Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown.

The therapeutic messenger RNA strategies, such as those using small interfering RNAs, take several advantages (versatility, efficiency and selectivity) over plasmid DNA-based strategies. However, the challenge remains to find nanovectors capable of properly loading the genetic material, transporting it through troublesome environments, like a tumoral site, and delivering it into the cytoplasm of target cells. Here, lipid nanoparticles, consisting of a gemini cationic/neutral helper lipid mixture, are proposed as siRNA nanovector. Cells from cervical and brain cancer overexpressing the green fluorescent protein (GFP) were chosen to analyse the biological response as well as the efficiency and safety of the siRNA-loaded nanovector according to the cell phenotype. Flow cytometry and epifluorescence or confocal microscopy were used to follow the gene knockdown in these overexpressed cells. The effect of the nanovector on cellular proliferation was evaluated with cytotoxicity assays while their potential oxidative stress generation was determined by quantifying the generation of reactive oxygen species. To explore the mechanism of cellular uptake, different inhibitors of endocytic pathways were used during incubation with cells. Finally, nanovectors were incubated in 3D-grown cells (spheroids) to see whether they can penetrate the complex tumoral microenvironments, their efficiency to knockdown GFP expression being monitored by confocal microscopy.

Telehealth for HIV care and management among people living with HIV in Australia: results from an online survey.

Background The aims of this study were to evaluate the experiences of telehealth for routine HIV care and identify preferred models of HIV routine care for the future. Methods Anonymous, online questionnaire among people living with HIV aged 18years or older. This survey was advertised via posters with a QR code in six sexual health clinics and one community organisation as well as on social media from November 2021 to December 2022. Results Of 89 participants, the majority were males (80/89, 89.9%), between 36 and 55years old (49/89, 55.1%), spoke English at home (74/89, 84.1%), had been living with HIV for >5years (68/89, 76.4%) and reported having a telehealth consultation since the COVID-19 pandemic began (69/89, 77.5%). The top three liked aspects of telehealth were: the convenience of not leaving home or work (50/69, 72.5%); less travel time (48/69, 69.6%); and avoiding contact with other people (30/69, 43.5%). The top three dislikes of telehealth were: they could not be screened for sexually transmitted infections (STIs) or have a physical examination at the same time (29/69, 42.0%); it was an impersonal experience (20/69, 29.0%); and it was more difficult to discuss health concerns (18/69, 26.1%). Among all participants, the preference for future consultations was to have a mix between in-person and telehealth (40/89, 44.9%); however, nearly one-quarter prefer in-person consultations only (20/89, 22.5%). Conclusions Use of telehealth during COVID-19 has been evaluated positively among people living with HIV that participated in this survey. Participants support the use of telehealth for routine care in conjunction with in-person consultations.

Hemorrhagic erucism due to Lonomia spp. in Peru - A call for action.

Envenomation due to exposure to caterpillars is an emerging public health problem. A life-threatening bleeding diathesis has been described in South America after exposure to Lonomia obliqua or L. acheolus. Deforestation, forest degradation, and global warming might increase the frequency of human exposure to these insects. Prompt recognition and administration of antivenom are crucial to ensure a favorable outcome.

Active case finding to detect symptomatic and subclinical pulmonary tuberculosis disease: implementation of computer-aided detection for chest radiography in Viet Nam.

Objective: In Viet Nam, tuberculosis (TB) prevalence surveys revealed that approximately 98% of individuals with pulmonary TB have TB-presumptive abnormalities on chest radiographs, while 32% have no TB symptoms. This prompted the adoption of the "Double X" strategy, which combines chest radiographs and computer-aided detection with GeneXpert testing to screen for and diagnose TB among vulnerable populations. The aim of this study was to describe demographic, clinical and radiographic characteristics of symptomatic and asymptomatic Double X participants and to assess multilabel radiographic abnormalities on chest radiographs, interpreted by computer-aided detection software, as a possible tool for detecting TB-presumptive abnormalities, particularly for subclinical TB. Methods: Double X participants with TB-presumptive chest radiographs and/or TB symptoms and known risks were referred for confirmatory GeneXpert testing. The demographic and clinical characteristics of all Double X participants and the subset with confirmed TB were summarized. Univariate and multivariable logistic regression modelling was used to evaluate associations between participant characteristics and subclinical TB and between computer-aided detection multilabel radiographic abnormalities and TB. Results: From 2020 to 2022, 96 631 participants received chest radiographs, with 67 881 (70.2%) reporting no TB symptoms. Among 1144 individuals with Xpert-confirmed TB, 51.0% were subclinical. Subclinical TB prevalence was higher in older age groups, non-smokers, those previously treated for TB and the northern region. Among 11 computer-aided detection multilabel radiographic abnormalities, fibrosis was associated with higher odds of subclinical TB. Discussion: In Viet Nam, Double X community case finding detected pulmonary TB, including subclinical TB. Computer-aided detection software may have the potential to identify subclinical TB on chest radiographs by classifying multilabel radiographic abnormalities, but further research is needed.

Cytomegalovirus chronic retinal necrosis with ganciclovir resistance: a case report.

BACKGROUND: Cytomegalovirus (CMV) chronic retinal necrosis (CRN) is a rare viral retinal infection that occurs in mildly immunocompromised people. It shares some features with both acute retinal necrosis and CMV retinitis. It is typically treated with combination intravitreal and systemic ganciclovir. We discuss the management of a case of CMV CRN with ganciclovir resistance. CASE PRESENTATION: An 80-year-old female presented with one month of blurry vision in the left eye. She was being treated with abatacept, methotrexate, and prednisone for rheumatoid arthritis. Examination revealed anterior chamber and vitreous cell along with peripheral retinal whitening. Fluorescein angiogram showed diffuse retinal non-perfusion. Aqueous fluid PCR testing returned positive for CMV. The retinitis was initially controlled with oral and intravitreal ganciclovir, but then recurred and progressed despite these therapies. Ganciclovir resistance was suspected and the patient was switched to intravitreal foscarnet injections, along with oral letermovir and leflunomide, which lead to resolution of the retinitis. The patient has now continued with letermovir and leflunomide for approximately 2.5 years without reactivation of the retinitis or need for further intravitreal anti-viral injections and with adequate control of her rheumatoid arthritis. CONCLUSION: The incidence of CMV CRN may increase in the future as the use of non-cytotoxic immunosuppressive therapies that result in relatively mild immunosuppression also increases. Treatment with ganciclovir is effective but frequently leads to resistance, as in our case. In this situation, combination therapy with letermovir and leflunomide, particularly in the setting of rheumatoid arthritis where leflunomide can also have an anti-inflammatory effect, can be considered.

Optical dark-field spectroscopy of single plasmonic nanoparticles for molecular biosciences.

An ideal sensor capable of quantifying analytes in minuscule sample volumes represents a significant technological advancement. Plasmonic nanoparticles integrated with optical dark-field spectroscopy have reached this capability, demonstrating versatility and expanding applicability across in vitro and in vivo subjects. This review underscores the applicability of optical dark-field spectroscopy with single plasmonic nanoparticles to elucidate a wide range of biomolecular characteristics, including binding constants, molecular dynamics, distances, and forces, as well as recording cell communication signals. Perspectives highlight the potential for the development of implantable nanosensors for metabolite detection in animal models, illustrating the technique's efficacy without the need for labeling molecules. In summary, this review aims to consolidate knowledge of this adaptable and robust technique for decoding molecular biological phenomena within the nano- and bio-scientific community.

The epidemiology of Chagas disease in the Americas.

Chagas disease is a complex parasitic zoonosis that still threatens public health across the Americas. Initiatives to control Trypanosoma cruzi transmission via blood transfusion and non-native triatomine-bug vectors have yielded crucial advances; native vectors, however, actively bridge wild and domestic/peri-domestic transmission cycles throughout the region, and tens of thousands of people become infected each year. Oral-transmission outbreaks, urbanisation, and vertical transmission are additional/emerging issues calling for innovative strategic thinking. While critical for advocacy and sustained public health action, assessing Chagas disease burden remains difficult; the often-asymptomatic nature of T. cruzi infection, healthcare access limitations, pervasive underreporting, and other methodological hurdles inherent to reliably measuring incidence, prevalence, and disease progression all contribute to the difficulty. Whether and how parasite, vector, and host genetic makeups affect transmission dynamics and epidemiology is also unclear. Continued high-quality research and long-term, adaptive strategies combining vector control surveillance with enhanced case detection and integral patient care remain critical to effectively address the ethical and societal challenge of Chagas disease control. This is the first in a Series of five papers about Chagas Disease. All papers in the Series are available at https://www.thelancet.com/series/chagasdisease.

All-Optical Trapping and Programmable Transport of Gold Nanorods with Simultaneous Orientation and Spinning Control.

Gold nanorods (GNRs) are of special interest in nanotechnology and biomedical applications due to their biocompatibility, anisotropic shape, enhanced surface area, and tunable optical properties. The use of GNRs, for example, as sensors and mechanical actuators, relies on the ability to remotely control their orientation as well as their translational and rotational motion, whether individually or in groups. Achieving such particle control by using optical tools is challenging and exceeds the capabilities of conventional laser tweezers. We present a tool that addresses this complex manipulation problem by using a curve-shaped laser trap, enabling the optical capture and programmable transport of single and multiple GNRs along any trajectory. This type of laser trap combines confinement and propulsion optical forces with optical torque to transport the GNRs while simultaneously controlling their rotation (spinning) and orientation. The proposed system facilitates the light-driven control of GNRs and the quantitative characterization of their motion dynamics including transport speed, spinning frequency, orientation, and confinement strength. We experimentally demonstrate that remote control of the GNRs can be achieved both near a substrate surface (2D trapping) and deep within the sample (3D all-optical trapping). The motion dynamics of two sets of off-resonant GNRs, possessing similar aspect ratios but different resonance wavelengths, are analyzed to highlight the role played by their optical and mechanical properties in the optical manipulation process. The experimental results are supported by a theoretical model describing the observed motion dynamics of the GNRs. This optical manipulation tool can significantly facilitate applications of light-driven nanorods.

Multi-organ clinical manifestations of Mpox: an umbrella review of systematic reviews.

BACKGROUND: Mpox is a severe viral zoonosis that has emerged as a public health concern due to its potential for human-to-human transmission and severe illness. Understanding its clinical manifestations is crucial for effective management and control. Several systematic reviews have assessed various manifestations of Mpox. This umbrella review synthesizes evidence on Mpox's manifestations across different organ systems. METHOD: We conducted an umbrella review, adhering to Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on systematic reviews of Mpox manifestations. We performed a literature search up to 25th September 2023, in databases like PubMed, Embase, and Web of Science. We included systematic reviews of observational studies, case reports, case series, or RCTs reporting any manifestations of Mpox in humans, focusing on a global scope. AMSTAR 2 was used to evaluate the quality of systematic reviews, and data has been synthesized in narrative and tabular manners. RESULTS: A total of 25 systematic reviews were included, uncovering diverse manifestations of Mpox, such as cutaneous, cardiovascular, oral, ophthalmic, gastrointestinal, respiratory, and pregnancy-related. Cutaneous manifestations (up to 100%) were the most prevalent, featuring lesions and rashes. Constitutional symptoms of viral illness were reported in ~ 60% to > 85% of the cases. Significant respiratory symptoms were present in ~ 50% of cases overall. Headaches were the leading neurological symptom present in > 30%. Symptoms of gastrointestinal involvement ranged from 39% (oral lesions) with decreasing frequency to low diarrhea at ~ 5%, with proctitis percentages ranging from high teens to mid-twenties. Ophthalmic manifestations (6% but with wide variations among studies). Many primary studies included in the systematic reviews consisted of case reports and case series. A wide range of manifestations across different organ systems was observed. Negative outcomes for pregnancies were reported, but evidence is limited. Adverse cardiovascular and neurological outcomes were identified, though only a few studies provided insights into these findings. CONCLUSION: Mpox exhibits diverse manifestations, impacting multiple organ systems, with substantial variations. The findings highlight the importance of ongoing, nuanced, and region-specific research and management strategies for Mpox. The reliance on case reports and series underscores the need for more high-quality, long-term studies to deepen our understanding and management of this significant public health concern.

Control strategies for emerging infectious diseases: Crimean-Congo hemorrhagic fever management.

Background and Aims: Crimean-Congo Hemorrhagic Fever (CCHF) is a significant public health concern transmitted by ticks. This study seeks to thoroughly grasp the epidemiology and transmission patterns of CCHF, which is caused by the CCHF virus (CCHFV), a member of the Nairovirus genus in the Bunyaviridae family. Methods: The study investigates the global distribution and endemicity of CCHF, its mortality rates, modes of transmission (including tick bites, contact with infected animal blood, and limited person-to-person transmission), and factors influencing its prevalence across different regions. Genetic diversity within CCHFV and its impact on transmission dynamics are explored, along with efforts to control the disease through tick prevention, antiviral treatment, and the development of vaccines and diagnostics. Results: CCHFV exhibits widespread distribution, particularly in the Middle East, Africa, Asia, and Eastern Europe, with an overall mortality rate of approximately 30% and a case fatality rate ranging from 10% to 40%. Transmission occurs primarily through tick bites and contact with infected animal blood, with limited person-to-person transmission. Livestock workers, slaughterhouse employees, and animal herders in endemic areas are most affected by their frequent interaction with sick animals and ticks. Genetic diversity within CCHFV contributes to variations in transmission dynamics, complicating control efforts. Antiviral ribavirin shows efficacy in treating CCHF infection. Conclusion: This study underscores the importance of further research to understand the enzootic environment, transmission routes, and genetic diversity of CCHFV for effective control measures, including the development of vaccines, treatment options, and diagnostics.

Suspension electrospinning of decellularized extracellular matrix: A new method to preserve bioactivity.

Decellularized extracellular matrices (dECM) have strong regenerative potential as tissue engineering scaffolds; however, current clinical options for dECM scaffolds are limited to freeze-drying its native form into sheets. Electrospinning is a versatile scaffold fabrication technique that allows control of macro- and microarchitecture. It remains challenging to electrospin dECM, which has led researchers to either blend it with synthetic materials or use enzymatic digestion to fully solubilize the dECM. Both strategies reduce the innate bioactivity of dECM and limit its regenerative potential. Herein, we developed a new suspension electrospinning method to fabricate a pure dECM fibrous mesh that retains its innate bioactivity. Systematic investigation of suspension parameters was used to identify critical rheological properties required to instill "spinnability," including homogenization, concentration, and particle size. Homogenization enhanced particle interaction to impart the requisite elastic behavior to withstand electrostatic drawing without breaking. A direct correlation between concentration and viscosity was observed that altered fiber morphology; whereas, particle size had minimal impact on suspension properties and fiber morphology. The versatility of this new method was demonstrated by electrospinning dECM with three common decellularization techniques (Abraham, Badylak, Luo) and tissue sources (intestinal submucosa, heart, skin). Bioactivity retention after electrospinning was confirmed using cell proliferation, angiogenesis, and macrophage polarization assays. Collectively, these findings provide a framework for researchers to electrospin dECM for diverse tissue engineering applications.

Comprehensive compilation of congener profiles to support health assessment of environmental exposures to polychlorinated biphenyl mixtures.

Exposure to polychlorinated biphenyls (PCBs) remains a potential human health risk due to their persistence in the environment, despite a global ban on their production. Understanding the composition of PCB mixtures is essential for the application of a mixtures-based approach to assessing health risks of PCB exposure. This work represents the most extensive effort to date to compile and make publicly available the PCB congener profiles for mixtures with toxicological data, providing a foundation for understanding toxicological potency of PCB mixtures in the environment. We searched for published congener profiles across 29 commercial and simulated environmental PCB mixtures, including various Aroclors, Phenoclors, Clophens, and Kanechlors, among others. A total of 117 references containing 401 distinct complete or partial tabularized profiles were found. Aroclor 1254 had the most published profiles, with 79 unique datasets characterizing multiple mixture lots. In contrast, no congener-specific composition data were identified for Fenclors, Clophen C, or Pyralenes. Eighty-seven of the most complete and clearly reported profiles underwent a detailed extraction of the congener data, PCB mixture source, and analytical methods. Challenges encountered during data extraction included congener coelutions, incomplete methods reporting, and inconsistencies in PCB nomenclature. These factors complicate data visualization, comparisons across datasets, and use of the data in subsequent analyses. Where possible, we have converted profiles to the same units and congener numbering convention to allow for easier comparison. The extracted data are publicly available online as interactive visuals and as a downloadable Microsoft Excel® workbook. This dataset provides researchers with an overview of the current PCB mixture profile landscape that can serve as a tool to support efforts to minimize the health impacts of environmental PCB exposure, including the exploration of links between mixture composition and toxicity and the identification of the most efficient and effective remediation strategies at contaminated sites.

Comparative analysis of the quality of the cement mantle in hip hemiarthroplasty after femoral neck fracture between three different surgical approaches: a single-center retrospective observational study.

PURPOSE: Achieving the initial stability of implants is necessary for hip hemiarthroplasty (HHA), especially in elderly patients, and this can be achieved with a cement mantle of quality. The direct anterior approach (DAA) for HHA lately has shown positive results. However, evidence is lacking of HHA in elderly patients with osteoporosis after femoral neck fracture (FNF). This study compares differences in cement mantle quality after HHA, its complications, radiological outcomes and functional status in elderly patients with FNF intervened through different approaches. METHODS: A non-interventional, retrospective case-control study was conducted. 150 cases were selected based on the surgical approach (DAA, DLA and PLA) in a 1:1:1 proportion between 2018 and 2019. Under 75 years old suspicion or confirmation of a pathological fracture were excluded. Antibiotic-loaded cement was utilized. Cement preparation involved vacuum centrifugation and standard instructions for preparation canal and filling, and prosthesis placement were followed. RESULTS: No statistically significant differences in cement mantle quality, radiological outcomes, and the majority of the postoperative complications and functional status considering the surgical approach (p > 0.05). However, the DAA was associated significantly with shorter hospital stays (8.3 days vs 11.3 and 13 days for DLA and PLA) a decrease in postoperative blood transfusion (22% vs 34% and 53%), and lower rate of loss of walking (8% vs 20% and 28.6%). CONCLUSION: The DAA for HHA in patients with FNF provides a high-quality cement mantle, similar to other approaches. Also, the DAA shows advantages like shorter hospital stays and lower transfusion rates in elderly patients.

Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer.

INTRODUCTION: No definitive answers currently exist regarding optimal first-line therapy for HER2-mutant NSCLC. Access to rapid tissue sequencing is a major barrier to precision drug development in the first-line setting. ctDNA analysis has the potential to overcome these obstacles and guide treatment. METHODS: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing and received systemic therapy at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx LungTM assay. Primary endpoints were time to the next treatment (TTNT) and overall survival (OS). RESULTS: Sixty-three patients were included in the primary analysis. Chemoimmunotherapy (33/63, 52.4 %) was the predominant first-line treatment with a median TTNT of 5.1 months (95 %CI 4.1 - 6.1) whereas 55.0 % (22/40) of patients who received second-line T-DXd obtained a median TTNT of 9.2 m (95 % CI, 0-22.2). Plasma ctDNA was tested before first-line therapy in 40 patients with a median OS of 28.0 months (95 % CI 21-34), in whom 31 patients (78.0 %) had detectable ctDNA. HER2 mutations were detected on ctDNA with a median turnaround time of 13 days, occasionally co-occurred with EGFR and MET alterations and were tracked longitudinally correlating with treatment response. Patients with detectable baseline ctDNA had significantly shorter OS (hazard ratio (HR), 5.25; 95 % CI, 1.2-23.9; p = 0.019). CONCLUSION: Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies.

Meta-analysis of Pregnancy Events in Biomedical HIV Prevention Trials in Sub-Saharan Africa: Implications for Gender Transformative Trials.

Historically, pregnant and lactating populations (PLP) have been excluded or disenrolled from biomedical HIV prevention trials, despite being more likely to acquire HIV during pregnancy and the post-partum period. We conducted a meta-analysis of pregnancy events in biomedical HIV prevention trials in sub-Saharan Africa to support trialists moving toward more inclusive clinical and implementation studies. We searched peer-reviewed literature reporting pregnancy events and contraceptive requirements in HIV prevention trials between 2001 and 2022. We hypothesized four variables to explain variation: contraceptive requirements, study start year, study product, and sub-region. We fit a meta-analytic model to estimate individual effect sizes and sampling variances, then conducted sub-group analyses to assess moderating effects. We identified 38 references for inclusion, across which the proportion of pregnancy events was 8% (95% confidence interval [CI]: 6-10%) with high heterogeneity (I2 = 99%). Studies not requiring contraceptives (21%, 95%CI: 7-48%) reported a significantly higher proportion of pregnancy events than studies requiring two methods (5%, 95%CI: 2-10%). Studies launched between 2001 and 2007 (11%, 95%CI: 8-16%), microbicide gel trials (12%, 95%CI: 8-18%), and studies conducted in Western Africa (28%, 95%CI: 13-51%) reported higher proportions of pregnancy events than reference groups. Together, these variables have a moderating effect on pregnancy events (p < 0.0001), explaining 63% of heterogeneity in trials. Results describe how, over time, more stringent contraceptive requirements reduced pregnancy events, which ensured necessary statistical power but limited reproductive choice by participants. With the move toward continuing PLP on experimental products, trialists can utilize estimated pregnancy events reported here to inform strategies that accommodate participants' changing fertility preferences.

Effects of swift heavy ions on metal nanoparticles embedded in silica: Using linearly polarized light to monitor the elongation kinetics.

The elongation of metallic nanoparticles (NPs) embedded in a dielectric matrix after irradiation with swift heavy ions is a phenomenon that has been known for several years. However, the precise mechanism behind this deformation process is still not fully understood, primarily due to the dearth of information during intermediate stages of deformation. In this study, we report the continuation of our previous work [Peña-Rodríguez et al., Sci. Rep. 7(1), 922 (2017)], exploiting the strong dependence of the localized surface plasmon resonance on the aspect ratio of elongated metal NPs to study the elongation kinetics in situ. In situ optical absorption spectra were measured using a polarizing beam splitter to separate the longitudinal and transverse plasmon modes of the anisotropic NPs. Then, the detailed geometrical and compositional parameters were determined from a fit of these spectra. The use of linearly polarized light allowed for a more accurate analysis of the elongation kinetics, particularly useful in the first stages, where longitudinal and transverse modes overlap.

Self-adaptive integrated photonic receiver for turbulence compensation in free space optical links.

In Free Space Optical (FSO) communication systems, atmospheric turbulence distorts the propagating beams, causing a random fading in the received power. This perturbation can be compensated using a multi-aperture receiver that samples the distorted wavefront on different points and adds the various signals coherently. In this work, we report on an adaptive optical receiver that compensates in real time for scintillation in FSO links. The optical front-end of the receiver is entirely integrated in a silicon photonic chip hosting a 2D Optical Antenna Array and a self-adaptive analog Programmable Optical Processor made of a mesh of tunable Mach-Zehnder interferometers. The photonic chip acts as an adaptive interface to couple turbulent FSO beams to single-mode guided optics, enabling energy and cost-effective operation, scalability to systems with a larger number of apertures, modulation-format and data-protocol transparency, and pluggability with commercial fiber optics transceivers. Experimental results demonstrate the effectiveness of the proposed receiver with optical signals at a data rate of 10 Gbit/s transmitted in indoor FSO links where different turbulent conditions, even stronger than those expected in outdoor links of hundreds of meters, are reproduced.

Pneumocystis jirovecii Pneumonia in HIV-Negative, Non-transplant Patients: Epidemiology, Clinical Manifestations, Diagnosis, Treatment, and Prevention.

Purpose of Review: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that is increasingly seen in HIV-negative patients with immune compromise due to other etiologies. We lack comprehensive clinical recommendations for this population. Recent Findings: In non-HIV cases, PJP has a mortality rate of up to 50%, which is unacceptable despite the presence of safe and effective prophylaxis and therapy. Steroid use is one of the most common risk factors for disease development. New data suggests that lower doses of the preferred treatment regimen, TMP-SMX, may be equally effective for treatment while limiting side effects. While commonly used, the benefit of corticosteroids for the treatment of PJP has recently been called into question, with a recent multicenter cohort demonstrating no benefit among solid organ transplant recipients. Summary: A high suspicion of PJP in individuals with pneumonia during immunosuppressant use is crucial. Therapeutic options are evolving to decrease potential side effects while maintaining efficacy in this highly morbid disease.