bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and Timing of Pigment Epithelial Detachment and Subretinal Fluid Development in Type 3 Macular Neovascularization associated with Age-related Macular Degeneration
Authors: Kim Jae Hui , Kim Jong Woo , Kim Chul Gu
Published: March 2023

Purpose:

To evaluate the incidence and timing of pigment epithelial detachment (PED) and subretinal fluid(SRF) development in type 3 macular neovascularization (MNV).

Methods:

This retrospective study included 84 patients who were diagnosed with treatment-naïve type 3 MNV who did not show SRF at diagnosis. All patients were initially treated with three loading injections of ranibizumab or aflibercept. Following the initial loading injections, as-needed regimen was performed for retreatment. The development of either PED or SRF was identified. The incidence and timing of PED development in patients without PED at diagnosis and that of SRF development in patients with PED at diagnosis were evaluated.

Results:

The mean follow-up period was 41.3±20.7 months after diagnosis. Among the 32 patients without serous PED at diagnosis, PED developed in 20 (62.5%) at a mean of 10.9±5.1 months after diagnosis. PED development was noted within 12 months in 15 patients (46.8%; 75.0% among the PED development cases). In 52 patients with serous PED and without SRF at diagnosis, 15 developed SRF (28.8%) at a mean of 11.2±6.4 months after diagnosis. SRF development was noted within 12 months in 9 patients (17.3%; 66.6% among the SRF development cases).

Conclusions:

PED and SRF developed in a substantial proportion of patients with type 3 MNV. The average period of development of these pathologic findings was within 12 months of diagnosis, suggesting the need for active treatment during the early treatment period to improve treatment outcomes.
SCLEROCHOROIDAL CALCIFICATION WITH OPTIC NERVE CALCIFICATION IN A PATIENT WITH PRIMARY HYPERPARATHYROIDISM AND SEVERE VISION LOSS
Authors: Sood Shefali , Friedman Scott
Published: March 2023

Background/Purpose:

To present a case of sclerochoroidal calcification (SCC) associated with dural calcification along the optic nerves and severe visual loss.

Methods:

Case report.

Results:

A 74-year-old white female patient with a 25-year history of primary hyperparathyroidism and surgical removal of a single parathyroid gland presented with blurred vision. On presentation, she had a calcium level of 12.6 mg/dL (reference range: 8.7–10.3 mg/dL). Her best-corrected visual acuity (BCVA) was 20/40 in both eyes, and she was diagnosed with bilateral SCC. After 2 years, the patient returned with a complaint of progressive vision loss, and the BCVA was 20/150 in the right eye and hand motion in the left eye. She had stable focal SCC on fundus examination with no significant changes from the previous examination. The fluorescein angiogram was unremarkable with no leakage. Optical coherence tomography (OCT) of the macula showed no edema or subretinal fluid and was not significantly changed from the first OCT. B-scan showed areas of calcification in the sclera consistent with the SCC. Computerized tomography (CT) scans showed dural calcifications along both optic nerves. She had no enlargement of SCC lesions and no other ocular or neurologic pathology associated with her vision loss.

Conclusion:

We present a patient with bilateral SCC and associated calcification in both globes. Unlike previous reports of SCC, our case demonstrated progressive severe vision loss because of dural calcification along the optic nerves. Patients with SCC and decreased vision should receive a CT scan to look for this rare associated finding.
INTRAVITREAL METHOTREXATE IN VEMURAFENIB-INDUCED UVEITIS
Authors: Dugauquier Artémise , Awada Ahmad Hussein , Motulsky Elie , Kisma Nacima
Published: March 2023

Purpose:

Vemurafenib, a BRAF inhibitor, has revolutionized the prognosis of late-stage melanoma patients, rising at the same time concerns about its potential adverse effects. Here is a case of vemurafenib-induced uveitis, peculiar in both its presentation and management.

Methods:

Case report, diagnostic, and therapeutic challenge.

Results:

Uveitis is a known side effect of vemurafenib. It is generally bilateral, moderate, manageable with topical steroids, and does not require cancer therapy cessation. We present a patient who suffered from a unilateral, severe uveitis after vemurafenib treatment that fully recovered thanks to intravitreal methotrexate injections because conventional corticosteroid therapy was contraindicated.

Conclusion:

Uveitis can be a serious ocular adverse effect of vemurafenib, whereas its risk factors and mechanisms remain unknown. As BRAF inhibitors are now used on a regular basis, it is important for clinicians to be aware of this potentially sight-threatening side effect. Intravitreal methotrexate injections may be considered as an effective treatment choice in severe targeted agents-induced uveitis.
THE LONG-TERM OUTCOME OF EYES WITH UNEXPLAINED VISUAL LOSS AFTER GAS TAMPONADE FOR MACULA-ON RETINAL DETACHMENT
Authors: Iuliano Lorenzo , Corbelli Eleonora , Bandello Francesco , Codenotti Marco
Published: March 2023

Purpose:

To analyze the long-term outcome of eyes suffering from unexplained visual loss after gas tamponade for primary macula-sparing rhegmatogenous retinal detachment.

Methods:

Cross-sectional analysis of all eyes with macula-on rhegmatogenous retinal detachment experiencing an unexplained loss of vision after gas reabsorption that were treated and followed from 2010 to 2019. The investigational work-up included: best-corrected visual acuity (BCVA), clinical examination, spectral-domain optical coherence tomography, and automated computerized perimetry.

Results:

The nine eyes of the nine patients were analyzed after 5.9 ± 2.4 years. Best-corrected visual acuity improved by 0.54 ± 0.50 logMAR from baseline, achieving a final value of 1.17 ± 0.52 logMAR (∼20/320; P = 0.0115). The thicknesses of the macula, of the macular ganglion cells, and of the retinal nerve fiber layers were unchanged compared with the baseline, and the rate of ellipsoid zone defects (22.2%). The proportion of eyes with microcystoid macular edema significantly decreased to 44.4% (P = 0.0294). Perimetry mean deviation increased from a baseline value of −18.06 ± 2.72 to −17.23 ± 2.29 dB (P = 0.0390), with an unchanged pattern SD (P = 0.1289). In general, a reduction of the scotomata relative depth from baseline was evident in all eyes.

Conclusion:

Eyes with macula-on rhegmatogenous retinal detachment suffering from unexplained visual loss after gas reabsorption, despite disclosing an overall unchanged structural macular morphology, showed a moderate, but significant, visual and perimetric improvement in the long-term.
A CASE OF HERPES SIMPLEX VIRUS AND CYTOMEGALOVIRUS RETINITIS COINFECTION
Authors: Lopez Jennifer , Hua Hong-Uyen , Toy Brian C.
Published: March 2023

Purpose:

The purpose of this study was to describe a case of a 64-year-old man presenting with cytomegalovirus and herpes simplex virus retinitis coinfection in the setting of Burkitt lymphoma.

Methods:

A case report including multimodal imaging and anterior chamber polymerase chain reaction results was used.

Results:

This case highlights the importance of the clinical examination and maintaining high diagnostic suspicion for viral retinitis in immunocompromised patients.

Conclusion:

Aqueous fluid PCR can be a useful adjunctive test to distinguish and confirm a diagnosis of viral retinitis. Given the limited sample volume of aqueous biopsy, it is important to prioritize the order of PCR testing based on clinical suspicion of the causative agent.
Automatic Detection of Benign Brain Tumors Using Statistical Analysis
Authors: Ali Nosiba M. , ElZubair Omnia M. , Hamza Alnazier O. , Elnour Hanan A. M. , Khider Mohamed O.
Published: March 2023

Tumor is an uncontrolled growth of harmful cells within the skull that raises intracranial pressure. In the field of medical research, medical picture classification is critical. Imaging plays a crucial role in the diagnosis of brain tumors. Magnetic resonance imaging is a noninvasive, 3-dimensional imaging technique that produces high-quality images. The interpretation of an image might not be completely precise and require the assistance of a second opinion, variability in diagnosis made by different doctors and even by the same doctor under different circumstances due to job load, observation accuracy for the physician, picture clarity, noise, or the physician's vision or mood. Based on the previously mentioned reasons, we have developed a computer-aided diagnosis system to aid in the identification or detection of benign tumor in brain magnetic resonance imaging scans. In the first stage of this study, image enhancement and correct segmentation processes have been conducted into the images in order to facilitate the system to give an accurate classification of brain tumor type. In the second stage, we investigated several statistical features using a technique called gray-level co-occurrence matrix. The implementation of this technique was done with software called MATLAB (Matrix Laboratory) to determine the best features for diagnosing benign tumors of the brain. Gray-level co-occurrence matrix is second-order statistical analysis that describes spatial relationships and the information about the pixel position that has a similar gray-level value; we have found that some features have a big cutoff range between normal and abnormal tissues. Classification was done using back-propagation artificial neural network. The detection findings and quantitative data analysis show that our suggested system is effective, with a detection accuracy of 99.8%.
Evaluation of Lumbar Spine Morphology in Magnetic Resonance Images Using Cobb's Method
Authors: Elnour Hanan Ahmed Mohamed
Published: March 2023

Lumbar lordosis represents one of the most prevalent postural disorders; it is classified as significant lumbar curving in the vertebral column's sagittal plane. The study's aims were to investigate lumbar spine morphology in Sudanese patients using Cobb's approach, as well as magnetic resonance imaging sagittal T2-weighted images. It was carried out between August 2015 and August 2016 in Khartoum Sudan's Advanced Diagnostic Center and Baraha Medical City hospital, with 140 patients (55 male and 85 female patients). The controlled cases involved in this study consisted of 40 patients (10 male and 30 female patients), ranging in age from 13 to 90 years. The results revealed substantial variation between the population having normal health and disc herniated patients in the Cobb angle (P = .000) and intervertebral disc space of L3 (P = .011), but no substantial improvement (P > .05) between individuals with abnormal values and control individuals in the lumbosacral angle, L1-L5 body vertebrae, and L1, L2, L4, and L5 intervertebral disc levels. In addition, there was a notable change among the LS and Cobb angles in the patients with abnormal values (P = .045), but not in the control individuals (P = .691). We discovered a straight linear correlation among the Cobb angle and vertebral body L5-L2 in patients with bulged disc at various levels, as well as the Cobb angle and the L5-L2 intervertebral disc spaces also exhibit an indirect linear connection. It is concluded that magnetic resonance imaging is good for diagnosing disease associated with soft tissues, particularly the spinal discs that are frequently affected and cause low back problems.
Medical Device Recalls for Electronic Components
Authors: Block Frank E. , Mackey Ross J.
Published: March 2023

Through the advancement of technology, an ever-increasing number of medical devices contain electronic components and sensors. As a result of these technological advances, smaller devices need more memory, sensors, processing power, and increased energy requirements. Ultimately, the performance of many medical devices is directly dependent on the functionality of these interconnected electronic components. In this article, medical device recalls are examined for malfunctions of electronic systems and components with respect to what system or component specifically did not perform as intended. From this examination, recalls related to electronic medical device systems and components are identified and grouped into common themes. By alerting the Food and Drug Administration to medical device failures, clinical engineering staff can help make manufacturers aware of issues that can be used to make future design changes or mitigations that can ultimately improve the performance and reliability of electronic medical devices.
Association of Occupational Exposures and Chronic Obstructive Pulmonary Disease Morbidity
Authors: Rous Jennifer S. , Lees Peter S. J. , Koehler Kirsten , Buckley Jessie P. , Quirós-Alcalá Lesliam , Han MeiLan K. , Hoffman Eric A. , Labaki Wassim , Barr R. Graham , Peters Stephen P. , Paine Robert , Pirozzi Cheryl , Cooper Christopher B. , Dransfield Mark T. , Comellas Alejandro P. , Kanner Richard E. , Drummond M. Bradley , Putcha Nirupama , Hansel Nadia N. , Paulin Laura M.
Published: March 2023

Objective

The aim of the study is to determine whether aggregate measures of occupational exposures are associated with chronic obstructive pulmonary disease (COPD) outcomes in the Subpopulations and Intermediate Outcome Measures in COPD study cohort.

Methods

Individuals were assigned to six predetermined exposure hazard categories based on self-reported employment history. Multivariable regression, adjusted for age, sex, race, current smoking status, and smoking pack-years determined the association of such exposures to odds of COPD and morbidity measures. We compared these with the results of a single summary question regarding occupational exposure.

Results

A total of 2772 individuals were included. Some exposure estimates, including “gases and vapors” and “dust and fumes” exposures resulted in associations with effect estimates over two times the estimated effect size when compared with a single summary question.

Conclusions

Use of occupational hazard categories can identify important associations with COPD morbidity while use of single-point measures may underestimate important differences in health risks.
Percutaneous management of ureteropelvic junction obstruction
Authors: Kominsky Hal D. , Johnson Brett A.
Published: March 2023

Purpose of review

The development of endoscopic and minimally invasive techniques has revolutionized the treatment of ureteropelvic junction obstruction (UPJO). Patients can now undergo successful UPJO repair without the morbidity and complications associated with open surgery. Laparoscopic and robotic repair has supplanted open surgery as the gold standard, but percutaneous endoscopic treatment remains a relevant alternative to more invasive surgery. This review will focus on the percutaneous approach for the treatment of UPJO.

Recent findings

Percutaneous endopyelotomy was popularized during the 1980 s due to advances in the field of endourology, allowing for well tolerated and reliable percutaneous access to the kidney. After percutaneous access to the kidney is achieved, the narrowed ureter at the UPJ is incised in a full thickness fashion in the posterolateral position from the ureteral lumen to the periureteral fat. Success rates for this procedure are nearly 90% at high-volume centres. The ideal patient who has success with percutaneous endopyelotomy has a short segment of narrowing less than 2 cm, no crossing vessel, good ipsilateral renal function and mild hydronephrosis.

Although the development of laparoscopic and robotic approaches to pyeloplasty has produced outcomes that surpass those of percutaneous endopyelotomy, it remains a viable option in the appropriately selected patient, but success rates tend to decrease with longer follow up.
A rare case of fulminant sepsis secondary to postpartum pyomyoma caused by Prevotella bivia: a case report
Authors: Ogawa Tatsuhiko
Published: March 2023

Introduction and importance:

Pyomyoma is rare but can cause life-threatening sepsis from uterine leiomyoma infection. Curative radical surgery to completely remove all infectious foci is preferable if conservative treatment fails, but for patients with fertility concerns, alternatives to uterine removal should be considered. The author reports a case of postpartum pyomyoma to remind clinicians of this rare disease and the need for rapid intervention to preserve patient fertility.

Case presentation:

A postpartum female with a fever of unknown origin was admitted to a public hospital. The patient’s general condition rapidly worsened, and surgical removal of the pyomyoma was assumed to be necessary for controlling the infection source. The patient initially refused surgery, as she had fertility concerns; however, she developed septic shock and acute respiratory distress syndrome. Subsequently, surgical intervention was considered imperative, and the patient consented to surgery. Normal uterus was carefully differentiated from degenerated intramural pyomyoma, and the endometrium remained intact. In the pyomyoma specimen, Prevotella bivia, an endogenous anaerobic bacterium that can colonize the lower genital tract, was detected.

Clinical discussion:

For patients with postpartum sepsis and leiomyoma, pyomyoma should be considered, even if the patient is immunocompetent and has no risk factors. Pyomyoma can be exacerbated into a fulminant and fatal course after subacute, insidious progression.

Conclusion:

Comprehensive treatment strategies, including source control of infection and uterine preservation, are required for future fertility. Strict vigilance and appropriate and prompt surgical intervention when conservative treatments fail are crucial to save the patient and preserve fertility.
Acute pancreatitis in pregnancy: how was it determined whether it was caused by pregnancy or by COVID-19? A case report
Authors: Bereda Gudisa
Published: March 2023

Background and importance:

Acute pancreatitis is a pancreatic inflammatory condition that has the potential to cause serious morbidity. Acute pancreatitis is a relatively uncommon and potentially fatal pregnancy condition. Abdominal pain, pancreatic damage, or acute pancreatitis may all be related to the coronavirus disease 2019 (COVID-19) infection.

Case presentation:

On 12 August 2022, a 33-year-old black woman, gravida three, para two, a housewife, was taken to the obstetric care unit at 24 weeks of pregnancy with a 1-week history of lethargy, fever, and a dry cough. Reverse transcriptase-PCR testing on a sample of her nasopharyngeal swab revealed the presence of the severe acute respiratory syndrome coronavirus 2 virus. An abdominal computed tomography scan indicated an atrophic pancreas with broad fatty infiltration, little fluid and fat stranding around the pancreas, and reactive lymph nodes. She received 24-h-long insulin infusion therapy in addition to potassium chloride administered intravenously. She received crystalloid isotonic intravenous fluid to treat her severe pancreatitis and stop the progression of acute respiratory distress syndrome.

Clinical discussion:

Severe consequences of the severe acute respiratory syndrome coronavirus 2 infection are more likely to affect pregnant women who already have diabetes as concomitant conditions. Acute pancreatitis caused by COVID-19 is uncommon and can occur after a mild infection or even after the viral infection has cleared up. Lipasemia typically manifests following the peak of systemic inflammatory activity that triggers the release of pancreatic enzymes like lipase.

Conclusion:

Symptoms of the digestive system, including anorexia, nausea, vomiting, stomach pain, and diarrhea, can be brought on by the COVID-19 infection. She had diarrhea as a clinical symptom, showing that the COVID-19 infection was the root cause of her acute pancreatitis. She had also refrained from vomiting, demonstrating that her acute pancreatitis was not related to pregnancy.
Evaluating the FRAIL Questionnaire as a Trigger for Palliative Care Consultation After Acute Stroke
Authors: Keiser Megan , Buterakos Roxanne , Stutzky Haley , Moran Laura , Hewelt Dawn
Published: March 2023

The American Heart Association and the American Stroke Association jointly released guidelines stating that all patients with a new diagnosis of stroke should receive palliative care consultation starting in the acute phase of care. The purpose of this project was to increase palliative care consultation rates for patients after an acute stroke by using a frailty score to trigger a palliative care consult. Provider education on palliative care and a 5-question fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) questionnaire was delivered by a presentation, handouts, and a follow-up email using previously developed content. Patients included adults admitted to the neuroscience critical care unit of a Midwestern comprehensive stroke center with an admission diagnosis of acute stroke (n = 120). The charge nurse completed the FRAIL questionnaire as a screening tool to trigger a palliative care consult. A survey was also distributed to providers (n = 54) to understand their knowledge, thoughts, and feelings toward palliative care. There was an increase in patients who received palliative care consultation from 14.9% to 21.7% after implementation of the FRAIL questionnaire. Also, providers felt better able to provide symptom management to patients after acute stroke. Further research is necessary to determine if the FRAIL survey is an adequate trigger for palliative care consultation.
Bing Neel Syndrome
Authors: Alexander Abigail L. , Jackson Devon , Donahue John E. , Chirkov Alexander , Banerjee Priya
Published: March 2023

Suicide rapidly increased in the United States by 30% from 2000 to 2020, accounting for more than 800,000 deaths (Neurosci Res Program Bull. 1972; 10: 384–8). Studies have shown that there are a multitude of underlying issues, including mental illness, that elevate an individual's risk of dying by suicide (CDC WONDER: Underlying cause of death, 1999–2019. Atlanta, GA: US Department of Health and Human Services, CDC; 2020). Presented here is a case of Bing Neel syndrome (BNS) found in a 69-year-old man who died by suicide by jumping off a 135′ bridge. His medical history was significant for traumatic brain injury, Waldenstrom macroglobulinemia (WM), major depressive disorder, suicidal ideation, and anxiety. Bing Neel syndrome is a rare central nervous system complication of WM. His wife reported an abrupt mental deterioration starting 5 years before his death, characterized by paranoia, depression, and insomnia. He had been a high-functioning university professor. His decline culminated with the loss of independence in his activities of daily living. At autopsy, it was found that he experienced blunt force injuries related to the fall, causing his death. A neuropathologic examination revealed a brisk and fulminant clonal CD20+/immunoglobulin M+ lymphocytic infiltrate, involving all sampled regions of his brain, consistent with WM. This workup was critical to obtaining an accurate pathologic diagnosis of BNS and understanding his full clinical status before death. Although BNS was not the proximate cause of death, this diagnosis aided the death investigation as a causal factor in his suicidality and was vital to providing his family closure.
Effectiveness for Diagnosis of Malignancy of Bile Pyruvate Kinase M2 in Patients with Indeterminate Biliary Stricture
Authors: Aguilar Olivos Nancy Edith , Oria-Hernández Jesús , Briones Nicole Somerville , Téllez Ávila Félix Ignacio
Published: March 2023

Background:

Up to 70% of the cases of biliary strictures are cholangiocarcinoma. Cholangiocarcinoma has a late diagnosis and poor outcomes; therefore, effective biomarkers are needed for malignant lesions detection at earlier stages.

Aim:

The aim was to assess the diagnostic utility of bile pyruvate kinase M2 (PKM2) as a biomarker for the detection of malignant biliary strictures in patients with an indeterminate biliary stricture.

Materials and Methods:

This is a prospective study to evaluate the diagnostic value of bile PKM2 for the diagnosis of malignant biliary strictures. Bile samples were collected during Endoscopic Retrograde Cholangio Pancreatography to quantify PKM2 levels and were used to compare their diagnostic value with biliary brush cytology, endoscopic ultrasound-guided fine needle biopsy, or clinical follow-up.

Results:

Forty-six patients were recruited for the study; 19 patients with malignant strictures and 27 with benign biliary strictures. The bile PKM2 levels were elevated in patients with malignant biliary strictures [median 0.045 ng/mL (IQR 0.014 to 0.092)] compared with those with benign strictures [median 0.019 ng/mL (IQR 0.00 to 0.047)]. Bile PKM2 had a receiver-operating characteristic curve of 0.66 (0.49 to 0.83) with a cutoff value of bile PKM2 of 0.0017 ng/mL. The sensitivity and specificity of bile PKM2 for the diagnosis of cholangiocarcinoma were 89% and 26%; the positive and negative predictive values were 46% and 78%, respectively.

Conclusion:

In patients with indeterminate biliary strictures, bile PKM2 may be a potential biomarker for the diagnosis of malignancy.
Exploring the Utility of Neurostimulation Therapies in the Treatment of Borderline Personality Disorder
Authors: Zou Michael , Broadbear Jillian Helen , Rao Sathya
Published: March 2023

The use of electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) in the treatment of people diagnosed with borderline personality disorder (BPD) highlights the need for systematic review of the evidence supporting this practice. A comprehensive literature search identified seven original clinical research studies investigating the use of brain stimulation therapies in people diagnosed with BPD. The lack of consistent study design, diagnostic methodology, treatment parameters, and outcome measures precluded analysis of aggregated study results. There were no ECT studies evaluating BPD symptom outcomes; however, studies of ECT in patients with comorbid BPD and depression suggested that depressive symptoms were less responsive to ECT compared with depression-only patients. The few studies available suggest that TMS may lead to clinically and statistically significant improvements in BPD symptoms and depressive symptoms. Similar overall improvements were reported despite the use of heterogeneous TMS treatment protocols, highlighting the importance of including a sham condition to investigate the contribution of the placebo effect to overall improvement. There is still no clear evidence supporting the use of ECT for treating people with BPD (with or without depression); therefore, the use of ECT in this population should be approached with caution. Although TMS shows early promise, the low numbers of participants in the few available studies suggest the urgent need for larger randomized controlled trials to provide an evidence base for this increasingly popular treatment.
Does malignancy status effect outcomes in patients with large vessel occlusion stroke and cancer that underwent endovascular thrombectomy?
Authors: Shalabi Fatma , Sacagiu Tzvika , Honig Asaf , Molad Jeremy , Itsekson-Hayosh Zeev , Hallevi Hen , Orion David , Aladin Shorooq , Gomori John M. , Cohen Jose E. , Leker Ronen R.
Published: March 2023

Background

Cancer is associated with an increased risk of acute ischemic stroke (AIS) including large vessel occlusions (LVO). Whether cancer status affects outcomes in patients with LVO that undergo endovascular thrombectomy (EVT) remains unknown.

Methods and Results

All consecutive patients undergoing EVT for LVO were recruited into a prospective ongoing multi-center database and the data was retrospectively analyzed. Patients with active cancer were compared to patients with cancer in remission. Association of cancer status with 90-day functional outcome and mortality were calculated in multivariable analyses. We identified 154 patients with cancer and LVO that underwent EVT (mean age 74±11, 43% men, median NIHSS 15). Of the included patients, 70 (46%) had a remote history of cancer or cancer in remission and 84 (54%) had active disease. Outcome data at 90 days post-stroke was available for 138 patients (90%) and was classified as favorable in 53 (38%). Patients with active cancer were younger and more often smoked but did not significantly differ from those without malignancy in other risk factors, stroke severity, stroke subtype or procedural variables. Favorable outcome rates among patients with active cancer did not significantly differ compared to those seen in patients without active cancer but mortality rates were significantly higher among patients with active cancer on univariate and multivariable analyses.

Conclusions

Our study suggests that EVT is safe and efficacious in patients with history of malignancy as well as in those with active cancer at the time of stroke onset although mortality rates are higher among patients with active cancer.

Clinical Perspectives

What is new?

The results of the current study suggest that EVT is safe and efficacious in patients with history of malignancy as well as in those with active cancer at the time of stroke onset although mortality rates are significantly higher and favorable outcome rates tend to be lower among patients with active cancer.

What are the clinical implications?

The results imply that all cancer patients with LVO stroke should be considered for EVT regardless of cancer status.
Enhanced motor noise in an autism subtype with poor motor skills
Authors: Mandelli Veronica , Landi Isotta , Ceccarelli Silvia Busti , Molteni Massimo , Nobile Maria , D’Ausilio Alessandro , Fadiga Luciano , Crippa Alessandro , Lombardo Michael V.
Published: March 2023

Early motor difficulties are a common in many, but not all, autistic individuals. These difficulties tend to be highly present in individuals carrying rare genetic mutations with high penetrance for autism. Many of these rare genetic mechanisms also cause neurophysiological dysregulation of excitation-inhibition balance (E:I). A predicted downstream consequence of E:I imbalance in motor circuitry would translate behaviorally into enhanced ‘motor noise’ – that is, increased variability in execution of motor actions. Here we tested the hypothesis that autistic individuals with the most pronounced motor difficulties would be most affected by enhanced motor noise. Unsupervised data-driven clustering on a standardized test of motor skills (n=156, age = 3-16 years) identified the presence of two robust and highly stable autism motor subtypes described by relatively intact versus highly impaired motor skills. With motor kinematics data recorded during a simple reach-to-drop task, we observed that enhanced motor noise is a specific characteristic of the autism subtype with highly impaired motor skills. Autistic individuals with poor motor skills may be differentially affected by E:I imbalance within motor circuitry.
Fast ripples reflect increased excitability that primes epileptiform spikes
Authors: Weiss Shennan A , Fried Itzhak , Engel Jerome , Sperling Michael R. , Wong Robert K.S. , Nir Yuval , Staba Richard J
Published: March 2023

The neuronal circuit disturbances that drive interictal and ictal epileptiform discharges remains elusive. Using a combination of extraoperative macro- and micro-electrode interictal recordings in six presurgical patients during non-rapid eye movement (REM) sleep we found that, exclusively in the seizure onset zone, fast ripples (FR; 200-600Hz), but not ripples (80-200 Hz), frequently occur <300 msec before an interictal intracranial EEG (iEEG) spike with a probability exceeding chance (bootstrapping, p<1e-5). Such FR events are associated with higher spectral power (p<1e-10) and correlated with more vigorous neuronal firing than solitary FR (generalized linear mixed-effects model, GLMM, p<1e-3) irrespective of FR power. During the iEEG spike that follows a FR, action potential firing is lower than during a iEEG spike alone (GLMM, p<1e-10), reflecting an inhibitory restraint of iEEG spike initiation. In contrast, ripples do not appear to prime epileptiform spikes. We next investigated the clinical significance of pre-spike FR in a separate cohort of 23 patients implanted with stereo EEG electrodes who underwent resections. In non-REM sleep recordings, sites containing a high proportion of FR preceding iEEG spikes correlate with brain areas where seizures begin more than solitary FR (p<1e-5). Despite this correlation, removal of these sites does not guarantee seizure freedom. These results are consistent with the hypothesis that FR preceding EEG spikes reflect an increase in local excitability that primes EEG spike discharges preferentially in the seizure onset zone and that epileptogenic brain regions are necessary, but not sufficient, for initiating interictal epileptiform discharges.
Anesthesiologists, Certified Registered Nurse Anesthetists and Anesthesiology Assistants: Overvaluation By Providers Or Undervaluation By Payers
Authors: Gupta Deepak
Published: March 2023

Background

Considering that National Health Expenditures (NHE) in the United States (U.S.) have mounted to 4,124 billion dollars with 593.1 billion dollars (14.4%) spent on physician services in 2020, it will be interesting to see how specialties fared in terms of percentage of billed dollars approved to reflect on how NHE would have been faring if 100% billed dollars were approved.

Objectives

Whether (and by how much), as compared to other healthcare providers in the U.S., anesthesia providers (anesthesiologists, certified registered nurse anesthetists (CRNAs) and anesthesiology assistants) are being differently reimbursed in terms of approved dollars by Centers for Medicare & Medicaid Services (CMS) as percentages of dollars billed by providers. Materials and Methods: The source of data about approved dollars by CMS as percentages of dollars billed by providers is Denniston Data Inc. at Provider Ranking System (PRS) which provided deidentified cumulative tabulated data sourced from CMS public access reimbursement data for the years 2012-2020 to the author who, as a private citizen, had enrolled for annually renewed subscription to PRS.

Results

Among the 73 specialties whose data was complete for all the nine years (2012-2020), the top three specialties with highest percentages of billed dollars which were approved (56% to 76%) were almost consistently chiropractic, optometry and clinical psychologist respectively and anesthesiology assistants, CRNAs and anesthesiologists respectively were consistently the bottom three specialties with lowest percentages of billed dollars which were approved (11% to 18%).

Conclusion

During 2012-2020, anesthesia providers got 11%-18% of their billed dollars approved by CMS and yet anesthesiologists averaging almost top 1% wages (99th percentile) nationally with CRNAs averaging top 5% wages (95th percentile) nationally pose the question what their wages would have been if their billed dollars were 100% approved by CMS.
A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell derived cardiomyocytes
Authors: Seguret Magali , Davidson Patricia , Robben Stijn , Jouve Charlène , Pereira Céline , Lelong Quitterie , Deshayes Lucille , Cerveau Cyril , Le Berre Maël , Rodrigues Ribeiro Rita S. , Hulot Jean-Sébastien
Published: March 2023

We developed a 96-well plate assay which allows fast, reproducible and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (PEG) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above. Tissues started contracting around the pillar at D1 and their fractional shortening increased until D7, reaching a plateau at 25±1%, that was maintained up to 14 days. The average stress, calculated from the compaction of the central pillar during contractions, was 1.4±0.4 mN/mm2. The cardiac constructs recapitulated expected inotropic responses to calcium and various drugs (isoproterenol, verapamil) as well as the arrhythmogenic effects of dofetilide. This versatile high-throughput assay allows multiple in situ mechanical and structural read-outs.
Effectiveness of Nirmatrelvir-Ritonavir for the treatment of patients with mild to moderate COVID-19 and at high risk of hospitalization: Systematic review and meta-analyses of observational studies
Authors: Miranda Souza Kathiaja , Carrasco Gabriela , Rojas-Cortés Robin , Michel Barbosa Mariana , Henrique Ferreira Bambirra Eduardo , Luis Castro José , Alvares-Teodoro Juliana
Published: March 2023

Objective

To assess the effectiveness of nirmatrelvir-ritonavir in the treatment of outpatients with mild to moderate COVID-19 who are at higher risk of developing severe illness, through a systematic review with meta-analyses of observational studies.

Methods

A systematic search was performed, in accordance with the Cochrane search methods, to identify observational studies that met the inclusion criteria. The outcomes of mortality and hospitalization were analyzed. Search was conducted on PubMed, EMBASE, and The Cochrane Library. Two reviewers independently screened references, selected the studies, extracted the data, assessed the risk of bias using ROBINS-I tool and evaluated the quality of evidence using the GRADE tool. This study followed the PRISMA reporting guideline.

Results

A total of 16 observational studies and 1,482,923 patients were finally included. The results of the meta-analysis showed that in comparison to standard treatment without antivirals, nirmatrelvir-ritonavir reduced the risk of death by 62% (OR= 0.38; 95% CI: 0.30-0.46; moderate certainty of evidence). In addition, a 53% reduction in the risk of hospital admission was observed (OR = 0.47; 95% CI: 0.36–0.60, with very low certainty of evidence). For the composite outcome of hospitalization and/or mortality, there was a 56% risk reduction (OR=0.44; 95% CI: 0.31-0.64, moderate certainty of evidence).

Conclusion

The results suggest that nirmatrelvir-ritonavir could be effective in reducing mortality and hospitalization. The results were valid in vaccinated or unvaccinated high-risk individuals with COVID-19. Data from ongoing and future trials may further advance our understanding of the effectiveness and safety of nirmatrelvir-ritonavir and help improve treatment guidelines for COVID-19.
Rare variants inPPFIA3cause delayed development, intellectual disability, autism, and epilepsy
Authors: Paul Maimuna S. , Michener Sydney L. , Pan Hongling , Pfliger Jessica M. , Rosenfeld Jill A. , Lerma Vanesa C. , Tran Alyssa , Longley Megan A. , Lewis Richard A. , Weisz-Hubshman Monika , Bekheirnia Mir Reza , Bekheirnia Nasim , Massingham Lauren , Zech Michael , Wagner Matias , Engels Hartmut , Cremer Kirsten , Mangold Elisabeth , Peters Sophia , Trautmann Jessica , Mester Jessica L. , Guillen Sacoto Maria J. , Person Richard , McDonnell Pamela P. , Cohen Stacey R. , Lusk Laina , Cohen Ana S.A. , Pichon Jean-Baptiste Le , Pastinen Tomi , Zhou Dihong , Engleman Kendra , Racine Caroline , Faivre Laurence , Moutton Sébastien , Pichon Anne-Sophie Denommé- , Schuhmann Sarah , Vasileiou Georgia , Russ-Hall Sophie , Scheffer Ingrid E. , Carvill Gemma L. , Mefford Heather , Network Undiagnosed Diseases , Bacino Carlos A. , Lee Brendan H. , Chao Hsiao-Tuan
Published: March 2023

PPFIA3encodes the Protein-Tyrosine Phosphatase, Receptor-Type, F Polypeptide-Interacting Protein Alpha-3 (PPFIA3), which is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family involved in synaptic vesicle transport and presynaptic active zone assembly. The protein structure and function are well conserved in both invertebrates and vertebrates, but human diseases related to PPFIA3 dysfunction are not yet known. Here, we report 14 individuals with rare mono-allelicPPFIA3variants presenting with features including developmental delay, intellectual disability, hypotonia, autism, and epilepsy. To determine the pathogenicity ofPPFIA3variantsin vivo, we generated transgenic fruit flies expressing either human PPFIA3 wildtype (WT) or variant protein using GAL4-UAS targeted gene expression systems. Ubiquitous expression with Actin-GAL4 showed that thePPFIA3variants had variable penetrance of pupal lethality, eclosion defects, and anatomical leg defects. Neuronal expression with elav-GAL4 showed that thePPFIA3variants had seizure-like behaviors, motor defects, and bouton loss at the 3rdinstar larval neuromuscular junction (NMJ). Altogether, in the fly overexpression assays, we found that thePPFIA3variants in the N-terminal coiled coil domain exhibited stronger phenotypes compared to those in the C-terminal region. In the loss-of-function fly assay, we show that the homozygous loss of flyLiprin-α leads to embryonic lethality. This lethality is partially rescued by the expression of humanPPFIA3WT, suggesting human PPFIA3 protein function is partially conserved in the fly. However, thePPFIA3variants failed to rescue lethality. Altogether, the human and fruit fly data reveal that the rarePPFIA3variants are dominant negative loss-of-function alleles that perturb multiple developmental processes and synapse formation.
mTOR inhibition improves the formation of functional T cell memory following COVID-19 vaccination of kidney transplant recipients
Authors: Perkins Griffith B. , Tunbridge Matthew J. , Chai Cheng Sheng , Hope Christopher M. , Yeow Arthur Eng Lip , Salehi Tania , Singer Julian , Shi Bree , Masavuli Makutiro G. , Mekonnen Zelalem Addis , Garcia-Valtanen Pablo , Kireta Svjetlana , Johnston Julie K. , Drogemuller Christopher J. , Sim Beatrice Z. , Spencer Shane M. , Sallustio Benedetta C. , Comerford Iain , Bouras George , Weiskopf Daniela , Sette Alessandro , Aggarwal Anupriya , Milogiannakis Vanessa , Akerman Anouschka , Turville Stuart , Hurtado Plinio R. , Ying Tracey , Hissaria Pravin , Barry Simon C. , Chadban Steven J. , Grubor-Bauk Branka , Coates P. Toby
Published: March 2023

Inadequate immune response to vaccination is a long-standing problem faced by immunosuppressed kidney transplant recipients (KTRs), requiring novel strategies to improve vaccine efficacy. In this study, the potential of mechanistic target of rapamycin inhibitors (mTORi) to improve T cell responses to COVID-19 vaccination was investigated. Following primary vaccination with adenoviral (ChAdOx1) or mRNA (BNT162b2) COVID-19 vaccines, KTRs receiving rapamycin demonstrated T cell responses greater than those of healthy individuals, characterized by increased frequencies of vaccine-specific central memory, effector memory and TEMRAT cells, in both the CD4+and CD8+compartments. Relative to standard-of-care triple therapy, mTORi-based therapy was associated with a 12-fold greater functional T cell response to primary vaccination of KTRs. The use of rapamycin to augment T cell responses to COVID-19 booster (third dose) vaccination was next investigated in a randomized, controlled trial. Immunosuppression modification with rapamycin was feasible and well-tolerated, but did not improve vaccine-specific T cell responses in this cohort. To understand the parameters for effective use of rapamycin as a vaccine adjuvant, mice were treated with rapamycin before primary or booster vaccination with ancestral and/or Omicron COVID-19 vaccines. Supporting the findings from KTRs, significant enhancement of functional and stem-like memory T cell responses was observed when rapamycin was administered from the time of primary, rather than booster, vaccination. Collectively, a positive effect of mTOR inhibitors on vaccine-induced T cell immunity against COVID-19 in humans was demonstrated.

One Sentence Summary

Rapamycin use at the time of primary COVID-19 vaccination augments the formation of functional, vaccine-specific T cell memory in immunosuppressed kidney transplant recipients.
Timing and magnitude of the next wave of COVID-19 in China: lessons from 189 countries and territories
Authors: Niu Beidi , Ji Shuyi , Zhao Shi , Lei Hao
Published: March 2023

Because of the fading immunity to COVID-19 and continuous evolution of the SARS-CoV-2 Omicron variants, the next epidemic wave of COVID-19 is inevitable. The Omicron variant has been the cause of several waves of the COVID-19 epidemics in the majority of countries. Thus, lessons from other countries may provide guidance regarding the timing and magnitude of the next COVID-19 wave of the pandemic in China. In this study, the COVID-19 surveillance data from 189 countries that experienced two or more waves of the SARS-CoV-2 Omicron variant were analysed. The median peak timing between the first and second/third waves of the SARS-CoV-2 Omicron variant was 164/243 days. The peaks of the second and third waves were much lower than that of the first wave. The median relative peaks of the second and third compared with the first waves were 14.5% and 11.2%, respectively. The time window between the peak timings of the first and second waves showed no significant rank correlation with the five socioeconomic factors included in this study. However, the relative peak of the second wave increased significantly with gross domestic product per capita (P<0.001), urbanisation rate (P=0.003), population density (P=0.007), and proportion of older adults >65 years (P<0.001), although decreased significantly with the proportion of 0-14 teenagers (P<0.001). In summary, the historical situations and progression of COVID-19 outbreaks in other countries may inform the risk assessment of incoming outbreaks in mainland China; however, the timing and magnitude of the next COVID-19 wave may also be influenced by several unknown factors, including rapid viral evaluation of SARS-CoV-2
Impact of marginal donor to marginal recipient kidney transplant on delayed graft function and outcome
Authors: Bocchi Federica , Beldi Guido , Kuhn Christian , Storni Federico , Müller Nathalie , Sidler Daniel
Published: March 2023

The demographics of donor and recipient candidates for kidney transplantation (KT) have substantially changed. Recipients tend to be older and polymorbid and KT to marginal recipients is associated with delayed graft function (DGF), prolonged hospitalization, inferior long-term allograft function, and poorer patient survival. In parallel, donors are also older, suffer from several comorbidities, and donations coming from circulatory death (DCD) predominate, which in turn leads to early and late complications. However, it is unclear how donor and recipient risk factors interact. In this retrospective cohort study, we assess the overall and combined impact of a KT from marginal donors to marginal recipients. We focused on: 1) DGF; 2) hospital stay and number of dialysis days after KT and 3) allograft function at 6 months. Among the 369 KT included, the overall DGF rate was 25% (n = 92) and median time from reperfusion to DGF resolution was 7.8 days (IQR: 3.0-13.8 days). Overall, patients received four dialysis sessions (IQR: 2-8). The combination of pre-KT anuria (< 200 ml/24h, 32%) and DCD procurement (14%) was significantly associated with DGF, length of hospital stay, and severe perioperative complications, predominantly in recipients 50 years and older.