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1.
J Gastrointest Surg ; 28(5): 738-745, 2024 May.
Article in English | MEDLINE | ID: mdl-38704208

ABSTRACT

BACKGROUND: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS: Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION: Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Hepatectomy , Liver Transplantation , Humans , Liver Transplantation/statistics & numerical data , Male , Female , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Middle Aged , Aged , Cholangiocarcinoma/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Treatment Outcome , Neoadjuvant Therapy/statistics & numerical data , Survival Rate , Databases, Factual , Proportional Hazards Models , Kaplan-Meier Estimate , Retrospective Studies , Neoplasm Staging
2.
Biomimetics (Basel) ; 9(4)2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38667263

ABSTRACT

To combat climate change, one approach is to manufacture products from biomass-fungi composite materials instead of petroleum-based plastics. These products can be used in packaging, furniture, and construction industries. A 3D printing-based manufacturing method was developed for these biomass-fungi composite materials, eliminating the need for molds, and enabling customized product design. However, previous studies on the 3D printing-based method showed significant shrinkage of printed samples. In this paper, an approach is proposed to reduce the shrinkage by incorporating ionic crosslinking into biomass-fungi composite materials. This paper reports two sets of experiments regarding the effects of sodium alginate (SA) and calcium chloride (CaCl2) on fungal growth and fungal viability. The first set of experiments was conducted using Petri dishes with fungi isolated from colonized biomass-fungi material and different concentrations of SA and CaCl2. Fungal growth was measured by the circumference of fungal colonies. The results showed that concentrations of SA and CaCl2 had significant effects on fungal growth and no fungal growth was observed on Petri dishes with 15% CaCl2. Some of these Petri dishes were also observed under confocal microscopy. The results confirmed the differences obtained by measuring the circumference of fungal colonies. The second set of experiments was conducted using Petri dishes with biomass-fungi mixtures that were treated with different concentrations of SA and exposure times in a CaCl2 (crosslinking) solution. Fungal viability was measured by counting colony-forming units. The results showed that the addition of the SA solution and exposure times in the crosslinking solution had statistically significant effects on fungal viability. The 2SA solution was prepared by dissolving 2 g of SA in 100 mL of water, the 5SA solution was prepared by dissolving 5 g of SA in 100 mL of water, and the crosslinking solution was prepared by dissolving 5 g of CaCl2 in 100 mL of water. The results also showed that fungal viability was not too low in biomass-fungi mixtures that included 2SA solution and were exposed to the crosslinking solution for 1 min.

3.
Am J Case Rep ; 25: e943133, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38449298

ABSTRACT

BACKGROUND Cysticercosis is a condition caused by infection with the larval form of Taenia solium, a pork tapeworm that uses pigs as an intermediate host. Humans become infected when they ingest water or food contaminated with tapeworm cysts. Cysticercosis is increasing in frequency in developed countries due to increased access to travel. Neurocysticercosis occurs when Taenia solium cysts embed within the nervous system. The clinical presentation of neurocysticercosis ranges from asymptomatic to life-threatening, largely depending on the brain parenchymal involvement. The diagnosis is typically made with a combination of clinical evaluation, serology, and neuroimaging. Treatment for parenchymal neurocysticercosis may involve anthelmintic agents, symptomatic agents, surgery, or a combination of methods. CASE REPORT A 52-year-old man with a medical history of migraine headaches, complicated type 2 diabetes mellitus, and obesity presented with a 4-month change in his migraines becoming severe, worse over his occiput bilaterally, and unresponsive to abortive therapy. His exposure history was unremarkable except for a habit of eating undercooked bacon, by which he would have developed neurocysticercosis via autoinfection. Neuroimaging and serology confirmed a diagnosis of neurocysticercosis and he was treated accordingly with antiparasitic and anti-inflammatory medications. CONCLUSIONS This presentation is nonspecific and can easily be overlooked, especially if there is an underlying known neurological condition such as migraine. This case illustrates that neurocysticercosis should be considered when an existing neuropathological condition displays a change in presentation or requires a change in therapeutic management, even without obvious risk factors.


Subject(s)
Cysticercosis , Cysts , Diabetes Mellitus, Type 2 , Migraine Disorders , Neurocysticercosis , Humans , Male , Middle Aged , Migraine Disorders/diagnosis , Neurocysticercosis/diagnosis , United States
5.
Transplantation ; 108(3): 607-608, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37677947
6.
JSES Rev Rep Tech ; 3(4): 454-460, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37928987

ABSTRACT

Purpose: Peripheral neuropathies after shoulder arthroscopy are rare, though likely under-reported. Many resolve spontaneously, but some patients are left with permanent neurological deficits. The purpose of this study was to review the literature to better characterize this patient population, diagnostic tests performed, the timing and type of surgical intervention, and report clinical outcomes. Methods: A systematic literature review was performed. Articles in English were identified from PubMed, EMBASE, and CINAHL in August 2021. Article titles and abstracts were screened for relevance by two authors and discordant abstracts were resolved by the senior author. Data were subsequently extracted from the included articles. Results: Seventeen articles were identified yielding a total of 91 patients. The average age was 53 ± 12 years, and most patients were male (72%). Rotator cuff repair (62%) was the most common procedure performed. A peripheral neuropathy was identified an average of 80 ± 81 days from the index procedure (range, 0-240 days). Most commonly, peripheral nerve injury presented as a mononeuropathy, with the median nerve (39%) and ulnar nerve (17%) affected predominantly. Seventeen percent of patients underwent a secondary surgery at an average of 232 ± 157 days after the index procedure. At the final follow-up, 55% of neuropathies had resolved, 14% partially improved, and 22% showed no clinical improvement. The most proposed etiologies were postoperative immobilization (29%) and intraoperative positioning (20%), but several possible etiologies have been suggested. Conclusions: Peripheral neuropathies after arthroscopic shoulder procedures are rare. While most spontaneously resolve, up to 1 in 5 patients may have persistent neuropathic symptoms. A high index of suspicion should be maintained throughout the postoperative period. When neurologic deficits are identified, patients should undergo a thorough diagnostic workup and be referred to a subspecialist in a timely manner.

7.
Am J Case Rep ; 24: e941992, 2023 Nov 12.
Article in English | MEDLINE | ID: mdl-37952083

ABSTRACT

BACKGROUND Stevens-Johnson syndrome (SJS) is a rare dermatologic disorder that is characterized by nonspecific flu-like prodrome with fever, malaise, myalgia, cough, rhinitis, and sore eyes, followed by a characteristic rash and mucocutaneous manifestations. It is triggered by medications in up to 80% of cases in adults. In each of these cases, the medication is oral or parenteral. Severe and progressive SJS can result in life-threatening complications. Adult-onset medication-induced SJS presents within 8 weeks of exposure to the offending substance, lasting 8 to 12 days. Recovery of denuded skin generally is complete within a month. There is no consensus on treatment, but supportive care with corticosteroids is often the initial intervention. CASE REPORT A 36-year-old woman with a flare of allergic rhinitis and tearing resistant to over-the-counter options was treated with topical ophthalmic ofloxacin. She began experiencing a diffuse mucocutaneous rash, with oral desquamation, tongue swelling, vaginal desquamation, and rash of the palms and soles within 24 h, which suggested the possibility of SJS. A skin biopsy was obtained, and pathology confirmed this suspicion. She was treated with parenteral antibiotics, corticosteroids, and supportive care, and after 10 days was discharged from the hospital. She had a complete recovery in 30 days. CONCLUSIONS The clinical course of SJS induced by the ophthalmic application of medication can be just as severe as the oral or parenteral routes. This is, to the best of our knowledge, the first documented case of SJS being triggered by topical ofloxacin.


Subject(s)
Exanthema , Stevens-Johnson Syndrome , Adult , Female , Humans , Ofloxacin/adverse effects , Stevens-Johnson Syndrome/diagnosis , Stevens-Johnson Syndrome/etiology , Anti-Bacterial Agents/adverse effects , Adrenal Cortex Hormones/therapeutic use
8.
Cureus ; 15(5): e39383, 2023 May.
Article in English | MEDLINE | ID: mdl-37378215

ABSTRACT

Brucellosis is a zoonotic infectious disease caused by the bacterial genus Brucella and is most commonly transmitted to humans globally via the consumption of contaminated unpasteurized products. In a significant minority of cases, Brucella has been found to be transmitted by contact with infected swine bodily fluids such as blood. Only a small proportion of all cases of brucellosis affects the central nervous system, and of the four species of Brucella that are known to infect humans, Brucella suis is unusual. Neurologic involvement occurs in a limited proportion of cases and can vary in presentation, ranging from encephalitis to radiculitis or from brain abscess to neuritis. In this case report, we present a 20-year-old male with an eight-day history of headache and neck pain and a high fever that started two days after the onset of the headaches. Three weeks prior, he had hunted, killed, butchered, cooked, and eaten a wild boar in the field. A workup was performed, and blood cultures eventually grew Brucella suis. Although an intensive broad-spectrum antibiotic protocol was implemented, his post-therapy course was complicated. He eventually discontinued his antibiotics after one year.

9.
Mycologia ; 115(4): 456-469, 2023.
Article in English | MEDLINE | ID: mdl-37196171

ABSTRACT

Filamentous fungi produce specialized cells called hyphae. These cells grow by polarized extension at their apex, which is maintained by the balance of endocytosis and exocytosis at the apex. Although endocytosis has been well characterized in other organisms, the details of endocytosis and its role in maintaining polarity during hyphal growth in filamentous fungi is comparatively sparsely studied. In recent years, a concentrated region of protein activity that trails the growing apex of hyphal cells has been discovered. This region, dubbed the "endocytic collar" (EC), is a dynamic 3-dimensional region of concentrated endocytic activity, the disruption of which results in the loss of hyphal polarity. Here, fluorescent protein-tagged fimbrin was used as a marker to map the collar during growth of hyphae in three fungi: Aspergillus nidulans, Colletotrichum graminicola, and Neurospora crassa. Advanced microscopy techniques and novel quantification strategies were then utilized to quantify the spatiotemporal localization and recovery rates of fimbrin in the EC during hyphal growth. Correlating these variables with hyphal growth rate revealed that the strongest observed relationship with hyphal growth is the distance by which the EC trails the apex, and that measured endocytic rate does not correlate strongly with hyphal growth rate. This supports the hypothesis that endocytic influence on hyphal growth rate is better explained by spatiotemporal regulation of the EC than by the raw rate of endocytosis.


Subject(s)
Fungal Proteins , Microfilament Proteins , Fungal Proteins/genetics , Fungal Proteins/metabolism , Microfilament Proteins/metabolism , Fungi/genetics , Fungi/metabolism , Membrane Glycoproteins/metabolism , Hyphae
10.
Sci Adv ; 9(20): eadg1448, 2023 05 19.
Article in English | MEDLINE | ID: mdl-37205758

ABSTRACT

Among sensitized patients awaiting a transplant, females are disproportionately represented, partly because of pregnancy-induced sensitization. Using female NHPs sensitized by pregnancy alone, we examined the efficacy of costimulation blockade and proteasome inhibition for desensitization. Three animals received no desensitization (control), and seven animals received weekly carfilzomib (27 mg/m2) and belatacept (20 mg/kg) before kidney transplantation. All animals received renal allografts from crossmatch-positive/maximally MHC-mismatched donors. Controls and three desensitized animals received tacrolimus-based immunosuppression. Four desensitized animals received additional belatacept with tacrolimus-based immunosuppression. Multiparous females had less circulating donor-specific antibody when compared to skin-sensitized males before transplantation. While females receiving desensitization showed only a marginal survival benefit over control females (MST = 11 days versus 63 days), additional belatacept to posttransplant maintenance significantly prolonged graft survival (MST > 164 days) and suppressed posttransplant DSA and circulating follicular helper T-like cells. This combination of therapies demonstrates great potential to reduce antibody-mediated rejection in sensitized recipients.


Subject(s)
Immunosuppressive Agents , Kidney Transplantation , Male , Pregnancy , Animals , Female , Abatacept/pharmacology , Abatacept/therapeutic use , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Tacrolimus/pharmacology , Tacrolimus/therapeutic use , Graft Rejection/prevention & control , Antibodies
12.
Transplant Proc ; 55(1): 56-65, 2023.
Article in English | MEDLINE | ID: mdl-36623960

ABSTRACT

BACKGROUND: To evaluate the effect of the Affordable Care Act (ACA) Medicaid expansion on payor mix among patients on the kidney and liver transplant waiting list as well as waiting list and post-transplant outcomes. DESIGN: Using the Scientific Registry of Transplant Recipients, we performed a secondary data analysis of all patients on the kidney and liver transplant waiting list from 2007 to 2018. We described changes in payor mix by timing of state Medicaid expansion. We used competing risks models to estimate cause-specific hazard ratios for the effects of insurance and era on death/delisting and transplant. We used a Poisson regression model to estimate the effect of insurance and era on incidence rate ratio of inactivations on the waiting list. We used Cox proportional hazards models to estimate the effect of insurance and era on graft and patient survival. RESULTS: A decade after implementation of the ACA, the prevalence of Medicaid beneficiaries listed for transplant increased by 2.5% (from 7.4% to 9.9%) for kidney and by 2.6% (15.3% to 17.9%) for liver. Expansion states had greater increases than nonexpansion states (kidney 3.8% vs 0.6%, liver 5.3% vs -1.8%). Among wait-listed patients, the magnitude of association of Medicaid insurance vs private insurance with transplant decreased over time for kidney candidates (era 1 subdistribution hazard ratio (SHR), 0.62 [95% CI, 0.60-0.64] vs era 3 SHR, 0.77 [95% CI, 0.74-0.70]) but increased for liver candidates (era 1 SHR, 0.85 [95% CI, 0.83-0.90] vs era 3 SHR 0.79 [95% CI, 0.77-0.82]). Medicaid-insured kidney and liver recipients had greater hazards of graft failure; this did not change over time (kidney: HR, 1.23 [95% CI, 1.06-1.44] liver: HR, 1.05 [95% CI, 0.94-1.17]). CONCLUSIONS: For the millions of patients with chronic kidney and liver diseases, implementation of the ACA has resulted in only modest increases in access to transplant for the publicly insured vs the privately insured.


Subject(s)
Liver Transplantation , Patient Protection and Affordable Care Act , United States , Humans , Medicaid , Registries , Kidney
13.
Orthop J Sports Med ; 11(1): 23259671221140853, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36655019

ABSTRACT

Background: The current literature lacks an updated review examining return to play (RTP) and return to prior performance (RTPP) after shoulder surgery in professional baseball players. Purpose: To summarize the RTP rate, RTPP rate, and baseball-specific performance metrics among professional baseball players who underwent shoulder surgery. Study Design: Systematic review; Level of evidence, 4. Methods: A literature search was performed utilizing the PubMed, MEDLINE, and CINAHL databases and according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were English-language studies reporting on postoperative RTP and/or RTPP in professional baseball players who underwent shoulder surgery between 1976 and 2016. RTP rates, RTPP rates, and baseball-specific performance metrics were extracted from qualifying studies. A total of 2034 articles were identified after the initial search. Meta-analysis was performed where applicable, yielding weighted averages of RTP and RTPP rates and comparisons between pitchers and nonpitchers for each type of surgery. Baseball-specific performance metrics were reported as a narrative summary. Results: Overall, 26 studies featuring 1228 professional baseball players were included. Patient-level outcome data were available for 529 players. Surgical interventions included rotator cuff debridement (n = 197), rotator cuff repair (RCR; n = 43), superior labrum from anterior to posterior repair (n = 124), labral repair (n = 103), latissimus dorsi/teres major (LD/TM) repair (n = 21), biceps tenodesis (n = 17), coracoclavicular ligament reconstruction (n = 15), anterior capsular repair (n = 5), and scapulothoracic bursectomy (n = 4). Rotator cuff debridement was the most common surgical procedure, while scapulothoracic bursectomy was the least common (37.2% and 0.8% of interventions, respectively). Meta-analysis revealed that the RTP rate was highest for LD/TM repair (84.5%) and lowest for RCR (53.5%), while the RTPP rate was highest for LD/TM repair (100.0%) and lowest for RCR (27.9%). RTP and RTPP rates were generally higher for position players than for pitchers. Nonvolume performance metrics were unaffected by shoulder surgery, while volume statistics decreased or remained similar. Conclusion: RTP and RTPP rates among professional baseball players were modest after most types of shoulder surgery. Among surgical procedures commonly performed on professional baseball players, RTP and RTPP rates were highest for LD/TM repair and lowest for RCR.

14.
J Pediatr Orthop ; 43(3): 181-186, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36649473

ABSTRACT

ABSTRACT: The authors describe their 11-year experience with 1 model for providing short-term (about 1 wk/y in country) pediatric orthopaedic surgical care in a limited resource environment. This paper provides a detailed narrative of 1 team's pediatric orthopaedic work at the Moore Pediatric Surgery Center in Guatemala City, how it has evolved over these 11 years, financial aspects of the model, and examines patient follow-up data for a consecutive 8-year period. The authors have reviewed financial records, case lists, patient charts from 2014 to 2022, and patient photographic records from The Moore Center and as provided via internet by a local contracted Guatemalan pediatric orthopaedic fellowship-trained surgeon to present a complete picture of how the service functions. Specific follow-up data included: last follow-up date, date discharged from follow-up, and major complications including infection, surgical wound dehiscence, return for unplanned surgery, major nerve injury, and recurrent hip dislocation for cases of closed or open reduction of developmental hip dislocation. A total of 297 consecutive pediatric orthopaedic surgical patients were identified from 2014 to 2022. Of these, charts were found for 235 patients (135 female, 110 male), of which 43% were from the urban Guatemala City region. Two hundred sixteen (72%) had at least 1 follow-up clinic visit, and 87 (37%) had at least 1-year follow-up or were discharged. All complications identified by this retrospective chart review included 4 recurrent hip dislocations (3 after closed reduction), 1 femur fracture after implant removal, 1 superficial infection requiring antibiotics, 1 partial dehiscence treated only with dressings, 1 thumb subluxation, and 1 failed graft with internal fixation for congenital pseudoarthrosis of tibia. CONCLUSIONS: The Moore Pediatric Surgery Center is a financially viable, sustainable, safe, and effective model for delivering short-term surgical care for many pediatric orthopaedic conditions in a limited resource environment. LEVEL OF EVIDENCE: None (descriptive).


Subject(s)
Joint Dislocations , Orthopedics , Plastic Surgery Procedures , Humans , Male , Child , Female , Retrospective Studies , Fracture Fixation, Internal , Open Fracture Reduction
15.
Ann Surg ; 277(2): 350-357, 2023 02 01.
Article in English | MEDLINE | ID: mdl-33843792

ABSTRACT

OBJECTIVE: To define textbook outcome (TO) for lung transplantation (LTx) using a contemporary cohort from a high-volume institution. SUMMARY BACKGROUND DATA: TO is a standardized, composite quality measure based on multiple postoperative endpoints representing the ideal "textbook" hospitalization. METHODS: Adult patients who underwent LTx at our institution between 2016 and 2019 were included. TO was defined as freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay >75th percentile of LTx patients, 90 day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, postoperative extracorporeal membrane oxygenation, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Recipient, operative, financial characteristics, and post-transplant outcomes were recorded from institutional data and compared between TO and non-TO groups. RESULTS: Of 401 LTx recipients, 97 (24.2%) achieved TO. The most common reason for TO failure was extubation >48 hours post-transplant (N = 119, 39.1%); the least common was mortality (N = 15, 4.9%). Patient and graft survival were improved among patients who achieved versus failed TO (patient survival: log-rank P < 0.01; graft survival: log-rank P < 0.01). Rejection-free and chronic lung allograft dysfunction-free survival were similar between TO and non-TO groups (rejection-free survival: log-rank P = 0.07; chronic lung allograft dysfunction-free survival: log-rank P = 0.3). On average, patients who achieved TO incurred approximately $638,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in LTx was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer providers and patients new insight into transplant center quality of care and highlight areas for improvement.


Subject(s)
Lung Transplantation , Quality Indicators, Health Care , Adult , Humans , Retrospective Studies , Lung , Transplantation, Homologous
16.
Fungal Genet Biol ; 163: 103747, 2022 11.
Article in English | MEDLINE | ID: mdl-36309094

ABSTRACT

Colletotrichum graminicola is an economically significant fungal pathogen of maize. The primary infective conidia of the fungus, falcate conidia, are splash-dispersed during rain events. The adhesion of the falcate conidia triggers germination and is required for the development of infection structures. Falcate conidia are capable of immediate adhesion upon encountering the substrate. We report that rapid adhesion in C. graminicola is polarized, with a single-sided strip of adhesive material running the length of a single side (or face) of the conidium between the tips. This strip of adhesive is co-localized with dynamic transverse actin cables, and both the adhesive strip and actin cables are formed after liberation of the conidium from its conidiogenous cell but prior to adhesion to the infection court. Orientation of conidia upon contact with substrate determines whether they will rapidly adhere, and those which do not initially adhere can be induced to do so by applying force to reorient or "flip" the conidia. We propose that C. graminicola possesses an adhesive mechanism resulting in an adhesion efficiency of approximately 50% upon initial contact with substrata, and that an increase in adhesion efficiency can be induced by disturbance.


Subject(s)
Adhesives , Colletotrichum , Spores, Fungal/genetics , Adhesives/analysis , Adhesives/metabolism , Actins/metabolism , Colletotrichum/genetics
17.
Pediatr Transplant ; 26(8): e14371, 2022 12.
Article in English | MEDLINE | ID: mdl-35938682

ABSTRACT

BACKGROUND: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immune system responds to the insult of both immunosuppression and allotransplantation is unknown. We examined the relationship of nutritional status with post-transplant outcomes and characterized the peripheral immune cell phenotypes of children from the Immune Development of Pediatric Transplant (IMPACT) study. METHODS: Ninety-eight patients from the IMPACT study were classified as having obesity, undernutrition, or normal nutrition-based pre-transplant measurements. Incidence of infectious and alloimmune outcomes at 1-year post-transplantation was compared between nutritional groups using Gray's test and Fine-Gray subdistribution hazards model. Event-free survival was estimated by Kaplan-Meier method and compared between groups. Differences in immune cell subsets between nutritional groups over time were determined using generalized estimating equations accounting for the correlation between repeated measurements. RESULTS: We did not observe that nutritional status was associated with infectious or alloimmune events or event-free survival post-transplant. We demonstrated that children with obesity had distinct T-and B-cell signatures relative to those with undernutrition and normal nutrition, even when controlling for immunosuppression. Children with obesity had a lower frequency of CD8 Tnaive cells 9-month post-transplant (p < .001), a higher frequency of CD4 CD57 + PD1- T cells, and lower frequencies of CD57-PD1+ CD8 and CD57-PD1- CD8 T cells at 12-month transplant (p < .05 for all). CONCLUSIONS: Children with obesity have distinct immunophenotypes that may influence the tailoring of immunosuppression.


Subject(s)
Kidney Transplantation , Malnutrition , Humans , Immunosuppression Therapy , CD8-Positive T-Lymphocytes , Malnutrition/complications , Obesity
19.
Cancer Immunol Res ; 10(8): 996-1012, 2022 08 03.
Article in English | MEDLINE | ID: mdl-35706413

ABSTRACT

Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity in the MBM TME, most notably multiple distinct neutrophil states, including an IL8-expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. In addition, we observed significant relationships between intracranial T-cell phenotypes and the distribution of T-cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data identify unique features of the MBM TME that may represent potential targets to improve clinical outcomes for patients with MBM.


Subject(s)
Brain Neoplasms , Melanoma , Humans , Immune Checkpoint Inhibitors , Tumor Microenvironment
20.
J Fungi (Basel) ; 8(6)2022 Jun 17.
Article in English | MEDLINE | ID: mdl-35736125

ABSTRACT

The prevalence and increasing incidence of fungal infections globally is a significant worldwide health problem. Cryptococcosis, primarily caused by the pathogenic yeast Cryptococcus neoformans, is responsible for approximately 181,000 estimated deaths annually. The scarcity of treatments and the increasing resistance to current therapeutics highlight the need for the development of antifungal agents which have novel mechanisms of action and are suitable for clinical use. Repurposing existing FDA-approved compounds as antimycotic therapeutics is a promising strategy for the rapid development of such new treatments. Sertraline (SRT), a commonly prescribed antidepressant, is a broad-spectrum antifungal agent with particular efficacy against C. neoformans. However, the effect of SRT on fungal physiology is not understood. Here, we report that SRT induces the formation of supersized lipid droplets (SLDs) in C. neoformans, and in Candida albicans, Saccharomyces cerevisiae, and Aspergillus fumigatus. SLDs were not induced in C. neoformans by treatment with the antifungal fluconazole (FLC), consistent with SRT and FLC acting differently to perturb C. neoformans physiology. The formation of SLDs in response to SRT indicates that this compound alters the lipid metabolism of C. neoformans. Moreover, the SRT-induced enlargement of LDs in other fungal species may indicate a common fungal response to SRT.

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