OBJECTIVE: We aimed in the current study to identify the predictive factors of ED occurrence in healthy individuals following penile fracture surgical repair as well as the effect of penile rehabilitation in the form of daily tadalafil 5 mg intake for 1 month for patients who suffered from ED after penile fracture incident.
METHODS: The current study was a prospective case-control study. Twenty-five patients were enrolled into the study starting from January (2022) to February (2023). Furthermore, time of presentation was determined, and length of tear intra-operative was measured, and then, a follow-up 1 week postoperatively in the outpatient clinic was conducted. All patients were instructed to start intercourse at least 2 weeks after the first visit provided that the wound epithelialized. Potent patients returned back home. A rehabilitation course of daily tadalafil 5 mg for 1 month was prescribed for patients who started complaining of ED that was confirmed by evaluation with the Arabic validated version of the international index of erectile function (ArIIEF-5). The rehabilitation therapy was terminated by resumption of normal erectile function. Thus, re-evaluation with the ArIIEF-5 was determined according to their response to therapy. Also, the patients were evaluated by hospital anxiety and depression scale (HADS) before and after penile fracture repair.
RESULTS: The current study had demonstrated that a 1% increase in age determines an increase in odds ratio for post-penile fracture ED with 73.6% and 1 cm increase in the length of tear determines an increase in odds ratio for post-penile fracture ED with 20.04 times.
CONCLUSIONS: The current study enhances the proper counseling of these patients prior to repairing the defect about the probability of ED occurrence as well as initiating early penile rehabilitation to help these patients resuming their normal sexual activity as soon as possible.

Quantification of in vivo amyloid and tau PET imaging relationships with postmortem measurements are critical for validating the sensitivity and specificity imaging biomarkers across clinical phenotypes with Alzheimer disease neuropathologic change (ADNC). This study examined the quantitative relationship between regional binding of in vivo 18F-florbetapir amyloid PET and 18F-flortaucipir tau PET with postmortem stereological counts of amyloid plaques and neurofibrillary tangles (NFT) in a case of primary progressive aphasia (PPA) with ADNC, where neurodegeneration asymmetrically targets the left hemisphere. Beginning 2 years prior to death, a 63-year-old right-handed man presenting with agrammatic variant PPA underwent a florbetapir and flortaucpir PET scan, and neuropsychological assessments and magnetic resonance imaging sessions every 6 months. Florbetapir and flortaucpir PET standard uptake value ratios (SUVRs) were quantified from 8 left and right hemisphere brain regions with stereological quantification of amyloid plaques and NFTs from corresponding postmortem sections. Pearson\'s correlations and measures of asymmetry were used to examine relationships between imaging and autopsy measurements. The three visits prior to death revealed decline of language measures, with marked progression of atrophy. Florbetapir PET presented with an atypical focal pattern of uptake and showed a significant positive correlation with postmortem amyloid plaque density across the 8 regions (r = 0.92; p = 0.001). Flortaucipir PET had a left-lateralized distribution and showed a significant positive correlation with NFT density (r = 0.78; p = 0.023). Flortaucipir PET and NFT density indicated a medial temporal lobe sparing presentation of ADNC, demonstrating that AD does not always target the medial temporal lobe. This study adds additional evidence, in a non-amnestic phenotype of ADNC, that there is a strong correlation between AD PET biomarkers, florbetapir and flortaucipir, with quantitative neuropathology. The atypical and focal presentation of plaque density and florbetapir PET uptake suggests not all amyloid pathology presents as diffuse across neocortex.

BACKGROUND Lurbinectedin (Lurbi) was first approved in June 2020 for metastatic small cell lung cancer (SCLC) patients with progression following platinum-based chemotherapy. Extrapulmonary small cell neuroendocrine cancers (SCNECs) are treated with regimens used for SCLCs. Tumor lysis syndrome (TLS) in solid SCLCs and SCNECs following Lurbi use has not been reported in the literature so far. CASE REPORT We report a case of Lurbi-induced TLS in a patient with metastatic SCNEC of the cecum following a single intravenous dose of Lurbi 3.2 mg/m2. She presented to the hospital with abdominal pain, anuria, and grade 4 TLS. She required emergent hemodialysis due to acute renal failure. Our patient had a high Ki-67 proliferation index (95%), harbored a huge disease burden, and had bilateral renal metastasis, thus making her more susceptible to develop TLS. CONCLUSIONS Although data regarding the occurrence of TLS due to Lurbi in solid tumors are scarce, it remains a potential complication of Lurbi in neuroendocrine tumors with high proliferation index and large tumor burden.

UNASSIGNED: Early, accurate diagnosis of Alzheimer disease (AD) is essential but remains challenging. Neuropathological hallmarks of AD are β-amyloid neuritic plaques and tau protein neurofibrillary tangles. 18F-Florbetapir is one of several available PET tracers for imaging cortical fibrillary β-amyloid plaques. 18F-Flortaucipir PET was recently approved for evaluating the distribution and density of aggregated neurofibrillary tangles. We present cases of mild cognitive impairment or suspected AD to depict the nuances of flortaucipir distribution and scan interpretation as well as how combined information from amyloid and tau PET may help with differential diagnosis and prognosis.

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Chronic traumatic encephalopathy (CTE) is a tauopathy associated to repetitive head trauma. There are no validated in vivo biomarkers of CTE and a definite diagnosis can only be made at autopsy. Recent studies have shown that positron emission tomography (PET) tracer AV-1451 (Flortaucipir) exhibits high binding affinity for paired helical filament (PHF)-tau aggregates in Alzheimer (AD) brains but relatively low affinity for tau lesions in other tauopathies like temporal lobal degeneration (FTLD)-tau, progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). Little is known, however, about the binding profile of this ligand to the tau-containing lesions of CTE.
To study the binding properties of [18F]-AV-1451 on pathologically confirmed CTE postmortem brain tissue samples.
We performed [18F]-AV-1451 phosphor screen and high resolution autoradiography, quantitative tau measurements by immunohistochemistry and Western blot and tau seeding activity assays in brain blocks containing hippocampus, superior temporal cortex, superior frontal cortex, inferior parietal cortex and occipital cortex from 5 cases of CTE, across the stages of disease: stage II-III (n = 1), stage III (n = 3), and stage IV (n = 1). Importantly, low or no concomitant classic AD pathology was present in these brains.
Despite the presence of abundant tau aggregates in multiple regions in all CTE brains, only faint or no [18F]-AV-1451 binding signal could be detected by autoradiography. The only exception was the presence of a strong signal confined to the region of the choroid plexus and the meninges in two of the five cases. Tau immunostaining and Thioflavin-S staining ruled out the presence of tau aggregates in those regions. High resolution nuclear emulsion autoradiography revealed the presence of leptomeningeal melanocytes as the histologic source of this off-target binding. Levels of abnormally hyperphosphorylated tau species, as detected by Western Blotting, and tau seeding activity were both found to be lower in extracts from cases CTE when compared to AD.
AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in CTE. The existence of disease-specific tau conformations may likely explain the differential binding affinity of this tracer for tau lesions in different tauopathies.

OBJECTIVE: Recent studies have found associations of increased brain amyloid beta (Aβ) accumulation and several abnormal sleep-wake patterns, including shorter latency and increased fragmentation in preclinical Alzheimer\'s disease (AD). There is little known about the relationship between sleep and tau. The objective of this study was to understand the associations of both tau and Aβ with early signs of sleep and night-time behavior changes in clinically normal elderly adults. Specifically, we have addressed the question of how informant-based subjective sleep reports are linked to regional [18F]flortaucipir and [18F]florbetapir uptake.
METHODS: Imaging and behavioral data from 35 subjects were obtained from the Alzheimer\'s Disease Neuroimaging Initiative. The Neuropsychiatric Inventory Sleep (NPI-sleep) Questionnaire was used to assess the sleep and night-time behavior changes. Regional tau-positron emission tomography (PET) (entorhinal, brainstem) and Aβ-PET (posterior cingulate, precuneus, medial orbitofrontal) uptake values were calculated. A series of linear regression analyses were used to determine the combination of sleep symptoms that built the best models to predict each pathology.
RESULTS: Informant-based reports of abnormal night-time behavior (NPI questions k3, k5, and k8) were significantly associated with increased entorhinal tau and Aβ (all regions) accumulation. Interestingly, informant-based reports of sleep deficiencies without abnormal nigh-time activity (NPI questions k1, k2, and k6) were negatively associated with entorhinal tau burden.
CONCLUSIONS: Detection of abnormal night-time behaviors (wandering, pacing, other inappropriate activities) by family members indicates early signs of both AD pathologies and may encourage the affected individuals to seek help by health care providers for detailed cognitive/neurobehavioral assessments.

BACKGROUND: THK5351 and flortaucipir tau ligands have high affinity for paired helical filament tau, yet diverse off-target bindings have been reported. Recent data support the hypothesis that THK5351 binds to monoamine oxidase B (MAO-B) expressed from reactive astrocytes and that flortaucipir has an affinity toward MAO-A and B; however, pathological evidence is lacking. We performed a head-to-head comparison of the two tau ligands in a sporadic Creutzfeldt-Jakob disease (CJD) patient and performed an imaging-pathological correlation study.
METHODS: A 67-year-old man visited our clinic a history of 6 months of rapidly progressive dementia, visual disturbance, and akinetic mutism. Diffusion-weighted imaging showed cortical diffusion restrictions in the left temporo-parieto-occipital regions. 18F-THK5351 PET, but not 18F-flortaucipir PET showed high uptake in the left temporo-parieto-occipital regions, largely overlapping with the diffusion restricted areas. Cerebrospinal fluid analysis was weakly positive for 14-3-3 protein and pathogenic prion protein was found. The patient showed rapid cognitive decline along with myoclonic seizures and died 13 months after his first visit. A post-mortem study revealed immunoreactivity for PrPsc, no evidence of neurofibrillary tangles, and abundant astrocytosis which was reactive for MAO-B antibody.
CONCLUSIONS: Our findings add pathological evidence that increased THK5351 uptake in sporadic CJD patients might be caused by an off-target binding driven by its high affinity for MAO-B.

Imaging of pathological tau with positron emission tomography (PET) has the potential to allow early diagnosis of the dementias and monitoring of disease progression, including assessment of therapeutic interventions, in vivo. The first generation of tau PET tracers, including the carbazole flortaucipir and the 2-arylquinolines of the THK series, are now used in clinical research; however, concerns have been raised about off-target binding and low sensitivity.With the aim to determine the nature of tau pathology depicted by structurally distinct tau ligands we carried out a microscopic neuropathological evaluation in post-mortem human brain tissue of cases with primary and secondary tauopathies. Carbazole and 2-arylquinoline binding was only observed in cases with Alzheimer\'s disease and one case with frontotemporal dementia and parkinsonism linked to chromosome 17 exhibiting a R406W MAPT mutation. In end stage Alzheimer\'s disease cases, fluorescent imaging with the carbazole T726 and the 2-arylquinoline THK-5117 revealed high inter- and intra-case variability of tracer binding, and this was corroborated by quantitative phosphorimaging with the PET tracer [18F]THK-5117. Microscopic analysis of the pathological inclusions revealed that the fluorescent tracers preferentially bind to premature tau aggregates. Whilst T726 binding was limited to neuronal tau, THK-5117 additionally depicted neuritic tau. Neither tracer depicted tau in pre-symptomatic disease.Our results highlight limitations of the first generation of tau PET tracers, in particular lack of correlation between pathological tau load and tracer binding, limited sensitivity to tau in early disease, and high variability in tracer binding between and within cases. Concerns remain that these limitations may also affect the next generation tracers as they target the same high affinity binding site. Therefore, it is crucial to assess inter- and intra-subject correlation of tracer binding with pathological tau load in post-mortem tissue studies, and to rigorously assess novel tau PET tracers before translation into clinical studies.

[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer\'s disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas. We and others have shown that [F-18]-AV-1451 exhibits off-target binding to neuromelanin, melanin and blood products on postmortem material; and this is important for the correct interpretation of PET images. In the present study, we further investigated [F-18]-AV-1451 off-target binding in the first autopsy-confirmed Parkinson\'s disease (PD) subject who underwent antemortem PET imaging. The PET scan showed elevated [F-18]-AV-1451 retention predominantly in inferior temporal cortex, basal ganglia, midbrain and choroid plexus. Neuropathologic examination confirmed the PD diagnosis. Phosphor screen and high resolution autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined with the exception of neuromelanin-containing neurons in the substantia nigra, leptomeningeal melanocytes adjacent to ventricles and midbrain, and microhemorrhages in the occipital cortex (all reflecting off-target binding), in addition to incidental age-related neurofibrillary tangles in the entorhinal cortex. Additional legacy postmortem brain samples containing basal ganglia, choroid plexus, and parenchymal hemorrhages from 20 subjects with various neuropathologic diagnoses were also included in the autoradiography experiments to better understand what [F-18]-AV-1451 in vivo positivity in those regions means. No detectable [F-18]-AV-1451 autoradiographic binding was present in the basal ganglia of the PD case or any of the other subjects. Off-target binding in postmortem choroid plexus samples was only observed in subjects harboring leptomeningeal melanocytes within the choroidal stroma. Off-target binding to parenchymal hemorrhages was noticed in postmortem material from subjects with cerebral amyloid angiopathy. The imaging-postmortem correlation analysis in this PD case reinforces the notion that [F-18]-AV-1451 has strong affinity for neurofibrillary tau pathology but also exhibits off-target binding to neuromelanin, melanin and blood components. The robust off-target in vivo retention in basal ganglia and choroid plexus, in the absence of tau deposits, meningeal melanocytes or any other identifiable binding substrate by autoradiography in the PD case reported here, also suggests that the PET signal in those regions may be influenced, at least in part, by biological or technical factors that occur in vivo and are not captured by autoradiography.