A bicentric comparative and prospective study between classic photovaporization and anatomical GreenLight laser vaporization for large-volume prostatic adenomas.

OBJECTIVE: Long-term outcome after prostate photovaporization (PVP) remains largely unknown, especially when performed on enlarged prostates. However, new vaporisation techniques (e.g., laser enucleation) are increasingly used. Our aim was to compare postoperative results after standard PVP to those of an anatomical technique. MATERIALS AND METHODS: This bicentric prospective study included males treated for enlarged prostate caused by benign prostatic hyperplasia using a GreenLight laser. Patients were preoperatively assessed according to prostate volume, post-void residual volume (PVR), maximum urinary-flow rate (Qmax), prostatic specific antigens, and International prostate symptom score (IPSS). Peroperative data included vaporization time, energy delivered, and operative length. Postoperative data at 1, 3, 6 and 12 months were compared with initial data; all complications were recorded. Comparisons were made between the conventional vaporization technique versus anatomical vaporization, which initially differentiated the peripheral zone of the prostate using an enucleation technique but no morcellation. RESULTS: Records from 106 surgical patients between December 2012 and December 2013 were analyzed. Operative length, vaporisation time, and energy used were greater in the anatomical PVP group. The average length of hospital stay (2.0 vs. 2.5 days), time with a catheter (1.3 vs. 1.9 days), IPSS (5.0 vs. 6.4), PVR (15.5 vs. 11.7mL), and Qmax (19.9 vs. 19.7mL/s) were comparable between the two groups. However, more complications occurred (27% vs. 37%), including stress urinary incontinence (0% vs. 8%) when using anatomic vaporization. CONCLUSION: Despite comparable groups and similar functional results, anatomical PVP caused more stress incontinence. However, the learning curve between the two techniques may explain this difference. LEVEL OF EVIDENCE: 4.

Somatostatin Receptor-PET/CT/MRI of Head and Neck Neuroendocrine Tumors.

BACKGROUND AND PURPOSE: Due to its high sensitivity, somatostatin receptor-PET may detect smaller lesions and more extensive disease than contrast-enhanced MR imaging, while the superior spatial resolution of MR imaging enables lesions to be accurately localized. We compared results of somatostatin receptor-PET/MRI with those of MR imaging alone and assessed the added value of vertex-to-thigh imaging for head and neck neuroendocrine tumors. MATERIALS AND METHODS: Somatostatin receptor-PET/CT was acquired as limited brain or head and neck imaging, with optional vertex-to-thigh imaging, following administration of 64CU/68GA DOTATATE. Somatostatin receptor-PET was fused with separately acquired contrast-enhanced MR imaging. DOTATATE activity was classified as comparable, more extensive, and/or showing additional lesions compared with MR imaging. Vertex-to-thigh findings were classified as positive or negative for metastatic disease or incidental. RESULTS: Thirty patients (with 13 meningiomas, 11 paragangliomas, 1 metastatic papillary thyroid carcinoma, 1 middle ear neuroendocrine adenoma, 1 external auditory canal mass, 1 pituitary carcinoma, 1 olfactory neuroblastoma, 1 orbital mass) were imaged. Five had no evidence of somatostatin receptor-positive lesions and were excluded. In 11/25, somatostatin receptor-PET/MRI and MR imaging were comparable. In 7/25, somatostatin receptor-PET/MRI showed more extensive disease, while in 9/25, somatostatin receptor-PET/MRI identified additional lesions. On vertex-to-thigh imaging, 1 of 17 patients was positive for metastatic disease, 8 of 17 were negative, and 8 of 17 demonstrated incidental findings. CONCLUSIONS: Somatostatin receptor-PET detected additional lesions and more extensive disease than contrast-enhanced MR imaging alone, while vertex-to-thigh imaging showed a low incidence of metastatic disease. Somatostatin receptor-PET/MRI enabled superior anatomic delineation of tumor burden, while any discrepancies were readily addressed. Somatostatin receptor-PET/MRI has the potential to play an important role in presurgical and radiation therapy planning of head and neck neuroendocrine tumors.

Multimodality Imaging in Primary Progressive Aphasia.

Primary progressive aphasia is a clinically and neuropathologically heterogeneous group of progressive neurodegenerative disorders, characterized by language-predominant impairment and commonly associated with atrophy of the dominant language hemisphere. While this clinical entity has been recognized dating back to the 19th century, important advances have been made in defining our current understanding of primary progressive aphasia, with 3 recognized subtypes to date: logopenic variant, semantic variant, and nonfluent/agrammatic variant. Given the ongoing progress in our understanding of the neurobiology and genomics of these rare neurodegenerative conditions, accurate imaging diagnoses are of the utmost importance and carry implications for future therapeutic triaging. This review covers the diverse spectrum of primary progressive aphasia and its multimodal imaging features, including structural, functional, and molecular neuroimaging findings; it also highlights currently recognized diagnostic criteria, clinical presentations, histopathologic biomarkers, and treatment options of these 3 primary progressive aphasia subtypes.

PET/MRI in Pediatric Neuroimaging: Primer for Clinical Practice.

Modern pediatric imaging seeks to provide not only exceptional anatomic detail but also physiologic and metabolic information of the pathology in question with as little radiation penalty as possible. Hybrid PET/MR imaging combines exquisite soft-tissue information obtained by MR imaging with functional information provided by PET, including metabolic markers, receptor binding, perfusion, and neurotransmitter release data. In pediatric neuro-oncology, PET/MR imaging is, in many ways, ideal for follow-up compared with PET/CT, given the superiority of MR imaging in neuroimaging compared with CT and the lower radiation dose, which is relevant in serial imaging and long-term follow-up of pediatric patients. In addition, although MR imaging is the main imaging technique for the evaluation of spinal pathology, PET/MR imaging may provide useful information in several clinical scenarios, including tumor staging and follow-up, treatment response assessment of spinal malignancies, and vertebral osteomyelitis. This review article covers neuropediatric applications of PET/MR imaging in addition to considerations regarding radiopharmaceuticals, imaging protocols, and current challenges to clinical implementation.

Errors in laparoscopic surgery: what surgeons should know.

Some two decades after its introduction, minimal access surgery (MAS) is still evolving. Undoubtedly, its significant uptake world wide is due to its clinical benefits to patient outcome. These benefits include reduced traumatic insult, reduction of pain, earlier return to bowel function, decrease disability, shorter hospitalization and better cosmetic results. Nonetheless complications due to the laparoscopic approach are not rare as documented by several studies on task specific or procedure related MAS morbidity. In all these instances, error analysis research has demonstrated that an understanding of the underlying causes of these complications requires a comprehensive approach addressing the entire system related to the procedure for identification and characterization of the errors ultimately responsible for the morbidity. The present review covers definition, taxonomy and incidence of errors in medicine with special reference to MAS. In addition, possible root causes of adverse events in laparoscopy are explored and existing methods to study errors are reviewed. Finally specific areas requiring further human factors research to enhance safety of patients undergoing laparoscopic operations are identified. The hope is that awareness of causes and mechanisms of errors may reduce incidence of errors in clinical practice for the final benefit of the patients.

Hemorrhagic Posterior Reversible Encephalopathy Syndrome as a Manifestation of COVID-19 Infection.

We describe 2 hospitalized patients with confirmed coronavirus 19 (COVID-19) infection in whom brain imaging showed hemorrhagic posterior reversible encephalopathy syndrome, and we discuss the possible reasons for these findings and their relationship to the infection.

Neurovascular Complications in COVID-19 Infection: Case Series.

We present a series of 10 hospitalized patients with confirmed coronavirus 2019 infections who developed severe neurovascular complications and discuss the possible reasons for these findings and their relationship to the novel Severe Acute Respiratory Syndrome coronavirus 2 infection.

A simple duplex-PCR protocol for routine diagnosis and follow up of canine leishmaniasis.

The introduction of PCR has efficiently improved diagnosis of canine leishmaniasis. In order to provide a robust, efficient and reliable diagnostic method, a duplex PCR assay targeting the Leishmania infantum kDNA minicircle and the canine GAPDH gene as inner control was designed. Sensitivity of the assay reached 0.15 parasites/ml blood. Development, testing and application of this system on a group of 10 dogs during therapy administration (60 days) are also described. Six dogs (out of eight that have been showing a positive PCR result on peripheral blood during the study) were tested negative at day 62, indicating a reduction of parasitaemia at the end of the treatment period. All the animals had a positive PCR on lymph node aspirate both at the beginning and at the end of treatment. These findings seem to suggest that, in order to test therapy efficacy, PCR on whole blood could be a useful assay in dogs that have a positive PCR at the beginning of the treatment, while PCR positivity on lymph nodes lasts longer than the observation period during therapy administration. The presence of the GAPDH inner control band efficiently contributed to prevent false negatives, by highlighting samples affected by haemoglobin inhibition or inappropriate DNA isolation.

Blocking effect of human serum but not of cerebrospinal fluid on ricin A chain immunotoxin potentiation by monensin or carrier protein-monensin conjugates.

The potentiation of monoclonal antibody/ligand toxin (immunotoxin) cytotoxicity by the ionophore monensin (Mo) or by human serum albumin-monensin (HSA-Mo) conjugates was investigated. Since disulfide cross-linked HSA-Mo (HSA-SPDP-Mo) is rapidly inactivated by human serum (M. Colombatti et al., Cancer Res., 50: 1385-1391, 1990), we synthesized thioether cross-linked HSA-Mo conjugates (HSA-SIA-Mo). HSA-SIA-Mo is resistant to treatment with reducing agents (e.g., glutathione, dithiothreitol) and shows potentiating activity identical to that of Mo or of HSA-SPDP-Mo, enhancing immunotoxin (IT) cytotoxicity 45-35,000-fold. Human leukemic and tumor cell lines are highly sensitive to treatment with IT in combination with Mo, HSA-SPDP-Mo, or HSA-SIA-Mo (concentration required to inhibit protein synthesis by 50%, 10(-10)-2.5 x 10(-13) M). IT potentiation by both types of HSA-Mo conjugates, however, is inhibited by whole human serum. In contrast, human cerebrospinal fluid has no effect on the potentiation of IT by Mo or HSA-Mo conjugates. The serum blocking factors reside mostly in a Mr 40,000-90,000 protein fraction. Serum components of low molecular weight (less than 10,000) show no detectable effect upon the stability of HSA-Mo conjugates. The toxicity of HSA-SIA-Mo in vivo was investigated by intrathecal injections in rats. Concentrations of up to 60 micrograms/kg can be injected into the brain with only transient neurological sequelae. We therefore conclude that if the systemic delivery of HSA-Mo conjugates for the potentiation of ricin A chain-IT presents some limitations due to the blocking effect of serum, the application of HSA-Mo conjugates in combination with ricin A chain-IT for regional tumor therapy in the brain appears more promising.

Optimized, Minimal Specific Absorption Rate MRI for High-Resolution Imaging in Patients with Implanted Deep Brain Stimulation Electrodes.

BACKGROUND AND PURPOSE: Obtaining high-resolution brain MR imaging in patients with a previously implanted deep brain stimulator has been challenging and avoided by many centers due to safety concerns relating to implantable devices. We present our experience with a practical clinical protocol at 1.5T by using 2 magnet systems capable of achieving presurgical quality imaging in patients undergoing bilateral, staged deep brain stimulator insertion. MATERIALS AND METHODS: Protocol optimization was performed to minimize the specific absorption rate while providing image quality necessary for adequate surgical planning of the second electrode placement. We reviewed MR imaging studies performed with a minimal specific absorption rate protocol in patients with a deep brain stimulator in place at our institution between February 1, 2012, and August 1, 2015. Images were reviewed by a neuroradiologist and a functional neurosurgeon. Image quality was qualitatively graded, and the presence of artifacts was noted. RESULTS: Twenty-nine patients (22 with Parkinson disease, 6 with dystonia, 1 with essential tremor) were imaged with at least 1 neuromodulation implant in situ. All patients were imaged under general anesthesia. There were 25 subthalamic and 4 globus pallidus implants. Nineteen patients were preoperative for the second stage of bilateral deep brain stimulator placement; 10 patients had bilateral electrodes in situ and were being imaged for other neurologic indications, including lead positioning. No adverse events occurred during or after imaging. Mild device-related local susceptibility artifacts were present in all studies, but they were not judged to affect overall image quality. Minimal aliasing artifacts were seen in 7, and moderate motion, in 4 cases on T1WI only. All preoperative studies were adequate for guidance of a second deep brain stimulator placement. CONCLUSIONS: An optimized MR imaging protocol that minimizes the specific absorption rate can be used to safely obtain high-quality images in patients with previously implanted deep brain stimulators, and these images are adequate for surgical guidance.

Percentage insula ribbon infarction of >50% identifies patients likely to have poor clinical outcome despite small DWI infarct volume.

BACKGROUND AND PURPOSE: Large admission DWI infarct volume (>70 mL) is an established marker for poor clinical outcome in acute stroke. Outcome is more variable in patients with small infarcts (<70 mL). Percentage insula ribbon infarct correlates with infarct growth. We hypothesized that percentage insula ribbon infarct can help identify patients with stroke likely to have poor clinical outcome, despite small admission DWI lesion volumes. MATERIALS AND METHODS: We analyzed the admission NCCT, CTP, and DWI scans of 55 patients with proximal anterior circulation occlusions on CTA. Percentage insula ribbon infarct (>50%, ≤50%) on DWI, NCCT, CT-CBF, and CT-MTT were recorded. DWI infarct volume, percentage DWI motor strip infarct, NCCT-ASPECTS, and CTA collateral score were also recorded. Statistical analyses were performed to determine accuracy in predicting poor outcome (mRS >2 at 90 days). RESULTS: Admission DWI of >70 mL and DWI-percentage insula ribbon infarct of >50% were among significant univariate imaging markers of poor outcome (P < .001). In the multivariate analysis, DWI-percentage insula ribbon infarct of >50% (P = .045) and NIHSS score (P < .001) were the only independent predictors of poor outcome. In the subgroup with admission DWI infarct of <70 mL (n = 40), 90-day mRS was significantly worse in those with DWI-percentage insula ribbon infarct of >50% (n = 9, median mRS = 5, interquartile range = 2-5) compared with those with DWI-percentage insula ribbon infarct of ≤50% (n = 31, median mRS = 2, interquartile range = 0.25-4, P = .036). In patients with admission DWI infarct of >70 mL, DWI-percentage insula ribbon infarct did not have added predictive value for poor outcome (P = .931). CONCLUSIONS: DWI-percentage insula ribbon infarct of >50% independently predicts poor clinical outcome and can help identify patients with stroke likely to have poor outcome despite small admission DWI lesion volumes.

Pathological alterations induced by neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi snake venom.

The pathological alterations induced by neuwiedase, a 22 kDa class P-I metalloproteinase from the venom of the South American pit viper Bothrops neuwiedi, were studied in mice. Neuwiedase was devoid of hemorrhagic activity when tested in the skin up to a dose of 200 microgram, and also after intramuscular injection in the gastrocnemius. However, it induced bleeding when applied onto the mouse cremaster muscle in intravital microscopy experiments, and caused pulmonary hemorrhage when injected intravenously at doses higher than 5 microgram/g. Median lethal dose (LD(50)) by the intravenous route was 5 microgram/g, whereas LD(50) of crude venom was 0.47 microgram/g. After intramuscular injection, neuwiedase induced a mild myotoxic effect, evidenced histologically and by the increment in plasma creatine kinase activity, but it was devoid of hemorrhagic and thrombotic effects. In contrast, crude B. neuwiedi venom induced prominent hemorrhage and myonecrosis in gastrocnemius muscle. Both venom and neuwiedase induced an inflammatory reaction in muscle tissue characterized by abundant polymorphonuclear leukocytes. Moreover, a conspicuous edema developed in the foot pad after subcutaneous injection of neuwiedase. Anti-neuwiedase antibodies produced in rabbits were effective in the neutralization of hemorrhagic activity of crude venom, evidencing immunological cross-reactivity between neuwiedase and other hemorrhagic metalloproteinases present in the venom, and suggesting that metalloproteinases devoid of, or having low, hemorrhagic activity could be good immunogens to generate antibodies effective against high molecular mass metalloproteinasas having potent hemorrhagic activity. It is concluded that neuwiedase, despite its lack of hemorrhagic effect when injected in the gastrocnemius muscle, contributes to local tissue damage by inducing edema, inflammatory infiltrate and mild myotoxicity, and by degrading extracellular matrix components. In addition, large doses of neuwiedase may contribute to pulmonary bleeding

Effectiveness of batimastat, a synthetic inhibitor of matrix metalloproteinases, in neutralizing local tissue damage induced by BaP1, a hemorrhagic metalloproteinase from the venom of the snake bothrops asper.

Batimastat (BB-94), a synthetic hydroxamate peptidomimetic matrix metalloproteinase inhibitor, was tested for its ability to inhibit proteolytic and toxic effects induced by BaP1, a 24-kDa hemorrhagic metalloproteinase isolated from the venom of Bothrops asper, the medically most important snake species in Central America and southern Mexico. Batimastat inhibited proteolytic activity on biotinylated casein, with anIC(50) of 80 nM. In addition, batimastat was effective in inhibiting hemorrhagic, dermonecrotic, and edema-forming activities of this metalloproteinase if incubated with the enzyme prior to the assays. When the inhibitor was administered i.m. at the site of the toxin injection without preincubation, rapidly after metalloproteinase administration, it totally abrogated the hemorrhagic and dermonecrotic effects of BaP1. Inhibition was less effective as the time lapse between toxin and batimastat injection increased, due to the extremely rapid development of BaP1-induced local tissue damage in this experimental model. On the other hand, batimastat was ineffective if administered by the i.p. route immediately after toxin injection. It is concluded that batimastat, and probably other synthetic metalloproteinase inhibitors, may become useful therapeutic tools aimed at the in situ inhibition of venom metalloproteinases, when injected at the site of the bite rapidly after envenomation.

Enhancement of ricin toxin A chain immunotoxin activity: synthesis, ionophoretic ability, and in vitro activity of monensin derivatives.

Site-selective toxin delivery was achieved by coupling monoclonal antibody to the A chain subunit of ricin (RTA-IT). The cell-killing potency of RTA-IT can be drastically increased in vitro by using ionophores such as monensin. To reduce the intrinsic toxicity of monensin and to enhance its in vitro and in vivo activity, we synthesized 7 derivatives characterized by different lipophilicities. These derivatives were also analyzed for ionophoretic activity on intact cells, toxicity, and RTA-IT-enhancing activity. Two different RTA-IT were assayed on a human leukemia cell line. A correlation between lipophilicity, ionophoretic activity, and RTA-IT enhancement was observed. The compounds with the highest polar charge showed low intrinsic toxicity, revealed moderate ionophoretic activity, and were able to enhance RTA-IT only at high concentrations, whereas more lipophilic compounds (with a C28 tail or a phenyl group) showed significant ionophoretic activity and good enhancing properties.

Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA.

The effectiveness of the chelating agent CaNa2EDTA and the peptidomimetic matrix metalloproteinase inhibitor batimastat (BB-94) to inhibit local tissue damage induced by Bothrops asper snake venom was studied in mice. Both compounds totally inhibited proteolytic, hemorrhagic, and dermonecrotic effects, and partially reduced edema-forming activity, when incubated with venom prior to injection. Much lower concentrations of batimastat than of CaNa2EDTA were required to inhibit these effects. In addition, batimastat, but not CaNa2EDTA, partially reduced myotoxic activity of the venom. When the inhibitors were administered at various time intervals after envenomation at the same site of venom injection, both compounds were effective in neutralizing local hemorrhage and dermonecrosis if administered rapidly after venom. Inhibition was not as effective as the time lapse between venom and inhibitor injections increased. Owing to the relevance of metalloproteinases in the pathogenesis of local tissue damage induced by B. asper and other pit viper venoms, it is suggested that administration of peptidomimetic metalloproteinase inhibitors or CaNa2EDTA at the site of venom injection may represent a useful alternative to complement antivenoms in the neutralization of venom-induced local tissue damage.

Purification and characterization of BaH4, a hemorrhagic metalloproteinase from the venom of the snake Bothrops asper.

A hemorrhagic metalloproteinase, named BaH4, was isolated from the venom of the snake Bothrops asper by a combination of ion-exchange chromatography on DEAE-Sepharose and gel filtration on Sephacryl S-200. BaH4 is a 69 kDa protein with a pI of 5.3. It was recognized by antibodies raised against hemorrhagic metalloproteinase BaH1 isolated from B. asper venom, with a reaction of partial immunologic identity. BaH4 shows proteolytic activity on biotinylated casein, hide powder azure and fibrin, although having lower activity than crude B. asper venom and metalloproteinase BaP1 isolated from the same venom. BaH4 hydrolyzed fibronectin, laminin and type IV collagen in vitro, albeit at a relatively high enzyme:substrate ratio. Proteolytic activity was inhibited by chelating agents and 2-mercaptoethanol, but not by soybean trypsin inhibitor. Prominent hemorrhage developed in gastrocnemius and cremaster muscles after administration of BaH4. Moreover, it induced lethality in mice after intravenous injection, with an LD50 of 0.37 microg/g. Histological observations showed conspicuous pulmonary hemorrhage when the enzyme was injected intravenously. BaH4 is a hemorrhagic metalloproteinase which may play a relevant role in local and systemic bleeding characteristic of B. asper envenomations.

Characterization of the local tissue damage induced by LHF-II, a metalloproteinase with weak hemorrhagic activity isolated from Lachesis muta muta snake venom.

Local tissue damage induced by LHF-II, a 22-kDa hemorrhagic metalloproteinase from Lachesis muta venom was studied. Intravital microscopy experiments evidenced hemorrhagic events 2 min after LHF-II application onto cremaster muscle, characterized by microhemorrhages in capillary vessels and venules. However, histological analysis showed only mild hemorrhage in the gastrocnemius muscle. LHF-II degraded laminin, fibronectin and type IV collagen upon incubation in vitro, but was not cytotoxic to capillary endothelial cells in culture. Intramuscular injection of LHF-II induced a mild myonecrosis, with early small increments in plasma creatine kinase activity. It also induced edema in the mouse footpad at doses where hemorrhage is absent. Injection of LHF-II induced the synthesis of matrix metalloproteinases evidenced in muscle homogenates and in exudate samples. It is concluded that LHF-II has weak hemorrhagic and myotoxic activities, and that its role in the pathogenesis of L. muta-induced local tissue damage is associated with edema formation and degradation of extracellular matrix components, either directly or by activation of endogenous matrix metalloproteinases.

Acaricidal activity of pine essential oils and their main components against Tyrophagus putrescentiae, a stored food mite.

Some essential oils obtained from the branches of four Pinus species (P. pinea L., P. halepensis Mill., P. pinaster Soil in Ait., and P. nigra Arnold) have been evaluated for their acaricidal activity by aerial diffusion against the stored food mite Tyrophagus putrescentiae (L.). All the essential oils showed a good efficacy, but P. pinea oil and its two constituents 1,8-cineole and limonene were the most effective compounds, showing 100% acaricidal activity at 8 microL; 1,8-cineole showed the same activity at 6 microL.

A symbiont of the tick Ixodes ricinus invades and consumes mitochondria in a mode similar to that of the parasitic bacterium Bdellovibrio bacteriovorus.

We have recently performed molecular characterisation of an intracellular alpha-proteobacterium, named IricES1, which resides in the ovarian tissue of female Ixodes ricinus ticks from Italy. A unique characteristic of this bacterium is its ability to invade the mitochondria of the cells in which it resides. Although some ultrastructural studies have been performed on close relatives of this bacterium from I. ricinus in England and Switzerland, a number of questions remain about its movement within ovarian tissues and mitochondria. We have performed the first detailed ultrastructural examination of IricES1 in engorged female adult I. ricinus. Among our findings was that the bacterium enters mitochondria in a similar way to that employed by the 'predatory' bacterium Bdellovibro bacteriovorus, that is, between the inner and outer membranes. It then appears to multiply, with the new 'colony' consuming the mitochondrial matrix. Despite having many of their mitochondria consumed, oocytes appear to develop normally, and the bacteria are likely to be vertically transferred to all eggs.