Pain management in cervical cancer.

Cervical cancer (CC) occupies the second place in incidence and mortality among women in México. Despite this, Cervical Cancer continues to have a late diagnosis which leads to a high rate of complications. Pain represents the most feared and disabling symptom, being present in up to 86% of patients with advanced disease. The approach to managing pain in this population has not been studied and described to a full extent. In addition, there is a pressing need to provide concise recommendations to promote adequate pain control. We performed a review of the literature in CC and had experts in the field of pain management evaluate the evidence found. We then issued relevant recommendations on pharmacology and interventional pain management. Thus, the approach to pain management must be comprehensive and individualized, considering the timely and appropriate use of pharmacologic treatment as well as interventional procedures.

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Pre-operative vs. post-operative stereotactic radiosurgery for operative metastatic brain tumors: study protocol for a phase III clinical trial.

BACKGROUND AND OBJECTIVES: Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS. METHODS: This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS. EXPECTED OUTCOMES: If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline. DISCUSSION: Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease. TRIAL REGISTRATION NUMBER: NCT03750227 (Registration date: 21/11/2018).

Genotypic study of Chlamydia trachomatis for lymphogranuloma venereum diagnosis in rectal specimens from men who have sex with men: a cost-effectiveness analysis.

PURPOSE: The significant proportion of asymptomatic patients and the scarcity of genotypic analysis of lymphogranuloma venereum (LGV), mainly among men who have sex with men (MSM), triggers a high incidence of underdiagnosed patients, highlighting the importance of determining the most appropriate strategy for LGV diagnosis, at both clinical and economical levels. MATERIALS AND METHODS: We conducted L1-L3 serovar detection by molecular biology in stored Chlamydia trachomatis-positive samples from MSM patients with HIV, another STI or belonging to a Pre-exposure prophylaxis program, to make a cost effectiveness study of four diagnostic strategies with a clinical, molecular, or mixed approach. RESULTS: A total of 85 exudates were analyzed: 35urethral (31 symptomatic/4 positive) and 50 rectal (22 symptomatic/25 positive), 70/85 belonging to MSM with associated risk factors. The average cost per patient was €77.09 and €159.55 for clinical (Strategy I) and molecular (Strategy IV) strategies respectively. For molecular diagnosis by genotyping of all rectal exudate samples previously positive for CT (Strategy II), the cost was €123.84. For molecular diagnosis by genotyping of rectal and/or urethral exudate samples from all symptomatic patients (proctitis or urethritis) with a previous positive result for CT (Strategy III), the cost was €129.39. The effectiveness ratios were 0.80, 0.95, 0.91, and 1.00 for each strategy respectively. The smallest ICER was €311.67 for Strategy II compared to Strategy I. CONCLUSIONS: With 30% asymptomatic patients, the most cost-effective strategy was based on genotyping all rectal exudates. With less restrictive selection criteria, thus increasing the number of patients with negative results, the most sensitive strategies tend to be the most cost-effective, but with a high incremental cost-effectiveness ratio.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and lateral flow immunochromatography for rapid identification of ß-lactamase-gene-harboring Enterobacterales in urine specimens: Performance and cost-benefit analyses.

In this single-center prospective study, we evaluated the performance to the MALDI-ToF MS based method in conjunction with lateral flow immunochromatographic (LFIC) in urine specimens for rapid diagnosis of bacterial Urinary Tract Infection (UTI) and detection of carbapenemase and/or extended-spectrum ß- lactamase (ESBL) enzymes produced by the involved bacteria, compared to standard culture, and antimicrobial susceptibility testing/genotypic resistance markers characterization performed on culture-grown colonies. In addition, a cost-benefit analysis comparing this approach against standard procedures was conducted. A total of 324 urines were included in the study, of which 288 (88.9 %) yielded concordant results by the MALDI-ToF MS and conventional culture (Kappa agreement, 0.82; P<0.001). Direct LFIC testing could be carried out in 249/324 urines. Bacterial species carrying ß-lactam genotypic resistance markers were identified in 35 urines (35 CTX-M and 2 OXA-48). Two ESBL-producing Escherichia coli were missed by LFIC (Kappa agreement with standard procedures of 0.96; P<0.001). The cost-benefit analysis indicated that our novel approach resulted in an improvement of clinical outcomes (less need of outpatient care) with a marginal incremental cost (€2.59).

The longitudinal risk of hemorrhage of melanoma brain metastases after Gamma Knife radiosurgery.

OBJECTIVE: The objective of this study was to analyze the hemorrhagic risk of melanoma brain metastases after Gamma Knife radiosurgery (GKRS). METHODS: A prospective institutional database was retrospectively queried to identify patients who underwent GKRS for melanoma brain metastases between 1990 and 2021. Lesional hemorrhage was defined as definite or possible based on radiologists' readings, and severity was graded according to Common Terminology Criteria for Adverse Events. RESULTS: Two hundred ninety-one patients with 1083 lesions treated in 419 sessions were identified. The mean (± SD) patient age was 60 ± 15 years, and 61% were male. The median follow-up period for overall survival (OS) was 11 (range 0-214) months with 581 patient-years. Definite/possible lesional hemorrhages occurred in 13% of lesions, with grade 3 hemorrhages observed in 4% of lesions. Surgical intervention was required in 2% of cases (5% of patients), and all resected lesions were pathologically consistent with melanoma. A decreased risk of definite/possible lesional hemorrhage was associated with a later time period between 2015 and 2021 (OR 0.45, 95% CI 0.266-0.75, p = 0.0021), increased marginal dose (OR 0.91, 95% CI 0.83-0.99, p = 0.037), antiplatelet use post-GKRS (OR 0.195, 95% CI 0.083-0.46, p < 0.001), and whole-brain radiotherapy (WBRT; OR 0.53, 95% CI 0.344-0.82, p = 0.0042). After 2015, more patients received anticoagulation, B-Raf proto-oncogene inhibitors, and immune checkpoint inhibitors, and fewer received bevacizumab (p < 0.001). The cumulative risk of lesional hemorrhage was 17%-20% at 36 months from GKRS, with 95%-96% of cases occurring within 12 months. The median patient OS was 11 (95% CI 9-13) months, and multivariate Cox regression analysis revealed that antiplatelet agents (hazard ratio [HR] 0.66, 95% CI 0.45-0.96, p = 0.031) and immune checkpoint inhibitors (HR 0.35, 95% CI 0.26-0.48, p < 0.001) were associated with longer OS, while WBRT (HR 1.36, 95% CI 1.02-1.81, p = 0.037) and definite/possible hemorrhage (HR 1.39, 95% CI 1.04-1.85, p = 0.024) were associated with shorter OS. CONCLUSIONS: The definite hemorrhage risk of melanoma brain metastases after GKRS was 17% in the first 3 years and 95% of the lesional hemorrhage occurred within the 1st year. Surgical intervention was needed in 5% of patients. Antiplatelet agents and immune checkpoint inhibitors were associated with improved OS, while definite/possible hemorrhage was associated with worse OS.

Methodological and analytical considerations for intra-operative microdialysis.

BACKGROUND: Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known as gliomas. Gliomas are mainly accessible at the time of surgery, but have rarely been analyzed via interstitial fluid collected via microdialysis. To that end, we obtained an investigational device exemption for high molecular weight catheters (HMW, 100 kDa) and a variable flow rate pump to perform microdialysis at flow rates amenable to an intra-operative setting. We herein report on the lessons and insights obtained during our intra-operative HMW microdialysis trial, both in regard to methodological and analytical considerations. METHODS: Intra-operative HMW microdialysis was performed during 15 clinically indicated glioma resections in fourteen patients, across three radiographically diverse regions in each patient. Microdialysates were analyzed via targeted and untargeted metabolomics via ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: Use of albumin and lactate-containing perfusates impacted subsets of metabolites evaluated via global metabolomics. Additionally, focal delivery of lactate via a lactate-containing perfusate, induced local metabolic changes, suggesting the potential for intra-operative pharmacodynamic studies via reverse microdialysis of candidate drugs. Multiple peri-operatively administered drugs, including levetiracetam, cefazolin, caffeine, mannitol and acetaminophen, could be detected from one microdialysate aliquot representing 10 min worth of intra-operative sampling. Moreover, clinical, radiographic, and methodological considerations for performing intra-operative microdialysis are discussed. CONCLUSIONS: Intra-operative HMW microdialysis can feasibly be utilized to sample the live human CNS microenvironment, including both metabolites and drugs, within one surgery. Certain variables, such as perfusate type, must be considered during and after analysis. Trial registration NCT04047264.

A rapid MALDI-TOF mass spectrometry-based method for categorization of Pseudomonas aeruginosa from blood cultures as susceptible or resistant to meropenem.

We developed and evaluated a simple, low-cost matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS)-based method for the detection of meropenem (MER) resistance in Pseudomonas aeruginosa directly from blood. A volume of 50 µL of positive-flagged blood culture (BC) was transferred in 450 µL brain heart infusion (BHI) broth to microtubes either containing MER (test) or not (control) at 25 or 50 mg/L. P. aeruginosa was categorized as resistant or susceptible on the basis of whether or not the isolates could be identified, respectively, in the presence of the antibiotic (3 h of incubation). When using BCs spiked with 99 P. aeruginosa isolates (64 MER-resistant and 35 MER-susceptible) the method correctly classified 88/99 isolates (88.9%). Correct categorization was achieved in 23/23 (100%) of P. aeruginosa isolates (17 MER-susceptible and 6 MER-resistant) from prospectively collected BCs. Our method may prove useful for early targeted or adjustment of empirical therapy in patients with P. aeruginosa bloodstream infections.

Sample Treatment with Trypsin for RT-LAMP COVID-19 Diagnosis.

The SARS-CoV-2 coronavirus is responsible for the COVID-19 pandemic resulting in a global health emergency. Given its rapid spread and high number of infected individuals, a diagnostic tool for a rapid, simple, and cost-effective detection was essential. In this work, we developed a COVID-19 diagnostic test, that incorporates a human internal control, based on the Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP). When working with synthetic SARS-CoV-2 RNA, the optimized RT-LAMP assay has a sensitivity of 10 viral copies and can be detected by fluorescence in less than 15 min or by the naked eye in 25 min using colorimetric RT-LAMP. To avoid the RNA extraction step, a pre-treatment of the sample was optimized. Subsequently, a validation was performed on 268 trypsin treated samples (including nasopharyngeal, buccal, and nasal exudates) and amplified with colorimetric RT-LAMP to evaluate its sensitivity and specificity in comparison with RT-qPCR of extracted samples. The validation results showed a sensitivity and specificity of 100% for samples with Ct ≤ 30. The rapid, simple, and inexpensive RT-LAMP SARS-CoV-2 extraction-free procedure developed may be an alternative test that could be applied for the detection of SARS-CoV-2 or adapted to detect other viruses present in saliva or nasopharyngeal samples with higher sensitivity and specificity of the antibody test.

MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series.

We present three cases of O6-Methylguanine-DNA Methyl-transferase (MGMT) methylated high grade gliomas with distant recurrence. All three patients had a radiographic stability of original tumor site at time of distant recurrence indicating impressive local control with Stupp protocol in patients with a MGMT methylated tumors. All patients had a poor outcome after distant recurrence. For one patient Next Generation Sequencing (NGS) was available for both original and recurrent tumor and did not reveal any difference other than high tumor mutational burden in the distant recurrent tumor. Understanding risk factors of distant recurrence in MGMT methylated tumors and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve survival of these patients.

Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas.

The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05-10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.

Molecular Characterization of the Convergent Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Strain K1-ST23, Collected in Chile during the COVID-19 Pandemic.

The aim of this study was to investigate the genomic features of a carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) isolate (K-2157) collected in Chile. Antibiotic susceptibility was determined using the disk diffusion and broth microdilution methods. Whole-genome sequencing (WGS) and hybrid assembly were performed, using data generated on the Illumina and Nanopore platforms. The mucoid phenotype was analyzed using both the string test and sedimentation profile. The genomic features of K-2157 (e.g., sequence type, K locus, and mobile genetic elements) were retrieved using different bioinformatic tools. Strain K-2157 exhibited resistance to carbapenems and was identified as a high-risk virulent clone belonging to capsular serotype K1 and sequence type 23 (ST23). Strikingly, K-2157 displayed a resistome composed of ß-lactam resistance genes (blaSHV-190, blaTEM-1, blaOXA-9, and blaKPC-2), the fosfomycin resistance gene fosA, and the fluoroquinolones resistance genes oqxA and oqxB. Moreover, several genes involved in siderophore biosynthesis (ybt, iro, and iuc), bacteriocins (clb), and capsule hyperproduction (plasmid-borne rmpA [prmpA] and prmpA2) were found, which is congruent with the positive string test displayed by K-2157. In addition, K-2157 harbored two plasmids: one of 113,644 bp (KPC+) and another of 230,602 bp, containing virulence genes, in addition to an integrative and conjugative element (ICE) embedded on its chromosome, revealing that the presence of these mobile genetic elements mediates the convergence between virulence and antibiotic resistance. Our report is the first genomic characterization of a hypervirulent and highly resistant K. pneumoniae isolate in Chile, which was collected during the coronavirus disease 2019 (COVID-19) pandemic. Due to their global dissemination and public health impact, genomic surveillance of the spread of convergent high-risk K1-ST23 K. pneumoniae clones should be highly prioritized. IMPORTANCE Klebsiella pneumoniae is a resistant pathogen involved primarily in hospital-acquired infections. This pathogen is characterized by its notorious resistance to last-line antibiotics, such as carbapenems. Moreover, hypervirulent K. pneumoniae (hvKp) isolates, first identified in Southeast Asia, have emerged globally and are able to cause infections in healthy people. Alarmingly, isolates displaying a convergence phenotype of carbapenem resistance and hypervirulence have been detected in several countries, representing a serious threat to public health. In this work, we analyzed the genomic characteristics of a carbapenem-resistant hvKp isolate recovered in 2022 from a patient with COVID-19 in Chile, representing the first analysis of this type in the country. Our results will provide a baseline for the study of these isolates in Chile, which will support the adoption of local measures aimed at controlling their dissemination.

[Multiple myeloma with laryngeal affectation: an uncommon cause of dysphonia].

Plasma cell proliferation leads to the formation of a single tumour (plasmacytoma) or to systemic disease (myeloma). Plasma cell myeloma involving laryngeal cartilage is unusual and clinical manifestations are similar to those of laryngeal carcinoma. We report the case of a 70-year-old man with disphonia after a recent diagnosis of multiple myeloma. Radiological and immunohistochemical studies showed laryngeal involvement. The patient is currently under treatment with lenalidomide, dexamethasone, and bortezomib.

INPH and parkinsonism: A positive shunt response with a negative tap test.

Introduction: The aim of this study was to compare clinical and functional performances of idiopathic normal pressure hydrocephalus (INPH) patients with and without parkinsonism at the initial evaluation, 72 h after the cerebrospinal fluid tap test (CSF TT), and 6 months after ventriculoperitoneal shunt (VPS) surgery. Materials and methods: This is an observational prospective study on patients with INPH who underwent VPS. Patients were classified into INPH with parkinsonism (INPH-P+) and without parkinsonism (INPH-P-). We used the time up and go (TUG) test, Tinetti Performance-Oriented Mobility Assessment (POMA) test, INPH grading scale (INHPGS), and modified Rankin scale (mRS) at baseline, 72 h after CSF TT, and 6 months after VPS surgery. Results: A total of 64 patients with probable INPH were included, 12 patients with INPH-P+ and 52 controls with INPH-P-. Patients with INPH showed significant improvement in all clinical and neurological parameters after VPS including TUG, Tinetti POMA, INPHGS, and mRS (p < 0.001) with the exception of mRS where there was no significant change 72 h after CSF TT compared to baseline for patients with INPH (p = 0.182). Patients with INPH-P+ performed significantly worse than patients with INPH-P- on Tinetti POMA and mRS at baseline, at 72 h post-CSF TT, and at 6 months post-VPS with INPHGS being worst at 72 h post-CSF TT. There was no difference between patients with INPH-P+ and patients with INPH-P- for TUG at baseline (p = 0.270), at 72 h post-CSF TT (p = 0.487), and at 6 months post-VPS (p = 0.182). Patients with INPH-P+ did not show any change in any of the parameters at 72 h post-CSF TT compared to baseline; however, there was a trend toward improvement on TUG (p = 0.058), Tinetti gait (p = 0.062), and Tinetti total (p = 0.067). INPH-P+ significantly improved in all parameters 6 months post-VPS compared to baseline except for mRS (p = 0.124). Patients with INPH-P- significantly improved in all parameters at 72 h post-CSF TT and at 6 months post-VPS compared to baseline, respectively, except on mRS 72 h after CSF TT (p = 0.299). Conclusion: Patients with INPH and parkinsonism overall do worse than patients without parkinsonism. An unsatisfying response to the CSF tap test in INPH patients with parkinsonism should not be used as an exclusion criterion from VPS surgery since patients with and without parkinsonism showed significant improvement post-VPS.

CSF dynamics in long-standing overt ventriculomegaly in adults.

OBJECTIVE: Long-standing overt ventriculomegaly in adults (LOVA) is a form of chronic hydrocephalus and its pathophysiology and treatment remain debated. An analysis of CSF dynamics in this condition has rarely been reported. The aim of this study was to analyze hydrodynamic characteristics of patients with suspected LOVA to discuss its pathophysiological mechanisms and the importance of CSF dynamics analysis for diagnosis and treatment of these patients. METHODS: This retrospective cohort study, conducted between May 2018 and October 2022, included adult patients aged > 18 years investigated in a department of neurosurgery through a lumbar infusion study for suspicion of LOVA (n = 23). These patients were then compared with a control cohort explored for suspicion of idiopathic normal pressure hydrocephalus (iNPH; n = 30). Clinical symptoms, radiological findings, and hydrodynamic parameters were analyzed. The authors specifically compared two hydrodynamic parameters: resistance to CSF outflow, or Rout, which relies on CSF resorption, and pressure-volume index (PVI), which reflect overall craniospinal compliance. The lumbar infusion study was considered pathological (confirming the diagnosis of chronic hydrocephalus) when at least one of these two parameters was altered. RESULTS: Rout was significantly less frequently increased (cutoff ≥ 12 mm Hg/ml/min) in patients with LOVA (52%) than in those with iNPH (97%; p < 0.001). In contrast, PVI was impaired (cutoff ≤ 25 ml) in both cohorts, i.e., in 61% of patients with LOVA and in 83% of patients with iNPH. Overall, the rate of pathological lumbar infusion study in LOVA (87%) was not statistically different than in iNPH (100%). However, PVI was the only impaired parameter most frequently found in those with LOVA (35%) compared with those with iNPH (3%; p = 0.002). CONCLUSIONS: This study suggests that there is a differential CSF dynamics pattern when comparing patients with LOVA versus those with iNPH. A higher proportion of patients with LOVA showed isolated compliance impairment. These findings highlight the utility of CSF dynamics analysis for the evaluation of patients with suspected chronic obstructive hydrocephalus such as LOVA. Future research with larger case series may help define diagnosis and treatment algorithms of chronic obstructive hydrocephalus based on CSF dynamics analysis, in addition to clinical and radiological criteria.

Objective assessment of patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement using activity-monitoring data: pilot study.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) results in significant morbidity in the elderly with symptoms of dementia, gait instability, and urinary incontinence. In well-selected patients, ventriculoperitoneal shunt (VPS) placement often results in clinical improvement. Most postshunt assessments of patients rely on subjective scales. The goal of this study was to assess the utility of remote activity monitoring to provide objective evidence of gait improvement following VPS placement for iNPH. METHODS: Patients with iNPH were prospectively enrolled and fitted with 5 activity monitors (on the hip and bilateral thighs and ankles) that they wore for 4 days preoperatively within 30 days of surgery and for 4 days within 30 days postoperatively. Monitors collected continuous data for number of steps, cadence, body position (upright, prone, supine, and lateral decubitus), gait entropy, and the proportion of each day spent active or static. Data were retrieved from the devices and a comparison of pre- and postoperative movement assessment was performed. The gait data were also correlated with formal clinical gait assessments before and after lumbar puncture and with motion analysis laboratory testing at baseline and 1 month and 1 year after VPS placement. RESULTS: Twenty patients fulfilled the inclusion and exclusion criteria (median age 76 years). The baseline median number of daily steps was 1929, the median percentage of the day spent inactive was 70%, the median percentage of the day with a static posture was 95%, the median gait velocity was 0.49 m/sec, and the median number of steps required to turn was 8. There was objective improvement in median entropy from pre- to postoperatively, increasing from 0.6 to 0.8 (p = 0.002). There were no statistically significant differences for any of the remaining variables measured by the activity monitors when comparing the preoperative to the 1-month postoperative time point. All variables from motion analysis testing showed statistically significant differences or a trend toward significance at 1 year after VPS placement. Among the significantly correlated variables at baseline, cadence was inversely correlated with percentage of gait cycle spent in the support phase (contact with ground vs swing phase). CONCLUSIONS: This pilot study suggests that activity monitoring provides an early objective measure of improvement in gait entropy after VPS placement among patients with iNPH, although a more significant improvement was noted on the detailed clinical gait assessments. Further long-term studies are needed to determine the utility of remote monitoring for assessing gait improvement following VPS placement.

Impact of cytomegalovirus immunodominant HLA-I donor-recipient matching on the incidence and features of virus DNAemia and virus-specific T-cell immune reconstitution in unmanipulated haploidentical hematopoietic stem cell transplantation.

BACKGROUND: We investigated whether donor-recipient mismatch involving one or more cytomegalovirus (CMV) immunodominant (ID) human leukocyte antigen (HLA)-I alleles may impact on the degree of CMV pp65/immediate-early 1 (IE-1) T-cell reconstitution and the incidence of CMV DNAemia in patients undergoing unmanipulated haploidentical hematopoietic stem cell transplantation with high-dose posttransplant cyclophosphamide (PT/Cy-haplo). METHODS: Multicenter observational study including 106 consecutive adult PT/Cy-haplo patients (34 CMV ID HLA-I matched and 72 mismatched). A real-time PCR was used for plasma CMV DNA load monitoring. Enumeration of CMV-specific (pp65/IE-1) interferon (IFN)-γ-producing T cells from several patients was performed by flow cytometry by days +30, +60, +90 and +180 after transplantation. RESULTS: The cumulative incidence of CMV DNAemia, clinically significant CMV DNAemia episodes (cs-CMVi), and recurrent CMV DNAemia was comparable across CMV ID HLA-I matched and mismatched patients (71.8% vs. 80.9%, p = .95; 40.7% vs. 44.2%, p = .85; 16.4% vs. 28.1%; p = .43, respectively). The percentage of patients exhibiting detectable CMV-specific IFN-γ-producing T-cell responses (either CD8+ or CD4+ ) was similar across groups; nevertheless, significantly higher CMV-specific CD8+ T-cell counts were enumerated in the CMV ID HLA-I matched compared to mismatched patients by day +60 (p = .04) and +180 (p = .016) after transplantation. CONCLUSION: CMV ID HLA-I matching may impact on the magnitude of CMV-pp65/IE-1-specific CD8+ T-cell reconstitution; yet, this effect seemed not to have an impact on the incidence of initial, recurrent CMV DNAemia, or cs-CMVi.

Mieloma múltiple con afectación laríngea: causa atípica de disfonía / Multiple myeloma with laryngeal affectation: an uncommon cause of dysphonia

Las neoplasias de células plasmáticas suponen un conjunto de enfermedades caracterizadas por la proliferación tumoral de dichas células en forma de lesión única (plasmocitoma) o enfermedad sistémica (mieloma). La afectación cartilaginosa laríngea es inusual y su manifestación clínica es similar a la de un carcinoma laríngeo. Describimos el caso de un paciente varón de 70 años con disfonía tras un diagnóstico reciente de mieloma múltiple. Después de realizar los estudios radiológico e inmunohistoquímico se diagnosticó la afectación laríngea por este tumor. Actualmente el paciente está siendo tratado con lenalidomida, dexametasona y bortezomib.(AU)

Plasma cell proliferation leads to the formation of a single tumour (plasmacytoma) or to systemic disease (myeloma). Plasma cell myeloma involving laryngeal cartilage is unusual and clinical manifestations are similar to those of laryngeal carcinoma. We report the case of a 70-year-old man with disphonia after a recent diagnosis of multiple myeloma. Radiological and immunohistochemical studies showed laryngeal involvement. The patient is currently under treatment with lenalidomide, dexamethasone, and bortezomib.(AU)