Frontline STI Screening Starts with Primary Care.

In this supplement to Family Practice, Heather M. Territo, MD, and Gale R. Burstein, MD, MPH discuss how primary care physicians play an essential role in screening for STIs in young patients.

Trichomonas Infection Rates in Males Presenting to the Emergency Department for Sexually Transmitted Infections.

BACKGROUND: Trichomonas vaginalis (TV) is one of the most common sexually transmitted infections (STIs). Overall prevalence is reported to be 3.1%, with rates approaching 12.9-14.4% in high-risk female populations. Although there is a plethora of data on TV in the female population, the corresponding data for the male population are limited. OBJECTIVE: Our aim was to determine the infection rate of TV in male patients seeking care for STIs in the emergency department (ED) and determine the symptoms associated with TV infection in male patients. METHODS: We conducted a retrospective study of male patients aged 13 years or older who presented to the ED for STI evaluation. Male patients included had nucleic acid amplification test (NAAT) TV testing as part of standard STI evaluation. RESULTS: Of the 2137 male patients included, 95 (4.4%) were positive for TV. Male patients who tested positive were significantly older (mean age 38.9 years vs. 30.7 years for male patients who tested negative; p < 0.05). Black male patients were more likely than White male patients to be positive for TV (6.3% prevalence vs. 1.8%; p < 0.05). TV-positive male patients were more likely to have discharge, specifically clear penile discharge, on examination (p < 0.05), and were less likely to have testicular pain or testicular tenderness (p < 0.05). Higher rates of TV were seen in an urban (4.9%) compared with suburban ED (1.6%; p < 0.05). CONCLUSIONS: Rates of TV in male patients who receive STI testing in the ED are similar to rates published previously for female patients. We found higher rates among older and African-American male patients. TV among male patients is prevalent and testing should continue when evaluating for STIs.

Genomic Surveillance of SARS-CoV-2 in Erie County, New York

Early in the SAR-CoV-2 pandemic, we established a whole genome sequencing pipeline to assess lineages circulating in Western New York. Initial sequences revealed entry into the region via Europe, similar to observations in New York City. However, as the pandemic progressed and variants of concern emerged, we observed distinct patterns in lineages relative to NYC. Notably, B.1.427 became dominant in Western New York, before it was displaced by B.1.1.7. Our hierarchical cluster analysis of B.1.1.7 lineages, which by May 2021 made up [~] 80% of all cases, indicated both multiple introductions and community spread. Our work highlights the importance of widespread, regional surveillance of SARS-CoV-2 across the United States.

Guidelines for the management of tracheal intubation in critically ill adults.

These guidelines describe a comprehensive strategy to optimize oxygenation, airway management, and tracheal intubation in critically ill patients, in all hospital locations. They are a direct response to the 4th National Audit Project of the Royal College of Anaesthetists and Difficult Airway Society, which highlighted deficient management of these extremely vulnerable patients leading to major complications and avoidable deaths. They are founded on robust evidence where available, supplemented by expert consensus opinion where it is not. These guidelines recognize that improved outcomes of emergency airway management require closer attention to human factors, rather than simply introduction of new devices or improved technical proficiency. They stress the role of the airway team, a shared mental model, planning, and communication throughout airway management. The primacy of oxygenation including pre- and peroxygenation is emphasized. A modified rapid sequence approach is recommended. Optimal management is presented in an algorithm that combines Plans B and C, incorporating elements of the Vortex approach. To avoid delays and task fixation, the importance of limiting procedural attempts, promptly recognizing failure, and transitioning to the next algorithm step are emphasized. The guidelines recommend early use of a videolaryngoscope, with a screen visible to all, and second generation supraglottic airways for airway rescue. Recommendations for emergency front of neck airway are for a scalpel-bougie-tube technique while acknowledging the value of other techniques performed by trained experts. As most critical care airway catastrophes occur after intubation, from dislodged or blocked tubes, essential methods to avoid these complications are also emphasized.

Sexual and Reproductive Health Care Services in the Pediatric Setting.

Pediatricians are an important source of health care for adolescents and young adults and can play a significant role in addressing their patients' sexual and reproductive health needs, including preventing unintended pregnancies and sexually transmitted infections (STIs), including HIV, and promoting healthy relationships. STIs, HIV, and unintended pregnancy are all preventable health outcomes with potentially serious permanent sequelae; the highest rates of STIs, HIV, and unintended pregnancy are reported among adolescents and young adults. Office visits present opportunities to provide comprehensive education and health care services to adolescents and young adults to prevent STIs, HIV, and unintended pregnancies. The American Academy of Pediatrics, other professional medical organizations, and the government have guidelines and recommendations regarding the provision of sexual and reproductive health information and services. However, despite these recommendations, recent studies have revealed that there is substantial room for improvement in actually delivering the recommended services. The purpose of this clinical report is to assist pediatricians to operationalize the provision of various aspects of sexual and reproductive health care into their practices and to provide guidance on overcoming barriers to providing this care routinely while maximizing opportunities for confidential health services delivery in their offices.

Autologous hematopoietic cell transplantation for multiple myeloma patients with renal insufficiency: a center for international blood and marrow transplant research analysis.

Autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients with renal insufficiency (RI) is controversial. Patients who underwent AHCT for MM between 2008 and 2013 were identified (N=1492) and grouped as normal/mild (⩾60 mL/min), N=1240, moderate (30-59), N=185 and severe RI (<30), N=67 based on Modification of Diet in Renal Disease. Multivariate analyses of non-relapse mortality (NRM), relapse, PFS and overall survival (OS) were performed. Of the 67 patients with severe RI, 35 were on dialysis prior to AHCT. Patients received melphalan 200 mg/m2 (Mel 200) in 92% (normal/mild), 75% (moderate) and 33% (severe) RI; remainder received 140 mg/m2 (Mel 140). Thirty four of 35 patients with severe RI achieved post-AHCT dialysis independence. The 5-year PFS for normal, moderate and severe RI was 35 (95% CI, 31-38)%, 40 (31-49)% and 27 (15-40)%, respectively, (P=0.42); 5-year OS for normal, moderate and severe RI was 68 (65-71)%, 68 (60-76)% and 60 (46-74)%, respectively, (P=0.69). With moderate RI, 5-year PFS for high-dose melphalan 140 mg/m2 was 18 (6-35)% and for Mel 200 was 46 (36-57)% (P=0.009). With severe RI, 5-year PFS Mel 140 was 25 (11-41) % and for Mel 200 was 32 (11-58)% (P=0.37). We conclude that AHCT is safe and effective in patients with MM with RI.

Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy.

MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma.

The activation of oncogenes can reprogram tumor cell metabolism. Here, in diffuse large B-cell lymphoma (DLBCL), serum metabolomic analysis revealed that oncogenic MYC could induce aberrant choline metabolism by transcriptionally activating the key enzyme phosphate cytidylyltransferase 1 choline-α (PCYT1A). In B-lymphoma cells, as a consequence of PCYT1A upregulation, MYC impeded lymphoma cells undergo a mitophagy-dependent necroptosis. In DLBCL patients, overexpression of PCYT1A was in parallel with an increase in tumor MYC, as well as a decrease in serum choline metabolite phosphatidylcholine levels and an International Prognostic Index, indicating intermediate-high or high risk. Both in vitro and in vivo, lipid-lowering alkaloid berberine (BBR) exhibited an anti-lymphoma activity through inhibiting MYC-driven downstream PCYT1A expression and inducing mitophagy-dependent necroptosis. Collectively, PCYT1A was upregulated by MYC, which resulted in the induction of aberrant choline metabolism and the inhibition of B-lymphoma cell necroptosis. Referred as a biomarker for DLBCL progression, PCYT1A can be targeted by BBR, providing a potential lipid-modifying strategy in treating MYC-High lymphoma.

Gemtuzumab ozogamicin in acute myeloid leukemia.

CD33 is variably expressed on leukemia blasts in almost all patients with acute myeloid leukemia (AML) and possibly leukemia stem cells in some. Efforts to target CD33 therapeutically have focused on gemtuzumab ozogamicin (GO; Mylotarg), an antibody-drug conjugate delivering a DNA-damaging calicheamicin derivative. GO is most effective in acute promyelocytic leukemia but induces remissions in other AML types and received accelerated approval in the US in 2000. However, because a large follow-up study showed no survival improvement and increased early deaths the drug manufacturer voluntarily withdrew the US New Drug Application in 2010. More recently, a meta-analysis of data from several trials reported better survival in adults with favorable- and intermediate-risk cytogenetics but not adverse-risk AML randomized to receive GO along with intensive induction chemotherapy. As a result, GO is being re-evaluated by regulatory agencies. Responses to GO are diverse and predictive biological response markers are needed. Besides cytogenetic risk, ATP-binding cassette transporter activity and possibly CD33 display on AML blasts may predict response, but established clinical assays and prospective validation are lacking. Single-nucleotide polymorphisms in CD33 may also be predictive, most notably rs12459419 where the minor T-allele leads to decreased display of full-length CD33 and preferential translation of a splice variant not recognized by GO. Data from retrospective analyses suggest only patients with the rs12459419 CC genotype may benefit from GO therapy but confirmation is needed. Most important may be markers for AML cell sensitivity to calicheamicin, which varies over 100 000-fold, but useful assays are unavailable. Novel CD33-targeted drugs may overcome some of GO's limitations but it is currently unknown whether such drugs will be more effective in patients benefitting from GO and/or improve outcomes in patients not benefitting from GO, and what the supportive care requirements will be to enable their safe use.