to 0.09). However, significant improvement was seen in the intervention group on days 4 (-1.07; 95% CI, -1.80 to -0.34) and 5 (-1.06; 95% CI, -1.84 to -0.27). Conclusions and Relevance: An intervention targeting the use of intravenous opioids may be associated with reduced opioid exposure while providing effective pain control to hospitalized adults.

Prevalence of environmental and other military exposure concerns in Operation Enduring Freedom and Operation Iraqi Freedom veterans.

OBJECTIVE: This study examined the prevalence of self-reported exposures in returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans and the relationship of exposure reports to current physical symptoms. METHODS: Using self-reports obtained immediately after return from deployment in a cohort of 760 enlisted Army reserve component military personnel, we assessed prevalence rates of environmental and other exposures and the association of these exposures to severity of physical symptoms. RESULTS: Reporting of environmental exposures was relatively low in veterans of OEF/OIF, but reporting more environmental and other exposures, in particular screening positive for a traumatic brain injury, was related to greater physical symptom severity immediately after deployment. CONCLUSIONS: Non-treatment-seeking, enlisted Army reserve component personnel reported relatively few exposures immediately after return from deployment; however, more exposures was modestly associated with greater severity of physical symptoms when controlling for predeployment symptoms, gender, and other deployment-related exposures.

Successful treatment of acute mania and perineal abscess using dexmedetomidine sedation as adjunctive therapy.

Acute psychiatric illness with agitation presents the clinician with a dangerous, potentially life-threatening situation often requiring complex management. Alteration in patients' insight and judgment may result in medication non-compliance, potentially further complicating therapy directed at the primary psychiatric illness as well as any co-existing conditions. Sedation is often necessary to control dangerous behaviour during the period of antipsychotic and mood-stabilising drug titration. Dexmedetomidine is a centrally acting selective α2-adrenergic agonist with anaesthetic and sedative properties widely used in intensive care units for sedation in critically ill patients. The authors report the case of a patient managed successfully with dexmedetomidine sedation while being treated for acute mania and perineal abscess.

B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma.

B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as "double-hit" lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathologic features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathologic spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we carried out case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32 to 91). Six patients had a history of grade 1 to 2 follicular lymphoma; review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 mo) was inferior to both BL (P=0.002) and IPI-matched DLBCL (P=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (P<0.0001), Mum1/IRF4 (P=0.006), Ki-67 <95% (P<0.0001), and absence of EBV-EBER (P=0.006). DHL commonly contained the t(8;22) rather than the t(8;14) seen in most BL controls (P=0.001), and exhibited a higher number of chromosomal aberrations (P=0.0009). DHL is a high-grade B-cell neoplasm with a poor prognosis, resistance to multiagent chemotherapy, and clinical and pathologic features distinct from other high-grade B-cell neoplasms. Familiarity with the morphologic and immunophenotypic spectrum of DHL is important in directing testing to detect concurrent IGH-BCL2 and MYC rearrangements when a karyotype is unavailable. The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches.

Carcinoma and multiple lymphomas in one patient: establishing the diagnoses and analyzing risk factors.

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient's follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development.