Neonatal Paratesticular Abscess as the Greatest Mimicker of Testicular Torsion.

INTRODUCTION: The management of acute scrotal swelling can be challenging in neonatal age, with scrotal abscess being great mimickers of testicular torsion. CASE PRESENTATION: We report a 12-day-old previously healthy male infant who presented with 72 h of increasing right-sided scrotal swelling, without fever or irritable behavior. The left testicle was palpable, but the right side was too swollen to palpate a testicle, with absent cremasteric reflex. Biochemical analysis was normal and Doppler sonography demonstrated a hypoechogenic avascular lesion compressing the right testis, without intratesticular flow. Due to these findings, surgical exploration was undertaken on suspicion of potential testicular torsion. Purulent material was encountered and cultured. The testis and epididymis were covered by thick necrotic fibrinous exudate, with no spermatic cord torsion. Gentamicin and vancomycin were begun immediately. The patient remained afebrile and the scrotal induration gradually subsided. Urine and blood cultures were sterile. On the second postoperative day, cultures yielded Escherichia coli sensitive to gentamicin. One-month follow-up testicular ultrasound demonstrated complete inflammation resolution. CONCLUSION: Paratesticular abscess may be considered as the greatest mimicker of testicular neonatal torsion, due to the frequent absence of classical signs of inflammation. Early surgical exploration can be diagnostic and therapeutic and should be performed in these cases.

Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents-In Vitro Evaluation against Breast Cancer Cells.

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.

Ureteroinguinal Herniation with Consecutive Ureteral Stricture in a 2-Month-Old Infant: Case Report.

Inguinal herniation of ureter is an uncommon finding among children, with scarce reported cases in the literature to date, that can potentially lead to obstructive uropathy. We report a case of ureteroinguinal herniation discovered during an inguinal hernia repair in a patient with antenatally ultrasound finding of hydronephrosis. A 2-month-old infant with antenatal left hydronephrosis presented with left inguinal mass. Preoperative ultrasound showed an anechoic tubular image producing a mass effect on the left testicle, with suspected bladder herniation and/or dilated ureter toward the inguinal canal. An open surgical inguinal exploration was performed, where the left inguinal canal revealed a peritoneal sac and sliding of the dilated left ureter behind the sac, with a significant change in diameter, corresponding to the paraperitoneal variant of ureteroinguinal herniation. Ligation of the sac and replacement of the ureter into the retroperitoneum were performed, with improvement in the hydronephrosis observed on the ultrasound 1 month after the intervention. However, 6 months later, hydronephrosis worsening as well as the obstructive pattern observed in the diuretic renogram required removal of the stenotic ureteral segment and reimplantation of the healthy proximal segment in the bladder by open approach (Cohen's reimplantation). Follow-up ultrasound of the renal tract showed no dilatation of the upper renal tract and the renal function tests were normal. Currently, the patient is 2 years old and he remains asymptomatic. In conclusion, s igns of ureteral obstruction such as hydronephrosis in patients with inguinal herniation may suggest the possibility of an ureteroinguinal hernia. Preoperative diagnostic suspicion is essential.

The Role of Neutrophyl-to-Lymphocyte Ratio as a Predictor of Ovarian Torsion in Children: Results of a Multicentric Study.

INTRODUCTION: Pediatric ovarian torsion (OT) is an emergency condition that remains challenging to diagnose because of its overall unspecific clinical presentation. The aim of this study was to determine the diagnostic value of clinical, ultrasound, and inflammatory laboratory markers in pediatric OT. METHODS: We performed a retrospective multicentric case-control study in patients with clinical and ultrasound suspicion of OT, in whom surgical examination was performed between 2016-2022 in seven pediatric hospitals. Patients were divided into two groups according to intraoperative findings: OT group (ovarian torsion), defined as torsion of the ovarian axis at least 360°, and non-OT group (no torsion). Demographics, clinical, ultrasound, and laboratory features at admission were analyzed. The diagnostic yield analysis was performed using logistic regression models, and the results were represented by ROC curves. RESULTS: We included a total of 110 patients (75 in OT group; 35 in non-OT group), with no demographic or clinical differences between them. OT-group patients had shorter time from symptom onset (8 vs. 12 h; p = 0.023), higher ultrasound median ovarian volume (63 vs. 51 mL; p = 0.013), and a significant increase in inflammatory markers (leukocytes, neutrophils, neutrophil-to-lymphocyte ratio, C-reactive protein) when compared to the non-OT group. In the ROC curve analysis, the neutrophil-to-lymphocyte ratio (NLR) presented the highest AUC (0.918), with maximum sensitivity (92.4%) and specificity (90.1%) at the cut-off point NLR = 2.57. CONCLUSIONS: NLR can be considered as a useful predictor of pediatric OT in cases with clinical and ultrasound suspicion. Values above 2.57 may help to anticipate urgent surgical treatment in these patients.

Management of Recurrent Sigmoid Volvulus in the Pediatric Population.

Sigmoid volvulus is a rare etiology of bowel obstruction in the pediatric population that can be easily misdiagnosed, leading to delayed treatment and potential complications. Given that sigmoid volvulus is a common cause of bowel obstruction in the adult population and the significant lack of literature on its management in children, treatment strategies for pediatric patients often follow standardized protocols for adults. We report the case of a 15-year-old boy who presented with recurrent episodes of sigmoid volvulus over a 1-month period. Computed tomography demonstrated a sigmoid volvulus without evidence of ischemia or bowel infarction. Colonoscopy demonstrated a descending megacolon, and bowel transit studies demonstrated normal transit time. Acute episodes were managed conservatively with colonoscopic decompression. After a complete study, laparoscopic sigmoidectomy was performed. This work demonstrates the importance of early recognition and treatment of sigmoid volvulus in the pediatric population to limit recurrent episodes.

Use of hem-o-lok clips for laparoscopic appendectomy in children: retrospective analysis and comparison to ligature loop and endoscopic surgical stapler.

BACKGROUND: There are multiple techniques used for laparoscopic appendectomy (LA): ligature loop (LL), surgical stapler (SS) (Endopath Ets-Flex-Endoscopic Articulating Linear Cutter 33 mm Standard Ref Atb 35. Ethicon, Somerville, New Jersey, US), and hem-o-lok clips (HOL) (Weck Closure System. Triangle Park, NC, USA). The application of the LL usually demands dexterity and training, whilst using HOL may be more advantageous due to its simplicity in terms of application and its low cost in contrast with the SS. The objective of this study is to determine safety and efficacy of the different devices that can be used in the surgical procedure. METHODS: From June 2016 to December 2019, 253 consecutive children aged to 1 to 18 years were retrospectively reviewed. They were divided into three groups depending on the device used to secure the appendix: (I) in the first group, the base of the appendix was secured by double LL, (II) in the second group the base of the appendix was secured with SS, and (III) in the third group the base of the appendix was secured with two non-absorbable HOL. The data collected includes age, gender, operative time, device used to ligate the base of the appendix, previous tests (blood analysis, imaging), antibiotic prophylaxis administered, length of hospital stay, intraoperative and postoperative complications, shoulder pain and histological study of the specimen. RESULTS: There were 253 patients that underwent laparoscopic appendectomy during the study time, with a mean age of 10.3±4.1 in the LL group, 9.4±2.7 in the SS group and 10.4±3.3 in the HOL group, P=0.165. Distribution by gender was 77.8% for males in the LL group, 65.2% in the SS group and 61.3% in the HOL group, P=0.559. The mean surgical time with IQR in brackets was 60.0 (10.0) minutes (min), in the first group in which the base of the appendix was secured with LL, in the second group in which the base of the appendix was secured with SS 60.0 (15.0) min and finally in the third in which the base of the appendix was secured with HOL 40.0 (30.0) min, P<0.001. HOL clips have a significantly lower cost than their analogues. Specifically, 5 HOL clips have a cost of EUR 26.75, while three LL have a cost of EUR 53.70 and a single SS has a cost of EUR 276.58. Postoperative complications were found in 14.3% of the LL group, 9.8% in the SS group and 4.6% in the HOL group, P=0.137. Efficacy and safety in controlling the base of appendix were the same in all groups. CONCLUSIONS: The HOL are safe and reduce surgical costs during laparoscopic appendectomy in children.

Transcriptional Changes in CD16+ Monocytes May Contribute to the Pathogenesis of COVID-19.

The COVID-19 pandemic has caused more than three million deaths globally. The severity of the disease is characterized, in part, by a dysregulated immune response. CD16+ monocytes are innate immune cells involved in inflammatory responses to viral infections, and tissue repair, among other functions. We characterized the transcriptional changes in CD16+ monocytes from PBMC of people with COVID-19, and from healthy individuals using publicly available single cell RNA sequencing data. CD16+ monocytes from people with COVID-19 compared to those from healthy individuals expressed transcriptional changes indicative of increased cell activation, and induction of a migratory phenotype. We also analyzed COVID-19 cases based on severity of the disease and found that mild cases were characterized by upregulation of interferon response and MHC class II related genes, whereas the severe cases had dysregulated expression of mitochondrial and antigen presentation genes, and upregulated inflammatory, cell movement, and apoptotic gene signatures. These results suggest that CD16+ monocytes in people with COVID-19 contribute to a dysregulated host response characterized by decreased antigen presentation, and an elevated inflammatory response with increased monocytic infiltration into tissues. Our results show that there are transcriptomic changes in CD16+ monocytes that may impact the functions of these cells, contributing to the pathogenesis and severity of COVID-19.

The impact of substance abuse on HIV-mediated neuropathogenesis in the current ART era.

Approximately 37 million people worldwide are infected with human immunodeficiency virus (HIV). One highly significant complication of HIV infection is the development of HIV-associated neurocognitive disorders (HAND) in 15-55% of people living with HIV (PLWH), that persists even in the antiretroviral therapy (ART) era. The entry of HIV into the central nervous system (CNS) occurs within 4-8 days after peripheral infection. This establishes viral reservoirs that may persist even in the presence of ART. Once in the CNS, HIV infects resident macrophages, microglia, and at low levels, astrocytes. In response to chronic infection and cell activation within the CNS, viral proteins, inflammatory mediators, and host and viral neurotoxic factors produced over extended periods of time result in neuronal injury and loss, cognitive deficits and HAND. Substance abuse is a common comorbidity in PLWH and has been shown to increase neuroinflammation and cognitive disorders. Additionally, it has been associated with poor ART adherence, and increased viral load in the cerebrospinal fluid (CSF), that may also contribute to increased neuroinflammation and neuronal injury. Studies have examined mechanisms that contribute to neuroinflammation and neuronal damage in PLWH, and how substances of abuse exacerbate these effects. This review will focus on how substances of abuse, with an emphasis on methamphetamine (meth), cocaine, and opioids, impact blood brain barrier (BBB) integrity and transmigration of HIV-infected and uninfected monocytes across the BBB, as well as their effects on monocytes/macrophages, microglia, and astrocytes within the CNS. We will also address how these substances of abuse may contribute to HIV-mediated neuropathogenesis in the context of suppressive ART. Additionally, we will review the effects of extracellular dopamine, a neurotransmitter that is increased in the CNS by substances of abuse, on HIV neuropathogenesis and how this may contribute to neuroinflammation, neuronal insult, and HAND in PLWH with active substance use. Lastly, we will discuss some potential therapies to limit CNS inflammation and damage in HIV-infected substance abusers.

The Effects of Opioids on HIV Neuropathogenesis.

HIV associated neurocognitive disorders (HAND) are a group of neurological deficits that affect approximately half of people living with HIV (PLWH) despite effective antiretroviral therapy (ART). There are currently no reliable molecular biomarkers or treatments for HAND. Given the national opioid epidemic, as well as illegal and prescription use of opioid drugs among PLWH, it is critical to characterize the molecular interactions between HIV and opioids in cells of the CNS. It is also important to study the role of opioid substitution therapies in the context of HIV and CNS damage in vitro and in vivo. A major mechanism contributing to HIV neuropathogenesis is chronic, low-level inflammation in the CNS. HIV enters the brain within 4-8 days after peripheral infection and establishes CNS reservoirs, even in the context of ART, that are difficult to identify and eliminate. Infected cells, including monocytes, macrophages, and microglia, produce chemokines, cytokines, neurotoxic mediators, and viral proteins that contribute to chronic inflammation and ongoing neuronal damage. Opioids have been shown to impact these immune cells through a variety of molecular mechanisms, including opioid receptor binding and cross desensitization with chemokine receptors. The effects of opioid use on cognitive outcomes in individuals with HAND in clinical studies is variable, and thus multiple biological mechanisms are likely to contribute to the complex relationship between opioids and HIV in the CNS. In this review, we will examine what is known about both HIV and opioid mediated neuropathogenesis, and discuss key molecular processes that may be impacted by HIV and opioids in the context of neuroinflammation and CNS damage. We will also assess what is known about the effects of ART on these processes, and highlight areas of study that should be addressed in the context of ART.

New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships.

The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and structure-activity relationships of a small molecules library. We have identified six phenylpiperazine derivatives that significantly inhibited HAdV infection. These six compounds showed the capacity to block HAdV and, in addition, human cytomegalovirus (HCMV) replications at low micromolar concentration, with little or no cytotoxicity. On the basis of our biological studies, these molecules block HAdV and HCMV infections in different phases of their life cycle, providing potential candidates for the development of a new family of antiviral drugs for the treatment of infections by DNA viruses.

Antiadenovirus drug discovery: potential targets and evaluation methodologies.

Human adenoviruses (HAdV) are the cause of many acute infections, mostly in the respiratory and gastrointestinal (GI) tracts, as well as conjunctivitis. HAdV diseases in immunocompetent individuals are mostly self-limiting; however, in immunocompromised individuals, especially in pediatric units, HAdV infections are the cause of high morbidity and mortality. Despite the significant clinical impact, there are currently no approved antiviral therapies for HAdV infections. Here, we provide an overview of the different targets that could be considered for the design of specific drugs against HAdV, as well as the available in vitro and in vivo tools for the screening and evaluation of candidate molecules.

Juvenile granulosa cell tumor of the testis: case report and review of literature.

Juvenile granulosa cell tumor of the testis is an infrequent tumor of the gonadal stroma characteristic of the pediatric age. It usually appears as a scrotal mass and less frequently as an abdominal or inguinal mass. It may be associated with ambiguous genitalia and/or abnormal sex chromosomes. The recommended treatment is orchiectomy alone because local recurrence or metastasis have never been observed. We describe a patient with a juvenile granulosa cell tumor of the testis and review the literature.