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Genital tucking (tucking) is the practice of hiding or minimizing the appearance of one's genitals and gonads. We aimed to better understand the prevalence of tucking and its potential effect on behavior and health. An online questionnaire was distributed to adults with a diagnosis of gender dysphoria or gender incongruence (n = 98). The risk of side effects increased with the length of tucking sessions (P = 0.046) with many patients avoiding medical care despite experiencing side effects. Health care providers should empathetically discuss tucking and its potential risks and benefits with transgender and gender diverse patients. Further research is needed to better quantify the potential risks involved with tucking and to assist in developing educational resources. Key words: gender affirming health care; genital tucking; gender incongruence; gender dysphoria; transgender; gender diverse individuals, INTRODUCTION Transgender and gender diverse individuals often experience significant harassment, abuse, and discrimination which can impact their self-beliefs and lead to negative health outcomes. (1,2) As a result, they require [...]

Background: Primary nonparasitic splenic cysts (NPSC) are typically diagnosed incidentally. The management of large ([greater than or equal to] 5 cm) asymptomatic cysts remains controversial; there is a lack of evidence guiding management. The purpose of this study was to describe the outcomes of nonoperative management of large NPSC. Methods: Patients diagnosed with NPSC between January 2004 and December 2019 were identified at our academic institution. Adult patients with an NPSC of at least 5 cm who had at least 1 additional hospital visit were included. Data are presented as medians with interquartile ranges (IQR). Results: We identified 512 medical records that included the term splenic cyst during the study period. Sixty-eight of the patients had no reported cyst size, 410 had cysts smaller than 5 cm, 1 patient underwent an elective splenectomy at another institution and 12 patients were excluded for other reasons; 21 patients with cysts of at least 5 cm were included in the study. Eight symptomatic patients underwent surgery at our institution. Of these, 2 presented acutely: 1 with hemoperitoneum who required admission for transfusions and later underwent elective laparoscopic splenectomy and 1 with increasingly severe abdominal pain who underwent laparoscopic cyst unroofing. The remaining 6 symptomatic patients had elective surgery for pain (4 cyst unroofing, 1 total splenectomy, 1 partial splenectomy). Thirteen patients were asymptomatic (10 female, median age 49.2 [IQR 38.1 to 64.6] yr). Two of these patients chose to undergo elective surgery. The remaining 11 asymptomatic patients, with a median initial cyst size of 8.0 (IQR 5.3 to 10.8) cm, were followed for a median of 31.0 (IQR 23.5 to 71.0) months. There was no change in median cyst size (0 [IQR -1 to 0] cm), and none of these patients underwent intervention for their NPSC. Conclusion: Asymptomatic patients managed nonoperatively for large NPSC did not become symptomatic or require intervention during the study period. This supports watchful waiting with serial radiologic and clinical monitoring for asymptomatic large NPSC. Contexte : Les kystes spléniques non parasitaires primaires (KSNPP) sont généralement découverts fortuitement. La prise en charge des kystes volumineux ([greater than or equal to] 5 cm) asymptomatiques ne fait pas l'unanimité; les données probantes manquent pour orienter le traitement. Cette étude avait pour but de décrire les résultats d'une prise en charge non chirurgicale des KSNPP. Méthodes : Nous avons identifié les patients ayant reçu un diagnostic de KSNPP entre janvier 2004 et décembre 2019 dans notre établissement universitaire. Nous avons inclus les patients adultes porteurs d'un KSNPP d'au moins 5 cm qui avaient consulté au moins 1 autre fois à l'hôpital. Les données sont présentées sous forme de médianes et d'écarts interquartiles (ÉI). Résultats : Nous avons recensé 512 dossiers médicaux incluant le terme kyste splénique durant la période de l'étude. Chez 68 patients, la taille du kyste n'était pas indiquée; 410 avaient un kyste de moins de 5 cm; 1 patient a subi une splénectomie non urgente dans un autre établissement et 12 ont été exclus pour d'autres raisons; 21 patients porteurs d'un kyste d'au moins 5 cm ont été retenus pour l'étude. Huit patients symptomatiques ont subi une chirurgie dans notre établissement. Parmi eux, 2 étaient des cas urgents : 1 cas d'hémopéritoine pour lequel le patient a dû être hospitalisé pour des transfusions et a ensuite subi une splénectomie laparoscopique non urgente, et 1 cas d'intense douleur abdominale croissante pour lequel le patient a subi une fenestration laparoscopique. Les 6 autres patients symptomatiques ont subi une chirurgie non urgente pour la douleur (4 fenestrations, 1 splénectomie totale, 1 splénectomie partielle). Treize patients étaient asymptomatiques (10 femmes, âge médian 49,2 [écart interquartile (ÉI) de 38,1 à 64,6] ans). Deux d'entre eux ont opté pour la chirurgie non urgente. Les 11 patients asymptomatiques restants, dont la taille médiane des kystes initiaux était de 8,0 (EI de 5,3 à 10,8) cm, ont été suivis pendant une durée médiane de 31,0 (ÉI de 23,5 à 71,0) mois. On n'a noté aucun changement de la taille médiane des kystes (0 [ÉI de -1 à 0] cm) et aucun de ces patients n'a subi d'intervention pour son KSNPP. Conclusion : Les patients asymptomatiques traités non chirurgicalement pour un KSNPP volumineux ne sont pas devenus symptomatiques et n'ont pas été obligés d'être opérés pendant la période de l'étude. Cela milite en faveur de l'attente vigilante, avec suivi radiologique et clinique, pour les cas de KSNPP volumineux asymptomatiques., Hydatid cysts are the most common subtype of splenic cysts worldwide. (1) However, in North America, splenic cysts are relatively rare, given the low prevalence of echinococcal disease. In fact, [...]

In the relentless battle against the COVID-19 pandemic, the deployment of mRNA vaccines has stood out as a beacon of hope. The successes of Pfizer-BioNTech NT162b2 and Moderna mRNA-1273 vaccines have been remarkable, marking a revolutionary advancement in the field of vaccinology. Despite their rapid development and impressive efficacy, challenges have emerged, particularly concerning the waning immune response over time and the evolving landscape of SARS-CoV-2 variants. The study published in this issue of JCI by Fazli et al. introduces an approach to potentially enhancing the immune responses generated by COVID-19 mRNA vaccines. The study meticulously examines the outcomes of nearly 1,000 participants who received one or two booster doses with the Pfizer-BioNTech NT162b2 vaccine either ipsilaterally or contralaterally in relation to the initial vaccine dose. Intriguingly, those who received the booster contralaterally exhibited a heightened antibody response that was particularly noteworthy in the later time points after boost., mRNA COVID-19 vaccination successes and limitations The advent of mRNA technology in vaccine development has been transformative, allowing scientists to respond rapidly to the urgent global need for effective COVID-19 [...]

BACKGROUND. Sanaria PfSPZ Vaccine, composed of attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), protects against malaria. We conducted this clinical trial to assess the safety and efficacy of PfSPZ Vaccine in HIV-positive ([HIV.sup.+]) individuals, since the HIV-infection status of participants in mass vaccination programs may be unknown. METHODS. This randomized, double-blind, placebo-controlled trial enrolled 18- to 45-year-old HIV-negative (HIV) and well-controlled [HIV.sup.+] Tanzanians (HIV viral load 500 cells/[micro]L). Participants received 5 doses of PfSPZ Vaccine or normal saline (NS) over 28 days, followed by controlled human malaria infection (CHMI) 3 weeks later. RESULTS. There were no solicited adverse events in the 9 [HIV.sup.-] and 12 [HIV.sup.+] participants. After CHMI, 6 of 6 NS controls, 1 of 5 [HIV.sup.-] vaccinees, and 4 of 4 [HIV.sup.+] vaccinees were Pf positive by quantitative PCR (qPCR). After immunization, anti-Pf circumsporozoite protein (anti-PfCSP) (isotype and IgG subclass) and anti-PfSPZ antibodies, anti-PfSPZ [CD4.sup.+] T cell responses, and V[delta][2.sup.+] [sigma][delta] [CD3.sup.+] T cells were nonsignificantly higher in [HIV.sup.-] than in [HIV.sup.+] vaccinees. Sera from [HIV.sup.-] vaccinees had significantly higher inhibition of PfSPZ invasion of hepatocytes in vitro and antibody-dependent complement deposition (ADCD) and Fc[gamma]3B binding by anti-PfCSP and ADCD by anti-cell-traversal protein for ookinetes and SPZ (anti-PfCelTOS) antibodies. CONCLUSIONS. PfSPZ Vaccine was safe and well tolerated in [HIV.sup.+] vaccinees, but not protective. Vaccine efficacy was 80% in HIV- vaccinees (P = 0.012), whose sera had significantly higher inhibition of PfSPZ invasion of hepatocytes and enrichment of multifunctional PfCSP antibodies. A more potent PfSPZ vaccine or regimen is needed to protect those living with HIV against Pf infection in Africa. TRIAL REGISTRATION. ClinicalTrials.gov NCT03420053. FUNDING. Equatorial Guinea Malaria Vaccine Initiative (EGMVI), made up of the Government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon Equatorial Guinea Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG; Swiss government, through ESKAS scholarship grant no. 2016.0056; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; NIH grant 1U01AI155354- 01., Introduction Our long-term goal is the development of a malaria vaccine against Plasmodium falciparum (Pf) malaria that can be used in endemic areas for mass vaccination programs (MVPs) to immunize [...]

Purpose Central venous catheter (CVC)-related thrombosis (CRT) is a known complication in critically ill patients. However, its clinical significance remains unclear. The objective of the study was to evaluate the occurrence and evolution of CRT from CVC insertion to removal. Methods A prospective multicenter study was conducted in 28 intensive care units (ICUs). Duplex ultrasound was performed daily from CVC insertion until at least 3 days after CVC removal or before patient discharge from the ICU to detect CRT and to follow its progression. CRT diameter and length were measured and diameter > 7 mm was considered extensive. Results The study included 1262 patients. The incidence of CRT was 16.9% (95% confidence interval 14.8-18.9%). CRT was most commonly found in the internal jugular vein. The median time from CVC insertion to CRT onset was 4 (2-7) days, and 12% of CRTs occurred on the first day and 82% within 7 days of CVC insertion. CRT diameters > 5 mm and > 7 mm were found in 48% and 30% of thromboses. Over a 7-day follow-up, CRT diameter remained stable when the CVC was in place, whereas it gradually decreased after CVC removal. The ICU length of stay was longer in patients with CRT than in those without CRT, and the mortality was not different. Conclusion CRT is a frequent complication. It can occur as soon as the CVC is placed and mostly during the first week following catheterization. Half of the thromboses are small but one-third are extensive. They are often non-progressive and may be resolved after CVC removal., Author(s): Chunshuang Wu [sup.1] [sup.2] [sup.3], Mao Zhang [sup.1] [sup.2] [sup.3], Wenjie Gu [sup.1] [sup.2] [sup.3], Caimu Wang [sup.4], Xudong Zheng [sup.5], Junfeng Zhang [sup.6], Xingwen Zhang [sup.7], Shijin Lv [...]

BACKGROUND. Disease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus. METHODS. Two randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2[DELTA]30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3[DELTA]30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2[DELTA]30 or rDEN3[DELTA]30 strain. RESULTS. TV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype. CONCLUSIONS. TV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model. TRIAL REGISTRATION. ClinicalTrials.gov NCT02317900 and NCT02873260. FUNDING. Intramural Research Program, NIH (contract HHSN272200900010C)., Introduction Dengue viruses are estimated to cause 100-400 million symptomatic illnesses each year, with a significant and expanding burden of severe disease and mortality in both endemic populations and travelers [...]

Purpose To assess the association between acute disease severity and 1-year quality of life in patients discharged after hospitalisation due to coronavirus disease 2019 (COVID-19). Methods We conducted a prospective cohort study nested in 5 randomised clinical trials between March 2020 and March 2022 at 84 sites in Brazil. Adult post-hospitalisation COVID-19 patients were followed for 1 year. The primary outcome was the utility score of EuroQol five-dimension three-level (EQ-5D-3L). Secondary outcomes included all-cause mortality, major cardiovascular events, and new disabilities in instrumental activities of daily living. Adjusted generalised estimating equations were used to assess the association between outcomes and acute disease severity according to the highest level on a modified ordinal scale during hospital stay (2: no oxygen therapy; 3: oxygen by mask or nasal prongs; 4: high-flow nasal cannula oxygen therapy or non-invasive ventilation; 5: mechanical ventilation). Results 1508 COVID-19 survivors were enrolled. Primary outcome data were available for 1156 participants. At 1 year, compared with severity score 2, severity score 5 was associated with lower EQ-5D-3L utility scores (0.7 vs 0.84; adjusted difference, - 0.1 [95% CI - 0.15 to - 0.06]); and worse results for all-cause mortality (7.9% vs 1.2%; adjusted difference, 7.1% [95% CI 2.5%-11.8%]), major cardiovascular events (5.6% vs 2.3%; adjusted difference, 2.6% [95% CI 0.6%-4.6%]), and new disabilities (40.4% vs 23.5%; adjusted difference, 15.5% [95% CI 8.5%-22.5]). Severity scores 3 and 4 did not differ consistently from score 2. Conclusions COVID-19 patients who needed mechanical ventilation during hospitalisation have lower 1-year quality of life than COVID-19 patients who did not need mechanical ventilation during hospitalisation., Author(s): Regis Goulart Rosa [sup.1] [sup.2] [sup.3], Alexandre Biasi Cavalcanti [sup.2] [sup.4], Luciano César Pontes Azevedo [sup.2] [sup.5], Viviane Cordeiro Veiga [sup.2] [sup.6], Denise de Souza [sup.1], Rosa da Rosa [...]

Despite the worldwide application of vaccination and other antiviral interventions, pulmonary viral infections remain a persistent threat to human health. The 1918 influenza pandemic killed more than 40 million people in just one year, and the SARS-CoV-2 pandemic has killed more than 6.9 million people since 2019. While the current approved COVID-19 vaccines are administered parenterally and induce systemic immunity, they only prevent the progression to severe disease. Thus, other vaccine platforms are still needed for completely preventing the disease and subsequent transmission. In this issue of the JCI, Kawai et al. present an adjuvant- free subunit (RBD-HA) fusion vaccine, which produces robust IgG and IgA antibody responses against SARS-CoV-2, enriched within the nasal cavity, by using the host's preexisting immunity to influenza infection. This preclinical study has tremendous implications for future mucosal vaccine design and provides a roadmap for generating a safer and effective intranasal vaccine against pulmonary infections., Mucosal vaccination against COVID-19 The SARS-CoV-2 pandemic brought an immense advancement in vaccine development, resulting in the worldwide distribution of mRNA vaccines. Although the current vaccines against COVID-19 are highly [...]

Intranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS- CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally inefficient in inducing an antigen-specific immune response without adjuvants. Here, we developed an adjuvant-free intranasal vaccine platform that utilizes the preexisting immunity induced by previous infection or vaccination to enhance vaccine effectiveness. We made RBD-HA, a fusion of the receptor- binding domain (RBD) of spike derived from SARS-CoV-2 as a vaccine target with HA derived from influenza A virus (IAV) as a carrier protein. Intranasal immunization of previously IAV- infected mice with RBD-HA without an adjuvant elicited robust production of RBD-specific systemic IgG and mucosal IgA by utilizing both HA-specific preexisting IgG and [CD4.sup.+] T cells. Consequently, the mice were efficiently protected from SARS-CoV-2 infection. Additionally, we demonstrated the high versatility of this intranasal vaccine platform by assessing various vaccine antigens and preexisting immunity associated with a variety of infectious diseases. The results of this study suggest the promising potential of this intranasal vaccine platform to address problems associated with intranasal vaccines., Introduction The SARS-CoV-2 pandemic has accelerated vaccine development at an unprecedented rate. Several types of COVID-19 vaccines, including mRNA and adenovirus-vector vaccines expressing the SARS-CoV-2 spike glycoprotein, provide highly effective [...]

Purpose Early accurate diagnosis of infection ± organ dysfunction (sepsis) remains a major challenge in clinical practice. Utilizing effective biomarkers to identify infection and impending organ dysfunction before the onset of clinical signs and symptoms would enable earlier investigation and intervention. To our knowledge, no prior study has specifically examined the possibility of pre-symptomatic detection of sepsis. Methods Blood samples and clinical/laboratory data were collected daily from 4385 patients undergoing elective surgery. An adjudication panel identified 154 patients with definite postoperative infection, of whom 98 developed sepsis. Transcriptomic profiling and subsequent RT-qPCR were undertaken on sequential blood samples taken postoperatively from these patients in the three days prior to the onset of symptoms. Comparison was made against postoperative day-, age-, sex- and procedure- matched patients who had an uncomplicated recovery (n =151) or postoperative inflammation without infection (n =148). Results Specific gene signatures optimized to predict infection or sepsis in the three days prior to clinical presentation were identified in initial discovery cohorts. Subsequent classification using machine learning with cross-validation with separate patient cohorts and their matched controls gave high Area Under the Receiver Operator Curve (AUC) values. These allowed discrimination of infection from uncomplicated recovery (AUC 0.871), infectious from non-infectious systemic inflammation (0.897), sepsis from other postoperative presentations (0.843), and sepsis from uncomplicated infection (0.703). Conclusion Host biomarker signatures may be able to identify postoperative infection or sepsis up to three days in advance of clinical recognition. If validated in future studies, these signatures offer potential diagnostic utility for postoperative management of deteriorating or high-risk surgical patients and, potentially, other patient populations., Author(s): Roman A. Lukaszewski [sup.1] [sup.4], Helen E. Jones [sup.1], Vivian H. Gersuk [sup.2], Paul Russell [sup.1] [sup.3], Andrew Simpson [sup.1], David Brealey [sup.4] [sup.5], Jonathan Walker [sup.6], Matt Thomas [...]

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD., Introduction Progression to organ failure is marked by fibrosis and loss of architecture in solid organs, such as the kidney. In almost all progressive chronic kidney diseases (CKDs), the features [...]

Purpose Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (T[alpha]1) treatment reduces the incidence of IPN in patients with predicted severe ANP. Methods We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score [greater than or equal to] 8 and a computed tomography (CT) severity score [greater than or equal to] 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of T[alpha]1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission. Results A total of 508 patients were randomised, of whom 254 were assigned to receive T[alpha]1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the T[alpha]1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI - 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%). Conclusion The immune-enhancing T[alpha]1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission., Author(s): Lu Ke [sup.1] [sup.25], Jing Zhou [sup.1] [sup.2], Wenjian Mao [sup.2], Tao Chen [sup.3], Yin Zhu [sup.4], Xinting Pan [sup.5], Hong Mei [sup.6], Vikesh Singh [sup.7], James Buxbaum [sup.8], [...]