Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

flepiMoP: The evolution of a flexible infectious disease modeling pipeline during the COVID-19 pandemic.

The COVID-19 pandemic led to an unprecedented demand for projections of disease burden and healthcare utilization under scenarios ranging from unmitigated spread to strict social distancing policies. In response, members of the Johns Hopkins Infectious Disease Dynamics Group developed flepiMoP (formerly called the COVID Scenario Modeling Pipeline), a comprehensive open-source software pipeline designed for creating and simulating compartmental models of infectious disease transmission and inferring parameters through these models. The framework has been used extensively to produce short-term forecasts and longer-term scenario projections of COVID-19 at the state and county level in the US, for COVID-19 in other countries at various geographic scales, and more recently for seasonal influenza. In this paper, we highlight how the flepiMoP has evolved throughout the COVID-19 pandemic to address changing epidemiological dynamics, new interventions, and shifts in policy-relevant model outputs. As the framework has reached a mature state, we provide a detailed overview of flepiMoP's key features and remaining limitations, thereby distributing flepiMoP and its documentation as a flexible and powerful tool for researchers and public health professionals to rapidly build and deploy large-scale complex infectious disease models for any pathogen and demographic setup.

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Left Ventricular Hypertrophy (ESES-LVH) Study: A Multicenter, Open-Label, Prospective, Interventional Study.

INTRODUCTION: In contrast to the antihypertensive effect of esaxerenone, there is little evidence of its cardioprotective effect. We investigated the efficacy and safety of esaxerenone in patients with uncontrolled hypertension and left ventricular hypertrophy taking a renin-angiotensin system inhibitor (RASi) or calcium-channel blocker (CCB). METHODS: This was a multicenter, open-label, exploratory study with a 24-week treatment period. Esaxerenone was orally administered at an initial dose of 2.5 mg/day (maximum dose: 5 mg/day). The primary endpoints were the change in morning home systolic blood pressure (BP)/diastolic BP and change and percentage change in left ventricular mass index (LVMI) from baseline to end of treatment (EOT). Key secondary endpoints included change from baseline in bedtime home and office BP, achievement rate of target BP, and safety. RESULTS: In total, 60 patients were enrolled. Morning home systolic/diastolic BP was significantly decreased from baseline to EOT in the total population (- 11.5/ - 4.7 mmHg, p < 0.001) and in both the RASi and CCB subcohorts (all p < 0.01). Significant reductions in bedtime home and office BP were shown in the total population and both subcohorts. LVMI was also significantly decreased from baseline to EOT in the total population (- 9.9 g/m2, - 8.5%, both p < 0.001) and both subcohorts (all p < 0.05). The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 35.0% and 3.3%, respectively; most were mild or moderate. No new safety concerns were identified. CONCLUSION: Esaxerenone showed favorable antihypertensive and cardioprotective effects and safety in hypertensive patients with cardiac hypertrophy. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs071190043).

Truncated GPNMB, a microglial transmembrane protein, serves as a scavenger receptor for oligomeric ß-amyloid peptide1-42 in primary type 1 microglia.

Glycoprotein non-metastatic melanoma protein B (GPNMB) is up-regulated in one subtype of microglia (MG) surrounding senile plaque depositions of amyloid-beta (Aß) peptides. However, whether the microglial GPNMB can recognize the fibrous Aß peptides as ligands remains unknown. In this study, we report that the truncated form of GPNMB, the antigen for 9F5, serves as a scavenger receptor for oligomeric Aß1-42 (o-Aß1-42 ) in rat primary type 1 MG. 125 I-labeled o-Aß1-42 exhibited specific and saturable endosomal/lysosomal degradation in primary-cultured type 1 MG from GPNMB-expressing wild-type mice, whereas the degradation activity was markedly reduced in cells from Gpnmb-knockout mice. The Gpnmb-siRNA significantly inhibits the degradation of 125 I-o-Aß1-42 by murine microglial MG5 cells. Therefore, GPNMB contributes to mouse MG's o-Aß1-42 clearance. In rat primary type 1 MG, the cell surface expression of truncated GPNMB was confirmed by a flow cytometric analysis using a previously established 9F5 antibody. 125 I-labeled o-Aß1-42 underwent endosomal/lysosomal degradation by rat primary type 1 MG in a dose-dependent fashion, while the 9F5 antibody inhibited the degradation. The binding of 125 I-o-Aß1-42 to the rat primary type 1 MG was inhibited by 42% by excess unlabeled o-Aß1-42 , and by 52% by the 9F5 antibody. Interestingly, the 125 I-o-Aß1-42 degradations by MG-like cells from human-induced pluripotent stem cells was inhibited by the 9F5 antibody, suggesting that truncated GPNMB also serve as a scavenger receptor for o-Aß1-42 in human MG. Our study demonstrates that the truncated GPNMB (the antigen for 9F5) binds to oligomeric form of Aß1-42 and functions as a scavenger receptor on MG, and 9F5 antibody can act as a blocking antibody for the truncated GPNMB.

Knee extension deficit during gait and knee extensor weakness persisting after saucerization and repair of discoid lateral meniscus tears.

BACKGROUND: Physical function and knee kinematics recovery after discoid lateral meniscus (DLM) tear surgery are essential for a better prognosis. However, these alterations remain unclear. Therefore, this study aimed to investigate changes in physical function and knee kinematics following saucerization and DLM tear repair. METHODS: We enrolled 16 patients who underwent saucerization and DLM tear repair. Postoperative changes in knee kinematics during gait, and physical function, were evaluated at 3, 6, and 12 months. RESULTS: The peak flexion angle of the operated limb during weight acceptance was significantly higher than that of the contralateral limb at 3 (operated limb: 34.6 ± 8.9°, contralateral limb: 23.7 ± 8.3°; P < 0.01) and 6 months (operated limb: 32.1 ± 9.7°, contralateral limb: 24.6 ± 8.2°; P = 0.03) postoperatively, but not at 12 months (operated limb: 27.1 ± 7.1°, contralateral limb: 23.1 ± 9.5°; P = 0.22) postoperatively. The knee extensor strength of the operated limb was significantly lower than that of the contralateral limb at 3 (operated limb: 1.00 ± 0.59 Nm/kg, contralateral limb: 1.37 ± 0.59 Nm/kg; P = 0.01), 6 (operated limb: 1.22 ± 0.55 Nm/kg, contralateral limb: 1.48 ± 0.60 Nm/kg; P < 0.01), and 12 months (operated limb: 1.39 ± 0.57 Nm/kg, contralateral limb: 1.55 ± 0.64 Nm/kg; P = 0.04) postoperatively. CONCLUSION: Knee extension deficits and extensor weakness persisted at 6 months after saucerization and repair of DLM tears. Postoperative rehabilitation should be focused on knee extension function.

Posterior Papillary Muscle Suspension for Treating Systolic Anterior Motion in Hypertrophic Obstructive Cardiomyopathy.

Systolic anterior motion of the anterior mitral leaflet can persist after ventricular septal myectomy for obstructive hypertrophic cardiomyopathy, resulting in residual pressure gradients and mitral regurgitation. However, additional procedures for systolic anterior motion involving mitral valve leaflet suturing and resection may lead to future valve disease. Therefore, we adopted posterior papillary muscle suspension, a subvalvular procedure for functional mitral regurgitation, to treat systolic anterior motion without directly intervening in the mitral valve leaflets. Papillary muscle suspension toward the posterior mitral annulus moved the papillary muscles away from the interventricular septum and successfully eliminated the systolic anterior motion and midventricular pressure gradient. In terms of avoiding direct mitral interventions, this procedure is a viable option for systolic anterior motion, especially in cases of very mild mitral regurgitation.

Reconstruction of right ventricular outflow tract with severe calcification: lantern procedure.

Right ventricular outflow tract reconstruction is repeatedly required after the Rastelli procedure. However, standard right ventricular outflow tract reconstruction using direct anastomosis on the posterior right ventricular outflow tract wall is unfeasible in cases with severe calcification. Herein, we present a novel technique called the "lantern procedure," which can fix the prosthetic pulmonary valve without anastomosis to the calcified right ventricular outflow tract wall.

Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub.

Importance: COVID-19 continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Objective: To project COVID-19 hospitalizations and deaths from April 2023-April 2025 under two plausible assumptions about immune escape (20% per year and 50% per year) and three possible CDC recommendations for the use of annually reformulated vaccines (no vaccine recommendation, vaccination for those aged 65+, vaccination for all eligible groups). Design: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023-April 15, 2025 under six scenarios representing the intersection of considered levels of immune escape and vaccination. State and national projections from eight modeling teams were ensembled to produce projections for each scenario. Setting: The entire United States. Participants: None. Exposure: Annually reformulated vaccines assumed to be 65% effective against strains circulating on June 15 of each year and to become available on September 1. Age and state specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. Main outcomes and measures: Ensemble estimates of weekly and cumulative COVID-19 hospitalizations and deaths. Expected relative and absolute reductions in hospitalizations and deaths due to vaccination over the projection period. Results: From April 15, 2023-April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November-January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% PI: 1,438,000-4,270,000) hospitalizations and 209,000 (90% PI: 139,000-461,000) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% CI: 104,000-355,000) fewer hospitalizations and 33,000 (95% CI: 12,000-54,000) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI: 29,000-69,000) fewer deaths. Conclusion and Relevance: COVID-19 is projected to be a significant public health threat over the coming two years. Broad vaccination has the potential to substantially reduce the burden of this disease.

A Case of Successful Pregnancy and Delivery in a Chronic Renal Failure Patient with Membranoproliferative Glomerulonephritis and Preeclampsia-related Nephrotic Syndrome.

A 37-year-old woman with chronic kidney disease stage (CKD) G4 with membranoproliferative glomerulonephritis was hospitalized for nephrotic syndrome and hypertension due to superimposed preeclampsia at 27 weeks into her third pregnancy. Proteinuria did not worsen significantly after pulse steroid therapy. Delivery was induced at 30 weeks' gestation due to the maternal renal function and fetal growth. No obvious fetal complications other than preterm delivery were observed. In this case, we successfully managed a high-risk patient with membranoproliferative glomerulonephritis complicated by advanced CKD, nephrotic syndrome, and hypertension, which are independent risk factors for pregnancy complications.

Usefulness of 3D T1-Turbo Spin Echo Imaging for the Evaluation of Intracranial Stent Placement.

Objective: Evaluation of intracranial stent placement by MRI suffers the problems of signal artifacts during time-of-flight MRA (TOF-MRA). Therefore, angiographic examination is required for detailed intravascular assessment of the stent placement site. Recently, 3D T1-turbo spin echo (3D-TSE) has been developed for evaluation of carotid artery stent placement. We investigated the use of the 3D-TSE imaging method for the evaluation of intracranial vascular stent placement. Methods: The subjects consisted of nine patients who underwent intracranial vascular stent placement between April 2015 and December 2019. Postoperatively, the lumens of the placed stents were measured by TOF-MRA, DSA, and 3D-TSE imaging. Analysis was performed by type of stent and placement site. Results: The stents used were Neuroform Atlas (3 patients), LVIS (3 patients), LVIS Jr (2 patients), and Integrity (1 patient). TOF-MRA of the stent placement site showed defects in the image or poor visualization in all nine patients, whereas 3D-TSE imaging visualized the lumen at the stent indwelling site in all patients. The blood vessel diameter measured by the DSA and 3D-TSE imaging exhibited positive correlations regardless of the stent type and placement site. Conclusion: 3D-TSE imaging allows visualization of the lumen of the site of an intracranial vascular stent, regardless of the type of stent or the vessel. Thus, this method may be useful for evaluating the vascular lumen of a lesion.

Impact of the COVID-19 Pandemic on Adherence to Denosumab Therapy: A Single Center Study.

STUDY DESIGN: A retrospective comparative study of denosumab therapy adherence before and during the coronavirus disease 2019 (COVID-19) pandemic. PURPOSE: To evaluate the effect of the COVID-19 pandemic on denosumab therapy adherence in Japan. OVERVIEW OF LITERATURE: Denosumab is a monoclonal antibody for osteoporosis treatment. Delayed denosumab injections are associated with reduced treatment responses, which was a concern during the COVID-19 pandemic. METHODS: Participants included 376 patients who received denosumab (60 mg every 6 months) from January 2013 to June 2021. The time from therapy initiation to discontinuation was used to measure persistence, and that between initial and subsequent injections was used to determine adherence. The pandemic period was from March 2020 to December 2021. RESULTS: Patients were divided into those treated after March 2020 (pandemic group, n=244) and those who discontinued treatment before March 2020 (non-pandemic group, n=132). Non-persistent cases accounted for 154, including 24 (20%), 64 (19%), and 66 (53%) aged ≤59 years, 60-79 years, and ≥80 years, respectively. The overall persistence rate at 78 months was 59.2%. Postponed cases were significantly lower in the non-pandemic group than in the pandemic group (8% vs. 15%, p =0.042). Postponement with a delay of 1-2 months did not significantly differ between the two groups, but with a significant difference for a delay of ≥3 months (0% vs. 36%, p =0.024). CONCLUSIONS: Denosumab adherence remained constant but postponed cases significantly increased during the COVID-19 pandemic. Better communication by health providers on denosumab adherence and alternative administration may reduce dosing interruptions in similar pandemic situations.

Association between misoprostol and nonsteroidal anti-inflammatory drug-induced kidney injury: A systematic review and meta-analysis.

AIMS: Misoprostol is a prostaglandin E1 analogue that is used to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal disorders. The aim of this systematic review and meta-analysis was to evaluate whether use of misoprostol also decreases the risk of NSAID-induced kidney injury. METHODS: Randomized controlled trials that compared misoprostol vs. placebo in an adult patient population were selected. The primary outcome was kidney injury and the secondary outcome was severe adverse events. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twelve studies were eligible for inclusion. Although the rates of kidney injury and severe adverse events did not differ significantly between misoprostol and placebo, a posthoc subgroup analysis that excluded studies in which different NSAIDs were used in the misoprostol and placebo groups suggested that misoprostol may reduce the risk of NSAID-induced kidney injury (risk difference -0.09, 95% confidence interval -0.15 to -0.03, P < .01, I2  = 87%; evidence of very low certainty). CONCLUSION: There is limited evidence that misoprostol reduces the risk of NSAID-induced kidney injury. Misoprostol possibly contributes to reducing the risk of kidney injury associated with chronic NSAID use. The findings of this meta-analysis suggest further high-quality clinical trials are warranted.

Changes in medical costs for adolescent idiopathic scoliosis over the past 15 years.

Use of instrumentation has become widespread in spinal surgery due to intraoperative spinal cord monitoring, navigation, and improvement and development of implant materials. However, recent advances in spine surgery may have also led to an increase in medical costs. The purpose of this study is to investigate the trends of operative resource utilization and the costs of surgery for adolescent idiopathic scoliosis (AIS) over 15 years. Surgery for AIS was performed for 118 patients from January 2004 to December 2019 at national University Hospital. Trends were examined through retrospective calculation of the costs for outpatient, inpatient, and surgical services, and changes over time and the characteristics of fees were examined. Differences between groups were analyzed by Mann-Whitney U test and Student t-test. During the 15-year period, the length of hospital stay decreased, but costs for scoliosis surgery increased by 1.6 times and the total cost increased by 1.3 times. The fee for intensive care per day per person increased by 1.5 times. There were slight increases in MRI and CT fees, but no changes in fees for radiography, rehabilitation, subsequent visits, and prescriptions. New charges for medical supervision, medical clerk support, medical safety measures, and prevention of infection were added at different times during the 15-year period. Itemized costs related to surgery have increased with technological advances. Although these results only show changes in costs for AIS surgery, the findings indicate the challenges faced by the healthcare economy and the need for spine surgeons to understand medical costs.

Repetitive postoperative extubation failure due to dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy.

BACKGROUND: This report describes a case of dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy that led to repeated post-operative extubation failure. CASE PRESENTATION: A 43-year-old woman who had undergone tracheostomy 25 years previously was admitted to our intensive-care unit (ICU) after coronary artery bypass graft surgery. On postoperative day (POD) 0, she was extubated, but stridor was observed. We suspected upper airway obstruction and she was therefore reintubated. Before reintubation, urgent laryngotracheoscopy revealed dynamic inspiratory airway collapse and obstruction concomitant with subglottic stenosis. Preoperative computed tomography showed mild subglottic stenosis. Although intravenous corticosteroids were administered to prevent tracheal mucosal edema and a cuff leak test was confirmed to be negative, she developed extubation failure on POD6. On POD12, we performed tracheostomy to reduce mechanical irritation from the endotracheal tube. Mechanical ventilation was withdrawn and she discharged from the ICU. On POD33, her tracheostomy tube was removed and she remained clinically asymptomatic. CONCLUSIONS: We should be aware of the history of tracheostomy, especially at high tracheostomy sites, even in the absence of respiratory symptoms as risk factors for dynamic inspiratory airway collapse concomitant with subglottic stenosis contributing to repeated respiratory failure after extubation. J. Med. Invest. 70 : 301-305, February, 2023.

Advent of paradoxical flow after antihypertensive treatment in mid-ventricular obstructive hypertrophic cardiomyopathy - A case report.

A 69-year-old woman was admitted our hospital due to acute cerebral infarction. Transthoracic echocardiography showed massive left ventricular (LV) hypertrophy with small ventricles and normal LV ejection fraction. Apical 4-chamber and longitudinal images showed mild LV obstruction. After treatment for hypertension, her blood pressure decreased from 208/129 mmHg to 150/68 mmHg. Pulsed Doppler echocardiography revealed new paradoxical flow at the mid-ventricle. Decreased LV pressure following treatment with antihypertensive medications may have contributed to the development of early mid-ventricular obstruction and paradoxical flow in the present case. Learning objective: In mid-ventricular obstructive cardiomyopathy, apical aneurysm may be present and cause serious complications such as rupture of the apex and sudden death. In the present case, apical aneurysm newly developed after treatment for hypertension was suggested by advent of paradoxical flow. This case suggests that intraventricular hemodynamic change may become a trigger of paradoxical flow and apical aneurysm, becoming a risk of serious complication.

Altered expression of synaptic proteins and adhesion molecules in the hippocampus and cortex following the onset of diabetes in nonobese diabetic mice.

Mounting evidence links Type 1 diabetes (T1D) with cognitive dysfunction, psychiatric disorders, and synaptic alterations; however, the underlying mechanism remains unclear. Numerous synaptic proteins and synaptic adhesion molecules (SAMs) that orchestrate synaptic formation, restructuring, and elimination are essential for proper brain function. Currently, it is unclear whether the pathogenesis of T1D is related to the expression of synaptic proteins and SAMs. Here, we investigated whether T1D mice exhibited altered synaptic protein and SAM expression in the hippocampus and cortex. We discovered that T1D mice exhibited partially decreased levels of excitatory and inhibitory synapse proteins and SAMs, such as neurexins, neuroligins, and synaptic cell adhesion molecules. We also found that compared to control mice, T1D mice showed a marginal decrease in body weight and a significant increase in plasma glycoalbumin levels (a hyperglycemia marker). These results provide novel molecular-level insights into synaptic dysfunction in mice with T1D.

Management of Cervical Internal Carotid Artery Stenosis or Occlusion in Tandem Lesion with Acute Ischemic Stroke: Which Is More Appropriate Percutaneous Transluminal Angioplasty or Stent?

OBJECTIVE: Carotid artery stenting (CAS) is the established treatment strategy of the cervical internal carotid artery (cICA) stenosis, but its use for acute tandem lesions remains controversial. We investigated the clinical and procedural outcomes of management of cICA lesions and evaluated the risk factors for complications. METHODS: Fifty patients who underwent acute mechanical thrombectomy for tandem lesion between January 2014 and June 2022 were included. Treatment of the cICA lesion was classified into the CAS group or the non-CAS group. The risk factors for postoperative ischemic events or symptomatic intracranial hemorrhage (sICH) were analyzed. RESULTS: The CAS group included 36 patients (72%) and the non-CAS group 14 (28%). Postoperative complications were observed in 9 patients (18%). Thromboembolic complications occurred in 4 patients (29%) of the non-CAS group but in 1 patient (3%) of the CAS group. Severe calcification of the cICA (P = 0.04), non-CAS (P = 0.018), and more than 60% residual stenosis (P = 0.016) were significant risk factors associated with thromboembolic complications. sICH occurred in 4 patients (11%) of the CAS group but in none of the non-CAS group. More than 80% stenosis improvement was significantly associated with sICH (P = 0.049). Twenty-nine patients (58%) had a good clinical outcome at 90 days after onset. CONCLUSIONS: Acute CAS is effective for the management for cICA tandem lesions during mechanical thrombectomy, but care not to overextend may be important to reduce the risk of sICH. Severe calcification of the cICA may increase the risk of postoperative thromboembolic complications using non-CAS treatment.

MRI characteristics of disc degeneration after condoliase injection in young patients: A consecutive case series.

BACKGROUND: Lumbar disc herniation (LDH) results in low back pain due to nerve root compression caused by nucleus pulposus degeneration. Chemonucleolysis of the nucleus pulposus by injection of condoliase is less invasive than surgery, but may cause disc degeneration. The purpose of the study was to examine outcomes of condoliase injection in patients in their teens and twenties using Pfirrmann criteria on MRI. METHODS: A single-center retrospective study was performed in 26 consecutive patients (19 men, 7 women) who underwent condoliase injection (1 mL, 1.25 U/mL) for LDH and had MRI scans at 3 and 6 months. Cases with and without an increase in Pfirrmann grade at 3 months post-injection were included in groups D (disc degeneration, n = 16) and N (no degeneration, n = 10). Pain was measured on a visual analogue scale (VAS). MRI findings were evaluated using the % change in disc height index (ΔDHI). RESULTS: The mean age of the patients was 21.1 ± 4.1 years and 12 were <20 years old. At baseline, 4, 21 and 1 were in Pfirrmann grades II, III and IV. In group D, no case had a further increase in Pfirrmann grade from 3 to 6 months. Pain significantly decreased in both groups. There were no adverse events. MRI showed a significant decrease in ΔDHI from 100% pre-injection to 89.4 ± 9.7% at 3 months in all cases (p < 0.05). There was a significant recovery in ΔDHI in group D from 3 to 6 months (85.4 ± 9.3% vs. 86.7 ± 9.1%, p < 0.05). CONCLUSIONS: These results suggest that chemonucleolysis with condoliase is effective and safe for LDH in young patients. Progression of Pfirrmann criteria at 3 months post-injection occurred in 61.5% of cases, but disc degeneration showed recovery in these patients. A longer-term study of the clinical symptoms related to these changes is required.

Severe hypotension during junctional rhythm in a patient with multiple cerebral infarcts.

An 82-year-old woman with parkinsonism and Lewy body dementia was re-admitted to our hospital due to convulsions and the recurrence of cerebral infarction. Parasternal transthoracic echocardiography showed normal left ventricular wall thickness and wall motion. To treat marked bradycardia and hypotension, she underwent temporary pacing. However, she lost her consciousness, when her blood pressure could not be measured. Simultaneous electrocardiogram and blood pressure monitoring showed that systolic blood pressure decreased by almost 30 mmHg from sinus rhythm to junctional rhythm. In the present case of acute cerebral infarction, severe hypotension occurred during junctional rhythm possibly contributed by parkinsonism and Lewy body dementia. Learning objective: As patients with junctional rhythm usually have no or mild symptoms, there are no specific guidelines for its evaluation and treatment. However, severe symptoms such as hypotension, cerebral infarction, loss of consciousness, or breathlessness may occur in some cases. Holter electrocardiogram with 24-hour noninvasive blood pressure monitoring may be helpful in such severe cases.