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Atrial switch surgery is performed in patients with transposition of the great arteries. One of the complications of this surgery is obstruction of the baffle created. We describe the computed tomography findings of one such case where there was delayed presentation of recurrent Mustard baffle obstruction in addition to pulmonary venous drainage obstruction in an adult previously operated on for intra-atrial repair of transposition of the great arteries.

A man in his early thirties with complaints of abdominal pain for 1 week was diagnosed with a fusiform, partially thrombosed aneurysm of the superior mesenteric artery (SMA), which was treated with an endovascular stent graft. Three months later, when the patient again presented with abdominal pain, there was an endoleak of type III as detected by computed tomography and digital subtraction angiography. This was treated by in-stent balloon angioplasty with complete resolution of the endoleak. The patient again presented 1 month later with abdominal pain, with a residual sac posterior to the stent, detected on digital subtraction angiography, which was confirmed to be type II endoleak as it was getting filled by one of the jejunal branches of SMA. This was treated by glue embolization of the patent component of the aneurysm after selectively cannulating the branch vessel. This case highlights changing nature of endoleak as a complication of SMA stenting.

Abstract Objectives Current American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) community‐acquired pneumonia (CAP) guidelines expand the CAP definition to include infections occurring in patients with recent health care exposure. The guidelines now recommend that hospital systems determine their own local prevalence and predictors of Pseudomonas aeruginosa and methicillin‐resistant Staphylococcus aureus (MRSA) among patients satisfying this new broader CAP definition. We sought to carry out these recommendations in our system, focusing on the emergency department, where CAP diagnosis and initial empiric antibiotic selection usually ooccur. Methods We performed a retrospective cohort study of patients admitted with CAP through any of 3 EDs in our hospital system in Northern California between November 2019 and October 2021. Inclusion criteria included an ED admission diagnosis of pneumonia or sepsis, fever or hypothermia, leukocytosis or leukopenia, and consistent chest imaging result. SARS‐CoV‐2‐positive cases were excluded. We abstracted variables historically associated with P. aeruginosa and MRSA. Outcome measures were prevalence of P. aeruginosa and MRSA in the overall clinically defined cohort and among microbiologically confirmed cases and predictors of P. aeruginosa or MRSA isolation, as determined by univariate logistic regression, bootstrapped least absolute shrinkage and selection operator, and random forest analyses. Additionally, we describe the iterative process used and challenges encountered in carrying out the new ATS/IDSA guideline recommendations. Results There were 1133 unique patients who satisfied our definition of clinically defined CAP, of whom 109 (9.6%) had a bacterial pathogen isolated. There were 24 P. aeruginosa isolates and 11 MRSA isolates in 33 patients. Thus, the prevalence P. aeruginosa and MRSA was 2.9% in the overall CAP cohort, but 30.3% in the microbiologically confirmed cohort. The most important predictors of either P. aeruginosa or MRSA isolation were tracheostomy (odds ratio [OR] 22.08; 95% confidence interval [CI] 10.39–46.96) and gastrostomy tube (OR 14.7; 95% CI 7.14–30.26). Challenges included determining the suspected infection type in patients admitted simply for “sepsis”; interpreting dictated radiology reports; determining functional status, presence of indwelling lines and tubes, and long‐term care facility residence from the electronic health record; and correctly attributing culture results to pneumonia. Conclusion Prevalence of MRSA and P. aeruginosa was low among patients admitted in our medical system with CAP – now broadly defined – but high among those with a microbiologically confirmed bacterial etiology. Our locally derived predictors of MRSA and P. aeruginosa can be used to aid our emergency physicians in empiric antibiotic selection for CAP. Findings from this project might inform efforts at other institutions.

Metastatic cutaneous squamous cell carcinoma (CSCC) is a highly morbid disease requiring radical surgery and adjuvant therapy, which is associated with a poor prognosis. Yet, compared to other advanced malignancies, relatively little is known of the genomic landscape of metastatic CSCC. We have previously reported the mutational signatures and mutational patterns of CCCTC-binding factor (CTCF) regions in metastatic CSCC. However, many other genomic components (indel signatures, non-coding drivers, and structural variants) of metastatic CSCC have not been reported. To this end, we performed whole genome sequencing on lymph node metastases and blood DNA from 25 CSCC patients with regional metastases of the head and neck. We designed a multifaceted computational analysis at the whole genome level to provide a more comprehensive perspective of the genomic landscape of metastatic CSCC. In the non-coding genome, 3′ untranslated region (3′UTR) regions of EVC (48% of specimens), PPP1R1A (48% of specimens), and ABCA4 (20% of specimens) along with the tumor-suppressing long non-coding RNA (lncRNA) LINC01003 (64% of specimens) were significantly functionally altered (Q-value < 0.05) and represent potential non-coding biomarkers of CSCC. Recurrent copy number loss in the tumor suppressor gene PTPRD was observed. Gene amplification was much less frequent, and few genes were recurrently amplified. Single nucleotide variants driver analyses from three tools confirmed TP53 and CDKN2A as recurrently mutated genes but also identified C9 as a potential novel driver in this disease. Furthermore, indel signature analysis highlighted the dominance of ID signature 13 (ID13) followed by ID8 and ID9. ID9 has previously been shown to have no association with skin melanoma, unlike ID13 and ID8, suggesting a novel pattern of indel variation in metastatic CSCC. The enrichment analysis of various genetically altered candidates shows enrichment of “TGF-beta regulation of extracellular matrix” and “cell cycle G1 to S check points.” These enriched terms are associated with genetic instability, cell proliferation, and migration as mechanisms of genomic drivers of metastatic CSCC.

Pulmonary artery dilatation comprises a heterogeneous group of disorders. Early diagnosis is important as the presentation may be incidental, chronic, or acute and life threatening depending upon the etiology. Cross-sectional imaging plays an important role, with CT pulmonary angiography being regarded as the first line investigation in the evaluation of pulmonary artery pathologies. Moreover, effects of pulmonary artery lesions on proximal and distal circulation can also be ascertained with the detection of associated conditions. Special attention should also be given to the left main coronary artery and the trachea-bronchial tree as they may be extrinsically compressed by the dilated pulmonary artery. In context of an appropriate clinical background, CT pulmonary angiography also helps in treatment planning, prognostication, and follow-up of these patients. This review mainly deals with imaging evaluation of the pulmonary arterial dilatations on CT with emphasis on the gamut of etiologies in the adult as well as pediatric populations.

Cutaneous squamous cell carcinoma (cSCC) of the head and neck region is the second most prevalent skin cancer, with metastases to regional lymph nodes occurring in 2%–5% of cases. To further our understanding of the molecular events characterizing cSCC invasion and metastasis, we conducted targeted cancer progression gene expression and pathway analysis in non-metastasizing (PRI-) and metastasizing primary (PRI+) cSCC tumors of the head and neck region, cognate lymph node metastases (MET), and matched sun-exposed skin (SES). The highest differentially expressed genes in metastatic (MET and PRI+) versus non-metastatic tumors (PRI-) and SES included PLAU, PLAUR, MMP1, MMP10, MMP13, ITGA5, VEGFA, and various inflammatory cytokine genes. Pathway enrichment analyses implicated these genes in cellular pathways and functions promoting matrix remodeling, cell survival and migration, and epithelial to mesenchymal transition, which were all significantly activated in metastatic compared to non-metastatic tumors (PRI-) and SES. We validated the overexpression of urokinase plasminogen activator receptor (uPAR, encoded by PLAUR) in an extended patient cohort by demonstrating higher uPAR staining intensity in metastasizing tumors. As pathway analyses identified epidermal growth factor (EGF) as a potential upstream regulator of PLAUR, the effect of EGF on uPAR expression levels and cell motility was functionally validated in human metastatic cSCC cells. In conclusion, we propose that uPAR is an important driver of metastasis in cSCC and represents a potential therapeutic target in this disease.

We report the case of 8-year-old girl with left lower limb edema due to superficial venous incompetence and varicosities. Color Doppler demonstrated compression of the left common iliac vein by an ectopic left kidney, which was partly relieved in right lateral decubitus position. CT demonstrated ectopic malrotated pelvic kidney, compressing the left common iliac vein against the L5 vertebra. A “May–Thurner” like syndrome due to visceral compression needs to be suspected in children with unilateral left lower limb varicosities.

Calcific uremic arteriolopathy, commonly referred to as “calciphylaxis,” is a rare life-threatening condition observed in patients with chronic kidney disease and end-stage renal disease on dialysis. This results in necrotic, ischemic, tender dermal lesions anywhere in the body, but mainly on the abdominal wall and lower extremities, where subcutaneous tissue is abundant. Histologically, it is defined by calcification in dermal capillaries, arterioles, and subcutaneous adipose tissues. It can occur in all advanced stages of chronic kidney disease as well as end-stage renal disease patients on hemodialysis or peritoneal dialysis. Our case highlights a successful case of calciphylaxis in a young female patient who underwent parathyroidectomy and intensification of peritoneal dialysis regimen along with the infusion of sodium thiosulphate injection resulting in complete resolution of the lesion in 3 months. With limited evidence of treatment options and increased frequency of this condition in a dialysis patient, our case highlights the key aspects of calciphylaxis management in a young end-stage renal disease patient who didn’t need a change of dialysis modality. We also review the risk factors and current practiced management options of this condition in our article.

TRC150094, a novel mitochondrial modulator, can restore metabolic flexibility by improving insulin resistance in preclinical studies. This study primarily aims to evaluate the safety, tolerability, and pharmacokinetics (PK) of oral TRC150094 after conducting two double-blind, randomized, Phase-I studies, single ascending dose (SAD) and multiple ascending dose (MAD), with n = 46, in overweight/obese adult and elderly subjects. In addition, the effect of TRC150094 on pharmacodynamic (PD) efficacy markers was evaluated. PK assessments, including maximum concentration (Cmax), area under the plasma concentration (AUC), time to Cmax (Tmax), and elimination half-life (t½), were assessed at pre-specified time points. PD assessments included apolipoprotein B (ApoB), triglycerides, hepatic fat by magnetic resonance spectroscopy (MRS) and cardiopulmonary exercise testing (CPET) parameters. TRC150094 was rapidly absorbed, and the AUC of TRC150094 increased in a dose-dependent manner across all doses in non-elderly and elderly cohorts. Cmax was more than the dose-proportional for all doses in all cohorts. Tmax ranged from 0.25 to 4 h, and t½ ranged from 15 to 18 h, making TRC150094 suitable for once-daily dosing. Food did not interfere with the overall absorption of the drug. The metabolites of TRC150094 were glucuronide and sulfate conjugates, and 20% of the drug was excreted unchanged in the urine. TRC150094 at 50 mg showed an improving trend in triglycerides. A significant reduction in Apo B was observed after 50 mg dose (−2.34 vs. 13.24%, p = 0.008), which was, however, not the case after 150 mg (8.78 vs. 13.24%, p = 0.1221). Other parameters such as hepatic fat and insulin sensitivity indices (HOMA-IR, MATSUDA Index derived from OGTT) showed an improving trend for the dose of 50 mg. In terms of safety, all the AEs reported were mild to moderate in severity. None of the adverse events was considered definitely or probably related to treatment, and there were no abnormal laboratory findings. In conclusion, the PK of TRC150094 was linear with no clinically significant food effect. TRC150094 and its metabolites suggest a lesser likelihood of drug-drug interactions. Overall, TRC150094 ensured safety and exhibited suitability for all subjects.Clinical Trial Registration: EUDRA CT: 2009-014941-10 (SAD) and CTR-India registration: CTRI/2009/091/000601 (MAD)

Abstract Background Next Generation Sequencing (NGS) experiments produce millions of short sequences that, mapped to a reference genome, provide biological insights at genomic, transcriptomic and epigenomic level. Typically the amount of reads that correctly maps to the reference genome ranges between 70% and 90%, leaving in some cases a consistent fraction of unmapped sequences. This ’misalignment’ can be ascribed to low quality bases or sequence differences between the sample reads and the reference genome. Investigating the source of the unmapped reads is definitely important to better assess the quality of the whole experiment and to check for possible downstream or upstream ’contamination’ from exogenous nucleic acids. Results Here we propose DecontaMiner, a tool to unravel the presence of contaminating sequences among the unmapped reads. It uses a subtraction approach to identify bacteria, fungi and viruses genome contamination. DecontaMiner generates several output files to track all the processed reads, and to provide a complete report of their characteristics. The good quality matches on microorganism genomes are counted and compared among samples. DecontaMiner builds an offline HTML page containing summary statistics and plots. The latter are obtained using the state-of-the-art D3 javascript libraries. DecontaMiner has been mainly used to detect contamination in human RNA-Seq data. The software is freely available at http://www-labgtp.na.icar.cnr.it/decontaminer. Conclusions DecontaMiner is a tool designed and developed to investigate the presence of contaminating sequences in unmapped NGS data. It can suggest the presence of contaminating organisms in sequenced samples, that might derive either from laboratory contamination or from their biological source, and in both cases can be considered as worthy of further investigation and experimental validation. The novelty of DecontaMiner is mainly represented by its easy integration with the standard procedures of NGS data analysis, while providing a complete, reliable, and automatic pipeline.

Roseomonas species, a rare Gram-negative microorganism, has seldom been reported to cause peritonitis in end-stage renal disease patients on peritoneal dialysis. Only seven cases of peritonitis by this rare microorganism have been reported worldwide. Treatment options can be challenging if not detected early and can lead to significant morbidity and mortality along with the switching of the dialysis modality to hemodialysis which is highly undesirable. Our patient is a 65-year-old Caucasian female who needed to be changed to emergency hemodialysis due to inability to perform peritoneal dialysis from suspected peritonitis and was subsequently discovered to have peritonitis from Roseomonas mucosa. She recovered with a prolonged antibiotics course and returned to peritoneal dialysis in 3 months following her treatment completion. Prompt diagnosis and prolonged antibiotics are a cornerstone in the management of this rare microorganism to prevent mortality and morbidity from peritonitis.

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl) pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC50 value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (EAT, solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile since all 51 computed physicochemical parameters fall within the recommended range for 95% of known drugs. The current study provides insight for further investigation of the antitumour potential of the molecule.

Peritonitis is a very serious complication encountered in patients undergoing peritoneal dialysis and healthcare providers involved in the management should be very vigilant. Gram-positive organisms are the frequent cause of peritonitis compared to gram-negative organisms. There has been recognition of peritonitis caused by uncommon organisms because of improved microbiological detection techniques. We report a case of peritonitis caused by Moraxella osloensis (M. osloensis), which is an unusual cause of infections in humans. A 68-year-old male, who has been on peritoneal dialysis for 2 years, presented with abdominal pain and cloudy effluent. Peritoneal fluid analysis was consistent with peritonitis and peritoneal fluid culture grew gram-negative bacteria. M. osloensis was identified by 16 S PCR phenotypic and sequencing techniques. Patient responded well to the treatment, with intraperitoneal cephalosporin, and repeat peritoneal fluid culture yielded no growth. M. osloensis rarely causes infection in humans and responds well to treatment, as reported in literature.

We present a case of hypercalcemia in a 79-year-old female likely secondary to uterine leiomyoma. To the best of our knowledge, hypercalcemia due to a benign tumor has only been described in five cases. Of these above five cases, uterine leiomyoma was thought to be the cause of hypercalcemia in three cases.

Yersinia enterocolitica is primarily a gastrointestinal tract pathogen known to cause gastroenteritis, although it may produce extra-intestinal infections like sepsis and its sequelae. However, primary cutaneous infections are extremely rare. We present a case of Y. enterocolitica thigh abscess in an immunocompetent adult. The portal of entry is unclear in this case. He did many outdoor activities that involved skin injuries and exposure to soil and contaminated water. Hence, direct inoculation as a result of exposure to contaminated water is postulated in the absence of evidence for a gastrointestinal route of infection.

Atrial switch surgery is performed in patients with transposition of the great arteries. One of the complications of this surgery is obstruction of the baffle created. We describe the computed tomography findings of one such case where there was delayed presentation of recurrent Mustard baffle obstruction in addition to pulmonary venous drainage obstruction in an adult previously operated on for intra-atrial repair of transposition of the great arteries. [ABSTRACT FROM AUTHOR]

A man in his early thirties with complaints of abdominal pain for 1 week was diagnosed with a fusiform, partially thrombosed aneurysm of the superior mesenteric artery (SMA), which was treated with an endovascular stent graft. Three months later, when the patient again presented with abdominal pain, there was an endoleak of type III as detected by computed tomography and digital subtraction angiography. This was treated by in-stent balloon angioplasty with complete resolution of the endoleak. The patient again presented 1 month later with abdominal pain, with a residual sac posterior to the stent, detected on digital subtraction angiography, which was confirmed to be type II endoleak as it was getting filled by one of the jejunal branches of SMA. This was treated by glue embolization of the patent component of the aneurysm after selectively cannulating the branch vessel. This case highlights changing nature of endoleak as a complication of SMA stenting. [ABSTRACT FROM AUTHOR]

This article, published in the Arab Journal of Interventional Radiology, discusses the diagnosis and endovascular management of dilated cardiomyopathy (DCM) as a primary presentation of aortitis in patients with Takayasu's arteritis (TA). TA is a form of large vessel granulomatous vasculitis that can present with pulseless upper extremities and involvement of the renal arteries. The diagnosis of TA is often delayed due to nonspecific symptoms, and cardiomyopathy is an uncommon complication seen in approximately 6% of patients with TA. The article describes five cases where patients were initially diagnosed with primary cardiac disorders but were later correctly diagnosed with TA through clinical and radiological investigations. The patients were managed either medically or through endovascular methods, such as angioplasty, which resulted in improved symptoms. The article emphasizes the importance of screening young patients with heart failure, renal failure, and/or hypertension for systemic vasculitis, as an anti-inflammatory approach can help avoid or reduce complications of vasculitis. The authors conclude that a holistic and interdisciplinary approach is necessary to establish the diagnosis of TA. [Extracted from the article]