Absence Of Response Research Articles

Guillain-Barré Syndrome Mimicking Brainstem Death Following Traumatic Intracerebral Hemorrhage (P12-7.006)

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 73-year-old man attended the ED following an assault where he sustained multiple traumatic blows to the head. He was alert, complained of headache but provided a detailed account. There were facial injuries but no clinical signs of cranial or skull base fractures. There was injury to the right eye, in which he had pre-existing visual impairment from previous injury. Vision was normal in the left. Right pupillary light reflex was absent but left was normal. The remainder of the neurological examination was unremarkable. CT-Head identified a small traumatic subarachnoid hemorrhage over the left cerebral convexity and a small contusion in the left temporo-parietal region. Vitreous hemorrhage was evident in the right eye. Clinically stable, follow-up CT on day 3 showed small intra-cerebral haemorrhage within the contusion, with minimal mass effect. However, on day 8, his GCS dropped and he was admitted to the ITU for airway management. Both pupils were non-responsive to light. Expansion of haemorrhage was suspected, however repeat CT was stable. EEG showed slowing over the left hemisphere without epileptiform activity. MRI excluded alternative causes for his neurological status such as brainstem ischaemia. With no clinical improvement, formal brainstem death testing was initiated. No potential confounders were recognised. The pupillary, corneal, oculocephalic, cough and gag reflexes were absent. Unexpectedly, deep tendon reflexes were absent in all limbs. A peripheral nerve stimulator using a train-of-four test protocol found no response. Post-traumatic Guillain-Barré syndrome (GBS) was suspected. Intravenous immunoglobulin was commenced. Nerve conduction studies found absent motor and sensory responses in all limbs. EMG showed fibrillation potentials and sharp waves. These findings were consistent with acute motor-sensory axonal neuropathy (AMSAN) variant of GBS. Serum Anti-GM1 antibodies were identified. After multiple rounds of plasmapheresis the patient was weaned from the ventilator. Nevertheless, severe neurological disability remained. <h3>Conclusions:</h3> NA <b>Disclosure:</b> Dr. Finegan has nothing to disclose. Dr. Ryan has nothing to disclose. Michael J. Hennessy has nothing to disclose. Kevin Murphy has nothing to disclose. Dr. Crowley has nothing to disclose. Dr. Elamin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche .

Acute Loss Of Brain Stem Reflexes Following Intracranial Hemorrhage (P5-7.004)

<h3>Objective:</h3> The objective of this case report is to present a case of acute immune mediate demyelinating polyneuropathy (AIDP) triggered by an intracranial hemorrhage (ICH), which was identified by early loss of brainstem reflexes. <h3>Background:</h3> AIDP is a phagocytic attack on Schwann cells and/or myelin in the peripheral nervous system, resulting in decreased nerve conduction and acute denervation. AIDP has rarely been observed with intracranial hemorrhage or ischemic stroke. Moreover, a diagnosis of fulminant AIDP with a clinical picture of brain death has only been previously described in few case reports, and never in the setting of intracranial hemorrhage. <h3>Design/Methods:</h3> This is a case report, where we describe a patient who underwent ICH evacuation which progressed to fulminant AIDP with loss of brainstem reflexes. <h3>Results:</h3> A 79-year-old female who presented with acute onset left hemiparesis was admitted to the ICU after evacuation of a right frontal-parietal ICH. Two weeks after, the patient’s neurological exam showed an acute loss of corneal, gag and cough reflexes, bilateral mydriasis and flaccid quadriplegia with areflexia. Repeat imaging did not reveal injury that would explain the change in clinical status. A lumbar puncture revealed albumino-cytologic dissociation. Serum studies returned positive for anti-GM1 and TPO antibodies. EMG revealed multiple absent motor and sensory conduction responses and decreased amplitude and conduction velocity. She was treated with intravenous immunoglobulin and plasma exchange therapy. Over the course of one week, she gradually recovered her reflexes, motor strength and became responsive to medical care. <h3>Conclusions:</h3> While the patient’s apparent comatose state and absent brainstem reflexes was suspicious for brain death, the severity of her hemorrhage was not consistent with it. Our diagnosis of fulminant AIDP was based on a combination of neurological examination, lumbar puncture and EMG studies and allowed for effective treatment and recovery of a patient showing signs of apparent brain death. <b>Disclosure:</b> Dr. Malerba has nothing to disclose. Dr. Davitz has nothing to disclose. Dr. Patterson has nothing to disclose. Dr. Nelson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Spark Healthcare. Dr. Nelson has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Healthcare. Dr. Nelson has received publishing royalties from a publication relating to health care. Dr. Tsetsou has nothing to disclose.

Leber Congenital Amaurosis: Leading Cause of Inherited Blindness in Children

Leber congenital amaurosis is a group of severe congenital retinal conditions and the leading cause of inherited blindness in children. Symptoms, typically present in the first 6 months of life, include nystagmus, strabismus, photophobia, abnormal or absent pupillary responses, and cataracts. Eye examinations and visual assessments are an essential part of well-child visits. The primary care practitioner may be the first to identify symptoms or hear parents’ concerning findings during routine eye examinations at well-child or episodic visits. Early recognition of deviations from normal that lead to prompt ophthalmology referrals can result in timely diagnosis and optimized treatment to improve outcomes and quality of life.

Vaginal Delivery in a Primipara with Glanzmann Thrombasthenia

Vaginal Delivery in a Primipara with Glanzmann Thrombasthenia

Abstract 668: The translational biology of small molecule GPR65 inhibitors: shared effects between mouse models and human primary tumors highlight the unique transformative potential of targeting a genetically validated innate immune checkpoint

Abstract Whilst the advent of Immune Checkpoint Blockade has revolutionized the management of cancer, a significant proportion of patients have limited or absent response to these therapies. A key cause of this immune insensitivity is the hostile solid tumor microenvironment (TME) dominated by immunosuppressive myeloid cells. We previously identified the acid sensing G protein coupled receptor (GPCR), GPR65, as a primary determinant of these suppressive cells. In mice, genetic deletion of Gpr65 or oral administration of small molecule GPR65 inhibitors in vivo causes a profound repolarization of immunosuppressive tumor associated macrophages, an increase in infiltrating effector cells and potent anti tumor effects in syngeneic models. In TCGA data, across all tumors, patients homozygous for a hypomorphic coding variant in GPR65 (I231L) show increased overall survival, providing compelling genetic evidence of the clinical potential of GPR65 inhibition. To further explore the translational potential of GPR65 we employed a range of techniques to define the human biology of this receptor in different contexts. At the mechanistic level, single cell RNA sequencing (scRNAseq) of human PBMCs obtained from healthy donors demonstrated a pronounced effect of low pH on the myeloid compartment, with a clear polarization of these cells toward an immunosuppressive character and modulation of GPR65 expression. In parallel, pharmacological inhibition of GPR65 in human monocyte derived macrophages exposed to low pH demonstrated that equivalent gene expression changes are primarily due to GPR65 activation. To examine the relevance of these findings to the intact acidic human TME, we performed studies in fresh primary human tumor histocultures from clear cell renal cell carcinoma (ccRCC) patients with immunohistochemically confirmed high macrophage infiltration and carbonic anhydrase 9 (CA9) expression. In these cultures, GPR65 inhibition caused a dose dependent suppression of a geneset closely overlapping with that modulated by GPR65 in primary macrophages. Furthermore, we observed a marked decrease in immune suppressive IL10 secretion with coincident elevation of specific proinflammatory chemokines. Consistent with these findings, in vivo administration of a small molecule GPR65 inhibitor elicited similar changes in human CA9 expressing RCC PDX tumors implanted in myeloid boosted CD34+ stem cell engrafted NCG mice. In summary, inhibition of GPR65 provides a unique and genetically validated approach to favorably modify the immunosupressive TME with features highly conserved between mouse and human contexts. We propose that GPR65 inhibition holds significant clinical promise, with specific evidence around ccRCC as a potential standout indication. Citation Format: Barbara Cipriani, Alastair Corbin, David Miller, Alan Naylor, Faraz Khan, Gavin Milne, Barbara Young, Rupert Satchell, Sourav Sarkar, Mussa Quareshy, Anastasia Nika, Preeti Singh, Gavin Knox, Darryl Turner, Satish Sankaran, Nandini Pal Basak, Toszka Bohn, Tobia Bopp, Surya Koturan, Bo Sun, Benjamin Fairfax, Tom McCarthy, Stuart Hughes. The translational biology of small molecule GPR65 inhibitors: shared effects between mouse models and human primary tumors highlight the unique transformative potential of targeting a genetically validated innate immune checkpoint [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 668.

OFF Starburst Amacrine Cells in the Retina Trigger Looming-evoked Fear Responses in Mice.

A rapidly approaching dark object evokes an evolutionarily conserved fear response in both vertebrates and invertebrates, young to old. A looming visual stimulus mimics an approaching object and triggers a similarly robust fear response in mice, resulting in freeze and flight. However, the retinal neural pathway responsible for this innate response has not been fully understood. We first explored a variety of visual stimuli that reliably induced these innate responses, and found that a looming stimulus with two-day acclimation consistently evoked fear responses. Because the fear responses were triggered by the looming stimulus with moving edges, but not by a screen flipping from light to dark, we targeted the starburst amacrine cells (SACs), crucial neurons for retinal motion detection. We utilized intraocular injection of diphtheria toxin (DT) in mutant mice expressing diphtheria toxin receptors (DTR) in SACs. The looming-evoked fear responses disappeared in half of the DT-injected mice, and the other mice still exhibited the fear responses. The optomotor responses were reduced or eliminated, which occurred independent of the disappearance of the fear responses. A histological examination revealed that ON SACs were reduced in both mouse groups preserved or absent fear responses. In contrast, the number of OFF SACs was different among two groups. The OFF SACs were relatively preserved in mice exhibiting continued fear responses, whereas they were ablated in mice lacking fear response to looming stimulation. These results indicate that OFF SACs and the direction-selective pathway in the retina play a role in looming-induced fear behaviors.Significance StatementIn response to a suddenly approaching dark object, mice exhibit a defensive response: either flight to a refuge or freeze in the same spot. How the visual system evokes this response in the mouse has not been fully understood. We focused on the initial neural component of the visual system, the retina, and examined a type of neuron known for sensing object motion: the starburst amacrine cell. We found that ablation of OFF starburst amacrine cells removed the dark object-evoked defensive responses. We believe that our findings will contribute to understanding the neural network connecting the visual system and the brain circuit regarding fear and emotion.

A Novel Approach to Screen for Somatosensory Evoked Potentials in Critical Care.

Somatosensory evoked potentials (SSEPs) help prognostication, particularly in patients with diffuse brain injury. However, use of SSEP is limited in critical care. We propose a novel, low-cost approach allowing acquisition of screening SSEP using widely available intensive care unit (ICU) equipment, specifically a peripheral "train-of-four" stimulator and standard electroencephalograph. The median nerve was stimulated using a train-of-four stimulator, and a standard 21-channel electroencephalograph was recorded to generate the screening SSEP. Generation of the SSEP was supported by visual inspection, univariate event-related potentials statistics, and a multivariate support vector machine (SVM) decoding algorithm. This approach was validated in 15 healthy volunteers and validated against standard SSEPs in 10 ICU patients. The ability of this approach to predict poor neurological outcome, defined as death, vegetative state, or severe disability at 6months, was tested in an additional set of 39 ICU patients. In each of the healthy volunteers, both the univariate and the SVM methods reliably detected SSEP responses. In patients, when compared against the standard SSEP method, the univariate event-related potentials method matched in nine of ten patients (sensitivity = 94%, specificity = 100%), and the SVM had 100% sensitivity and specificity when compared with the standard method. For the 49 ICU patients, we performed both the univariate and the SVM methods: a bilateral absence of short latency responses (n = 8) predicted poor neurological outcome with 0% FPR (sensitivity = 21%, specificity = 100%). Somatosensory evoked potentials can reliably be recorded using the proposed approach. Given the very good but slightly lower sensitivity of absent SSEPs in the proposed screening approach, confirmation of absent SSEP responses using standard SSEP recordings is advised.

Obstructive Sleep Apnoea Syndrome and Association of AHI Scores with Sensorineural Hearing Loss: An Early Predictor

Obstructive sleep apnoea syndrome (OSAS) is a condition that is characterised by frequent apnoea and hypopnoea attacks occurring during sleep. The blood supply to cochlea and acoustic nerves is from terminal arteries, thereby making them susceptible to hypoxia. To compare the audiological profiles in patients with OSAS according to Apnoea Hypopnoea index (AHI) score. Descriptive study was conducted in 32 patients diagnosed to have OSAS in a tertiary referral centre over two year period. The study group was divided into mild, moderate, severe OSAS based on AHI score. The hearing evaluation was done using pure tone audiogram (PTA) and distortion product otoacoustic emission test (DPOAE). Moderate and severe OSAS participants had elevated thresholds at higher frequencies in PTA (4 kHz, 8 kHz), although this was not statistically significant. We also noticed, absent DPOAE responses at higher frequencies (4 k, 6 k, 8 k), with increase in the severity of OSAS at higher frequency, which was statistically significant (p value < 0.05). This study revealed elevated hearing thresholds at higher frequencies (4 kHz, 8 kHz) in PTA and DPOEA with an increase in the severity of OSAS. All OSAS patients, especially with AHI > 30 should be regularly screened for hearing loss.

Apoptosis of type I spiral ganglion neuron cells in Otof-mutant mice

Otof, which encodes otoferlin, knockout mice are considered model mice for auditory neuropathy spectrum disorder, which is characterized by an absent auditory brainstem response (ABR) despite preserved distortion product otoacoustic emission (DPOAE). Although otoferlin-deficient mice lack neurotransmitter release at the inner hair cell (IHC) synapse, it remains unclear how the Otof mutation affects spiral ganglions. Thus, we used Otof-mutant mice carrying the Otoftm1a(KOMP)Wtsi allele (Otoftm1a) and analyzed spiral ganglion neurons (SGNs) in Otoftm1a/tm1a mice by immunolabeling type Ⅰ SGNs (SGN-Ⅰ) and type II SGNs (SGN-II). We also examined apoptotic cells in SGNs. Four-week-old Otoftm1a/tm1a mice had an absent ABR but normal DPOAEs. The number of SGNs was significantly lower in Otoftm1a/tm1a mice on postnatal day 7 (P7), P14, and P28 compared with that of wild-type mice. Moreover, significantly more apoptotic SGNs were observed in Otoftm1a/tm1a mice than in wild-type mice on P7, P14, and P28. SGN-IIs were not significantly reduced in Otoftm1a/tm1a mice on P7, P14, and P28. No apoptotic SGN-IIs were observed under our experimental conditions. In summary, Otoftm1a/tm1a mice showed a reduction in SGNs accompanied by apoptosis of SGN-Ⅰs even before the onset of hearing. We speculate that the reduction in SGNs with apoptosis is a secondary defect caused by a lack of otoferlin in IHCs. Appropriate glutamatergic synaptic inputs may be important for the survival of SGNs.

Susceptibility weighted imaging can be a sensitive sequence to detect brain damage in neonates with kernicterus: a case report

BackgroundKernicterus in the acute phase is difficult to diagnose. It depends on a high signal on T1 at the globus pallidum and subthalamic nucleus level. Unfortunately, these areas also show a relatively high signal on T1 in neonates as an expression of early myelination. Therefore, a less myelin-dependent sequence, like SWI, may be more sensitive to detecting damage in the globus pallidum area.Case presentationA term baby developed jaundice on day three following an uncomplicated pregnancy and delivery. Total bilirubin peaked at 542 μmol/L on day four. Phototherapy was started, and an exchange transfusion was performed. ABR showed absent responses on day 10. MRI on day eight demonstrated abnormal high signal globus pallidus on T1w, isointense on T2w, without diffusion restriction, and high signal on SWI at globus pallidal and subthalamus level and phase image at globus pallidal level. These findings were consistent with the challenging diagnosis of kernicterus. On follow-up, the infant presented with sensorineural hearing loss and had a work-up for cochlear implant surgery. At 3 months of age, the follow-up MR shows normalization of the T1 and SWI signals and a high signal on T2.ConclusionsSWI seems more sensitive to injury than the T1w and lacks the disadvantage of the T1w sequence, where early myelin confers a high signal.

Evaluation of vestibular evoked myogenic potential values in elder patients with hip fractures: A prospective controlled study

Background/Aim: Hip fractures among the elderly are a major public health problem that cause high rates of morbidity and mortality. There are many studies regarding prevention and defining the underlying causes of hip fractures. The purpose of this study was to evaluate the cervical vestibular evoked myogenic potential (cVEMP) test responses of elderly patients without vestibular symptoms hospitalized due to fall-related hip fractures in order to evaluate the subclinical vestibular dysfunction rates in patients with hip fractures. Methods: Twenty-two patients aged 67-79 hospitalized due to fall-related hip fractures and 24 control patients presenting to the orthopedic clinic due to knee pain were included in the study. The participants underwent detailed otological examination and cVEMP tests. The two groups’ cVEMP records were then compared. Results: The demographic characteristics of the participants in the patient and control groups including age, gender, and race were similar. There was no statistically significant difference between the groups’ absent VEMP response rates. No significant difference in terms of P1 and N1 latencies was determined between the right and left ears in either group. The hip fracture group (study group) had significantly increased P1 and N1 latencies in cVEMP which is associated with central vestibular dysfunction. (P=0.008 and P=0.007, respectively). Conclusion: The rate of subclinical peripheral vestibular dysfunction, which can be identified by cVEMP evaluation, is increased in elderly patients with hip fractures caused by low energy trauma. Precautions like vestibular rehabilitation can be a preventive measure for hip fractures in the elderly.

Identifying spastic variant of type II achalasia after treatment with high-resolution manometry and FLIP Panometry.

Panesophageal pressurization (PEP) defines type II achalasia on high-resolution-manometry (HRM) but some patients exhibit spasm after treatment. The Chicago Classification (CC) v4.0 proposed high PEP values as predictor of embedded spasm, yet supportive evidence is lacking. Fifty seven type II achalasia patients (47 ± 18 years, 54% males) with HRM and LIP Panometry before and after treatment were retrospectively identified. Baseline HRM and FLIP studies were analyzed to identify factors associated with post-treatment spasm, defined on HRM per CC v4.0. Seven patients (12%) had spasm following treatment (peroral endoscopic myotomy 47%; pneumatic dilation [PD] 37%; laparoscopic Heller myotomy 16%). At baseline, greater median maximum PEP pressure (MaxPEP) values on HRM (77 vs 55 mmHg, p= 0.045) and spastic-reactive contractile response pattern on FLIP (43% vs 8%, p= 0.033) were more common in patients with post-treatment spasm while absent contractile response on FLIP was more common in patients without spasm (14% vs 66%, p= 0.014). The strongest predictor of post-treatment spasm was the percentage of swallows with MaxPEP ≥70 mmHg (best cut-off: ≥30%), with AUROC of 0.78. A combination of MaxPEP <70 mmHg and FLIP 60 mL pressure < 40 mmHg identified patients with lower rates of post-treatment spasm (3% overall, 0% post-PD) compared to those with values above these thresholds (33% overall, 83% post-PD). High maximum PEP values, high FLIP 60 mL pressures and contractile response pattern on FLIP Panometry prior to treatment identified type II achalasia patients more likely to exhibit post-treatment spasm. Evaluating these features may guide personalized patient management.

Stem Cell Therapy for Erectile Dysfunction: A Step towards a Future Treatment.

Background: The improvement of absent or partial response in the medical treatment of erectile dysfunction (ED) has led to the development of minimally invasive new treatment modalities in the field of regenerative medicine. Methods: A literature review on stem cell therapy for the treatment of ED was performed. We searched for the terms "erectile dysfunction" and "stem cell therapy" in PubMed and Clinicaltrials.gov. Literature searching was conducted in English and included articles from 2010 to 2022. Results: New treatment modalities for ED involving stem cell therapy are not only conceived with a curative intent but also aim to avoid unnecessary adverse effects. Several sources of stem cells have been described, each with unique characteristics and potential applications, and different delivery methods have been explored. A limited number of interventional studies over the past recent years have provided evidence of a safety profile in their use and promising results for the treatment of ED, although there are not enough studies to generate an appropriate protocol, dose or cell lineage, or to determine a mechanism of action. Conclusions: Stem cell therapy is a novel treatment for ED with potential future applications. However, most urological societies agree that further research is required to conclusively prove its potential benefit.

Do differences in abdominal movement patterns during coughing and forced expiration affect cranioventral bladder neck displacement in healthy nulliparous subjects?

Aims:Abdominal movement patterns during coughing and forced expiration (FE) fall into two categories: abdominal inward movement (AIM) and abdominal outward movement (AOM). These abdominal movement patterns are thought to affect cranioventral (CV) bladder neck displacement differently. However, many studies have described an absent or altered PFM response during coughing, assuming PFM dysfunction, without considering the impact of abdominal movement pattern differences. The aim of this study was to observe abdominal movement patterns during coughing and FE and compare the associated (CV) bladder neck displacement patterns. Method:Participants performed three maximal expulsive coughs, followed by three FEs, during which the respiratory inductive plethysmography (RIP) method was used to identify abdominal movement patterns. Concurrently, perineal 2D ultrasound was applied to assess CV bladder neck displacement. All measurements were done in the standing and crook lying position. Descriptive statistics were computed for abdominal movement patterns and bladder neck displacement. Chi-squared tests were used to compare abdominal movement patterns and CV bladder neck displacement. Results:One hundred and forty-nine healthy nulliparous women without PFM dysfunction participated in the study. During both coughing and FE in the standing position, women who displayed an AIM pattern had a significantly higher occurrence of CV bladder neck displacement compared to those presenting AOM. In the crook lying position, there was a significantly higher occurrence of bladder neck displacement during coughing in subjects showing AIM compared to those with AOM. Conclusion:Significant differences were found in abdominal movement patterns during coughing and FE in healthy nulliparous subjects in standing and crook lying positions. Most of the subjects showed AOM during coughing or FE in both standing and lying positions. This is contrary to the existing literature and needs further investigation. Abdominal movement patterns impacted CV bladder neck displacement during coughing and FE while standing and during coughing in the crook lying position. Clinicians should be aware of different abdominal movement patterns, which should be considered for diagnosis and treatment.

Direct cochlear nerve stimulation monitoring through evoked muscle responses during retrosigmoid vestibular schwannoma resection surgery: technical note.

Cochlear nerve preservation during surgery for vestibular schwannoma (VS) may be challenging. Brainstem auditory evoked potentials and cochlear compound nerve action potentials have clearly shown their limitations in surgeries for large VSs. In this paper, the authors report their preliminary results after direct electrical intraoperative cochlear nerve stimulation and recording of the postauricular muscle response (PAMR) during resection of large VSs. The details for the electrode setup, stimulation, and recording parameters are provided. Data of patients for whom PAMR was recorded during surgery were prospectively collected and analyzed. PAMRs were recorded in all patients at the ipsilateral vertex-earlobe scalp electrode, and in 90% of the patients they were also observed in the contralateral electrode. The optimal stimulation intensity was found to be 1 mA at 1 Hz, with a good cochlear response and an absent response from other nerves. At that intensity, the ipsilateral cochlear response had an initial peak at a mean (± SEM) latency of 11.6 ± 1.5 msec with an average amplitude of 14.4 ± 5.4 µV. One patient experienced a significant improvement in his audition, while that of the other patients remained stable. PAMR monitoring may be useful in mapping the position and trajectory of the cochlear nerve to enable hearing preservation during surgery.

Appropriateness of Proton Pump Inhibitor Prescription Evaluated by Using Serological Markers.

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.

Waning Humoral Response 6 Month after Double Vaccination with the mRNA-BNT162b2 Vaccine in Hemodialysis Patients.

Although most hemodialysis patients (HDP) exhibit an initial seroresponse to vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), studies have shown this response to be lower compared to healthy subjects. This fact raised concerns regarding the durability of the immune response and effective protection against severe Coronavirus disease 2019 (COVID-19) in this vulnerable population. The aim of our study was to evaluate the change in antibody levels over time in HDP population. We performed a prospective multicenter study, evaluating antibody response among HDP at 2 and at 6 months after complete two-dose vaccination course with the mRNA-BNT162b2 (Pfizer-BioNTech) vaccine. The study was performed in 14 hemodialysis units of a private dialysis provider in Lithuania. The serum samples of 189 HDP were tested for SARS-CoV-2 IgG against the Spike glycoprotein. 189 HDP participated in the study. Patients were 64.3±15.7 years of age, 116 (61.4%) were males and 73 (38.6%) were females. Among them, 183 (96.8%) were seropositive for anti-S IgG at 2 months after the second immunization dose. Six months after the second dose only 145 (76.7%) of study participants had positive anti-S IgG titers. The median level of anti-S IgG titers after 2 months was 383.1 BAU/mL (166.2-995.6) and after 6 months this level significantly decreased to 51.4 BAU/mL (22.0-104.0) (p<0.001). Seroresponses at both time points inversely correlated with increasing patient's age. Risk factor for absent response after 2 months included oncologic disease. Systemic autoimmune disease and a history of myocardial infarction increased risk to be seronegative 6 months after the second vaccine dose. The majority of hemodialysis patients seroresponded after BNT162b2/Pfizer vaccination, but vaccine-induced humoral immunity wanes over time.

Macular Pseudocoloboma in Achromatopsia

A 13-year-old girl with a history of nystagmus from 4 to 18 months of age developed intense photophobia. Examination showed poor vision (0.8 logarithm of the minimum angle of resolution in both eyes). Fundus photographs (A, B), autofluorescence imaging (C), and spectral domain OCT (D) showed stable, deep, coloboma-like central macular lesions in both eyes. We observed absent cone responses but normal rod responses on full-field electroretinogram. Molecular genetic testing detected a pathogenic c.1561C>T (p.Gln521∗) homozygous mutation in the exon 13 of ATF6. The presence of clinically extended lesions of the macula, usually a sign of cone-rod dystrophies when not postinfectious, does not always preclude the diagnosis of achromatopsia (Magnified version of Figure A-D is available online at www.aaojournal.org).

Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response.

With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling.

Comparison of Intraoperative Neural Response Telemetry Results and Postoperative Neural Response Telemetry Results in Case of Children with Congenital Bilateral Severe to Profound Sensorineural Hearing Loss Undergoing Single Sided Cochlear Implantation.

This study is designed to compare the Intra Operative Neural Response Telemetry (NRT) results with Post-Operative NRT results of the cochlear implanted children, to assess the importance of Intra Operative NRT thresholds in device activation and/or switch on of the audio processor and to evaluate the importance of Intra and post operative AutoNRT results in predicting behavioural thresholds during mapping of prelingual Cochlear Implanted children. A total of thirty (30) children (16 boys, 14 girls) with congenital Bilateral (B/L) severe to profound Sensorineural hearing loss (SNHL) were included in this study. Children between the age range of 12 to 60 months were participated in this study. All the participants were implanted with Nucleus 24 cochlear implant system. In each patient, the intra operative NRT-thresholds were measured for all 22 active electrodes. Then Intra Operative NRT thresholds were correlated with Post-Operative NRT thresholds at the time of switch on and the behavioural map after six months of switch on of the device (Audio Processor). There is a significant enhancement observed in thresholds of postoperative NRT responses which were raised or absent during intraoperative session. There is a gain in NRT thresholds marked after 6 months of postoperative follow up in comparison with first measurement at the time of Switch On of the device but the change not that significant. During postoperative mapping, there was a significant positive correlation noticed between neural response telemetry level measurements and behavioural threshold level. Absent or elevated NRT responses during intraoperative testing for some electrodes especially basal electrodes does not mean that electrode is out of order or outside the cochlea, because an improvement in NRT thresholds usually occurs postoperatively. In case of children with congenital B/L severe to profound SNHL, the NRT values have a very useful role in predicting the behavioural thresholds. Combination of NRT values with behavioural thresholds and observations of Auditory Verbal Therapist can help in providing best suitable Map to the recipient. The online version contains supplementary material available at 10.1007/s12070-022-03284-x.