Neighborhood disadvantage, insurance status, and molecular profiling of patients with acute myeloid leukemia.

Next-generation sequencing (NGS) is important for prognostication and determining eligibility for targeted therapies in acute myeloid leukemia (AML). The use of NGS has increased in clinical practice, but variability in testing patterns still exist. The purpose of this study was to assess trends in molecular genetic sequencing in AML based on insurance status and area deprivation index (ADI), a validated metric of neighborhood disadvantage. Patient demographics, clinical characteristics, cytogenetic and molecular data, and treatment patterns were collected retrospectively for 275 patients diagnosed with AML at a single institution. No significant differences in practice patterns and patient outcomes based on ADI rank were observed. In contrast, patients with Medicare or underinsured status were less likely to have genetic sequencing performed, were treated with less intensive regimens, and had inferior overall survival compared to those with Medicaid or private insurance. On univariate analysis, molecular genetic sequencing was associated with improved overall survival, suggesting that NGS data allows for better risk stratification and more informed therapeutic decision-making. These data highlight the current barriers to molecular genetic sequencing, demonstrate the positive benefits of NGS on clinical outcomes, and support universal coverage of NGS for all patients with AML.

Allogeneic transplant following CAR T-cell therapy for large B-cell lymphoma.

Allogeneic hematopoietic cell transplantation (alloHCT) can potentially salvage large B-cell lymphoma (LBCL) patients experiencing treatment failure after chimeric antigen receptor T-cell therapy (CAR T). Nonetheless, data on the efficacy and toxicities of alloHCT after receipt of CAR T are limited. We report a multicenter retrospective study assessing the safety, toxicities, and outcomes of alloHCT in LBCL patients following CAR T failure. Eighty-eight patients with relapsed, refractory LBCL received an alloHCT following anti-CD19 CAR T failure. The median number of lines of therapy between CAR T infusion and alloHCT was one (range, 0-7). Low intensity conditioning was used in 77% (n=68) and peripheral blood was the most common graft source (86%, n=76). The most common donor types were matched unrelated donor (39%), followed by haploidentical (30%) and matched related donor (26%). Median follow-up of survivors was 15 months (range, 1-72). One-year overall survival, progression-free survival, and graft-versus-host disease-free relapse-free survival were 59%, 45%, and 39% respectively. One-year non-relapse mortality and progression/relapse were 22% and 33% respectively. On multivariate analysis, <2 lines of intervening therapy between CAR T and alloHCT and complete response at time of alloHCT were associated with better outcomes. In conclusion, alloHCT after CAR T failure can provide durable remissions in a subset of patients.

Pregnancy in a Transgender Male: A Case Report and Review of the Literature.

Introduction: Pregnancy in transgender men is an area of increasing study due to data showing that pregnancy can occur in this population despite the reduction in fertility that generally accompanies treatment with gender-affirming hormone therapies. Case: In this case, we describe a healthy 21-year-old transgender man who was able to achieve pregnancy without reproductive assistance after stopping his testosterone therapy for 2 months. Discussion. Our case is important as it highlights how little is known in regards to gender-affirming hormone therapy on fertility. While testosterone is known to reduce fertility by inducing anovulation and altering ovarian histology, its long-term effects on conception rates and pregnancy are largely unknown. Some studies demonstrate that transgender men, treated with gender-affirming hormone therapy (GAHT), including testosterone, have similar oocyte quantity and quality, as well as similar ovarian reserve, when compared to cisgender women, suggesting that resumption of fertility may be possible after cessation of GAHT. Long-term outcomes for the pregnancy and the offspring of those who have been treated with GAHT are unknown. Conclusion: Recent studies have shown that pregnancy is possible for transgender men who desire biological children and have received gender-affirming hormonal therapy without fertility-preserving measures. Further research is needed to help determine rates of fertility, the likelihood of recovery of fertility, conception rates, and long-term pregnancy outcomes. Such information would help guide physicians in providing education and counseling to their transgender patients regarding reproductive options.

Maturity-Onset Diabetes of Young Type 5: Diabetes with Extrapancreatic Features.

OBJECTIVE: This case involves a new-onset diabetes patient diagnosed during pregnancy with the congenital dysplastic right kidney. Case Report. Clinical presentation, biochemical features, imaging in a patient with diabetes diagnosed during pregnancy, and congenital dysplastic right kidney. Discussion. We present a case of a 22-year-old female with the congenital dysplastic right kidney diagnosed with gestational diabetes mellitus after failing a 1-hour oral glucose tolerance test, requiring insulin during pregnancy. Because of the family history of diabetes and morphologic renal abnormalities at young ages on the maternal side of the family, our patient was evaluated for maturity-onset diabetes of adult and was found to have HNF-1ß mutation. CONCLUSION: This case highlights the importance of considering the diagnosis of maturity-onset diabetes of young and particularly MODY-5 in individuals with extrapancreatic features. MODY-5 should also be considered in a patient undergoing renal transplant at young ages with a family history of morphologic renal abnormalities.

Systemic Options for Malignant Peripheral Nerve Sheath Tumors.

OPINION STATEMENT: Malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal neoplasms that represent a profound therapeutic challenge due to their high proclivity for recurrence and metastasis and relatively poor response to systemic therapy regimens. While our understanding of the pathophysiology of MPNST is growing, including loss of the tumor suppressor gene neurofibromin and subsequent activation of the Ras pathway, targeted therapy to modify the poor prognosis seen in MPNST patients has thus far been without success. Correspondingly, MPNST patients are treated as per soft tissue sarcoma treatment algorithms with anthracycline-based therapy as the front-line therapy of choice for patients with unresectable, locally advanced, or metastatic MPNST. Beyond first-line anthracycline-based therapy, other standard cytotoxic chemotherapy agents used in advanced MPNST include the alkylating agent ifosfamide and the topoisomerase II inhibitor etoposide. Notably, soft tissue sarcoma regimens are used in MPNST despite distinct systemic therapy sensitivity and prognosis. This is particularly notable for neurofibromatosis type 1 (NF1)-associated MPNST, which is associated with poorer response to systemic therapy and prognosis than sporadic MPNST. As such, NF1-associated MPNST is a particular area in need of novel therapeutic strategies. Given the lack of benefit in the targeting of unique aspects of MPNST disease biology thus far, pre-clinical studies to identify novel rational therapies are critical to inform future clinical trials.

Polycythemia and Anemia in Hereditary Hemochromatosis.

Introduction Hereditary hemochromatosis is a syndrome of dysregulated iron homeostasis resulting in the excessive deposition of iron. Hemochromatosis causes pulmonary, pancreatic, and hepatic dysfunction, all of which are risk factors for anemia in the general population. Conversely, iron overload states are thought to predispose to polycythemia. The effect of the homozygosity and heterozygosity of hereditary hemochromatosis-associated genes on hemoglobin levels has not been sufficiently studied. Materials and methods We conducted a retrospective cohort study at West Virginia University of all patients who underwent HFE gene analysis and carried the diagnosis of hemochromatosis. Charts were reviewed to identify relevant variables and the patients' clinical course. Results A total of 213 patients were included with 143 male participants (67.13%). The mean age was 53.6 years (SD: 15.2). A total of 108 patients were homozygous for the C282Y mutation. The prevalence of baseline characteristics are as follows: tobacco use 46.3%, chronic obstructive pulmonary disease 16.4%, malignancy 20.1%, cirrhosis 16.8%, anticoagulant use 6.5%, and chronic renal insufficiency 13.1%. The mean hemoglobin of the population was 15.0 mg/dL (SD 2.21). Anemia was seen in 23 patients (10.80%) and 59 patients (27.6%) had polycythemia. Concurrent malignancy and the presence of chronic renal insufficiency were significantly associated with anemia in both the univariate and multivariate analysis (p-values < 0.001). Patients with homozygosity for C282Y were more likely to receive phlebotomy as compared to other patients. Serum ferritin was not associated with anemia or polycythemia on multivariate analyses (p-values 0.197 and 0.105, respectively). Conclusion Despite the high prevalence of comorbidities that are known risk factors for anemia in the general population, few patients with hereditary hemochromatosis develop anemia. Female patients with hereditary hemochromatosis are relatively protected against polycythemia, affecting only one-fourth of all patients with hemochromatosis, with most patients' serum hemoglobin reported within normal limits.

Epidemiology and antibiogram of common mastitis-causing bacteria in Beetal goats.

BACKGROUND AND AIM: Mastitis has been identified as the most prevalent and economically imperative disease among dairy animals. Thus, understanding its common bacterial pathogens and risk factors is necessary to improve udder health at herd, region, or country level. However, scientific research on caprine mastitis, especially on Beetal breed, has remained to be insufficient in Pakistan. Therefore, this study aimed to evaluate the epidemiology and antibiogram assay of common mastitis-causing bacterial agents, that is, Staphylococcus, Streptococcus, and Escherichia coli, in dairy goats. MATERIALS AND METHODS: In total, 500 Beetal goats, irrespective of age and those that were not treated with any kind of antimicrobial agents during the past 120 h, were screened using California Mastitis Test in Pattoki, Kasur District, whereas epidemiological factors were recorded. The milk samples of mastitic goats were then collected and processed using standard methods. Each sample was primarily cultured on nutrient agar. Using a specific medium, each bacterial colony was separated using several streak methods. Six antibiotic disks belonging to different antibiotic groups were used for antibiogram profiling of bacterial isolates. Chi-square test was used to assess the association of baseline characteristics and mastitis occurrence. Meanwhile, multivariable logistic regression (p<0.001) was utilized to determine the risk factors associated with positive and negative dichotomous outcome of mastitis. RESULTS: The results revealed that the overall prevalence of goat mastitis was 309 (61.8%), in which 260 (52%) and 49 (9.8%) cases were positive for subclinical mastitis (SCM) and clinical mastitis (CM), respectively. Streptococcus and E. coli were found to be the predominant isolates causing SCM and CM, respectively (p<0.001). It was observed that amoxicillin+clavulanic acid was highly sensitive to isolates of Staphylococcus and Streptococcus and ceftiofur sodium to isolates of Streptococcus and E. coli., while enrofloxacin was found to be sensitive to isolates of Streptococcus and E. coli. Risk factors such as herd structure, deworming, vaccination, presence of ticks, use of teat dip and mineral supplements, feeding type, age, parity, housing, blood in the milk, milk leakage, milk taste, and milk yield were found to have the strongest association with mastitis occurrence, while ease of milking has moderate association. CONCLUSION: In the area examined, cases of SCM were found to be higher compared with that of CM, and ceftiofur sodium has been identified as the preferred treatment in both clinical and subclinical forms of caprine mastitis in Beetal goats. Risk factors for mastitis that was identified in this study can form the basis for the creation of an udder health control program specific for dairy goats. We hope our findings could raise awareness of the risk factors and treatment approaches for common mastitis-causing bacterial agents.

Phytochemistry and pharmacological potential of Cassia absus - a review.

OBJECTIVES: Cassia absus is a plant of the family fabaceae with Ayurvedic ethnomedical records. It is used in traditional medicine for the treatment of bronchitis, asthma, cough, conjunctivitis, leucoderma, renal and hepatic diseases, constipation, tumors, venereal ulcer, headache, hemorrhoids and wound healing. Preliminary in vitro and in vivo studies have provided valuable scientific evidence for its use. This review aims to summarize reported pharmacognosy, traditional uses, phytochemistry and pharmacological potential of C. absus while identifying potential areas of further research of plant. KEY FINDINGS: The review comprises literature pertaining to the evidence base therapeutic potential, pharmacognosy and phytochemistry of C. absus spanning from 1935 to 2016 using published articles in peer-reviewed journals, ethno botanical text books, and worldwide accepted scientific databases via electronic search (Elsevier, Google Scholar, PubMed, Scopus, Springer, Web of Science, Wiley online library). Kew Botanical Garden databases and the Plant List were used to authenticate the scientific names. Different pharmacological experiments in many in-vitro and in-vivo models have proved the potential of C. absus with antihypertensive, antifertility, antifungal, anti-inflammatory, anti-hyperglycemic, anti-glycation, antibacterial activity, α- amylase inhibitory activity, antioxidant and reducing activitity etc. chaksine, iso-chaksine, saturated and unsaturated fatty acids, chrysophanol, aloe-emodin and a wide range of chemical compounds have also been reported. Toxicity studies reveal the nontoxic nature of C. absus at a dose of 2000 mg/kg, however, plant possess reproductive toxicity and can be used as birth control or abortifacient. SUMMARY: Reported activities suggest that there is sufficient pharmacological potential for developing C. absus as a drug for hypertension, infections, diabetes and its complications. However, heterogeneity in study protocol and conflicting results mask the ability to replicate these studies. So, future studies should be replicated in line with best practices. More toxicological studies would aid the progress to clinical trial studies. Various ethno medical uses of C. absus have not been evaluated yet.