Treatment of refractory ascites: Current strategies and new landscape of non-selective beta-blockers.

Ascites is the fluid accumulation in the peritoneal cavity, and it is the consequence of a wide variety of entities, being liver cirrhosis the most common one. In this kind of patients, the development of ascites results from splanchnic vasodilation; decreased effective circulating volume; the activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system; and a systemic inflammatory process. Its management is diverse and depends on the severity of the hemodynamic disturbance and other clinical manifestations. In recent years, therapeutic strategies have been developed, but they tend to result unconventional, so new evidence demonstrates the advantages of non-selective beta-blockers for the survival rate of patients with end-stage cirrhosis and ascites.

BalanCI: Head-Referenced Cochlear Implant Stimulation Improves Balance in Children with Bilateral Cochleovestibular Loss.

INTRODUCTION: To determine the impact of a head-referenced cochlear implant (CI) stimulation system, BalanCI, on balance and postural control in children with bilateral cochleovestibular loss (BCVL) who use bilateral CI. METHODS: Prospective, blinded case-control study. Balance and postural control testing occurred in two settings: (1) quiet clinical setting and (2) immersive realistic virtual environment (Challenging Environment Assessment Laboratory [CEAL], Toronto Rehabilitation Institute). Postural control was assessed in 16 and balance in 10 children with BCVL who use bilateral CI, along with 10 typically developing children. Children with neuromotor, cognitive, or visual deficits that would prevent them from performing the tests were excluded. Children wore the BalanCI, which is a head-mounted device that couples with their CIs through the audio port and provides head-referenced spatial information delivered via the intracochlear electrode array. Postural control was measured by center of pressure (COP) and time to fall using the WiiTM (Nintendo, WA, USA) Balance Board for feet and the BalanCI for head, during the administration of the Modified Clinical Test of Sensory Interaction in Balance (CTSIB-M). The COP of the head and feet were assessed for change by deviation, measured as root mean square around the COP (COP-RMS), rate of deviation (COP-RMS/duration), and rate of path length change from center (COP-velocity). Balance was assessed by the Bruininks-Oseretsky Test of Motor Proficiency 2, balance subtest (BOT-2), specifically, BOT-2 score as well as time to fall/fault. RESULTS: In the virtual environment, children demonstrated more stable balance when using BalanCI as measured by an improvement in BOT-2 scores. In a quiet clinical setting, the use of BalanCI led to improved postural control as demonstrated by significant reductions in COP-RMS and COP-velocity. With the use of BalanCI, the number of falls/faults was significantly reduced and time to fall increased. CONCLUSIONS: BalanCI is a simple and effective means of improving postural control and balance in children with BCVL who use bilateral CI. BalanCI could potentially improve the safety of these children, reduce the effort they expend maintaining balance and allow them to take part in more complex balance tasks where sensory information may be limited and/or noisy.

Aligning digital CD8+ scoring and targeted next-generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early-stage squamous cell lung carcinoma.

AIMS: To study programmed death ligand 1 (PD-L1) expression, tumour-infiltrating T lymphocytes (TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas (SCCs). METHODS AND RESULTS: The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next-generation sequencing (NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD-L1 IHC expression in tumour cells (TCs). Furthermore, high SP142 PD-L1 expression in immune cells (ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD-L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD-L1-positive TCs with the three antibodies were found in samples with cyclin-dependent kinase 6 (CDK6) amplification, with high amplification of proto-oncogene C-Myc (CMYC) or with cyclin D1-PI3 kinase subunit alpha (CCND1-PIK3CA) co-amplification. High SP142 PD-L1 IHC expression in ICs showed a non-significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 (FGFR1) amplification were negative for all PD-L1 clones. CONCLUSIONS: Our preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD-L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors.

The ALK translocation in advanced non-small-cell lung carcinomas: preapproval testing experience at a single cancer centre.

AIMS: To study the ALK translocation in patients with advanced non-small-cell lung carcinomas (NSCLCs) seen at a European cancer centre, and its association with EGFR mutations, KRAS mutations and MET amplification. METHODS AND RESULTS: The study included samples from 86 patients diagnosed with advanced NSCLC. ALK fluorescence in-situ hybridization (FISH) was performed using the ALK break-apart probe set (Vysis). ALK FISH-positive cases were defined as those with more than 15% break-apart signals or isolated red signals in 50 cells. EGFR and KRAS mutations were determined by direct sequencing. All ALK-positive cases were analysed retrospectively for MET amplification using a FISH assay, and for ALK mutations by sequencing. We found nine (10.5%) ALK-positive cases, all in adenocarcinomas and the majority in female patients (88.9%). Signet ring cells were observed in four (44.4%) of the nine patients. None of the ALK translocated cases showed MET amplifications or EGFR, KRAS and ALK mutations. CONCLUSIONS: The prevalence of ALK translocation in an unselected population of European patients with advanced NSCLCs was 10%. This alteration was mutually exclusive with EGFR and KRAS mutations, as well as with MET amplification. If multiplexing is considered at the preanalytical phase, lung biopsy specimens are sufficient for performing several predictive assays.

[Weston-Hurst syndrome. A case report and literature review]. / Síndrome de Weston Hurst. Reporte de un caso y revisión de la literatura.

Background: Acute disseminated encephalomyelitis is an autoimmune and demyelinating disease. It is rare in adults. It has 3 main variants. One of them is Weston-Hurst syndrome, also called acute hemorrhagic leukoencephalitis. The objective was to share the experience in the diagnostic and therapeutic approach of this rare disease, as well as make a review of the current bibliography, in order to collaborate in the knowledge of this disease. Clinical case: 27-year-old woman, with a viral respiratory infection 2 weeks prior to the development of a neurological syndrome characterized by paresthesia, motor deficit, status epilepticus and acute encephalopathy, progressing rapidly to coma, with evidence in MRI of diffuse hemorrhagic lesions in cerebral white matter with demyelination and peripheral edema. It was administered steroid treatment for 5 days, with improvement of symptoms, but with motor and sensory deficits persisting. Conclusion: Acute disseminated encephalomyelitis and its variants are rare entities, with an important range of differential diagnosis, which must be identified and quickly treated to avoid their lethal or disabling outcome.

Introducción: la encefalomielitis aguda diseminada es una enfermedad autoinmune y desmielinizante. Es rara en el adulto. Cuenta con tres variantes principales. Una de ellas es el síndrome de Weston Hurst, también conocido como leucoencefalitis hemorrágica aguda. El objetivo fue compartir la experiencia en el abordaje diagnóstico y terapéutico de esta rara enfermedad, así como hacer una revisión de la bibliografía actual, a fin de colaborar con el conocimiento de esta. Caso clínico: mujer de 27 años con cuadro de infección respiratoria viral 2 semanas previas al desarrollo de síndrome neurológico caracterizado por parestesias, déficit motor, estatus epiléptico y encefalopatía aguda, el cual progresó a estado de coma y evidenció en resonancia magnética lesiones difusas hemorrágicas en sustancia blanca cerebral con desmielinización y edema periférico. Se inició tratamiento con esteroides por 5 días con mejora de síntomas, aunque persistió el déficit motor y sensitivo. Conclusión: la encefalomielitis aguda diseminada y la variante hemorrágica de esta son entidades raras, con una importante gama de diagnóstico diferencial, que deben ser identificadas y tratadas de forma rápida para evitar su letal o incapacitante desenlace.

Predicting Maximal Costal Cartilage Graft Size for Laryngotracheal Reconstruction.

OBJECTIVES/HYPOTHESIS: Current methods of assessing rib cartilage dimensions for laryngotracheal reconstruction (LTR) are inexact, making surgical planning difficult. The purpose of this study was to determine the most appropriate rib for costal cartilage graft LTR to minimize the number of ribs harvested and improve surgical outcomes. STUDY DESIGN: Retrospective review. METHODS: Computed tomography imaging of chest scans in 25 children aged 1 to 18 years was evaluated. The lengths and widths of medial and lateral cartilaginous segments of ribs 4 to 7 were measured bilaterally. Right and left cartilaginous rib dimensions were compared using a two-sample t-test. Linear mixed-effect regression was performed to develop models quantifying the relationship between rib size and patient height, rib side, and rib number. RESULTS: Regression analysis established strong models for medial rib length (R2  = 0.89) and for medial and lateral rib width (R2  = 0.71, 0.77, respectively). There was no difference in rib dimensions across chest sides. Rib length and width increased with child height. Total cartilaginous rib length increased from superiorly to inferiorly, primarily due to an increase in the dimensions of the medial portion of each rib. CONCLUSION: Cartilaginous rib lengths and widths were associated with patient height, with taller children having longer ribs. Inferior ribs were longer than superior ribs, suggesting that inferior ribs may be preferred for LTR. There was no difference in cartilaginous rib length across chest side. Results may help surgeons with preoperative planning. LEVEL OF EVIDENCE: NA Laryngoscope, 132:1682-1686, 2022.

Impact of the sensory environment on balance in children with bilateral cochleovestibular loss.

BACKGROUND: The aim of the present study was to determine the role of auditory and visual sensory input on balance in children with bilateral cochlevestibular loss. The prevalence of vestibular impairment, and specifically bilateral vestibular loss (BVL) in children with sensorineural hearing loss (SNHL) is high and children with profound cochleovestibular loss (SNHL-BVL) have impaired balance (Suarez et al., 2007; Suarez et al., 2019). Given that both hearing and vestibular impairments are often congenital or acquired in early life, it remains difficult to tease out the individual developmental impact of either one on balance and spatial awareness in children who experience both of these sensory deficits. While cochlear implants (CI) can provide or restore access to sound in children with SNHL-BVL, there is currently no vestibular prosthetic available for clinical use in this population. These children may also use their intact sensory inputs (i.e. vision) to a greater extent to support balance. Alternately, restoring or providing access to sound may, on its own, help these children to balance better. We hypothesized that balance in children with SNHL-BVL who use bilateral CIs is: 1) improved in the presence of directional sound and 2) impaired when visual cues are dynamic (moving) rather than static. METHODS: Balance was assessed in 18 children with SNHL-BVL and 34 typically developing children with intact vestibular function and normal hearing by performing the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2) balance subtest in a virtual-reality simulator under 4 sensory conditions of graded complexity. Randomized conditions combined 2 auditory (moving directional street sounds vs. directionless static white noise) and 2 visual (dynamic street scene vs. stationary street scene) stimuli designed to recreate a "real-world" busy downtown street. Balance ability in children with SNHL-BVL was also compared with CI on and off. RESULTS: As expected and similar to previous work, balance was significantly worse in the children with SNHL-BVL compared to typically developing children in all sensory conditions (p<0.0001). As a group, the mean balance skills of the children with SNHL-BVL were equivalent to that of a 4.4-year-old child despite being much older (mean age =13.8 years). Balance ability improved slightly but significantly when children with SNHL-BVL had access to any sound through their CI (p=0.047) and was positively correlated with duration of implant use (p=0.02). Balance ability did not change further in the presence of moving directional sounds compared to static white noise (p=0.42), or when coupled to a moving visual environment (p=0.32) in children with SNHL-BVL, however opposite to what was hypothesized, in the typically developing group, there was a decrement in performance that occurred in the presence of moving directional sound compared to directionless, static white noise (p=0.02). CONCLUSIONS: Balance ability in children with SNHL-BVL who use bilateral CI was, as expected, poorer than their typically developing peers in all sensory conditions but improved slightly when they had access to any sound through their implants, with this benefit increasing as duration of implant use increased. This suggests that providing sound inputs through bilateral CIs positively affects balance in children with SNHL-BVL where vestibular and/or auditory inputs are compromised. This benefit was achieved even with auditory inputs that were devoid of moving directional cues (i.e. directionless static white noise) and is consistent with poor spatial hearing in children using bilateral CI.

Impact of Cold Ischemia Time in Clinical Outcomes in Deceased Donor Renal Transplant.

BACKGROUND: Renal transplants (RTs) from deceased donors have increased in Mexico because of the high need of people with terminal kidney damage. The objective of this study is to determine the impact of cold ischemia time (CIT) on clinical outcomes in the deceased donor kidney transplant. METHODS: A retrospective, observational study of deceased donor RTs performed from 2013 to 2017 in the RT unit of the CMN Siglo XXI was completed. Data were collected from 202 patient records in this period; 7 clinical outcomes were determined, and logistic regression analysis was performed with CIT and extended criteria. The statistical package SPSS version 25 was used. RESULTS: No risk was observed for clinical outcomes with a CIT of 1080 minutes, risk of delayed function and medical complications was observed with a CIT of 1260 minutes, and risk of surgical complications was observed with a CIT of 1309 minutes. There was a correlation of 0.556 between the Maryland classification score and post-transplant medical complications. The extended criteria are related to risk for death with an odds ratio of 6.91 (95% CI, 2.27-21.01; P = .001) CONCLUSIONS: CIT continues to be an extremely important factor in renal graft survival and post-transplant clinical conditions. The extended criteria represent a considerable risk of death.

Children with unilateral cochlear nerve canal stenosis have bilateral cochleovestibular anomalies.

OBJECTIVES/HYPOTHESIS: To investigate the cochleovestibular apparatus bilaterally in children with isolated unilateral bony cochlear nerve canal (bCNC) stenosis. STUDY DESIGN: Retrospective review. METHODS: Imaging studies of children with unilateral bCNC stenosis (<1.0 mm) on computed tomography imaging (N = 36) were compared with controls imaged due to trauma without temporal bone injury (N = 32). Twenty-six measurements were obtained in each ear, assessing the bony internal auditory canal (IAC), cochlea, and vestibular end-organs, and were analyzed using one-way analysis of variance for intersubject comparisons and paired t tests for intrasubject comparisons with a Bonferroni adjustment for multiple comparisons (P = .0006). RESULTS: Patients with bCNC stenosis had a smaller IAC (P < .000) and cochlea (P < .000) on the stenotic side as compared with controls. Although the vestibular end-organ was also smaller in bCNC ears, this difference was not significant. The contralateral ear also had a smaller bCNC (P < .000) and cochlea (P < .000) as compared with controls, although to a lesser degree than the stenotic side. CONCLUSIONS: Children with unilateral bCNC stenosis have abnormal biometry of both the cochlea and the vestibular end-organ in the affected and the normal contralateral ear as compared with controls. LEVEL OF EVIDENCE: 3b Laryngoscope, 129:2403-2408, 2019.

Natural History of Tympanic Membrane Retraction in Children with Cleft Palate.

OBJECTIVES: The natural history of tympanic membrane retraction is unpredictable. To obtain prognostic information for guiding surveillance and treatment, a cohort of children with retraction from cleft palate were prospectively followed for over 5 years. MATERIALS AND METHODS: This was a prospective observational study at a tertiary academic institution. Children with pars tensa retraction were selected from a cohort of 143 children with cleft palate. Thirty-seven ears were assessed with otoendoscopic image capture and audiometry at a median age of 9 years and reassessed at a median follow-up interval of 6.4 years. The severity of tympanic membrane retraction in the serial images of each ear was compared by four pediatric otolaryngologists blinded to the dates of the images. RESULTS: Initially, 19/37 retractions (51%) demonstrated contact with the incus and/or promontory. Follow-up images were rated as stable (n=16) or better (n=12) for 28/37 retractions (76%). Of the nine retractions that became more extensive, two developed cholesteatoma (5% of the total). No ossicular erosion developed in ears without cholesteatoma. Conductive hearing loss (4-tone average air-bone gap >25 decibels hearing level) was initially present in five ears, worsened in one, and normalized without intervention in others. No ears with initial normal hearing developed hearing loss. CONCLUSION: Most tympanic membrane retractions remained stable or improved over time in this cohort of children who were at a risk of persistent eustachian tube dysfunction. Clinically significant progression occurred infrequently, justifying the conservative approach taken to manage these retractions. Such data are necessary to weigh the potential benefit of preventive intervention over observation.

Unilateral Hearing Loss Is Associated With Impaired Balance in Children: A Pilot Study.

OBJECTIVE: To determine if children with unilateral sensorineural hearing loss (UHL) demonstrate impaired balance compared with their normal hearing (NH) peers. STUDY DESIGN: Prospective, case-control study. METHODS: Balance was assessed in14 UHL and 14 NH children using the Bruininks-Oseretsky Test-2 (BOT-2) and time to fall (TTF) in an immersive, virtual-reality laboratory. Postural control was quantified by center of pressure (COP) using force plates. The effect of vision on balance was assessed by comparing scores and COP characteristics on BOT-2 tasks performed with eyes open and closed. RESULTS: Balance ability as measured by the BOT-2 score was significantly worse in children with UHL compared with NH children (p = 0.004). TTF was shorter in children with UHL compared with NH children in the most difficult tasks when visual and somatosensory inputs were limited (p < 0.01). Visual input improved postural control (reduced COP variability) in both groups in all tasks (p < 0.05) but postural control as measured by COP variability was more affected in children with UHL when visual input was removed while performing moderately difficult tasks (i.e., standing on one foot) (p = 0.02). CONCLUSION: In this pilot study, children with UHL show poorer balance skills than NH children. Significant differences in TTF between the two groups were only seen in the most difficult tasks and therefore may be missed on routine clinical assessment. Children with UHL appear to rely more on vision for maintaining postural control than their NH peers. These findings may point to deficits not only in the hearing but also the vestibular portion of the inner ear.

Lung transplantation from out-of-hospital non-heart-beating lung donors. one-year experience and results.

There is currently no method for preservation and functional evaluation of clinical out-of-hospital non-heart-beating lung donors (NHBLD) that can be applied practically and systematically in clinical lung transplantation programs. A new method of preservation and functional evaluation of the lung has been developed in NHBLD that is based on the knowledge of various experimental studies. Initially, the viability of lungs harvested this way was proved from preliminary functional and histologic tests. In November 2002, we started using lung allografts from non-heart-beating donors. Five lung transplantations (4 bipulmonary and 1 unipulmonary) were performed successfully. The short and mid-term results have been excellent and all recipients are alive. We report our initial experience, which we hope will be of help to those involved in clinical lung transplantation programs worldwide.

Diabetic glomerulopathy: unusual patterns and dual disease.

Diabetic glomerulopathy is a well-recognized consequence of both type I and type II diabetes. Occasionally, pathologic diagnosis may be challenging for the pathologist. These circumstances include atypical light microscopy or diabetic change with a second superimposed glomerulopathy (dual disease). We have compiled a selection of 12 renal biopsies from diabetic patients that show either an unusual pattern of nephropathy or "dual disease," as well as 2 cases in which the patient had no history of diabetes but had renal biopsies exhibiting changes consistent with diabetic nephropathy. The salient diagnostic features are discussed. To accurately assess these biopsies, immunofluorescence and electron microscopy become essential, and a broadened differential diagnosis must be considered.

Collapsing glomerulopathy as a complication of interferon therapy for hepatitis C infection.

We present the case of a patient with chronic hepatitis C and diabetes, who rapidly progressed to end stage renal disease upon initiation of IFNalpha therapy for his HCV infection. A kidney biopsy revealed advanced collapsing glomerulopathy.

Renal allograft biopsies in the era of C4d staining: the need for change in the Banff classification system.

C4d immunostaining in the peritubular capillaries (PTC) is a marker of antibody-mediated rejection (AMR). We evaluated the histopathologic diagnoses of 388 renal transplant biopsies since the implementation of routine C4d immunostaining at our center. Of these, 155 (40%) biopsies had evidence of acute cellular rejection (ACR), out of which 119 (77%) had pure ACR, 31 (20%) had ACR with concomitant features of AMR, and five (3%) had ACR with focal C4d staining. Sixty-four (16%) biopsies exhibited features of AMR [33 (52%) pure AMR, and 31(48%) concomitant AMR and ACR]. One hundred and fifty-five (40%) biopsies had features of interstitial fibrosis and tubular atrophy (IFTA). Of these, 20 (13%) had concomitant AMR [13 (8.5%) had pure AMR and seven (4.5%) had concomitant ACR and AMR]. Creatinine at the time of biopsy was higher in patients with mixed ACR and AMR and the clinical behavior of mixed lesions is more aggressive over time. Despite having a lower serum creatinine at the time of biopsy, patients with IFTA experienced gradual decline in graft function over time. The pathologic findings in renal allograft biopsies are often mixed and mixed lesions appear to have more aggressive clinical behavior. These findings suggest the need for change in the Banff classification system to better capture the complexity of renal allograft pathologies.

C4d peritubular capillary staining in chronic allograft nephropathy and transplant glomerulopathy: an uncommon finding.

The true incidence of positive C4d staining in the peritubular capillaries of biopsies with chronic allograft nephropathy (CAN) and transplant glomerulopathy (TGP) remains controversial. We retrospectively reviewed all transplant biopsies performed at Saint Louis University Hospital between June 2002 and May 2004. We examined the incidence of positive C4d staining in the peritubular capillaries of biopsy specimens with pure CAN with or without features of TGP. We identified 54 biopsies in 43 patients showing CAN. The average age was 46 +/- 13 years. The average creatinine at the time of biopsy was 308 +/- 211 micromol/l (3.5 +/- 2.4 mg/dl). Twenty (37%) biopsies exhibited features consistent with TGP. Only two biopsies had positive C4d staining in the peritubular capillaries. The C4d positive biopsies were from two different patients; one patient had donor specific antibodies (DSA) against HLA class 1 at the time of biopsy and the other patient had no detectable DSA. None of the TGP biopsies showed peritubular C4d staining. C4d staining of the peritubular capillaries appears to be rare in patients with pure CAN with and without TGP features.