United States

Background: Peripheral nerve injuries present a major challenge due to limited functional and sensory recovery with current treatments. Human amniotic and umbilical cord membranes show promise in tissue regeneration but are limited by the quantity and variety of growth factors they release. This study evaluates the efficiency of umbilical cord and placental membranes as biological scaffolds for lysozyme delivery. The assessment includes investigating the binding capacity of double-walled microspheres (DWMS) loaded with lysozyme to the membranes and characterizing the subsequent lysozyme release kinetics.

Methods: Lysozyme, chosen for its similar properties to glial-derived neurotrophic factor (GDNF), was encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA)/poly lactic acid (PLA) microspheres using a water-oil-water emulsion solvent evaporation technique. The binding capacity and release kinetics of lysozyme from DWMS bound to cryopreserved and lyophilized umbilical cord and placental membranes were assessed over 1, 6, and 24 hours, using the Bicinchoninic Acid assay.

Results: Our findings demonstrated that lysozyme-loaded DWMS bound similarly to both cryopreserved and lyophilized umbilical cord membranes. However, placental membranes soaked for 1 and 24 hours exhibited significantly higher lysozyme release (p&lt;0.05) compared to non-loaded membranes. Notably, placental membranes soaked for 24 hours released 1.57 times more lysozyme than those soaked for 1 hour at the 72-hour mark. Furthermore, lysozyme release from both cryopreserved and lyophilized umbilical cord membranes was significantly greater after 6 and 24 hours of DWMS treatment compared to placental membranes (p&lt;0.05). Cryopreserved umbilical cord membranes specifically showed a greater release than lyophilized membranes when assessed at these time points (p&lt;0.05).

Conclusion: Placental membranes demonstrated superior efficacy as scaffolds for lysozyme-loaded DWMS delivery, particularly with longer incubation periods. Cryopreserved umbilical cord membranes were more effective than lyophilized ones, suggesting that preservation methods impact therapeutic potential. These findings highlight a novel approach for enhancing peripheral nerve regeneration through improved drug delivery systems.


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Umbilical Cord &amp; Placental Membranes as Biological Scaffolds for Drug Delivery in Nerve Regeneration

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Background: Peripheral nerve injuries present a major challenge due to limited functional and sensory recovery with current treatments. Human amniotic and umbilical cord membranes show promise in tissue regeneration but are limited by the quantity and variety of growth factors they release. This study evaluates the efficiency of umbilical cord and placental membranes as biological scaffolds for lysozyme delivery. The assessment includes investigating the binding capacity of double-walled microspheres (DWMS) loaded with lysozyme to the membranes and characterizing the subsequent lysozyme release kinetics.

Methods: Lysozyme, chosen for its similar properties to glial-derived neurotrophic factor (GDNF), was encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA)/poly lactic acid (PLA) microspheres using a water-oil-water emulsion solvent evaporation technique. The binding capacity and release kinetics of lysozyme from DWMS bound to cryopreserved and lyophilized umbilical cord and placental membranes were assessed over 1, 6, and 24 hours, using the Bicinchoninic Acid assay.

Results: Our findings demonstrated that lysozyme-loaded DWMS bound similarly to both cryopreserved and lyophilized umbilical cord membranes. However, placental membranes soaked for 1 and 24 hours exhibited significantly higher lysozyme release (p<0.05) compared to non-loaded membranes. Notably, placental membranes soaked for 24 hours released 1.57 times more lysozyme than those soaked for 1 hour at the 72-hour mark. Furthermore, lysozyme release from both cryopreserved and lyophilized umbilical cord membranes was significantly greater after 6 and 24 hours of DWMS treatment compared to placental membranes (p<0.05). Cryopreserved umbilical cord membranes specifically showed a greater release than lyophilized membranes when assessed at these time points (p<0.05).

Conclusion: Placental membranes demonstrated superior efficacy as scaffolds for lysozyme-loaded DWMS delivery, particularly with longer incubation periods. Cryopreserved umbilical cord membranes were more effective than lyophilized ones, suggesting that preservation methods impact therapeutic potential. These findings highlight a novel approach for enhancing peripheral nerve regeneration through improved drug delivery systems.

Umbilical Cord & Placental Membranes as Biological Scaffolds for Drug Delivery in Nerve Regeneration

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Using Digested and Lyophilized Bone Matrices for Enhanced Retention and Sustained Release of BMP-2 for Bone Regeneration
Background
Human recombinant bone morphogenetic protein 2 (rhBMP-2) is an FDA-approved growth factor that promotes bone formation but includes safety risks like inflammation and ectopic bone formation. Current research aims to enhance rhBMP-2 delivery strategies, as prolonged, controlled release improves bone healing and reduces side effects compared to short-term release. Currently, collagen sponges are often used for the delivery of rhBMP-2 but suffer from poor structural stability and inadequate release profiles. A previous study developed a sponge- like matrix from decellularized, demineralized, and enzymatically digested porcine bone, demonstrating biocompatibility and bone regeneration. In this study, we created a similar digested and lyophilized bone matrix (DLBM) while adding synthetic BMP2 (sBMP2) and stabilizing with glutaraldehyde (GL) crosslinking in the hopes of creating a safe and efficacious BMP2 delivery system.
Methods
The digested and lyophilized bone matrix (DLBM) was fabricated using established methods, with synthetic BMP2 peptide (sBMP2) infused and stabilized through glutaraldehyde (GL) crosslinking. This DLBM/BMP2/GL construct was compared to a DLBM/BMP2 scaffold without crosslinking. Over four weeks, we assessed in vitro degradation and BMP2 release of both constructs at various time points. The in vivo efficacy of the DLBM/BMP2/GL scaffold was evaluated using a non-healing tibial defect model in a rat model, analyzing bone growth via CT and histology after eight weeks.
Results
In vitro degradation experiments showed that the DLBM/BMP2/GL scaffold retained significantly more of its original mass (~40%) compared to the non-GL scaffold (~17%). Additionally, we found significantly higher retention of sBMP2 in the DLBM/BMP2/GL scaffold at all time points. CT analysis and histological examinations further indicated that the DLBM/BMP2/GL scaffold exhibited enhanced regenerative capability over the DLBM scaffold in vivo, demonstrating improved efficacy.

Conclusion
Our study underscores the potential of the DLBM/BMP2/GL scaffold as a promising platform for bone tissue engineering. We found that a sponge-like matrix, comprised of the digested and lyophilized bone matrix (DLBM) of pig bone, could effectively retain BMP2 peptide after chemical crosslinking using glutaraldehyde (DLBM/BMP2/GL). Further, we found a much more sustainable and controllable release profile of the BMP2 from the DLBM/BMP2/GL matrix when compared to the same BMP2-infused DLBM structure without any chemical crosslinking applied. Our in vivo evaluations demonstrate the improved biocompatibility, osteogenicity, and bone regenerative capacity of the DLBM/BMP2/GL scaffold compared to DLBM alone. Overall, our findings contribute to advancing innovative strategies for optimizing bone tissue engineering outcomes, thereby enhancing clinical efficacy and safety in bone repair and regeneration applications.

Using Digested and Lyophilized Bone Matrices for Enhanced Retention and Sustained Release of BMP-2 for Bone Regeneration

Background 
Vaginal rejuvenation refers to a variety of procedures that aim to improve genitourinary function or cosmetics. Local estrogen is the current standard of care to address complaints of vulvovaginal atrophy and vaginal laxity. However, energy-based treatments have become an emerging treatment option. Following an FDA statement in 2018 expressing concern over alleged lack of supporting evidence, laser and radiofrequency treatment of the vagina remains somewhat controversial.
Methods
The PubMed, EMBASE, and CENTRAL databases were queried for English-language studies published between November 2018 and June 2024 with terms associated with vaginal rejuvenation, including but not limited to, “vaginal” or “vagina” and “genitourinary syndrome of menopause” or “rejuvenation” or “vulvovaginal atrophy” or “vaginal atrophy”. Searches also included “laser” or “erbium-doped yttrium aluminum garnet” or “diode” or “carbon dioxide” or “CO2” or “radiofrequency” or “thermal”. 
Studies were included if they included at least one patient 18 years of age and older undergoing laser or radiofrequency therapy of the vagina for a specific vaginal or lower urinary complaint. Studies with purely cosmetic indications were excluded, as were studies with combined therapies, animal or cadaver models, or participants with active infectious or neoplastic pathology of the genitourinary system. Additionally, studies must have been available in full text and reported clinical outcome data, including standardized measures of patient reported outcomes and qualitative symptom data. Studies that did not explicitly report the presence or absence of adverse effects were excluded. 
Results
A total of 1374 studies were identified (EMBASE=792, PubMed=376, CENTRAL=206). 337 duplicates were excluded and 1059 studies were ultimately screened. 77 studies were included with a total number of 5,143 patients. 27 of these were randomized controlled trials, 40 were prospective interventional studies, and 10 were retrospective studies. A majority (79%) used laser treatment for vaginal rejuvenation. Indication for rejuvenation was stress urinary incontinence in 18 studies and genitourinary syndrome of menopause or its related symptoms in 
the remaining. 93.5% (N=72/77) of the studies reported improvements in patient-reported outcomes. Just under half (49.4%) of the studies reported at least minor or transient adverse effects of the treatment. These included vaginitis, leukorrhea, vaginal pain, dysuria, and urinary tract infection.
Conclusion 
Laser and radiofrequency treatment of the vagina has demonstrated improvement in patientreported outcomes for genitourinary symptoms associated with vaginal atrophy and urinary incontinence. Adverse effects of vaginal rejuvenation in the literature are minor, suggesting that this is a safe and effective option for patients with post-menopausal complaints requiring vaginal rejuvenation.

Vaginal Rejuvenation by Laser or Radiofrequency: A Systematic Review of the 
Literature

Background: Reduced sensation frequently occurs after reduction mammaplasty. However, the degree of sensation can vary among individuals. The aim of this study is to assess how body mass index (BMI) and weight of breast tissue excised during reduction mammaplasty affects postoperative sensation. 

Methods: Patients undergoing reduction mammaplasty with superomedial or superior pedicle and Wise pattern incisions were prospectively followed. One month after surgery, neurosensory testing was completed using a pressure-specified sensory device to record sensation on a scale from 0 to 100, where higher values indicate greater sensitivity. An average sensation score was calculated per breast from 9 breast regions. Patient demographics, BMI, and weight of breast tissue excised were recorded. Linear regression analysis was run to predict postoperative sensation from BMI, specimen weight, and ratio of BMI to specimen weight. Student t-test were used to detect differences between BMI groups (BMI <30 vs. BMI >30) and specimen weight (weight <1,000 g vs. weight >1,000 g). 

Results: Sensory testing was completed on 28 breasts in 14 patients. Multiple linear regression analysis revealed that specimen weight (t=-2.59, p=0.02) was a significant predictor of postoperative sensation, but BMI was not (t=-0.32, p=0.75). The ratio of BMI to specimen weight was also a significant predictor of postoperative sensation (t=2.65, p=0.01). Our result is robust to the normal assumption. Even using nonparametric Spearman’s coefficient test, the results remain significant. The Spearman’s Correlation coefficient was -0.46 for specimen weight (p=0.01) and 0.49 for ratio of BMI to specimen weight (p=0.01). A t-test revealed a significant difference in average postoperative sensation between patients with less than 1,000 g excised (68.39 ± 15.47) and 1,000 g or more excised (53.17 ± 18.93) (p=0.03). There was no difference between average postoperative sensation in obese (64.97 ± 16.74) and non-obese patients (60.28 ± 20.07) (p=0.51). 

Conclusions: This study revealed that specimen weight was a predictor for postoperative sensation, with more tissue excised resulting in worse sensation. The ratio of BMI to specimen weight was also found to be a significant predictor, suggesting that specimen weight is predictive of sensation irrespective of BMI. These parameters can guide preoperative counseling and may suggest a benefit for nerve reinnervation in certain groups that need a larger amount of breast tissue excised during reduction. Future work will investigate how BMI and specimen weight affect long-term sensation following mammaplasty.

Weighing In: Predicting Postoperative Sensation After Breast Reduction

INTRODUCTION: Loneliness is associated with increased morbidity and mortality and has been considered the latest global health epidemic. The COVID-19 pandemic has further exacerbated loneliness across all age groups, particularly older adults who are more vulnerable to the negative effects of quarantining and social distancing. This study aims to assess the relationship between loneliness, depression, and suicidality among older adults during the COVID-19 pandemic using data from the All of Us (AoU) Research Program. 

METHODS: We analyzed cross-sectional data from the National Institutes of Health AoU Research Program, a research initiative encompassing diverse US residents. We focused on older adults aged 65 (N=17,084) who completed a COVID-19-related survey administered between May 2020 and February 2021. Participants were divided into quartiles based on their UCLA Loneliness Scale Short Form-8 scores. Descriptive statistics and chi-square tests were employed for demographic analysis, and logistic regression models were used to test associations between loneliness quartiles and both depression (via Patient Health Questionnaire-9 [PHQ-9] score 10) and suicidal ideation (via PHQ-9 item 9 positive response). The models were adjusted for age, gender, race, ethnicity, education, marital status, employment status, housing status, health insurance status, and social support rating.

RESULTS: Among the 17,084 older adult participants (mean [SD] age of 72.0 [5.3]), 55.0% were female, 89.8% identified as White, 2.1% identified as Hispanic, 66.9% were married, 72.0% were college graduates, 70.3% were retired, 7.8% met the criteria for moderate-severe depression, and 3.5% endorsed experiencing suicidal ideation. Individuals in the highest quartile of loneliness were more likely to be younger, female, have lower social support, and lack of marital, educational, housing, or insurance status (all ps<0.05). Compared to individuals in the 1st quartile of loneliness, those in the 2nd, 3rd, and 4th (highest) quartile of loneliness had adjusted odds ratios (aORs) of 2.42 (95% confidence interval [CI]:1.57-3.77), 7.91 (95% CI: 5.29-11.82), and 39.50 (95% CI: 26.76-58.30), respectively, of meeting criteria for moderate-severe depression. Similarly, participants in the 2nd, 3rd, and 4th quartile of loneliness had greater odds of suicidal ideation (aORs of 3.73 (95% CI: 1.64-5.52), 12.31 (95% CI: 5.69-26.59), and 65.48 (95% CI: 30.85-138.97), respectively).

CONCLUSION: 
Older adults in the highest quartile of loneliness were nearly 40 and 65-times more likely to be depressed and suicidal, respectively, during the COVID-19 pandemic. To our knowledge, this is the largest US population-level investigation of its kind, and our findings underscore the need for targeted interventions to mitigate loneliness.

Dose-Dependent Association of Loneliness with Depression and Suicidal Ideation Among Older Adults During the COVID-19 Pandemic

Background: Extended-release (XL) bupropion hydrochloride (HCl) received FDA approval for Major Depressive Disorder (MDD) in 2003 and for Seasonal Affective Disorder (SAD) in 2006. XL bupropion hydrobromide (HBr) (Aplenzin®) received FDA approval in 2008 for both MDD and SAD following demonstration of pharmacokinetic bioequivalence to XL bupropion HCl. However, no human clinical efficacy trials of XL bupropion HBr have been completed and none comparing it to XL bupropion HCl. We wanted to compare equivalent FDA-approved dosing of XL bupropion HBr to generic XL bupropion HCl in patients with Treatment-Resistant Depression (TRD). There is only one FDA-approved oral TRD combination medication, fluoxetine-olanzapine, that carries cardiometabolic side effects and sedation, and one approved adjunctive nasal spray, esketamine, that requires 2-hour in-office monitoring limiting access. 
Methods: We obtained informed consent from each patient prior to conducting a de-identified retrospective chart review of 30 adults with TRD (18 females, 12 males) who directly switched from their maximally tolerated dose of generic XL bupropion HCl, due to inadequate response and/or side effects, to an equivalent dose of XL bupropion HBr. PHQ-9 scales were administered by a blinded rater. 
Results: Patients had a mean age of 38.7 +/- 14.7 years, failed a mean of 4 +/- 2 antidepressants, and had a mean baseline PHQ-9 score of 20.9 +/- 4.3 prior to taking a mean XL bupropion HCl dose of 300 mg/day (range 150‒450 mg/day) for a mean duration of 88.8 weeks (range 4‒480 weeks). After 2 weeks on a mean XL bupropion HBr dose of 348 mg/day (range 174‒522 mg/day), these patients demonstrated improvement in PHQ-9 scores from a mean of 15.3 +/- 5.3 on XL bupropion HCl to a mean of 6.4 +/- 5.0 on XL bupropion HBr (t = −8.63, p < 0.00001). The most commonly encountered side effects with generic XL bupropion HCl were insomnia (21 patients), anxiety (19 patients), and gastrointestinal upset (2 patients), which resolved on XL bupropion HBr except for residual insomnia (3 patients). 96.7% of patients (29 of 30) chose to continue on XL bupropion HBr rather than change back to generic XL bupropion HCl.
Conclusion: Adult patients suffering from TRD experience rapid and significant improvement in mood with greater tolerability when switching from generic XL bupropion HCl to an equivalent dose of XL bupropion HBr. A further double-blind study could enable the first FDA-approved oral monotherapy for TRD.

Extended-Release Bupropion Hydrobromide for Treatment-Resistant Depression

Abstract

Objective: To analyze differences in impulsivity, emotional regulation, symptom severity, cognitive perofrmance, and presence of comorbid psychiatric conditions between focused and automatic subtypes of SPD.

Methods: 83 adults aged 18-65 with skin-picking disorder were enrolled at the University of Chicago and separated into four skin-picking subtype groups based on levels of focused/automatic picking scores on the Milwaukee Inventory for the Dimension of Adult Skini Picking . Each group completed the same assessments and ANOVA or Chi-Squared tests were used to analyze differences in clinical and neurocognitive outcomes. 

Results: Higher focused-picking scores were significantly associated with greater symptom severity, impairment, and presence of comorbid depression and ADHD. Differences in levels of automatic/focused picking did not seem to be associated with impulsivity, emotional/behavior regulations, or neurocognitive outcomes. 

Conclusion: The findings suggest that focused and automatic picking may not be particularly useful in subtyping SPD. Future research should examine whether classifying SPD subtypes based on focused/automatic pulling have statistical or clinical utility.

Picking Apart the Disorder: A Comparative Study of Focused and Automatic Skin Picking Disorder Subtypes

Background 

Transcranial Magnetic Stimulation (TMS) has consistently demonstrated safety and effectiveness in adults, particularly for treatment-resistant depression (TRD) and its potential application in generalized anxiety disorder (GAD). Although this FDA-approved method has been in use for over a decade, studies on TMS efficacy in geriatric and pediatric populations remain inconclusive. Our research explores TMS efficacy across different age groups to determine if certain populations respond more favorably. 

Methods 

Data was extracted from the Olympia Center for TMS & Psychiatry Electronic Health Record. 288 patients with TRD who completed 36 standard repetitive TMS or theta burst stimulation treatments between 2020 and 2023 were selected. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores were used to assess depression and anxiety severity before and after treatments. Patients were categorized into three age groups: ≤21 years (pediatrics), 22–64 years (adults), and ≥65 years (geriatrics). 

In a clinical setting, treatment response was defined as a 50% reduction in PHQ-9 or GAD-7 scores. The percentage of responders in each age group was calculated, and a Chi-square analysis was performed. Treatment efficacy was measured by averaging the initial and final PHQ-9 or GAD-7 scores and conducting a paired t-test for each age group. 

Results 

Out of 288 patients with TRD, 39 were pediatrics, 192 were adults, and 57 were geriatrics. Overall, 74% of participants responded to treatment: 51% of pediatrics, 77% of adults, and 81% of geriatrics (p-value 0.002). Improvement in mean PHQ-9 scores was observed overall and in each age group (p-values < 0.001). Among the 288 patients, 204 had initial GAD-7 scores ≥10, indicating co-existing moderate to severe anxiety. Of these, 26 were pediatrics, 151 were adults, and 27 were geriatrics. Overall, 54% responded to treatment for anxiety: 31% of pediatrics, 58% of adults, and 56% of geriatrics (p-value 0.03). Improvement in mean GAD-7 scores was observed overall and in each age group (p-values < 0.001). 

Conclusion 

TMS treatment produced clinically meaningful changes in depressive and anxiety symptom severity across all age groups. The evidence supports the potential of incorporating TMS as a routine adjunct to pharmacotherapy in treating depression and anxiety. This result is notable given the adverse effects associated with pharmacotherapy, including increased suicide risk with SSRI use in adolescents and polypharmacy among geriatric patients. Limitations of this study include the absence of sham groups for comparison and relatively small sample sizes for certain age demographics, which warrant consideration.

Pulses of Potential: Assessing the Efficacy of Transcranial Magnetic Stimulation Across Age Groups

Eating disorders (ED) are a group of psychiatric conditions that impair both physical health and psychosocial functioning. Anorexia nervosa (AN) is an ED characterized by an inability to maintain an adequate, healthy body weight, along with persistent disturbances in eating behavior and body image. AN is a disorder with considerable morbidity and mortality, with a weighted annual mortality rate of 5 per 1,000 person-years. Although AN can resolve acutely, many patients relapse soon after weight-restoring treatment and more than half of patients with AN show signs of the disorder for years. We believe that aberrant processing of social information is a key component that contributes to the development and maintenance of the disease. We hypothesized that a more negative view of both self and social environment in adolescent AN patients and increased sensitivity to negative social interaction contribute to the pathology of AN. The project followed a cohort of adolescents receiving treatment for AN as well as matched healthy controls (HC) recruited from two clinical sites: Children’s Medical Center Plano and Children’s Hospital of Pennsylvania. Clinical status assessments at baseline, 3 months, and 6 months were assessed through percent expected body weight (%EBW), responses on the 13-point abbreviated eating disorder examination questionnaire (EDEQ-13) and the 25-point abbreviated Revised Child Anxiety and Depression Scale (RCADS-25). Social self-report questionnaires at the three timepoints included an abbreviated 14-point Internal Personal Situational Attribution Questionnaire (IPSAQ), the Rosenberg Trait Self-Esteem Scale (RSES), and the Social Reward Questionnaire (SRQ). AN adolescents had significantly lower %EBW compared to HC (M = 80.28, M = 101.77, p <0.0001). Total EDEQ-13 scores at baseline were also significantly higher in the AN group compared to HC (M = 2.95, M = 1.40, p = 0.0003). The RSES score was significantly lower in the AN group compared to HC (M = 22.22, M = 30.62, p = 0.0038) and of the five subscale scores of the SRQ, the AN group had significantly higher scores for prosocial interactions compared to HC (M = 28.67, M = 26.39, p = 0.0362). Responses to these selected social questionnaires suggest that AN adolescents have lower global self-esteem and a tendency towards self-blame in negative social scenarios compared to their HC. Additionally, the AN group had a significantly higher SRQ prosocial interactions sub-scale score when compared to their healthy counterparts, reflecting a value of fairness and equality in social interactions.

Self-concept and Social Processing in Adolescents with Eating Disorders

Objectives: To assess if adolescent suicide in the United States changed with the onset of the COVID-19 pandemic, and if there are significant differences between demographics.
Hypothesis: Adolescent suicides in the US increased during the COVID-19 pandemic.
Methods: We analyzed national mortality data from the Centers for Disease Control and Prevention, National Center for Health Statistics, public database for adolescents (age 10-19) from January 2018 until December 2022. Monthly numbers of suicides (per 100,000 individuals) were extracted and stratified based on sex, race, and region of residency in the United States. Data were analyzed using fisher's exact test, Chi square test, Z-test, and correlation analysis to look for associations between groups.
Results:
Of the 14139 adolescent suicides per 100,000 individuals, in the 60 months analyzed, there were no significant differences in the total rate of suicides prior to and during COVID (z = 0.358, p = 0.358). However, suicide of Black adolescents increased (z = 4.157, p = 0), which correlated with Black adolescent all-cause mortality (r (59) = 0.41, p = 0.001), and with suicide of all Black individuals (r (59) = 0.43, p = 0.001). In contrast, suicide rates for White adolescents (z = -2.23, p = 0.025) and adolescents living in the Midwest (z = -2.21, p = 0.027) decreased.
Conclusions:
Although the rate of adolescent suicides did not change significantly during the COVID pandemic, suicides of White teens and Midwestern adolescents decreased, whereas Black adolescent suicides increased over the same period. This increase in suicide rate among Black teens was associated with increased all-cause mortality of Black adolescents and suicide rates of all Black individuals during the pandemic. While there has been an increase in access to and acceptance of mental health care recently, we need more tailored anti-suicide strategies to address the disparities faced by communities of color and specifically Black adolescents. 
Limitations:
Study limitations include data obtained, which are per 100,000 individuals, likely underestimating the true numbers of suicides and deaths. Moreover, as there have been multiple events and unmeasured factors that occurred during the COVID-19 pandemic, the study cannot identify specific causes resulting in the suicide and death rates.

White and Midwestern Adolescents Show Fewer Suicides than Black Adolescents During the COVID19 Pandemic When Compared to PrePandemic Numbers

Diffuse Alveolar Hemorrhage: Importance of Early Recognition and Treatment

Granulomatosis with Polyangiitis (GPA) is a small-vessel vasculitis classically associated with focal necrotizing vasculitis, necrotizing glomerulonephritis, and necrotizing granulomas in the lungs and upper airway. GPA can be classified as limited or severe. Those with severe disease were older at disease onset, had a higher likelihood of diffuse alveolar hemorrhage (DAH), and had a higher probability of previous thyroid disease. Common presentations of this disease are chronic sinusitis and perforation of the nasal septum, hematuria with red cell casts, cough, hemoptysis, and dyspnea. Renal involvement occurs in 77-85% throughout the disease course, while DAH occurs in 5-45% of patients. DAH is characterized by bleeding into the alveoli. It has a high mortality rate and requires supportive treatment and aggressive treatment of GPA.

We present the case of a 69-year-old male, who presented to the emergency department with generalized weakness and hematuria. The weakness progressed over several months to the point where the patient was fatigued and dyspneic with minimal exertion. The patient was found to have atrial fibrillation and renal insufficiency (creatinine of 3.6 with unknown baseline) and was admitted for further workup. Over the next few days, his renal function deteriorated (creatinine maximum: 8.2). The patient developed progressive dyspnea associated with hemoptysis and acute hypoxic respiratory failure. Chest x-ray (CXR) demonstrated pulmonary vascular congestion. The patient was started on broad-spectrum antibiotics on 1/1/24 and transferred to the ICU and hemodialysis was initiated. Repeat CXR showed no improvement after dialysis. The patient’s status deteriorated requiring intubation, vasopressors, and amiodarone. Workup revealed c-ANCA positivity and he was transferred to a referral center. Bronchoalveolar lavage revealed DAH secondary to GPA. The patient was treated with high-dose pulsed steroids (1 g Solumedrol, 5-day course) and transitioned to 80 mg prednisone. He was also started on cyclophosphamide. After 9 days the patient was extubated. Hemoglobin counts rebounded to 8.4-9 from previous levels of 6.9.

DAH is a rare but serious consequence of GPA associated with a mortality rate of 35-50%. Nearly two-thirds of patients require mechanical ventilation, and kidney involvement was not predictive of respiratory failure. Treatment focuses on supportive measures as well as treating the GPA. Current treatment includes high-dose pulsed steroids and rituximab or cyclophosphamide. Plasma exchange may be necessary. Long-term rituximab has also been shown to achieve higher remission rates than cyclophosphamide. Early recognition and initiation of treatment provide the best chances for survival.

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