Comparing Patient-Reported Outcomes Among Anti-TNF-Experienced Patients with Crohn's Disease Initiating Vedolizumab Versus Ustekinumab.

BACKGROUND: Primary and secondary non-response to anti-tumor necrosis factor (TNF) therapy is common in patients with Crohn's disease (CD), yet limited research has compared the effectiveness of subsequent biological therapy. OBJECTIVE: We sought to compare the effectiveness of vedolizumab and ustekinumab in anti-TNF-experienced patients with CD, focusing on patient-prioritized patient-reported outcomes (PROs). METHODS: We conducted a prospective, internet-based cohort study nested within IBD Partners. We identified anti-TNF-experienced patients initiating with CD vedolizumab or ustekinumab and analyzed PROs reported approximately 6 months later (minimum 4 months, maximum 10 months). Co-primary outcomes were Patient-Reported Outcome Measurement Information System (PROMIS) domains of Fatigue and Pain Interference. Secondary outcomes included patient-reported short Crohn's disease activity index (sCDAI), treatment persistence, and corticosteroid use. Inverse probability of treatment weighting (IPTW) was used to control for a number of potential confounders and incorporated into linear and logistic regression models for continuous and categorical outcomes, respectively. RESULTS: Overall, 141 vedolizumab and 219 ustekinumab initiators were included in our analysis. After adjustment, we found no differences between treatment groups in our primary outcomes of Pain Interference or Fatigue or the secondary outcome of sCDAI. However, vedolizumab was associated with lower treatment persistence (OR 0.4, 95% CI 0.2-0.6) and higher corticosteroid use at follow-up assessment (OR 1.7, 95% CI 1.1-2.6). DISCUSSION: Among anti-TNF experienced patients with CD, Pain Interference or Fatigue was not significantly different 4-10 months after starting ustekinumab or vedolizumab. However, reduced steroid use and increased persistence suggest superiority of ustekinumab for non-PRO outcomes.

Low genetic confirmation rate in South Indian subjects with a clinical diagnosis of maturity-onset diabetes of the young (MODY) who underwent targeted next-generation sequencing for 13 genes.

PURPOSE: To screen for maturity-onset diabetes of the young (MODY) variants in subjects with an early age of onset and positive family history of diabetes mellitus. METHODS: 60 subjects with onset of diabetes between 3 and 30 years of age and parental history (onset < 35 years) of diabetes were recruited after excluding autoimmune, pancreatic and syndromic forms of diabetes. Detailed pedigree chart and clinical data were recorded. MODY genetic testing (MODY 1-13) was performed and variant classification was done adhering to the ACMG guidelines. RESULTS: Baseline characteristics of subjects were as follows: mean age of onset of diabetes 19.9 ± 7 years, mean duration of diabetes 6.3 ± 6.8 years, BMI 23.3 ± 3 kg/m2 and C-peptide 1.56 ± 1.06 nmol/l. Four out of sixty (6.6%) were positive for variants classifiable as pathogenic/likely pathogenic: one patient with HNF4Ac.691C > T, (p.Arg231Trp), two with HNF 1A c.746C > A(p.Ser249Ter) and c.1340C > T(p.Pro447Leu), and one with ABCC8 c.4544C > T (p.Thr1515Met). MODY 1 and MODY 3 variants were documented in the paediatric age group (< 18 years). CONCLUSION: A genetic diagnosis of MODY could be confirmed in only 6.6% (4/60) of patients clinically classifiable as MODY. This is less than that reported in clinically diagnosed MODY subjects of European descent. Newly published population data and more stringent criteria for assessment of pathogenicity and younger age of onset of type 2 diabetes in Indians could have contributed to the lower genetic confirmation rate. Apart from variants in the classical genes (HNF1A, HNF4A), a likely pathogenic variant in a non-classical gene (ABCC8) was noted in this study.

Report of a new meq gene size: The first study on genetic characterisation of Marek's disease viruses circulating in Iranian commercial layer and backyard chicken.

1. In recent months, several outbreaks with clinical signs of MDV-1 were reported in Iranian parent and laying hen farms, in addition to backyard chickens. Several meq gene sequences from these outbreaks were amplified and molecularly characterised.2. The meq protein sequences revealed three different sizes, namely the standard 339 aa, a shorter form of 338 aa lacking a proline residue at position 191, and a very short (vs) size of 265 aa. Based on sequence and size, the 265 aa meq has never been reported from international research groups before. The protein has only one PPPP repeat motif suggesting it belongs to a highly virulent strain.3. The standard meq sequences showed 100% BLAST identity to the vv+ isolate Polen5. However, the 338 aa form clustered to the clade usually reported from North America.4. This is the first report on genetic analysis of MDV-1 from Iran, but further study is required to obtain a better picture of the diversity and prevalence of different MDV-1 strains circulating in the country's farms, backyard poultry and other bird species.

Endovascular and percutaneous transabdominal embolisation of pseudoaneurysms in pancreatitis: an experience from a tertiary-care referral centre.

AIM: To analyse the technical challenges, clinical success, and associated complications of endovascular and percutaneous embolisation of pancreatitis-related pseudoaneurysms. MATERIALS AND METHODS: A retrospective study of patients referred for embolisation of pancreatitis-related pseudoaneurysms between January 2014 and March 2019 was conducted. Computed tomography angiography (CTA) was performed to assess the morphology of the aneurysms prior to any intervention. Percutaneous or endovascular embolisation was performed. Details of CTA and methods of embolisation were recorded. Technical success, clinical success, and complications were reported. RESULTS: A total of 80 patients (mean age, 40.69 ± 13.41 years, 73 male) underwent embolisation during the study period. Pseudoaneurysms were related to chronic pancreatitis (CP) in 44 (55%) patients and acute pancreatitis (AP) in 36 (45%) patients. Pseudoaneurysms were detected in 65 (81.2%) patients on CTA. The most common site of pseudoaneurysms was gastroduodenal artery (GDA) followed by splenic artery. Seven patients were treated with percutaneous thrombin injection and five were treated with percutaneous glue injection under ultrasound/fluoroscopy guidance. The remaining patients (n=68) underwent catheter angiography with endovascular embolisation. Technical success was achieved in 4/7 (57%) percutaneous thrombin cases and in all the cases (5/5, 100%) with percutaneous glue or endovascular (68/68,100%) embolisation. CONCLUSION: Endovascular or percutaneous embolisation of pseudoaneurysms has high technical success with an excellent safety profile.

Assessment of materno-foetal transmission of SARS-CoV-2: A prospective pilot study.

BACKGROUND: The issue of vertical transmission of SARS-CoV-2 infection to the foetus has not yet been resolved. Its main reason is lack of a bigger study to analyse this question. The evidence of the affection of the foetus during antenatal or intrapartum period is limited to some anecdotal reports. To look for the possibility of vertical transmission of Severe Acute Respiratory Syndrome - Corona Virus-2 (SARS-CoV-2) infection to the foetus, this prospective pilot study was conducted at a tertiary health care COVID-19 designated centre of Armed Forces. METHODS: This study was conducted during 01 June 2020 and 15 October 2020 and included 54 covid-positive pregnant mothers. During delivery, amniotic fluid and cord blood samples were collected in a sterile manner. Amniotic fluid samples were not collected during vaginal deliveries as chances of contamination was very high. These samples were tested for the presence of SARS-CoV-2 gene by Reverse Transcriptasee Polymerase Chain Reaction (RT-PCR) test, and the results were analysed. Newborns were allowed to room in with mother, and they underwent throat and nasal swab RT-PCR testing of covid within 24-48 h of delivery. RESULTS: A total of 1520 pregnant mothers underwent RT-PCR test during the study period. Total positivity rate among our pregnant women was 2.8%. Out of 54 covid-positive women during the study period, amniotic fluid RT-PCR tests were carried out for 43 women, and cord blood was tested for 45 women. CONCLUSION: RT-PCR test of amniotic fluid, cord blood and nasal and throat swab of all newborns delivered by SARS-CoV-2-positive pregnant women were negative. Based on our study, the possibility of intrauterine vertical transmission of SARS-CoV-2 infection appears to be unlikely.

Molecular characterisation and phylogenetic analysis of Marek's disease virus in Turkish layer chickens.

1. There is no current data about the genotypes of Marek's disease virus (MDV) in Turkish poultry flocks; hence, this study was performed to analyse CVI988/Rispens, turkey herpesvirus (HVT) vaccine viruses and MDV field viruses as well as to perform phylogenetic analysis of MDV in Turkish layer chickens. 2. In 2017 and 2018, a total of 602 spleen samples from 49 layer flocks were collected from the Marmara, West Black Sea and Aegean regions. DNA was extracted from the spleen samples and the samples were analysed by real-time PCR probe assay to detect CVI988/Rispens and HVT vaccine viruses and MDV field strains. Samples found positive for MDV by real-time PCR were subjected to PCR using the Meq gene primers for phylogenetic analysis. 3. Amongst 49 flocks, virulent MDV was detected in nine flocks. CVI988/Rispens and HVT vaccine strains were detected in 47 flocks and HVT in all 49 flocks. Splenomegaly, hepatomegaly and tumours in the oviduct were observed in chickens of affected flocks. Virulent MDV was detected in 120 out of 602 spleen samples. Sequencing and phylogenetic analyses showed that MDVs detected in this study were closely related to MDV strains from Italy, Poland, Saudi Arabia, Iraq, India and China but showed diversity with MDV strains from Egypt and Hungary. Multiple sequence analysis of the Meq protein revealed several point mutations in deduced amino acid sequences. Interestingly, CVI988/Rispens vaccine virus from China (AF493555) showed mutations at position 66 (G66R) and 71 (S66A) along with two other vaccine strains from China (GU354326.1) and Russia (EU032468.1), in comparison with the other vaccine strain CVI988/Rispens (DQ534538). The molecular analyses of the Meq gene suggested that Turkish field strains of MDV are in the class of virulent or very virulent pathotypes. 4. The results have shown that MDV still affects poultry health, and the phylogenetic and amino acid variation data obtained will help in vaccination and control strategies.

Effect of pembrolizumab on CD4+ CD25+ , CD4+ LAP+ and CD4+ TIM-3+ T cell subsets.

Tumor immune evasion involves the expansion of avidly proliferating immunosuppressive cells and inhibition of effector T cell proliferation. Immune checkpoints (IC) block the activation pathways of tumor-reactive T cells. IC pathways are often exploited by tumor cells to evade immune destruction, and blocking these pathways through IC inhibitors (ICI) has shown promising results in multiple malignancies. In this study, we investigated the effects of an ICI, pembrolizumab, on various T cell subsets in vitro. We compared the suppressive activity of CD4+ CD25+ regulatory T cells (conventional Treg ) with T cells expressing T cell immunoglobulin-3+ (TIM-3+ ) and latency-associated peptide (LAP)+ T cells. We found that LAP-expressing T cells were more suppressive than conventional Treg , but TIM-3-expressing T cells were not suppressive. Our results show that pembrolizumab does not modulate functions of Treg and mediates its immunostimulatory effects via the release of effector T cells from suppression. These findings may assist in the development of agents designed to intervene in IC pathways to overcome Treg resistance to ICI.

Molecular detection of Marek's disease virus in feather and blood samples from young laying hens in Colombia.

Marek's disease virus (MDV) is an immunosuppressive pathogen that can cause low production efficiency and high mortality rates in chickens. There is no current information on the MDV serotypes and pathotypes circulating in vaccinated commercial farms in Colombia where the birds are vaccinated in the incubator with Gallid herpesvirus (GaHV-2) and Meleagrid herpesvirus 1 (MeHV-1). Based on that, the main focus of this study was to understand the MDV's infection dynamics for the three known serotypes and to detect wild-virus pathogenic strains in 4-layer poultry farms in Antioquia. Samples of blood, feathers and spleens were collected from three randomly chosen animals according to age category: 1, 15, 30, 60, 90, and 120 days. Quantitative real-time PCR (qPCR) that differentiates between the three serotypes of MDV was used to assess viral loads over time, and phylogenetic analysis of the Meq oncogene was done to compare the strains of MDV with those of known pathogenicity. Meleagrid herpesvirus 1 (MeHV-1) was detected in all blood and feather follicle samples with an average number of genome copies (per 10,000 cells) of 31.44 in blood as expected as a result of vaccination. GaHV-2 was also detected in almost 100% of the blood and feather follicle samples throughout all defined age categories, with an average of 10.65 genome copies in blood samples. Gallid herpesvirus 3 (GaHV-3) was detected in 72% of blood and 84.61% of feather samples, with less than 1 copy per 10,000 cells. Based on the number of 132 bp repeats of the BamHI-H and BamHI-D regions in pooled feather samples, there were 70% (8/25) of attenuated MDV and 30% (17/25) of virulent MDV strains circulating in the farms. Virus isolation was performed successfully from every farm. In conclusion, different strains of MDV are circulating for up to 120 days in layers in Antioquia-Colombia and could be of major impact in poultry health. Keywords: Marek's disease virus (MDV); Antioquia-Colombia; qPCR; PCR; Meq gene phylogeny.

Belatacept Conversion in an HIV-Positive Kidney Transplant Recipient With Prolonged Delayed Graft Function.

We report an HIV-positive renal transplant recipient with delayed graft function who was converted from tacrolimus to belatacept in an attempt to improve renal function. The patient had kidney biopsies at 4 and 8 weeks posttransplant that revealed acute tubular necrosis and mild fibrosis. After 14 weeks of delayed function, belatacept was initiated and tacrolimus was weaned off. Shortly after discontinuing tacrolimus, renal function began to improve. The patient was able to discontinue dialysis 21 weeks posttransplant. HIV viral load was undetectable at last follow-up. To our knowledge, this is the first report of belatacept use in a patient with HIV.

Effect of Impurities on the Josephson Current through Helical Metals: Exploiting a Neutrino Paradigm.

In this Letter we study the effect of time-reversal symmetric impurities on the Josephson supercurrent through two-dimensional helical metals such as on a topological insulator surface state. We show that, contrary to the usual superconducting-normal metal-superconducting junctions, the suppression of the supercurrent in the superconducting-helical metal-superconducting junction is mainly due to fluctuations of impurities in the junctions. Our results, which are a condensed matter realization of a part of the Mikheyev-Smirnov-Wolfenstein effect for neutrinos, show that the relationship between normal state conductance and the critical current of Josephson junctions is significantly modified for Josephson junctions on the surface of topological insulators. We also study the temperature dependence of the supercurrent and present a two fluid model which can explain some of the recent experimental results in Josephson junctions on the edge of topological insulators.

Evaluation of Legacy Phosphorus Storage and Release from Wetland Soils.

To better manage legacy phosphorus (P) in watersheds, reliable techniques to predict P storage and release from uplands, ditches, streams, and wetlands must be developed. Techniques such as the P saturation ratio (PSR) and the soil P storage capacity (SPSC), originally developed for upland soils, are hypothesized to be applicable to wetland soils as well. Surface soils were collected from eight beef ranches within the Lake Okeechobee Watershed, FL, to obtain a threshold PSR value and to evaluate the use of PSR and SPSC for identifying legacy P storage and release from wetland soils. Water-soluble P (WSP) was determined for all soils; the equilibrium P concentration (EPC) was determined for selected soils through the generation of Langmuir isotherms. The threshold PSR for wetland soils, calculated from P, Fe, and Al in a Mehlich 1 solution, was determined to be 0.1; SPSC, calculated using the threshold PSR, was found to be related to WSP. When SPSC was positive, WSP and EPC were minimal. However, both WSP and EPC increased once SPSC became negative. Organic matter (OM) varied from 0.4 to 90 g kg for both positive and negative SPSC, suggesting that OM in wetland soils does not have any effect on P retention and release below the threshold PSR. Moreover, when a wetland or drainage ditch is heavily P impacted, it could be a P source; wetland vegetation may no longer be able to assimilate additional P, resulting in P loss from the soil. This study suggests that the PSR-SPSC concept could be a valuable tool for evaluating legacy P release from wetlands.

Petroselinum crispum extract attenuates hepatic steatosis in rats fed with fructose enriched diet.

Non alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and ongoing research efforts are focused on understanding the underlying pathophysiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. This study investigated the Petroselinum crispum extract in hepatic steatosis in rats fed with fructose enriched diet. Rats were divided into the 4 groups: Group 1 rats received standard pellet diet with corn starch for the entire experimental period of 8 weeks. Group 2 rats received standard pellet diet and 2 gm/kg body weight crude Parsley leaf ethanol extract for the entire experimental period of 8 weeks. Group 3 rats received modified fructose diet. Group 4 rats received modified fructose diet and 2gm/kg crude Parsley leaf ethanol extract. Hepatic function and structure was evaluated in these rats. Modified fructose diet produced dyslipidemia, hepatic steatosis and infiltration of inflammatory cells in the liver and higher plasma hepatic markers. Petroselinum crispum extract reversed metabolic changes such as abnormal crispum extract attenuated chronic changes in modified fructose diet induced NAFLD (Tab. 2, Fig. 3, Ref. 43).

Confidential Review of Maternal Deaths in Kerala: a country case study.

The Confidential Review of Maternal Deaths (CRMD) in Kerala was started in 2004, with support from the World Health Organization and modelled on the United Kingdom Confidential Enquiries into Maternal Deaths. It is carried out by the Kerala Federation of Obstetrics and Gynaecology with support from the government of Kerala. The leading causes of maternal deaths identified during the period 2004-09 were haemorrhage, hypertension, amniotic fluid embolism, heart disease and sepsis. Follow-up actions in the form of advocating for emergency preparedness, proper transport and standard protocols for management were initiated. Recently the international arm of the United Kingdom National Institute for Health and Clinical Excellence has helped to establish standards to improve obstetric care in Kerala based on the findings of the CRMD Kerala.

A comparative study on mesozooplankton abundance and diversity between a protected and an unprotected coastal area of Andaman Islands.

The study was carried out to understand the variability in phytoplankton production (Chlorophyll a) and mesozooplankton diversity from two different shallow coastal regions of south Andaman viz. Port Blair Bay (PBB), the only real urban area among the islands and Mahatma Gandhi Marine National Park, a Marine Protected Area (MPA) at Wandoor. Seasonal sampling was carried out during the Northeast monsoon (NEM--November 2005), Intermonsoon (IM--April 2006), and Southwest monsoon (SWM--August 2006). Significant (P < 0.05) seasonal variation was observed in the environmental variables at both the regions. Higher average chlorophyll a (Chl. a) and mesozooplankton standing stock were observed at PBB compared to MPA, but the seasonal variation observed was marginal at both the study areas. Chl. a showed a steep increasing gradient from outer to the inner regions of the PBB. The number of zooplankton taxa recorded at both areas was quite similar, but marked differences were noticed in their relative contribution to the total abundance. Eventhough the Copepoda dominated at both the areas, the non-copepod taxa differed significantly between the regions. Dominance of carnivores such as siphonophores and chaetognaths were noticed at PBB, while filter feeders such as appendicularians and decapod larvae were more abundant at MPA. A total of 20 and 21 copepod families was recorded from PBB and MPA, respectively. Eleven species of chaetognaths were observed as common at both areas. Larval decapods were found to be predominant at MPA with 20 families; whereas, at PBB, only 12 families were recorded. In the light of the recent reports on various changes occurring in the coastal waters of the Andaman Islands, it is suspected that the difference in Chl. a as well as the mesozooplankton standing stock and community structure observed between the two study areas may be related to the various anthropogenic events influencing the coastal waters.

Population Density and Health Outcomes in Women with HIV in the Southern United States: A Retrospective Longitudinal Analysis.

Purpose: Published studies have revealed challenges for people with human immunodeficiency virus (HIV) living in rural areas compared to those in urban areas, such as poor access to HIV care, insufficient transportation, and isolation. The purpose of this study was to examine associations between population density and multiple psychosocial and clinical outcomes in the largest cohort of women with HIV (WWH) in the United States. Methods: Women's Interagency HIV Study (WIHS) participants from Southern sites (n = 561) in 2013-2018 were categorized and compared by population density quartiles. The most urban quartile was compared with the most rural quartile in several psychosocial and clinical variables, including HIV viral load suppression, HIV medication adherence, HIV care attendance, depression, internalized HIV stigma, and perceived discrimination in healthcare settings. Results: Although women in the lowest density quartile were unexpectedly more highly resourced, women in that quartile had greater odds of not attending an HIV care visit in the last six months (odds ratio [OR] = 0.64, 95% confidence interval [CI] [0.43-0.95]), yet higher odds for having fully suppressed HIV when compared to women in the highest density quartile (OR = 1.64, 95% CI [1.13-2.38]). Highly urban WWH had greater likelihood of unsuppressed HIV, even after controlling for income, employment, and health insurance, despite reporting greater HIV care adherence and similar medication adherence. Discussion: Further investigation into the reasons for these disparities by population density is needed, and particular clinical attention should be focused on individuals from high population density areas to help maximize their health outcomes.

Age, Gender, and Liver Enzyme Impact Hospital Stay in COVID-19 Minority Patient with Cancer in the USA: Does Race Matters in the Pandemic?

Patients with cancer are known to have a poor prognosis when infected with SARS-CoV-2 infection. We aimed in this study to assess health outcomes in COVID-19 patients with different cancers in comparison to non-cancer COVID-19 patients from different centers in the United States (US). We evaluated medical records of 1,943 COVID-19 Cancer patients from 3 hospitals admitted between December 2019 to October 2021 and compared them with non-cancer COVID-19 patients. Among 1,943 hospitalized COVID-19 patients, 18.7% (n=364) have an active or previous history of cancer. Among these 364 cancer patients, 222 were African Americans (61.7%) and 121 were Caucasians (33.2%). Cancer patients had significantly longer hospitalization compared to controls (8.24 vs 6.7 days). Overall, Lung cancer is associated with high mortality. Patients with a previous history of cancer were more prone to death (p=0.04) than active cancer patients. In univariate and multivariate analyses, predictors of death among cancer patients were male sex, older age, presence of dyspnea, elevated troponin, elevated AST (0.001) and ALT (0.05), low albumin (p=0.04) and mechanical ventilation (p=0.001). Patients with a previous history of cancer were more prone to death when compared to active cancer COVID-19 patients. Early recognition of cancer COVID-19 patients' death-associated risk factors can help determine appropriate treatment and management plans for better prognosis and outcome.

Thin film rechargeable electrodes based on conductive blends of nanostructured olivine LiFePO4 and sucrose derived nanocarbons for lithium ion batteries.

The present study provides the first reports of a novel approach of electrophoretic co-deposition technique by which titanium foils are coated with LiFePO4-carbon nanocomposites synthesized by sol gel route and processed into high-surface area cathodes for lithium ion batteries. The study elucidates how sucrose additions as carbon source can affect the surface morphology and the redox reaction behaviors underlying these cathodes and thereby enhance the battery performance. The phase and morphological analysis were done using XRD and XPS where the LiFePO4 formed was confirmed to be a high purity orthorhombic system. From the analysis of the relevant electrochemical parameters using cyclic voltammetry and electrochemical impedance spectroscopy, a 20% increment and 90% decrement in capacity and impedance values were observed respectively. The composite electrodes also exhibited a specific capacity of 130 mA h/g. It has been shown that cathodes based on such composite systems can allow significant room for improvement in the cycling performance at the electrode/electrolyte interface.

Allogeneic haematopoietic stem cell transplantation: the Army hospital experience.

BACKGROUND: We analysed the results of allogeneic haematopoietic stem cell transplantation (HSCT) in various genetic disorders, bone marrow failures and haematological malignancies done from 2002 to 2010 at the Army Hospital, Research and Referral, Delhi. METHODS: A total of 119 matched-related allogeneic- HSCTs (allo-HSCTs) were done in 114 patients (men 76, women 38) aged between 2 and 60 years. Peripheral blood stem cells (n=75) and bone marrow (n=43) were used as the source of stem cells. RESULTS: The overall survival was 62.3% (71/114) at a median follow-up of 34 months. Graft versus host disease (GVHD) was seen in 42 (36.8%) patients; grade III/IV acute GVHD in 17 (15%) and chronic GVHD in 24 (21%) patients. There were 4 (3.5%) graft rejections and one nonengraftment. The overall mortality was 37.7% (n=43) and the main causes of death were GVHD (32%), infections (26%), relapse (23%) and regimen-related toxicity (11%). CONCLUSION: Our results are comparable to published data in most disease conditions. With improvements in GVHD prophylaxis and better supportive care, we need to further reduce our mortality and morbidity.

Management of penoscrotal extramammary Paget disease: case series and review of the literature.

Extramammary Paget disease (empd) is a rare, slow-growing neoplasm, considered to be an adenocarcinoma of the apocrine glands. In men, the penoscrotal region is the most commonly affected area. The disease can present as carcinoma in situ or as invasive disease that can subsequently metastasize to lymph nodes and distant sites. Because of the rarity of empd, the medical literature available to guide management of the disease is limited, particularly in patients with metastases. In addition, metastatic disease may pose a diagnostic challenge, because invasive cancer of the genitourinary or gastrointestinal tract can occur in association with empd. In the present case series, we describe our experience in treating penoscrotal empd with multimodality therapy, and we review the existing literature concerning its diagnosis and management.