Emerging perspectives of synaptic biomarkers in ALS and FTD.

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions and genetic mutations. Both diseases involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated with synaptic function or structure, offer insights into disease mechanisms, progression, and treatment responses. These biomarkers can detect disease early, track its progression, and evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and blood, correlating with disease progression. TDP-43 is another key ALS biomarker, its mislocalization linked to synaptic dysfunction. In FTD, TDP-43 and tau proteins are studied as biomarkers. Synaptic biomarkers like neuronal pentraxins (NPs), including neuronal pentraxin 2 (NPTX2), and neuronal pentraxin receptor (NPTXR), offer insights into FTD pathology and cognitive decline. Advanced technologies, like machine learning (ML) and artificial intelligence (AI), aid biomarker discovery and drug development. Challenges in this research include technological limitations in detection, variability across patients, and translating findings from animal models. ML/AI can accelerate discovery by analyzing complex data and predicting disease outcomes. Synaptic biomarkers offer early disease detection, personalized treatment strategies, and insights into disease mechanisms. While challenges persist, technological advancements and interdisciplinary efforts promise to revolutionize the understanding and management of ALS and FTD. This review will explore the present comprehension of synaptic biomarkers in ALS and FTD and discuss their significance and emphasize the prospects and obstacles.

Extended Boari-flap reconstruction in isolated tuberculous pan-ureteral stricture.

A 53-year-old female presented with left loin pain and imaging showed left pan-ureteral stricture secondary to tuberculosis. The renal unit was salvaged by percutaneous nephrostomy. She was planned for ileal ureteric replacement. An extended Boari flap was constructed for her as the bladder capacity was good and Boari bladder flap reached the renal pelvis without tension. Follow-up nephrostogram revealed wide pyelovesical junction with prompt drainage. She completed antituberculous treatment. Extended Boari flap is rarely used for upper ureteric reconstruction. It should be considered as an option for complete ureteric reconstruction in the unilateral pan-ureteral stricture in selected cases.

High rectourethral fistula following TURP: repair possible only after transvesical prostatectomy.

We report a case of iatrogenic rectourethral fistula (RUF) in an elderly man with benign prostatic enlargement and acute urinary retention, following a transurethral resection of prostate (TURP). This patient presented a unique challenge of tackling the RUF in the presence of a large residual prostate gland and urinary tract infection. RUF was repaired only after getting the access to the fistula following transvesical prostatectomy. Follow-up imaging showed well-healed repair of RUF. Transvesical prostatectomy is a useful adjunctive procedure in repair of RUF when associated with a large prostate. This case also highlights the importance of technique selection while planning for surgery on large prostate glands. TURP is not the preferred first modality of choice for larger glands as noted in this case.

Diagnostic Accuracy of Prebiopsy Ga-68 PSMA PET/CT in Detecting Primary Prostate Carcinomas with Prostate-Specific Antigen <50 ng/ml.

BACKGROUND AND AIM: Serum prostate-specific-antigen (PSA) guided systematic transrectal ultrasound (TRUS)-guided biopsies are known to have a low predictive value in detection of primary prostate carcinomas (PCa). Our aim was to evaluate the accuracy of gallium-68 (Ga-68) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for the detection of PCa with serum PSA <50 ng/ml. PATIENTS AND METHODS: We retrospective analyzed prebiopsy Ga-68 PSMA PET/CT's of all patients with suspected PCa from October 2019 to March 2020. Several quantitative clinical and PET/CT variables were compared in benign and malignant groups and assessed for significance using an independent t-test. Diagnostic performance of PSMA PET/CT for detection of cancer was evaluated and compared with the diagnostic performance of cancer risk predicting calculator (European Randomized Study for Screening of Prostate Cancer [ERSPC3]). The standard of reference was 12-core TRUS-guided biopsies. RESULTS: Sixty-four patients were included with mean age 70 years (range 48-94 years); mean PSA 15.67 ng/ml (range 1.74-44), mean PSA density 0.32 ng/ml2 (range 0.01-0.99) and mean prostate volume 54.55 cc (range 16.5-182). 64% (n = 41/64) patients had benign histology and 36% (n = 23/64) had carcinoma. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PSMA PET/CT for detecting PCa reported using the prostate cancer molecular imaging standardized evaluation (PROMISE) was 74%, 92%, 85%, 86%, and 86%, respectively. Mean prostate maximum standardized uptake value (SUVmax) was significantly higher in PCa versus Benign lesions (19.56 ± 18.11 vs. 4.21 ± 1.5, P = 0.00001), in patients with PSA >20 ng/ml versus PSA <20 ng/ml (19.1 ± 20.6 vs. 6.01 ± 5.4, P-0.0052), and in patients with Gleason's score (GS) score >7 versus GS ≤7 (28.1 ± 20.3 vs. 10.2 ± 8.9, P-0.010). SUVmax cutoff value of 5.6 on PSMA PET/CT showed a sensitivity of 95% and specificity of 90.9% (area under the curve 0.990, P < 0.0001). CONCLUSION: Ga-68 PSMA PET/CT can differentiate benign and malignant lesions of the prostate with very high accuracy and when used alongside with ERSPC3 calculator and magnetic resonance imaging, could potentially reduce painful and often unnecessary prostate biopsies.

Non Transecting Dorsal Onlay and Ventral Inlay Buccal Mucosal Substitution Urethroplasty for Obliterative Bulbar Urethral Strictures.

BACKGROUND: Dorsal or ventral single layer repair can be impractical when there is an inadequate strip of urethra. Staged urethroplasty and non-transecting bilayer substitution urethroplasty are the other alternatives. OBJECTIVES: To assess the safety and outcome of non-transecting dorsal onlay and ventral inlay buccal mucosal substitution urethroplasty technique. METHOD: Between January 2014 and December 2018, 21 patients underwent non-transecting, double-layer, buccal mucosal urethroplasty for inflammatory bulbar urethral strictures. Four weeks after surgery, foley catheters were removed and voiding trial was given. Clinical examination and uroflowmetry (UFM) were done at 1, 3, and 6 months after surgery. Annual follow-up with flow rate and post-void residual assessment were also recorded. Failure was defined as a condition when there was flow rate deterioration (<15 mL/s) or when there is stricture recurrence (<20 Fr). RESULTS: The mean age was 49.5 years. There was no significant difference in comorbidities among the patients. The mean duration of operative time was 259 min. The mean blood loss was 190 mL. The follow-up duration ranged from 12 to 66 months. The average length of stricture was 3.9 cm. The mean diameter of stricture segment was 1.96 mm. Comparison of UFM trend during follow-up was statistically significant (p = 0.05). One patient had Clavien-dindo grade 1, while 2 patients had grade 3b complications. Two patients had soft anastomotic site stricture and were treated successfully with endoscopic internal urethrotomy. The success rate was 90.47%. CONCLUSIONS: Non-transecting bilayer substitution urethroplasty is safe and has better short-term outcome in case of obliterative inflammatory urethral strictures.

Primitive neuroectodermal tumour of the kidney presenting as diplopia secondary to skull metastasis.

A 20-year-old man presented to the department of neurology with diplopia, occipital headache and right flank pain for 1-week duration. CT of the brain revealed skull metastasis with heterogeneously enhancing dural-based mass lesion at the occipital region. Positron emission tomography revealed tracer avid soft tissue mass involving the upper pole of the right kidney with loss of fat planes with the inferior surface of the liver. Multidisciplinary team approach was discussed. He underwent palliative nephrectomy with lymph nodal mass excision. Biopsy from the renal mass was suggestive of primitive neuroectodermal tumour. He developed progressive liver metastases in spite of adjuvant chemotherapy denoting very aggressive disease.

Retrograde Pyelogram during intended Cystogram: A Rare complication of a common procedure.

Inadvertent placement of the urinary catheter into the ureter can cause several complications. We describe a rare complication during cystogram due to unrecognized inadvertently placed urinary catheter in ureter, resulting in a life-threatening situation. A 47-year-old multiparous female underwent total laparoscopic hysterectomy for adenomyosis. During early postoperative period, she developed vesicovaginal fistula and transvaginal repair of fistula was done. During filling cystography done at 2 weeks, she developed right loin pain and urosepsis. Contrast extravasation was seen in the right renal subcapsular space with Foley's catheter inside the right ureter. Subsequently, she recovered well.