Complement and Non-Complement Binding Anti-HLA Antibodies Are Differentially Detected with Different Antigen Bead Assays in Renal Transplant Recipients.

Two semi-quantitative, Luminex-based, single-antigen bead (SAB) assays are available to detect anti-HLA antibodies and evaluate their reactivity with complement binding. Sera from 97 patients with positive panel reactive antibody tests (>5%) were analyzed with two SAB tests, Immucor (IC) and One-Lambda (OL), for anti-HLA antibody detection and the evaluation of their complement-binding capacity. IC detected 1608/8148 (mean fluorescent intensity (MFI) 4195 (1995-11,272)) and 1136/7275 (MFI 6706 (2647-13,184)) positive anti-HLA class I and II specificities, respectively. Accordingly, OL detected 1942/8148 (MFI 6185 (2855-12,099)) and 1247/7275 (MFI 9498 (3630-17,702)) positive anti-HLA class I and II specificities, respectively. For the IC assay, 428/1608 (MFI 13,900 (9540-17,999)) and 409/1136 (MFI 11,832 (7128-16,531)) positive class I and II specificities bound C3d, respectively. Similarly, OL detected 485/1942 (MFI 15,452 (9369-23,095)) and 298/1247 (MFI18,852 (14,415-24,707)) C1q-binding class I and II specificities. OL was more sensitive in detecting class I and II anti-HLA antibodies than IC was, although there was no significant difference in the number of class II specificities per case. MFI was higher for complement vs. non-complement-binding anti-HLA antibodies in both assays. Both methods were equal in detecting complement-binding anti-HLA class I antibodies, whereas the C3d assay was more sensitive in detecting complement-binding anti-HLA class II antibodies.

Cerebrospinal Fluid Anti-Neuronal Autoantibodies in COVID-19-Associated Limbic Encephalitis with Acute Cerebellar Ataxia and Myoclonus Syndrome: Case Report and Literature Review.

Since the outbreak of coronavirus (COVID-19) in 2019, various rare movement disorders and cognitive changes have been recognized as potential neurological complications. The early treatment of some of these allows rapid recovery; therefore, we must diagnose these manifestations in a timely way. We describe the case of a 76-year-old man infected with severe acute respiratory syndrome coronavirus-2 who presented with confusion and hallucinations and was admitted to our hospital 14 days after the onset of symptoms. One day later, he developed generalized myoclonus, dysarthria and ataxia, and tonic clonic seizures and was admitted to the intensive care unit. A diagnosis of COVID-19-associated autoimmune encephalitis with characteristics of limbic encephalitis and immune-mediated acute cerebellar ataxia and myoclonus syndrome was supported by alterations in the limbic system shown in magnetic resonance imaging, lateralized discharges shown in electroencephalography, a slightly elevated protein level in the cerebrospinal fluid (CSF), and indirect immunofluorescence in the CSF with autoantibody binding to anatomical structures of the cerebellum and hippocampus. The patient improved with 2 weeks of corticosteroid treatment and four sessions of plasmapheresis. Our current case study describes a rare case of COVID-19-related limbic encephalitis with immune-mediated acute cerebellar ataxia and myoclonus syndrome (ACAM syndrome) and strengthens the need for tissue-based assays (TBAs) to screen the serum and/or CSF of patients highly suspected to have autoimmune encephalitis. We believe that the timely diagnosis and targeted aggressive immunotherapy were mainly responsible for the patient's total recovery.

Prospective De Novo Donor-Specific Antibody Monitoring in Renal Transplant Patients.

BACKGROUND: De novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection leading to kidney transplant failure. However, many transplant patients are stable with no signs of graft dysfunction at the time of dnDSA detection at screening test. METHODS: We prospectively studied 26 kidney transplant patients for 3 years, with dnDSA detected using the Luminex single-antigen bead assay in a routine test. Proteinuria and estimated glomerular filtration rate were evaluated along with dnDSA monitoring at least annually. RESULTS: Graft loss associated with dnDSA occurred in 8 (31%) patients, 14 ± 11 months after the initial detection of dnDSA. These patients had more frequently multiple dnDSA (P = .004) and remarkable proteinuria, more than 1 g daily (P < .001). The remaining 18 patients were followed for 38 ± 15 months and considered stable as there was no deterioration regarding estimated glomerular filtration rate and proteinuria. In 7 (39%) of these patients, dnDSA waned and were not detected anymore at follow-up. Antibodies against HLA class I had a significantly (P < .001) lower mean fluorescence intensity (MFI) (2603 ± 1098) compared with those against HLA class II (11,109 ± 6414). In regression analysis, they were predictive of dnDSA wane (P = .043; odds ratio, 0.18; 95% confidence interval, 0.04-0.94). Despite fluctuations during follow-up, there was no significant change in MFI for those who retained the dnDSA. CONCLUSIONS: The presence of dnDSA is transient in a significant proportion of stable renal transplant patients, especially in those with antibodies against HLA class I and a low MFI. Multiple dnDSA and severe proteinuria adversely affect renal graft survival.

Neurological and neurourological complications of electrical injuries.

Electrical injury can affect any system and organ. Central nervous system (CNS) complications are especially well recognised, causing an increased risk of morbidity, while peripheral nervous system (PNS) complications, neurourological and cognitive and psychological abnormalities are less predictable after electrical injuries. PubMed was searched for English language clinical observational, retrospective, review and case studies published in the last 30 years using the key words: electrical injury, electrocution, complications, sequelae, neurological, cognitive, psychological, urological, neuropsychological, neurourological, neurogenic, and bladder. In this review, the broad spectrum of neurological, cognitive, psychological and neurourological consequences of electrical trauma are discussed, and clinical features characteristic of an underlying neurological, psychological or neurourological disorder are identified. The latest information about the most recently discovered forms of nervous system disorders secondary to electrical trauma, such as the presentation of neurological sequelae years after electrocution, in other words long-term sequelae, are presented. Unexpected central nervous system or muscular complications such as hydrocephalus, brain venous thrombosis, and amyotrophic lateral sclerosis are described. Common and uncommon neuropsychological syndromes after electrical trauma are defined. Neurourological sequelae secondary to spinal cord or brain trauma or as independent consequences of electrical shock are also highlighted.

Bilateral subcutaneous pyelovesical bypass in a Hautmann neobladder followed by a mononeuropathy multiplex and an underlying polyarteritis nodosa diagnosis.

Subcutaneous pyelovesical bypasses are the best choice for the long-term palliative treatment of ureteral obstructions. In rare cases this obstruction is due to polyarteritis nodosa. We present the only reported patient with a bilateral Detour bypass in a Hautmann's neobladder. The patient also suffers from polyarteritis nodosa.

A surgical approach to squamous cell carcinoma of penis that also resolved the psychological dysfunction of the patient.

In this case study, we present an unusual case with squamous cell carcinoma surrounding the penis involving foreskin and glans of penis. In addition, multiple satellite nodules were noted in the pubis. A 57-year-old circumcised heterosexual male patient presented with a penile lesion existing for 10 years. At the same time, he was referred to an outpatient memory clinic because of persistent subjective memory complaints associated with depression and anxiety. The patient was operated under general anaesthesia. The lesion was resected circumferentially with macroscopic clearance, resulting in complete degloving of the penile shaft. Neurovascular bundles were preserved. Histopathological analysis of the lesion revealed an invasive and poorly differentiated squamous cell carcinoma, and the surgical margins were free from tumour. The patient was followed for 18 months. He did not have voiding difficulty. Pelvic tomographic and physical examination findings did not reveal any episode of recurrence or metastasis. Treatment of carcinoma resulted in a simultaneous full recovery of his memory decline and he remained free of depression and anxiety symptoms over time.

Cognitive and Psychological Impacts of Different Treatment Options for Prostate Cancer: A Critical Analysis.

OBJECTIVES: Psychological morbidity as well as cognitive impairment are increasingly reported in prostate cancer (PCa) patients. However, despite growing numbers of PCa survivors and the well estimated negative impact of cognitive decline and emotional distress on survivors' quality of life, no study has assessed the whole range of cognitive and psychological sequelae as a response to treatment options for PCa. The objective of the present review was to systematically characterize the types and estimate the prevalence of the cognitive impairment and emotional burdens that were found in PCa survivors secondary to different treatment options. METHODS: Systematic, general reviews, meta-analysis, and overviews of review studies in English, that were published in PubMed during the last 10 years until l August 2019 and that reported psychological distress, anxiety, depression, cognitive decline, or dementia among individuals with PCa exposed to a particular treatment option were analyzed. RESULTS: A total of 21 articles were reviewed. Some of the studies described one or more cognitive or psychological consequences of only one therapeutic strategy while others compared the psychological impacts among different strategies. Most of these studies suggested that either radical prostatectomy or active surveillance and radiotherapy were well-tolerated treatments in terms of psychological modifications. However, many of these patients may require additional emotional support. There is also increasing evidence that androgen deprivation therapy may be associated with depression, while controversy surrounding the association between cognitive dysfunction, dementia, and androgen deprivation therapy remains ambivalent. CONCLUSION: Emotional distress and cognitive decline may accompany every PCa treatment option to different degrees. Accurate information on the short- and long-term effect of treatments on cognitive and psychological aspects should be provided to patients during treatment decision-making. There is also a need to develop well-targeted psychological and neurological interventions that could help those experiencing ongoing post-treatment difficulties.

Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research.

: Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials' methodological issues have also been criticized. Drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers-such as Tau positron emission tomography, neurofilament light chain (blood and Cerebrospinal fluid (CSF) biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)-to clinical trials allows more precise staging of AD. Additionally, use of Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are assessed in clinical trials. The above-mentioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are relevant to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

Donepezil Treatment for Alzheimer's Disease in Chronic Dialysis Patients.

Donepezil is one of the cholinesterase inhibitors that are indicated for the treatment of mild to moderate Alzheimer's disease (AD). Pharmacokinetic analysis has shown that donepezil is primarily eliminated by renal excretion rather than biliary excretion in humans. Therefore, patients with impaired renal function are at high risk of toxicity caused by accumulation of this drug. It is also well known that dialysis patients have very often cholinergic disorders. On the other hand, with the increasing number of long-term chronic dialysis patients, the prevalence of cognitive disorders is increasing in elderly dialysis patients. Because of the above-mentioned special risks of these patients, acetylcholinesterase inhibitors, such as donepezil, are avoided to be prescribed for them. We studied 5 cases of chronic hemodialysis outpatients (3 men [70, 72, and 86 years old] and 2 women [65 and 71 years old]) who were diagnosed as having moderate AD. We administered donepezil at 2.5 mg/day orally to the patients. After 1 month's treatment, their behavioral symptoms were improved, without them having any adverse events. We enhanced the dose to 5 mg/day without the patients experiencing any episodes of drug toxicity. After 3 months of treatment with the higher dose, their cognitive and executive functions were slightly improved and their behavioral disorders were remarkably milder, without them experiencing any episodes of drug toxicity. The patients' condition remained stable for 6 months after the initial administration of the drug. All of them were followed for the 10 following years, showing a mild cognitive decline per year for the first 5 years and more severe decline for the remaining years of the follow-up. Our cases indicate that donepezil treatment under prudent use may be well tolerated and have a beneficial impact on chronic hemodialysis patients with AD.

Merkel cell carcinoma with kidney metastasis in a 81-year-old man. A rare case report.

Merkel cell carcinoma (MCC) is a primary neuroendocrine carcinoma of the skin. The prognosis of the disease is considered poor. Secondary metastasis is common, however a secondary metastasis to kidney from Merkel cell is a very rare phenomenon. We report a case of a man with a MCC metastasis to the right kidney. The suggested management is surgery and afterwards a platinum-based chemotherapy.

Isolated corpus spongiosum injury after sexual intercourse.

Penile fractures are generally rare and underreported. The mechanism of injury is due to a rupture of the corpora cavernosa following blunt or sexual trauma to the penis when fully erect. Penile fractures usually present with a 'popping' sound with concomitant sudden swelling and ecchymosis of the penis followed by rapid detumescence. Urethral involvement occurs only in a small part of the cases. Isolated spongiosal injury after sexual intercourse is also extremely rare. The cardinal sign of urethral injury is blood at the meatus. A small laceration can be repaired by simple closure with absorbable sutures, while a complete rupture requires a more complex anastomotic repair. We report a case of a typically presenting penile fracture that was eventually proven to be an isolated corpus spongiosum injury, with no corpora cavernosa involvement.

Neutropenia with fatal outcome in a multiple sclerosis patient 23 days after alemtuzumab infusion.

A 47-year-old Caucasian female with relapsing- remitting Multiple Sclerosis, received alemtuzumab after a serious relapse. She had ceased receiving any treatment during the previous year. 23 days after alemtuzumab infusion she developed severe early neutropenia, which resulted in septic shock by Staphylococcus aureus and death. This is the first report of alemtuzumab infusion-related death due to early neutropenia in non-immunocompromised MS patients. We suggest that the long existing safety guidelines for alemtuzumab infusion in B-cell chronic lymphocytic leukemia might be also beneficial in the MS setting. Weekly blood test for the first two months after the first infusion could prevent major infections.

Conservative management of a bladder leiomyosarcoma in a 43-year-old patient.

Leiomyosarcoma of the bladder is an aggressive and rare tumor, with less than 200 reported cases. The treatment of bladder leiomyosarcoma is controversial although in most cases an aggressive surgical therapy is preferred. Usually, a radical cystectomy is performed, as it is considered to have a better disease-specific survival rate. A 43-year-old man presented to our Urology Department with painless macroscopic hematuria. He was submitted to transurethral resection of the tumor. The transurethral resection was complete and revealed only this small single lesion and the rest of the bladder was normal with no other lesion or suspicious lesion. The final histology revealed leiomyosarcoma of the bladder. Due to his age and the aggressiveness of the tumor after a thorough and detailed discussion with the patient a conservative management with aggressive follow up was decided. The patient a year after the diagnosis is in perfect condition without sign of a recurrence or metastastes.