Donor matters: Donor selection impact on hematopoietic stem cell transplantation outcomes in Hispanic patients with B-cell acute lymphocytic leukemia: Insights from a myeloablative HSCT study.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients. METHODOLOGY: This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023. RESULTS: Compared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036). CONCLUSION: Our data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients.

Case report: Pulse cyclophosphamide for treatment of multi-agent-refractory hepatic graft-versus-host disease.

Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] post-haploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as GVHD prophylaxis. A liver biopsy confirmed the diagnosis of GVHD, while other possible etiologies were excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment, we decided to administer 1,000 mg/m2 (1,600 mg) of cyclophosphamide ("pulse Cy"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized ("complete response") within 55 days without relapses. The patient remains in good health with no recurrence of hepatic GVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting.

Concordance of Next-Generation Sequencing and Multiparametric Flow Cytometry Methods for Detecting Measurable Residual Disease in Adult Acute Lymphoblastic Leukemia: Optimizing Prediction of Clinical Outcomes From a Single-Center Study.

INTRODUCTION: Detection of measurable residual disease (MRD) in adults with acute lymphoblastic leukemia (ALL) is a vital biomarker in risk prediction and treatment selection. Next-generation sequencing (NGS) offers greater sensitivity relative to multiparametric flow cytometry (MFC) and may be a better predictive tool for identifying ALL patients at risk of relapse. PATIENTS AND METHODS: This single-center retrospective study compares MRD detection by NGS versus MFC in 52 adult B- and T-ALL patients treated at our institution between 2018 and 2023. Pretreatment bone marrow samples were used for assay calibration, while post-treatment MRD assessment was completed up to 4.5 months after the first complete remission (CR1) using an MRD cutoff of 10-6 for distinguishing relapse risk. RESULTS: The 2-year cumulative incidence of relapse (CIR) among patients who were MRD positive using MFC and NGS was 39.5% and 46.2%, respectively. Unlike MFC, post-CR1 MRD positivity with NGS significantly predicted CIR (HR = 9.47, P = .028). In patients who were MRD negative by MFC, low levels of MRD detected by NGS distinguished patients at high risk of relapse (HR 10.3, P = .026, 2-year CIR 51.6%). CONCLUSION: Our data suggests that assessment of post-CR1 MRD using a highly sensitive NGS assay can identify ALL patients undergoing frontline therapy at increased risk of relapse and guide the use of adjuvant therapy.

Unique challenges to diagnosing sweet syndrome following induction chemotherapy for relapsed Acute Myeloid Leukemia (AML): A case and brief-review.

Background: Sweet Syndrome (SS) is a rare inflammatory skin condition characterized by the sudden appearance of tender, erythematous or violaceous papules, plaques, and nodules typically found on the face, neck, shoulder, upper extremities, and trunk. Often, SS is difficult to diagnose because of its various non-specific manifestations, including fever, arthralgia, myalgia and ocular involvement. In most cases described in literature, cutaneous and pulmonary symptoms of SS present in a concomitant manner. Several reported cases of pulmonary SS have shown that if left untreated, acute respiratory distress syndrome can ensue and progress to fatal respiratory failure. Case report: A 58-year-old female with acute myeloid leukemia (AML) secondary to chronic lymphocytic leukemia (CLL) presented with new nodular lesions, dyspnea, and fevers. Chest X-ray revealed pulmonary infiltrates. The patient developed new facial lesions and worsening hypoxic respiratory failure. Further infectious workup was negative. She was found to have SS with pulmonary involvement and initiated on high-dose intravenous (IV) steroids with marked clinical improvement. Conclusions: Major and minor criteria for the diagnosis of lung-associated SS should be carefully evaluated, especially when a biopsy is unavailable. The following case report describes the clinical course and outcomes from treatment for this patient.

Investigating the Link Between Low Back Ache, Abdominal Discomfort and Oliguria: A Unique Case of Histopathology-Proven Retroperitoneal Fibrosis.

Retroperitoneal fibrosis (RPF) is a rare condition characterized by systemic inflammation and the proliferation of fibroinflammatory tissues in the retroperitoneum. It may lead to the formation of a retroperitoneal mass and can encase the aorta, its branches and ureters. The pathogenesis of RPF is not fully known. We report a case of a 52-year-old male presented with low back ache, flank pain, swelling of legs, oliguria and features of obstructive uropathy, later diagnosed to be RPF. The mainstay of diagnosis includes blood workup, imaging and biopsy. The first line of treatment is corticosteroids. Surgical intervention is carried out when medical measures have failed or when contraindicated. Early diagnosis and prevention of complications is the key, and a high degree of suspicion is needed.

TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma.

The present study was the first comprehensive investigation of genetic mutation and expression levels of the p53 signaling genes in cutaneous melanoma through various genetic databases providing large datasets. The mutational landscape of p53 and its signaling genes was higher than expected, with TP53 followed by CDKN2A being the most mutated gene in cutaneous melanoma. Furthermore, the expression analysis showed that TP53, MDM2, CDKN2A, and TP53BP1 were overexpressed, while MDM4 and CDKN2B were under-expressed in cutaneous melanoma. Overall, TCGA data revealed that among all the other p53 signaling proteins, CDKN2A was significantly higher in both sun and non-sun-exposed healthy tissues than in melanoma. Likewise, MDM4 and TP53BP1 expressions were markedly greater in non-sun-exposed healthy tissues compared to other groups. However, CDKN2B expression was higher in the sun-exposed healthy tissues than in other tissues. In addition, various genes were expressed significantly differently among males and females. In addition, CDKN2A was highly expressed in the SK-MEL-30 skin cancer cell line, whereas, Immune cell type expression analysis revealed that the MDM4 was highly expressed in naïve B-cells. Furthermore, all six genes were significantly overexpressed in extraordinarily overweight or obese tumor tissues compared to healthy tissues. MDM2 expression and tumor stage were closely related. There were differences in gene expression across patient age groups and positive nodal status. TP53 showed a positive correlation with B cells, MDM2 with CD8+T cells, macrophages and neutrophils, and MDM4 with neutrophils. CDKN2A/B had a non-significant correlation with all six types of immune cells. However, TP53BP1 was positively correlated with all five types of immune cells except B cells. Only TP53, MDM2, and CDKN2A had a role in cutaneous melanoma-specific tumor immunity. All TP53 and its regulating genes may be predictive for prognosis. The results of the present study need to be validated through future screening, in vivo, and in vitro studies.

Asparaginase toxicity in Hispanic adult and pediatric patients with acute lymphoblastic leukemia: current understanding.

INTRODUCTION: Asparaginase is essential to chemotherapy regimens for acute lymphoblastic leukemia (ALL). Survival of patients with ALL has improved since incorporating asparaginase into chemotherapy backbones. Hispanic patients have a higher incidence of ALL than other ethnicities and suffer inferior outcomes. The inferior outcome of Hispanics is due to several factors, including the increased incidence of high-risk genetic subtypes and susceptibility to treatment-related toxicity. AREAS COVERED: We summarize the current knowledge of asparaginase-related toxicity by comparing their incidence between Hispanic and non-Hispanic patients. These toxicities include hypersensitivity, hepatotoxicity, pancreatitis, thrombosis, and hypertriglyceridemia. The PubMed database and Google Scholar were used to search for this review from October 2022 to June 2023. EXPERT OPINION: Except for hepatotoxicity and hypertriglyceridemia secondary to asparaginase-based treatments, which may develop more frequently among Hispanic patients with ALL, other toxicities were comparable between Hispanic and non-Hispanic patients. Nevertheless, studies with larger cohorts and more accurate capturing of Hispanic ethnicity should be conducted to fill the gaps in the current knowledge.

Allogenic Lenticular Implantation for Correction of Refractive Error and Ectasia: Narrative Review.

INTRODUCTION: Intrastromal lenticule implantation is a promising treatment option for corneal pathologies, from refractive error to ectasia. In this narrative review, we intend to feature up-to-date literature supporting the use of lenticular tissue, a compelling method that can be customized for a variety of applications, providing an additional source of donor tissue for treating corneal diseases. METHODS: We searched databases PubMed, Mendeley, and Scopus last accessed 10 May 2023, for literature on stromal lenticules and narrowed based on relevance. Review articles, animal studies, ex vivo studies, and book chapters were excluded, while assessable and relevant articles published in English were included. RESULTS: Storage methods from using fresh lenticules to dehydration have proven successful, with cryopreservation maintaining structure and cellular viability for up to 10 years. Successful use of lenticules for treatment of numerous pathologies including corneal ectasias, hyperopia, and presbyopia with additional insight into the treatment of corneal ulcers and perforations are highlighted in this narrative review. CONCLUSION: Lenticular implantation is an innovative and advantageous treatment for various ocular pathologies, offering increased bioavailability, flexibility, and customization for patients. They can treat previously untreatable diseases and serve as a replacement for synthetic implants, with promising outcomes worldwide. Lenticular implantation has the potential to become a leading approach in ophthalmologic surgery. Further studies should aim to provide evidentiary support for a standardization of lenticule banking.

Structural Diversity, Spectral Data, and Pharmacological Effects of Genus Nigella.

Nigella is one of the most studied plants because of its pharmacological properties like anti-parasitic, anti-inflammatory, neuro-protective, hepatoprotective, and anti-cancerous. In this study, about 20 species of the genus Nigella were reviewed and among them, N. damascene, N. glandulifera, and N. sativa are widely studied for their phytochemical and pharmacological effects. This review describes the phytochemical composition of the genus Nigella, which constitutes many of the compounds including alkaloids, flavonoids, saponins, and terpenoids. The extracts produced by using different solvents and the isolated compounds displayed a wide range of biological activity. These compounds were identified by different spectral techniques. The spectral detail of some advanced techniques including EIS-MS, UV/VIS, IR, 13 C-NMR, and 1 H-NMR of some important phytoconstituents of Nigella spp. has been compiled for the first time in this review which will be helpful to explore and further investigate the chemical composition of this genus.

Comparison between traumatic and atraumatic over-the-scope clips in patients with duodenal ulcer bleeding: a retrospective analysis with propensity score-based matching.

BACKGROUND AND AIMS: Over-the-scope clips (OTSCs) substantially improved the endoscopic armamentarium for the treatment of severe GI bleeding and can potentially overcome limitations of standard clips. Data indicate a superiority of OTSCs in hemostasis as first- and second-line therapy. However, the impact of the OTSC designs, in particular the traumatic (-t) or atraumatic (-a) type, in duodenal ulcer bleeding has not been analyzed so far. METHODS: This was a retrospective analysis of a prospective collected database from 2009 to 2020 of 6 German endoscopic centers. All patients who underwent emergency endoscopy and were treated using an OTSC for duodenal ulcer bleeding were included. OTSC-t and OTSC-a patients were compared by the Fisher exact test, χ2 test, or Mann-Whitney U test as appropriate. A propensity score-based 1:1 matching was performed to obtain equal distribution of baseline characteristics in both groups. RESULTS: The entire cohort comprised 173 patients (93 OTSC-a, 80 OTSC-t). Age, gender, anticoagulant therapy, Rockall score, and treatment regimen had similar distributions in the 2 groups. However, the OTSC-t group showed significantly more active bleeding ulcers (Forrest Ia/b). Matching identified 132 patients (66 in both groups) with comparable baseline characteristics. Initial bleeding hemostasis (OTSC-a, 90.9%; OTSC-t, 87.9%; P = .82) and 72-hour mortality (OTSC-a, 4.5%; OTSC-t, 6.0%; P > .99) were not significantly different, but the OTSC-t group revealed a clearly higher rate of recurrent bleeding (34.9% vs 7.6%, P < .001) and necessity of red blood cell transfusions (5.1 ± 3.4 vs 2.5 ± 2.4 concentrates, P < .001). CONCLUSIONS: For OTSC use, the OTSC-a should be the preferred option for duodenal ulcer bleeding.

Frequency of Smoking and Marginal Bone Loss around Dental Implants: A Retrospective Matched-Control Study.

This dental record-based retrospective study aimed to compare the marginal bone loss (MBL) around dental implants in a group of smokers in relation to a matched group of non-smokers, with a special focus on five different frequencies of daily smoking (non-smokers, and frequency of 1-5, 6-10, 11-15, and 20 cig./day). Only implants with a minimum of 36 months of radiological follow-up were considered. Univariate linear regression models were used to compare MBL over time between 12 clinical covariates, after which a linear mixed-effects model was built. After matching of the patients, the study included 340 implants in 104 smokers, and 337 implants in 100 non-smokers. The results suggested that smoking degree (greater MBL for higher degrees of smoking), bruxism (greater MBL for bruxers), jaw (greater MBL in maxilla), prosthesis fixation (greater MBL for screw-retained prosthesis), and implant diameter (greater MBL for 3.75-4.10 mm) had a significant influence on MBL over time. There appears to be a positive correlation between the degree of smoking and the degree of MBL, meaning, the higher the degree of smoking, the greater the MBL. However, the difference is not apparent for different degrees of smoking when this is high, namely above 10 cigarettes per day.

Real world experience: Examining outcomes using letermovir for CMV prophylaxis in high-risk allogeneic hematopoietic stem cell patients in the setting of using T-cell depletion as GVHD prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) infection significantly impacts the morbidity and mortality of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Despite monitoring and pharmacologic prophylaxis with drugs such as valganciclovir or ganciclovir, rates of early CMV reactivation have continually persisted, contributing to increased rates of morbidity and mortality in allogeneic-HSCT patients. This study evaluates the outcomes of letermovir in preventing CMV reactivation and CMV-related complications in HSCT recipients with initiation of therapy at +21 days in high-risk patients. METHODS: We retrospectively analyzed adult patients at University of Southern California (USC) Norris Cancer Hospital who received allogeneic-HSCT from 2018 to 2020 with subsequent serial CMV monitoring and treatment. CMV reactivation was determined in patients if they had clinically significant serum CMV viremia (viremia requiring treatment) or organ involvement by day+100. Primary endpoint assessed was day+100 rates of CMV reactivation. Secondary end-points included 1-year OS, 1-year RFS, and incidence of GVHD. Descriptive statistics were used to compare characteristics between groups used in this study, with a significance level of α = 0.05. RESULTS: Between 2018 and 2020, 116 adult HSCT recipients were reviewed. 51% were male and 49% were female; donor sources consisted of 27% match related donor (MRD) 28% match-unrelated donor (MUD), and 45% haploidentical donor. Of the 116 patients, 92 were identified as high-risk for CMV reactivation. 71 patients received letermovir prophylaxis, and 21 patients received no prophylaxis. In high-risk patients, after adjusting for GVHD status and transplant type, patients that received letermovir had no statistically significant difference of having D + 100 CMV reactivation compared to patients that did not receive letermovir. 1.02 (95% CI: 0.35, 3.20) (p = 0.97). Moreover, there were no statistically significant difference observed between letermovir treatment and 1-year OS, 1-year RFS, and incidence of GVHD. CONCLUSION: Patients in the high-risk letermovir group had outcomes that were comparable to the lower risk "non-letermovir" group. There was no significant difference in CMV D + 100 reactivation between high-risk patients who did not receive letermovir compared to the patients who did. While other studies have shown that early initiation of letermovir may be associated with improved outcomes, our study shows that the use of letermovir with initiation at 21 days may not necessarily translate to improved secondary outcomes such as overall survival. Further prospective studies evaluating the time of initiating therapy and outcomes are needed.

Inflammatory Bowel Disease Guidelines for Corneal Refractive Surgery Evaluation.

Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition that can potentially adversely affect surgical outcomes in patients receiving elective ophthalmic procedures. In this case series, 21 eyes of 11 patients with ulcerative colitis or Crohn's disease underwent laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), or small incision lenticule extraction (SMILE). Their surgical outcomes were followed up for an average of 8.9 ± 4.6 months. All the patients in this study did well, with 100% of eyes corrected for distance vision achieving uncorrected distance visual acuity 20/20 by postoperative month three. Common symptoms noted during the postoperative period included dry eyes, irritation, foreign body sensation, and blurry vision, all of which improved in prevalence and severity over the follow-up period, and none of the patients experienced a flare-up of their disease. Despite the successful outcomes in these patients, the authors recognize the inherent risks of operating on patients with IBD. Currently, there are no consensus guidelines for clinicians to follow to ensure that they are adequately screening these patients for eligibility, so the authors are suggesting a relevant, focused review of systems, a brief IBD history-related questionnaire, and a preliminary surgical decision-making flowchart for use in surgical evaluation.

Application of artificial intelligence in diagnosis of pancreatic malignancies by endoscopic ultrasound: a systemic review.

Background: Pancreatic cancer (PC) is a highly fatal malignancy with a global overall 5-year survival of under 10%. Screening of PC is not recommended outside of clinical trials. Endoscopic ultrasonography (EUS) is a very sensitive test to identify PC but lacks specificity and is operator-dependent, especially in the presence of chronic pancreatitis (CP). Artificial Intelligence (AI) is a growing field with a wide range of applications to augment the currently available modalities. This study was undertaken to study the effectiveness of AI with EUS in the diagnosis of PC. Methods: Studies from MEDLINE and EMBASE databases reporting the AI performance applied to EUS imaging for recognizing PC. Data were analyzed using descriptive statistics. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the quality of the included studies. Results: A total of 11 articles reported the role of EUS in the diagnosis of PC. The overall accuracy, sensitivity, and specificity of AI in recognizing PC were 80-97.5%, 83-100%, and 50-99%, respectively, with corresponding positive predictive value (PPV) and negative predictive value (NPV) of 75-99% and 57-100%, respectively. Types of AI studied were artificial neural networks (ANNs), convolutional neural networks (CNN), and support vector machine (SVM). Seven studies using other than basic ANN reported a sensitivity and specificity of 88-96% and 83-94% to differentiate PC from CP. Two studies using SVM reported a 94-96% sensitivity, 93%-99% specificity, and 94-98% accuracy to diagnose PC from CP. The reported sensitivity and specificity of detection of malignant from benign Intraductal Papillary Mucinous Neoplasms (IPMNs) was 96% and 92%, respectively. Conclusion: AI reported a high sensitivity with high specificity and accuracy to diagnose PC, differentiate PC from CP, and differentiate benign from malignant IPMN when used with EUS.

Unique Challenges to Diagnosing Human Herpesvirus-6 (HHV-6) Encephalitis Following Post-Hematopoietic Stem Cell Transplant: A Case and Brief Review.

A patient with an ultimate diagnosis of human herpesvirus-6 (HHV-6) encephalitis developed central nervous system (CNS) symptoms 13 days after undergoing myeloablative haploidentical allogeneic hematopoietic stem cell transplant (HSCT). Due to the patient's body habitus, magnetic resonance (MR) imaging was not obtained until the onset of retrograde amnesia on day +24. MR imaging and other clinical findings eliminated all skepticism of HHV-6 encephalitis and HHV-6 antivirals were initiated on day +28, leading to gradual recovery. This case demonstrates some of the factors that may complicate the diagnosis of post-alloHSCT HHV-6 encephalitis. Because HHV-6 encephalitis and viremia can occur without warning, a single negative study should not exclude future development, especially if CNS symptoms are present. Acute graft-versus-host disease and cord blood transplantation are both significant risk factors for HHV-6 encephalitis. Human leukocyte antigen (HLA) mismatch, engraftment complications, or certain HLA alleles have also been associated with HHV-6 encephalitis. Chromosomally integrated HHV-6 must also be ruled out to prevent inappropriate and potentially harmful administration of antivirals. Due to the severe short- and long-term sequelae of HHV-6 encephalitis, appropriate treatment should be administered as soon as possible.

Plant in vitro cultures: A promising and emerging technology for the feasible production of antidiabetic metabolites in Caralluma tuberculata.

Caralluma tuberculata, a medicinal and edible plant of the genus Caralluma, belongs to the family Asclepiadaceae. Traditionally, its succulent stems are used as folk medicine for life-threatening diabetes mellitus (DM) disease. Its antidiabetic potential is ascribed to the presence of various secondary metabolites (e.g., pregnane glycosides, flavone glycosides, megastigmane glycosides, polyphenols, ferulic acid, quercetin, and bitter principles, among others) that act as effective and safe antidiabetic agents. The mechanisms of these bioactive secondary metabolites in C. tuberculata herbal medicine include lowering the blood glucose level, stimulating B cells of the pancreas to release more insulin, enhancing the sensitivity of the insulin receptor, inhibiting the action of glucagon and the hydrolysis of glycogen, and increasing the use of glucose in tissues and organ. However, overexploitation, alterations in natural environmental conditions, lower seed viability, and slow growth rate are responsible for the extinction of species from natural habitats, then becoming critically endangered species according to the International Union for Conservation of Nature Red List categories. Therefore, its limited availability does not meet the higher worldwide market demand of C. tuberculata as an antidiabetic drug. Thus, for its conservation and sustainable utilization, researchers across the globe are working on devising strategies to conserve and improve biomass along with the secondary metabolite profiles of C. tuberculata using in vitro approaches. The current review describes the recent progress on antidiabetic phytoconstituents, their cellular mechanisms, and their subsequent clinical outcomes in the drug discovery management of DM. Moreover, in vitro methods such as callus culture, micropropagation, and nano-elicitation strategies for conserving and producing bioactive secondary metabolites have been concisely reviewed and discussed.

In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial.

BACKGROUND: Loss of mitochondrial function contributes to fatigue, exercise intolerance and muscle weakness, and is a key factor in the disability that develops with age and a wide variety of chronic disorders. Here, we describe the impact of a first-in-class cardiolipin-binding compound that is targeted to mitochondria and improves oxidative phosphorylation capacity (Elamipretide, ELAM) in a randomized, double-blind, placebo-controlled clinical trial. METHODS: Non-invasive magnetic resonance and optical spectroscopy provided measures of mitochondrial capacity (ATPmax) with exercise and mitochondrial coupling (ATP supply per O2 uptake; P/O) at rest. The first dorsal interosseous (FDI) muscle was studied in 39 healthy older adult subjects (60 to 85 yrs of age; 46% female) who were enrolled based on the presence of poorly functioning mitochondria. We measured volitional fatigue resistance by force-time integral over repetitive muscle contractions. RESULTS: A single ELAM dose elevated mitochondrial energetic capacity in vivo relative to placebo (ΔATPmax; P = 0.055, %ΔATPmax; P = 0.045) immediately after a 2-hour infusion. No difference was found on day 7 after treatment, which is consistent with the half-life of ELAM in human blood. No significant changes were found in resting muscle mitochondrial coupling. Despite the increase in ATPmax there was no significant effect of treatment on fatigue resistance in the FDI. CONCLUSIONS: These results highlight that ELAM rapidly and reversibly elevates mitochondrial capacity after a single dose. This response represents the first demonstration of a pharmacological intervention that can reverse mitochondrial dysfunction in vivo immediately after treatment in aging human muscle.

Change in Refractive Error Associated With the Use of Cannabidiol Oil.

Cannabinoid (CBD) products have gained popularity since their legalization in 2018, causing a plethora of unregulated CBD products to be sold in the United States. These products are available in various combinations for topical and oral consumption, claiming credit for potentially improving various diseases. In this report, we present a newfound case reporting a shift in refraction that may be associated with the regular use of CBD oil supplements. A 57-year-old woman with a history of diabetes mellitus type 2, hyperlipidemia, obstructive sleep apnea, with no change in medications, diet, or lifestyle was found to have a hyperopic shift in vision with the recent daily addition of CBD oil intake. This case report highlights the possible association of CBD oil and vision changes after regular consumption of CBD oil in an otherwise stable patient. Further study is required to understand the mechanisms of CBD oil-associated shift in refractive error. Because the patient is diabetic and the refraction shift was hyperopic, other etiologies, such as un-noted lenticular change, cannot be ruled out. CBD products are unregulated and marketed in many mixed forms, and thus can cause unforeseen effects on susceptible individuals. This warrants Food and Drug Administration (FDA) regulation of such products and extensive research before considering them for therapeutic usage.