Targeting host deoxycytidine kinase mitigates Staphylococcus aureus abscess formation.

Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that (R)-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates Staphylococcus aureus abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (R)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (R)-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.

Androgen exposure impairs neutrophil maturation and function within the infected kidney.

Urinary tract infections (UTIs) in men are uncommon yet carry an increased risk for severe pyelonephritis and other complications. In models of Escherichia coli UTI, C3H/HeN mice develop high-titer pyelonephritis (most with renal abscesses) in a testosterone-dependent manner, but the mechanisms underlying this phenotype are unknown. Here, using female mouse models, we show that androgen exposure impairs neutrophil maturation in the upper and lower urinary tract, compounded by a reduction of neutrophil function within the infected kidney, enabling persistent high-titer infection and promoting abscess formation. Following intravesical inoculation with uropathogenic E. coli (UPEC), kidneys of androgen-exposed C3H mice showed delayed local pro-inflammatory cytokine responses while robustly recruiting neutrophils. These were enriched for an end-organ-specific population of aged but immature neutrophils (CD49d+, CD101-). Compared to their mature counterparts, these aged immature kidney neutrophils exhibited reduced function in vitro, including impaired degranulation and diminished phagocytic activity, while splenic, bone marrow, and bladder neutrophils did not display these alterations. Furthermore, aged immature neutrophils manifested little phagocytic activity within intratubular UPEC communities in vivo. Experiments with B6 conditional androgen receptor (AR)-deficient mice indicated rescue of the maturation defect when AR was deleted in myeloid cells. We conclude that the recognized enhancement of UTI severity by androgens is attributable, at least in part, to local impairment of neutrophil maturation in the urinary tract (largely via cell-intrinsic AR signaling) and a kidney-specific reduction in neutrophil antimicrobial capacity.IMPORTANCEAlthough urinary tract infections (UTIs) predominantly occur in women, male UTIs carry an increased risk of morbidity and mortality. Pyelonephritis in androgen-exposed mice features robust neutrophil recruitment and abscess formation, while bacterial load remains consistently high. Here, we demonstrate that during UTI, neutrophils infiltrating the urinary tract of androgen-exposed mice exhibit reduced maturation, and those that have infiltrated the kidney have reduced phagocytic and degranulation functions, limiting their ability to effectively control infection. This work helps to elucidate mechanisms by which androgens enhance UTI susceptibility and severity, illuminating why male patients may be predisposed to severe outcomes of pyelonephritis.

Predictive Value of Vertebral Bone Destruction Classification Based on Computed Tomography in Diagnosing on Adult Spinal Tuberculosis.

OBJECTIVE: Although magnetic resonance imaging (MRI) is well-established for evaluation of spinal tuberculosis (TB), the importance of computed tomography (CT) should not be overlooked. The purpose of this study was to determine the characteristics of spinal TB and the relationship between spinal TB and the bone lesion pattern seen on three-dimensional CT images. METHODS: One hundred and sixty-one subjects were divided into a TB-positive group and a TB-negative group based on laboratory (X-pert mycobacterium tuberculosis/ rifampin) results and then subdivided further according to whether the bone lesion pattern seen on three-dimensional CT images was fragmentary, osteolytic, sclerotic, or had no evidence of bone destruction. The diagnostic value of the bone lesion pattern was compared between the TB-positive and TB-negative groups. RESULTS: Ninety-nine of the 161 patients were TB-positive and 62 were TB-negative. Fifty-six (34.8%) of the 161 patients had fragmentary/osteolytic lesions, seventy-four (45.9%) had absolute osteolytic lesions, 13 (8.1%) had osteosclerotic lesions, and 18 (11.2%) had no evidence of bone destruction. The fragmentary/osteolytic lesion pattern was strongly predictive of spinal TB (odds ratio 3.33), and when combined with 3 MRI findings (thin abscess wall, more than one half of the vertebral body destroyed, and subligamentous spread) had an even stronger diagnostic value (odds ratio 15.58). CONCLUSIONS: The absolute osteolytic pattern was the most common of the bone lesion patterns. The fragmentary/osteolytic pattern is highly suggestive of spinal TB, especially when combined with MRI findings of a thin abscess wall, destruction of more than one half of the vertebral body, and subligamentous spread.

Multifocal lesions in a kidney allograft.

BACKGROUND: Common complications following kidney transplant include infection, rejection, and malignancy. Multiple masses in a transplanted kidney raise suspicion for malignancy. CASE PRESENTATION: A 20-year-old female with chronic kidney disease stage 3 T presented with graft tenderness, acute kidney injury, and heterogeneous masses in her transplanted kidney visualized via ultrasound. She was inadequately treated for chlamydia 1 month prior and retested positive upon admission. Initial workup revealed anemia, hyperglycemia, hyperuricemia, and elevated lactate dehydrogenase. Magnetic resonance imaging revealed complex masses of varying sizes in the transplanted kidney. Biopsy grew Streptococcus agalactiae, informing the diagnosis of multiple perinephric abscesses. Additional evaluations for infectious etiology were unremarkable. Her perinephric abscesses resolved with several months of antibiotics. CONCLUSIONS: Even without a clear source, serious infections may develop in kidney transplant patients who otherwise have concern for malignancy. Chlamydial infections may lead to serious intra-abdominal infections in immunocompromised patients. The inadequately treated chlamydia likely led to polymicrobial ascension of the genitourinary tract that seeded the transplanted kidney. A high index of suspicion for infection is essential in immunosuppressed patients. Biopsy is crucial for a timely diagnosis.

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.

Lately Diagnosed Acanthamoeba Keratitis Manifesting as an Intrastromal Corneal Abscess: A Case Report.

ABSTRACT: A 42-year-old female contact lens wearer presented to a local emergency department with a 3-day history of decreased vision and ocular discomfort in her right eye. She was started on topical fluorometholone and oral acyclovir with initial diagnosis of herpes simplex keratitis. After 3 weeks of worsening symptoms, she was diagnosed with bacterial corneal ulcer and treated with levofloxacin eye drops every 2 hr. After 14 days of no improvement, she was referred to our clinic for further workup. Slitlamp examination demonstrated a solitary dense 3×3-mm infiltration involving anterior and central corneal stroma. The overlying epithelium was intact, and there was no subepithelial infiltration, radial perineuritis, keratic precipitates, or anterior chamber reaction. Corneal sensation was normal. Confocal microscopy and corneal biopsy were definitive for Acanthamoeba infection. The patient received polyhexamethylene biguanide 0.02% every 2 hr and oral ketoconazole 200 mg twice a day, which resulted in improvement in her signs and symptoms within 10 days. The medications were gradually tapered off over 5 months per clinical response. At the 9-month follow-up visit, the best-corrected visual acuity was 5/10 with a superficial central stromal scar at slitlamp examination. Acanthamoeba infection should be considered in contact lens wearers who present with intrastromal corneal abscess.

Pulmonary lesions with asteroid bodies in a pig experimentally infected with Actinobacillus pleuropneumoniae serovar 15.

Five pigs experimentally infected with Actinobacillus pleuropneumoniae serovar 15 isolated in our previous study were pathologically examined. One pig died at 2 days post inoculation (dpi) and four pigs were euthanized at 7 dpi. Autopsy revealed fibrinohemorrhagic pleuropneumonia in all pigs. Histopathologically, the lesions were characterized by extensive hemorrhage and necrosis, fibrin deposition, and multifocal abscesses composed of numerous neutrophils including oat cells and numerous Gram-negative bacilli. In one survived pig, asteroid body formation was confirmed in the lung. The bacteria within the abscesses and asteroid bodies were immunohistochemically positive for antiserum raised against A. pleuropneumoniae serovar 15. This is the first report describing porcine pleuropneumonia with asteroid bodies in a pig experimentally infected with A. pleuropneumoniae serovar 15.

Computed tomography of suppurative and neoplastic diseases involving the canine omenta and omental bursa.

The greater and lesser omenta are fused peritoneal folds that largely delimit the omental bursa (lesser peritoneal cavity). The omental bursa is a potential space within the abdominal cavity that communicates with the greater peritoneal cavity via the omental (epiploic) foramen: it is subdivided into the omental vestibule, caudal omental recess, and splenic recess. Aims of this retrospective case series study were to describe the frequencies of CT findings of dogs with confirmed inflammatory or neoplastic disease of the omenta, omental bursa, or both. The sample included seven adult, medium-to-large breed dogs. All had fluid in the greater peritoneal cavity and 5/7 (71%) dogs also had fluid in the omental bursa. Primary suppurative inflammatory disease was present in three dogs, each dog had a large abscess with central gas in either the omental vestibule (two dogs) or caudal omental recess (one dog). Both abscesses in the omental vestibule arose from the papillary process of the caudate liver lobe and were surgically removed without complication. Neoplasia was present in four dogs and either arose from omentum (hemangiosarcoma, carcinoma) or infiltrated the omentum from an adjacent organ (splenic leiomyosarcoma, gastric adenocarcinoma). Neoplasms created mass-like tumors, infiltrative tumors, or both and had variable distribution (focal, multifocal, or locally extensive). All dogs with neoplasia were euthanized. CT signs of inflammatory and neoplastic disease overlapped, but the presence of gas might prioritize abscessation. CT signs helped decide feasibility of surgery based on extent of local invasion, especially involvement of structures passing through the porta hepatis.

Occipital Nocardia Abscess Presenting With Positive Visual Phenomenon and Quadrantanopsia.

ABSTRACT: A 74-year-old man with chronic obstructive pulmonary disease, glaucoma, and Stage IIIB squamous cell lung cancer experienced several minutes of flashing lights in his right visual hemifield, followed by onset of a right visual field defect. On examination, the patient had a right homonymous hemianopsia that was most dense inferiorly by confrontation testing. Emergent CT scan of the head revealed a 2.5 × 3 cm hypodensity in the left occipital lobe, which was interpreted as an acute stroke. Continuous EEG monitoring captured left posterior quadrant seizures that were temporally correlated to the positive visual phenomena. Subsequent MRI of the brain with and without contrast revealed a conglomerate of centrally necrotic and peripherally enhancing mass lesions. On biopsy, a thick purulent material was drained and Gram stain of the sample revealed gram-positive beaded rods, which speciated to Nocardia farcinica . The patient was treated with a six-week course of intravenous meropenem and a one-year course of oral trimethroprim-sulfamethoxazole. On follow-up, the patient experienced resolution of the right visual field deficit.

Atrial giant cell myocarditis with preserved left ventricular function: a case report and literature review.

Giant cell myocarditis (GCM) is a rare and fatal inflammatory disorder induced by T-lymphocytes, typically affecting young adults. Generally, this disease presents with a rapidly progressive course and a very poor prognosis. In recent years, atrial GCM (aGCM) has been recognized as a clinicopathological entity distinct from classical GCM. As described by retrievable case reports, although its histopathological manifestations are highly similar to those of classical GCM, this entity is characterized by preserved left ventricular function and atrial arrhythmias, without ventricular arrhythmias. aGCM tends to show benign disease progression with a better clinical prognosis compared with the rapid course and poor prognosis of vGCM. We report a patient with aGCM with a history of renal abscess whose persistent myocardial injury considered to be associated with a history of renal abscess. Infection could be a potential trigger for the development of aGCM in this patient. An extensive literature review was also performed and the following three aspects were summarized: (1) Epidemiology and histopathological characteristics of aGCM; (2) The role of imaging in the evaluation of aGCM; (3) Diagnostic points and therapeutic decisions in aGCM.

Odynophagia as the first symptom of monkeypox infection.

A 50-year-old patient with confirmed monkeypox infection presented with odynophagia and nocturnal dyspnea. Clinically, there was a lesion on the tongue without any skin lesions and fibrinous plaques on the right tonsil with asymmetry of the palatoglossal arch. Due to a suggested abscess in the CT scan, a tonsillectomy à chaud was performed. By pan-orthopox-specific polymerase chain reaction (PCR) the monkeypox infection was also confirmed in the tonsil tissue. Isolated oral findings may represent a monkeypox infection and should be considered as a currently important differential diagnosis, especially for patients at risks.

[The effect of surgical treatment of tuberculous abscesses and tuberculoma of the brain on the dynamics of neurological symptoms]. / Vliyanie khirurgicheskogo lecheniya tuberkuleznykh abstsessov i tuberkulem golovnogo mozga na dinamiku nevrologicheskoi simptomatiki.

OBJECTIVE: To evaluate the efficacy of surgery in reducing neurological symptoms in patients with focal brain tuberculosis. MATERIAL AND METHODS: Seventy-four patients with tuberculosis meningoencephalitis were studied. Among them, 20 people with a life expectancy of at least 6 months were identified, in whom foci with a ring-shaped accumulation of contrast along the periphery were determined during MSCT of the brain. Formed tuberculomas and abscesses were removed from 7 patients (group 1) under neuronavigation control. Indications for the operation were: the absence of a reduction in size for 3-4 months, the limitation of the lesion to 1-2 foci with reduction of perifocal edema according to MSCT and normalization of cerebrospinal fluid. Six patients had contraindications or refusals from operations (group 2). In 7 patients, there was a decrease in formations by the control period (group 3). Neurological symptoms in the groups at the beginning of the observation were similar. The duration of observation was 6-8 months. RESULTS: In group 1, patients were discharged with improvement, postoperative cysts were determined in all of them at discharge. In group 2, 67% died. In group 3, 43% of patients had a complete reduction of foci during conservative treatment, in 57% cysts formed in place of foci. Neurological symptoms decreased in all groups, with the most decrease in group 1. However, statistical analysis did not show significant differences between the groups regarding the reduction of neurological symptoms. A significant difference in the mortality criterion between groups 1 and 2 was obtained. CONCLUSION: Despite the absence of a significant effect on the reduction of neurological symptoms, the high survival rate of operated patients shows the need to remove tuberculosis formations in all the cases.

[Odynophagia as the first symptom of monkeypox infection]. / Odynophagie als erstes Symptom bei Affenpocken-Infektion.

A 50-year-old patient with confirmed monkeypox infection presented with odynophagia and nocturnal dyspnea. Clinically, there was a lesion on the tongue without any skin lesions and fibrinous plaques on the right tonsil with asymmetry of the palatoglossal arch. Due to a suggested abscess in the CT scan, a tonsillectomy à chaud was performed. By pan-orthopox-specific polymerase chain reaction (PCR) the monkeypox infection was also confirmed in the tonsil tissue. Isolated oral findings may represent a monkeypox infection and should be considered as a currently important differential diagnosis, especially for patients at risks.

Retrospective characterisation and outcome of surgical treatment for cervical lymph node abscessation in 15 dogs.

CASE HISTORIES: Medical records of a private referral hospital (Veterinary Emergency Clinic, Toronto, Canada) and a university teaching hospital (Louisiana State University, Baton Rouge, LA, USA) were reviewed, using the search terms lymphadenectomy, lymph node extirpation, cervical lymphadenitis, and lymph node abscessation. Dogs (n = 15) with a diagnosis of cervical lymph node abscessations confirmed through histopathology that underwent surgery for treatment from January 2015-May 2022 were included in the study. Long-term follow-up data was obtained by an in-person visit or telephone interview with each owner. Dogs that met the inclusion criteria were of various breeds with a median age of 6 (min 0.5, max 12) years. All cases presented with cervical swelling and lethargy, with inappetence and fever in 5/15 dogs. The range of duration of clinical signs prior to treatment was 1-3 weeks. Seven dogs were treated with a short course of antibiotics, with or without prednisone, without successful resolution, before referral. CLINICAL FINDINGS: Diagnostic imaging using CT or cervical ultrasound revealed enlargement of unilateral mandibular and retropharyngeal lymph nodes with regional cellulitis and oedema in four dogs, enlargement of unilateral retropharyngeal lymph nodes with regional cellulitis in eight dogs, and a right ventral cervical abscess infiltrating the right medial retropharyngeal lymph nodes with oedema in one dog. Unilateral or bilateral cervical lymph node abscessation was diagnosed by lymphadenectomy and histopathology of affected lymph nodes. Bacterial cultures from samples of excised lymph nodes were positive in six cases. TREATMENT AND OUTCOME: Cervical exploration and lymphadenectomy were performed in all cases. Thirteen dogs received antibiotics along with surgical treatment. Resolution was defined as absence of cervical swelling or enlarged lymph node(s) at the time of long-term follow-up (median 300 (min 240, max 1,072) days). Most patients had resolution of clinical signs following surgical excision of affected lymph nodes. Two dogs had complications including recurrence of clinical signs and development of open wounds following surgery. Their clinical signs resolved following additional administration of antibiotics. CONCLUSIONS AND CLINICAL RELEVANCE: All dogs in this series had lymphadenectomy of abscessed lymph nodes and showed resolution of clinical signs with a favourable outcome. As 13/15 dogs also received antibiotics in conjunction with surgical treatment, appropriate use of antimicrobials may also play a role in treatment of this disease process.

The role of environmental enrichment in the aetiopathogenesis of Staphylococcus aureus facial, periorbital and retroorbital abscesses in mice.

In this observational retrospective study, an outbreak of Staphylococcus aureus abscesses was correlated with the presence of sharp edges in damaged plastic environmental enrichment within the cages. In 2010, Lawson reported cases of S. aureus mandibulofacial and maxillofacial abscess in mice and proposed excessive barbering or grooming, leading to the mastication and fragmentation of hair, as an aetiopathogenesis of S. aureus abscesses. In contrast, in this study, the presence of hair was not found in any of the histopathology, and abscesses were present in the periorbital area. S. aureus colonises the skin, nasopharynx and intestines, and may cause pyogenic infections if a breach in local defences promotes staphylococcal invasion. Whole genome sequencing and analysis supported the hypothesis that this outbreak resulted from clonal expansion of S. aureus infected C57BL6/J mice imported into the area and infection transmission from humans to mice was ruled out. An additional aetiopathogenesis is proposed for S. aureus abscesses with the sharp edges of damaged plastic environmental enrichment items leading to oral mucosal injury allowing S. aureus entrance into tissues, its carriage into the submucosa, followed by abscess formation.

CT diagnosis of pituitary abscess, suppurative meningitis, and atlanto-occipital septic arthritis in a pony.

A 15-year-old pony was presented for acute neurological signs. Neurological examination suggested a brainstem lesion, blood laboratory tests detected an active inflammatory process, and upper respiratory endoscopy identified a suppurative lesion at the dorsal aspect of the right guttural pouch. Computed tomography was performed and findings were consistent with pituitary abscess, meningitis, and atlanto-occipital joint septic arthritis. Imaging findings were confirmed based on cerebrospinal and synovial fluid cultures and necropsy. Computed tomography provided important information for identifying the cause of the patient's neurological signs and helped the owner make a final decision for euthanasia.

Genome-wide DNA methylation of Munro's microabscess reveals the epigenetic regulation in the pathogenesis of psoriasis.

Introduction: Munro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed. Methods: Performed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted. Results: We observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess. Discussion: In conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.

Left pancreaticoduodenostomy after removal of the right lobe and the head of the pancreas in a cat.

OBJECTIVE: To report a surgical technique for pancreaticoduodenostomy and its outcomes in a cat. ANIMALS: A 14-year-old domestic cat. STUDY DESIGN: Case report. METHODS: A cat was referred to our hospital with a large abdominal mass. On ultrasonographic examination, this mass was identified as a large fluid-filled cavity in place of the right pancreatic duct and involved the pancreatic and accessory pancreatic ducts. A small echoic cavity was observed in the left pancreatic lobe. Serous fluid was collected from the large cavity. On cytology, the small cavity was consistent with an abscess. A partial left pancreatectomy was performed to remove the abscess. The large cavity was excised with the remnant of the right pancreatic lobe and body. After ligation of the pancreatic ducts, the left pancreatic duct was isolated and an end-to-side pancreaticoduodenostomy was performed. RESULTS: The cat recovered without complications. Histological examination was consistent with chronic pancreatitis and peripheral inflammation. No evidence of postoperative pancreatic insufficiency was detected on clinical examination or laboratory findings. A focal ampulla-like dilation of the pancreatic duct was noted on ultrasonography, with no other complications at the anastomosis. The cat presented 225 days postoperatively with respiratory distress. Multiple nodules were identified throughout the lung parenchyma on radiographs. Abnormalities on ultrasonographic examination included an enlarged liver infiltrated with nodules. Due to poor prognosis, the cat was euthanized. Final histopathological diagnosis was diffuse carcinoma. CONCLUSION: Pancreaticoduodenostomy restored pancreaticointestinal continuity after extensive pancreatectomy involving the pancreatic ducts and resulted in long-term survival in the cat reported here.