Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

INTRODUCTION: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. METHODS: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. RESULTS: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. DISCUSSION: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. HIGHLIGHTS: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.

Longitudinal detection of gait alterations associated with hypertension-induced cerebral microhemorrhages in mice: predictive role of stride length and stride time asymmetry and increased gait entropy.

Cerebral microhemorrhages (CMHs) are of paramount importance as they not only signify underlying vascular pathology but also have profound implications for cognitive function and neurological health, serving as a critical indicator for the early detection and management of vascular cognitive impairment (VCI). This study aimed to investigate the effects of hypertension-induced CMHs on gait dynamics in a mouse model, focusing on the utility of advanced gait metrics as sensitive indicators of subclinical neurological alterations associated with CMHs. To induce CMHs, we employed a hypertensive mouse model, using a combination of Angiotensin II and L-NAME to elevate blood pressure, further supplemented with phenylephrine to mimic transient blood pressure fluctuations. Gait dynamics were analyzed using the CatWalk system, with emphasis on symmetry indices for Stride Length (SL), Stride Time (ST), and paw print area, as well as measures of gait entropy and regularity. The study spanned a 30-day experimental period, capturing day-to-day variations in gait parameters to assess the impact of CMHs. Temporary surges in gait asymmetry, detected as deviations from median gait metrics, suggested the occurrence of subclinical neurological signs associated with approximately 50% of all histologically verified CMHs. Our findings also demonstrated that increases in gait entropy correlated with periods of increased gait asymmetry, providing insights into the complexity of gait dynamics in response to CMHs. Significant correlations were found between SL and ST symmetry indices and between these indices and the paw print area symmetry index post-hypertension induction, indicating the interdependence of spatial and temporal aspects of gait affected by CMHs. Collectively, advanced gait metrics revealed sensitive, dynamic alterations in gait regulation associated with CMHs, resembling the temporal characteristics of transient ischemic attacks (TIAs). This underscores their potential as non-invasive indicators of subclinical neurological impacts. This study supports the use of detailed gait analysis as a valuable tool for detecting subtle neurological changes, with implications for the early diagnosis and monitoring of cerebral small vessel disease (CSVD) in clinical settings.

Preventing spontaneous cerebral microhemorrhages in aging mice: a novel approach targeting cellular senescence with ABT263/navitoclax.

Emerging evidence from both clinical and preclinical studies underscores the role of aging in potentiating the detrimental effects of hypertension on cerebral microhemorrhages (CMHs, or cerebral microbleeds). CMHs progressively impair neuronal function and contribute to the development of vascular cognitive impairment and dementia. There is growing evidence showing accumulation of senescent cells within the cerebral microvasculature during aging, which detrimentally affects cerebromicrovascular function and overall brain health. We postulated that this build-up of senescent cells renders the aged cerebral microvasculature more vulnerable, and consequently, more susceptible to CMHs. To investigate the role of cellular senescence in CMHs' pathogenesis, we subjected aged mice, both with and without pre-treatment with the senolytic agent ABT263/Navitoclax, and young control mice to hypertension via angiotensin-II and L-NAME administration. The aged cohort exhibited a markedly earlier onset, heightened incidence, and exacerbated neurological consequences of CMHs compared to their younger counterparts. This was evidenced through neurological examinations, gait analysis, and histological assessments of CMHs in brain sections. Notably, the senolytic pre-treatment wielded considerable cerebromicrovascular protection, effectively delaying the onset, mitigating the incidence, and diminishing the severity of CMHs. These findings hint at the potential of senolytic interventions as a viable therapeutic avenue to preempt or alleviate the consequences of CMHs linked to aging, by counteracting the deleterious effects of senescence on brain microvasculature.

[Penile epithelioid hemangioma]. / A hímvesszo epithelioid haemangiomája.

Epithelioid hemangioma is a benign vascular tumor. Complete surgical excision is curative, there is no tendency to recurrence or metastasize. Its penile occurrence is extremely rare, only 33 cases have been reported in English literature. A patient with epithelioid hemangioma of the deep dorsal vein of the penis is reported. To our knowledge, this is the first report of penile epithelioid hemangioma in Hungarian literature. The 64-year-old patient presented to our department with painful erection caused by a palpable penile mass. Physical examination revealed a mobile subcutaneous nodule on the dorsum of the penis. Penile ultrasound showed a 10 mm homogeneous, well circumscribed lesion superficial to the tunica albuginea of the corpora cavernosa without intralesional blood flow. Local excision was performed through a dorsal longitudinal penile incision. The deep dorsal vein was dissected circumferentially, then the lesion was removed following ligation of the vein proximal and distal to the mass. Histopathological examination revealed epithelioid hemangioma. At three months after surgery, the patient reported complete resolution of pain, his International Index of Erectile Function Score was 21. At four years after the operation, there were no signs of recurrence or metastasis. Successful treatment of epithelioid hemangioma of the penis requires in-depth knowledge of processes resulting in penile subcutaneous masses, therefore the differential diagnosis is detailed in discussion. Orv Hetil. 2023; 164(21): 836-840.

A New Modified Bipedicle Scrotal Skin Flap Technique for the Reconstruction of Penile Skin in Patients with Paraffin-Induced Sclerosing Lipogranuloma of the Penis.

PURPOSE: We introduce a new modified penile skin reconstruction technique to treat paraffin-induced sclerosing lipogranuloma of the penis. MATERIALS AND METHODS: From 2017 to 2020, 49 patients underwent the procedure. Complete removal of the lipogranuloma-involved penile skin was performed. A subcutaneous tunnel was then created between a horizontal scrotal incision and a proximal penile circumferential incision. The denuded penis was pulled through the tunnel, and a subcoronal and longitudinal dorsal penile suture line was made. An inverted V-shaped incision was made on the scrotum on the ventral side of the penis, followed by longitudinal closure. Outcomes and complications of the procedure were retrospectively studied. The long-term effect of surgery on sexual function and overall satisfaction was measured using a patient-reported questionnaire, which was completed by 30 patients. RESULTS: The overall complication rate was 26.5%. Clavien-Dindo grade 1, 2, 3a, 3b, 4 and 5 complications occurred in the postoperative period 5, 0, 8, 1, 0 and 0 times, respectively, in 13 patients. Surgery was successful in 27 (90%) patients according to the patient-reported questionnaire. Erectile dysfunction, pain/tension during erection, premature ejaculation and penile lymphedema were observed in 2, 3, 1 and 1 patients, respectively. All patients reported sexual intercourse ability. CONCLUSIONS: The type of penile skin reconstruction after the removal of sclerosing lipogranuloma of the penis is controversial. The reconstruction technique presented herein is an effective single-stage treatment option with a high success rate in patients with sclerosing lipogranuloma of the penis with intact scrotal skin.

Staged penile skin reconstruction for sclerosing lipogranuloma / A hímvesszo borének helyreállítása szklerotizáló lipogranuloma okozta deformitás miatt.

Összefoglaló. Bevezetés: A hímtag körméretének növelése érdekében, az annak bore alá bejuttatott zsírnemu anyag szklerotizáló lipogranulomát okoz. Hazánkban a szklerotizáló lipogranuloma okozta hímvesszo-deformitások kezelésének legelterjedtebb módszere a két ülésben végzett borpótlás. Ennek ellenére a magyar nyelvu szakirodalomban kevés adat áll rendelkezésre a kétüléses mutét eredményességérol és várható szövodményeirol. Célkituzés: Tanulmányunkban a szklerotizáló lipogranuloma okozta deformitások miatti - két ülésben végzett - hímvesszobor-helyreállítással szerzett tapasztalatainkról, a mutét után kialakuló szövodményekrol számolunk be retrospektív adatgyujtés alapján. Módszer: 2008. március 1. és 2020. március 1. között a Debreceni Egyetem Urológiai Klinikáján 17 betegen végeztünk kétüléses hímvesszobor-helyreállító mutétet. A szklerotizáló lipogranuloma által érintett bort teljes mértékben eltávolítottuk, majd a lecsupaszított hímtagot a herezacskó elülso felszínén kialakított subcutan csatornába helyeztük. A második ülés során a herezacskó bore alá ültetett hímvesszot felszabadítottuk. Eredmények: A Clavien-Dindo-beosztás szerint az elso ülés után három, a második ülés után egy I. gradusú szövodmény alakult ki; II-V. gradusú szövodményt nem figyeltünk meg. Azon 9 beteg közül, akik mindkét ülésen átestek, 7 beteg elégedett volt a beavatkozás eredményével, 2 beteg korrekciós mutéten esett át fél és 9 évvel a második ülés után. A 8 beteg közül, akik csak ez elso ülést vállalták, egy korrekciós mutét történt 4 hónappal a mutét után. Következtetés: A hímvesszo szklerotizáló lipogranulomája esetén az érintett borterület kimetszése után hímvesszobor-helyreállítás szükséges. A herezacskó-borlebeny alkalmazásának elonye, hogy a herezacskó színe és elaszticitása a hímvesszoboréhez hasonló, a tapintás- és erogén érzet megmarad. A kétüléses hímvesszobor-helyreállítás kevés szövodménnyel, plasztikai sebészeti jártasság nélkül elvégezheto. Orv Hetil. 2021; 162(35): 1413-1417. INTRODUCTION: Subcutaneous injection of liquid fatty materials to enhance penile girth induce sclerosing lipogranuloma of the penis. In spite of its well known severe consequences there has been a persistent use of this practice in non-medical circumstances. OBJECTIVE: The aim of this paper is to present our observations with staged penile skin reconstruction for sclerosing lipogranuloma and to evaluate postoperative complications in a retrospective manner. METHOD: Between 2008 and 2020, 17 patients underwent surgery to treat sclerosing lipogranuloma of the penis by staged penile skin reconstruction at our department. Complete exscision of the involved tissue was performed, then the denuded penile shaft was inserted into a subcutaneous channel on the anterior side of the scrotum during the first stage. The second stage of reconstruction consisted of releasing the penile shaft from the scrotum. The second stage was performed merely on 9 in 17 patients. RESULTS: According to the Clavien-Dindo classification system, 3 grade I and 1 grade I complications occurred in the postoperative period after the first and second stage, respectively. Grade II-V complications were not observed. 7 of 9 patients who underwent both stages were satisfied with the final result, 2 patients had minor correction surgery 6 months and 9 years following the second stage. 1 of 8 patients who underwent only the first stage had minor correction surgery 4 months following the operation. CONCLUSION: In case of sclerosing lipogranuloma of the penis, excision of the affected tissue and reconstruction of the penile skin are indicated. Advantages of using scrotal skin flaps are that colour and elasticity of the scrotal skin are similar to penile skin, erogenous sensation of the scrotal flap remains intact. Applying staged penile skin reconstruction with scrotal skin flap has the advantage of few postoperative complications and it is easy to perform. Orv Hetil. 2021; 162(35): 1413-1417.

[The Great Imitator. Case report]. / A nagy imitátor.

Authors present two patients suffering from renal tuberculosis, which caused differential diagnostic problems. The first patient was examined because of fever and left flank pain. Computed tomography revealed renal shrinkage on the left side. Retrograde pyelography demonstrated ureteric stricture and dilated calices. Urine culture showed Mycobacterium tuberculosis. Two months after initiation of the antituberculotic therapy nephrectomy was performed. The second patient was referred to the department because of fever after unsuccessful antibiotic treatment. Ultrasound examination showed a staghorn stone, dilated renal pelvis and perirenal abscess on the left side. Double J catheter insertion and percutaneous puncture of the abscess were performed. Culture of the pus aspirated proved Proteus morganii. Fever and complaints of the patient relieved after antibiotic treatment. Two months later double J catheter was changed because of persistent pyelonephritis. One week later the patient returned to the hospital with fever, which could not be reduced with intravenous antibiotics. Computed tomography showed purulent fluid in the left kidney, and nephrectomy was performed. Histology revealed renal tuberculosis. The authors summarize the diagnosis and treatment of renal tuberculosis on the basis of these two cases.

Present practice of thrombosis prophylaxis of radical prostatectomy in a European country: a Hungarian multicenter study.

Venous thromboembolism is a possible fatal complication after pelvic surgery. There is a lack of trials assessing the effect of prophylactic measures in urology. The aim of the study was to evaluate the practice of thrombosis prophylaxis in a Central European country. A questionnaire of performed radical prostatectomies, way of thrombosis prophylaxis and number of experienced thrombotic events was posted to all departments of urology in Hungary. With a response rate of 59%, 506 radical prostatectomies were reported. Low molecular weight heparin was administered by 100% of the departments. Graduated support stockings were applied by 37% of the patients. Early mobilization was the most common form of mechanic prophylaxis (57%). Thrombotic events were experienced in 1.4%, 0.2% were fatal. The thrombosis prophylaxis of patients undergoing radical prostatectomy is not unified. Due to the potential mortality of thrombotic complications it should be evaluated and prophylaxis should be recommended in urological guidelines.

Laparoscopic removal of a paracaval air gun bullet in a child.

Air guns are known as low-velocity arms and are considered harmless. However, injuries from air weapons can be serious and even fatal, particularly in children. We present a potentially life-threatening penetrating retroperitoneal injury of a 3-year-old boy caused by an air gun, and the successful removal of the bullet via a laparoscopic approach. The patient was brought to our center with a penetrating air gunshot wound on his right side in the waist area. He was accidentally shot by his brother at their home. The patient's clinical condition was stable. Computed tomography scan showed the bullet in the retroperitoneum near the inferior vena cava. A three-port laparoscopic transperitoneal approach was performed. The bullet was found just 0.5 cm caudal to the right renal hilum and 0.5 cm near the inferior vena cava; it was then removed. Operation time was 42 min and the postoperative course was uneventful. Thanks to improvements in laparoscopic surgical techniques, laparoscopy has become a feasible and effective treatment modality even for the removal of foreign bodies in children.

[Nondetectable prostate cancer in radical prostatectomy specimens]. / Kimutathatatlan prosztatarák radikális prostatectomiás szövetmintákban.

UNLABELLED: Since the widespread use of prostate-specific antigen, early diagnosis of prostate cancer at an early stage has been increased. Consequently, a greater frequency of low-volume disease or no tumor has been found in radical prostatectomy specimen. AIMS: In the present study authors analyzed patients classified as pT0 after radical prostatectomy at their center. METHODS: 1134 radical prostatectomies were evaluated retrospectively at the author's center between 1996 and 2010. If there was no evidence of prostate cancer in the specimen, patient was staged as pT0. Patients were divided into two groups: received neoadjuvant hormonal therapy or not. RESULTS: Overall 32 (2.8%) patients were staged as pT0. The rate of pT0 staging was 9.3% and 1.2% in the hormonally treated group and non-hormonally treated group. False-positive prostate biopsy was found in 2 cases. The rate of pT0 staging was higher in patients with incidental prostate cancer, low Gleason score and enlarged prostate. Biochemical relapse was observed in 3 pT0 patients in the hormonally treated group, among them there was one clinical relapse. In non-hormonally treated group no recurrence was detected. CONCLUSION: The rate of pT0 staging was higher in the hormonally treated group. Because of biochemical and clinical relapse despite vanishing prostate cancer phenomenon, these cases are considered not to be true pT0. On the basis of present study and other reports the rate of pT0 staging is about one percentage in non-hormonally treated patients. Prognosis of these patients is excellent.

Very late relapse of testicular tumour in combination with renal cancer and their retroperitoneoscopic removal.

Late relapse of a testicular cancer is an uncommon occurrence. We report a case of late relapse of a testicular tumour combined with a renal cancer and their successful removal with retroperitoneoscopy. The 36-year-old patient underwent left orchiectomy, retroperitoneal lymph node dissection, and chemotherapy, because of mixed tumor including teratoma and embryonal carcinoma. 18 years after the successful primary therapy elevated serum alpha-fetoprotein level had been confirmed, then MRI and PET-CT scans demonstrated a 30 mm left renal mass and 22 mm retroperitoneal lymph node above the bifurcation of the left common iliac artery. We performed retroperitoneoscopic lymph node dissection and left renal tumour resection in the same session. The histology revealed embryonal carcinoma for the retroperitoneal lymph node and renal cell carcinoma for the left renal mass. We can conclude that late followup of patients with testicular tumour is important. Retroperitoneoscopy is feasible approach for the removal of retroperitoneal lymph node metastasis and resection of renal tumor.