Strategies and outcomes of extracorporeal membrane oxygenation use in peripartum patients: a single institution experience.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) use in peripartum patients is rare, and there is a gap in the literature on the outcomes and guidance on using ECMO in peripartum patients. This study describes ECMO strategies our institution uses for peripartum patients and reports outcomes of ECMO use in peripartum patients with respiratory and/or cardiac failure. METHODS: A case series of all peripartum patients, defined as pregnant or up to 6 weeks after delivery of an infant >20 weeks gestation, from 2018 to 2023 from a single center requiring ECMO support. Patients were included if ECMO was initiated in the setting of cardiac, pulmonary, or combined failure. Patient demographics, operative details, ECMO data, and adverse outcomes for maternal, fetus, and neonates were all collected. RESULTS: Eighteen patients met the inclusion criteria. The cohort had a mean maternal age of 30.7 years old and was racially diverse. A majority of this cohort tested positive for COVID-19 (n = 10, 55%). ECMO was a bridge to recovery for all patients, of whom 14 (78%) were discharged out of the hospital alive. No patients received transplantation or a durable mechanical device. The most common complications were infection (25%) and postpartum hemorrhage (22%). CONCLUSIONS: ECMO use in peripartum patients in a single tertiary center was associated with a high survival rate. Furthermore, a strong multidisciplinary team, careful reevaluation of clinical trajectory, and consideration of complications and risks associated with using ECMO in peripartum patients are possible frameworks to use when challenged with critically ill peripartum patients.

HLA Sensitization in Patients Bridged to Lung Transplantation With Extracorporeal Membrane Oxygenation.

Lung transplantation is a definitive therapy for many end-stage lung pathologies. Extracorporeal membrane oxygenation (ECMO) is increasingly being used as a bridge to lung transplantation (BTT). HLA sensitization is a major barrier to lung transplantation. The development of HLA sensitization while undergoing ECMO support as a BTT has recently been reported in a 2-patient series. Methods: We performed a retrospective analysis of patients undergoing ECMO as a BTT at a single large academic medical center from January 2016 to April 2022. The study was approved by the institutional review board. We selected patients who had undergone ECMO support for at least 7 d with either negative HLA before cannulation or initial negative HLA on ECMO (3 patients). Results: We identified 27 patients bridged to lung transplantation with available HLA data. Of this group, 8 patients (29.6%) developed significant HLA sensitization (>10%). We did not identify any factors predisposing to sensitization, including infection episodes or blood product transfusion. Sensitized patients demonstrated a trend toward an increased primary graft dysfunction rate, a need for posttransplant ECMO support, and a decreased 1-y survival; however, these did not meet statistical significance. Conclusions: Our study is the largest series today describing the association between HLA sensitization and ECMO therapy. We suggest that interaction between the immune system and ECMO circuit contributes to allosensitization pretransplant, similar to that occurring with ventricular assist device. Further work is needed to better characterize the incidence of HLA sensitization in a multicenter cohort and to identify potentially modifiable factors associated with HLA sensitization.

Bilateral Lung Transplantation With Donor Positive for COVID-19 Infection on Bronchoalveolar Lavage: A Case Report.

Initial experience with lung transplant of COVID-19-positive donors was marked by disappointing results, including a reported case of mortality through donor to recipient transmission of infection. However, since that time a number of improvements in preventative and therapeutic measures against COVID-19 have been developed. We present the case of a 51-year-old woman with scleroderma-associated interstitial lung disease who was awaiting lung transplant. A potential donor with excellent lung physiology was located; however, initial testing on bronchoalveolar lavage (BAL) was positive for COVID-19. The donor had tested positive 2 weeks prior and had symptomatically recovered. Our patient had been fully vaccinated but not seroconverted. Given the history of a donor with recovering COVID infection and a fully immunized recipient, our multidisciplinary team elected to proceed with the transplant. The patient successfully underwent bilateral lung transplant with standard induction immunosuppression. Bebtelovimab was given post-transplant day 1 because the recipient remained seronegative to COVID-19. Serial bronchoalveolar lavages post transplant have been negative for COVID-19. The patient has done well after transplant. She was seen in the clinic 2 months post transplant and is ambulatory without supplemental oxygen requirements. To our knowledge, this represents the first reported successful case of lung transplant with a donor positive for COVID-19 on lower respiratory tract sampling.

Repair of Tracheal Dehiscence After Heart-Lung Transplant Complicated by SARS-CoV-2 Infection.

Airway complications are a major cause of morbidity after thoracic transplantation. Airway ischemia, necrosis, and tracheobronchial anastomotic dehiscence are associated with early mortality. We describe a case of tracheal anastomotic dehiscence after en bloc heart-lung transplant complicated by severe acute respiratory syndrome coronavirus 2 infection. Timely surgical management and reconstruction with a bovine pericardial patch and double muscle flap were performed. After 8 months of follow-up, there are no airway complications and normalized allograft function.

1-Year Outcomes of Lung Transplantation for Coronavirus Disease 2019-Associated End-Stage Lung Disease in the United States.

BACKGROUND: Lung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)-associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up. METHODS: Characteristics of deceased donors and adult lung transplant recipients for COVID-19-associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non-COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection. RESULTS: During the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non-COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non-COVID, 86.3%). Post-transplant, COVID-19-associated deaths were 9.2% of all deaths among lung transplant recipients. CONCLUSIONS: Lung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non-COVID-19 etiology.

State of the art - Extracorporeal membrane oxygenation as a bridge to thoracic transplantation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has revolutionized the treatment of refractory cardiac and respiratory failure, and its use continues to increase, particularly in adults. However, ECMO-related morbidity and mortality remain high. MAIN TEXT: In this review, we investigate and expand upon the current state of the art in thoracic transplant and extracorporeal life support (ELS). In particular, we examine recent increase in incidence of heart transplant in patients supported by ECMO; the potential changes in patient care and selection for transplant in the years prior to updated United Network for Organ Sharing (UNOS) organ allocation guidelines versus those in the years following, particularly where these guidelines pertain to ECMO; and the newly revived practice of heart-lung block transplants (HLT) and the prevalence and utility of ECMO support in patients listed for HLT. CONCLUSIONS: Our findings highlight encouraging outcomes in patients bridged to transplant with ECMO, considerable changes in treatment surrounding the updated UNOS guidelines, and complex, diverse outcomes among different centers in their care for increasingly ill patients listed for thoracic transplant.

Antiepileptic-drug tapering and seizure recurrence: Correlation with serum drug levels and biomarkers in persons with epilepsy.

OBJECTIVES: Antiepileptic-drug (AED) serum level and inflammatory biomarkers are primarily monitored/assessed during epilepsy treatment for effective seizure control; however, their correlation with seizure recurrence (SR) following AED-tapering has not been established, and this is being investigated in this study. MATERIALS AND METHODS: This prospective observational study enrolled persons with epilepsy (PWE) on AED monotherapy and going to start tapering after being seizure-free for ≥2 years. Data regarding seizure episodes, AED-treatment, and adverse events (using Liverpool Adverse Event profile [LAEP]-score) were recorded. Serum AED levels using high-performance liquid chromatography and biomarkers levels through enzyme-linked immunosorbent assay kits were estimated at AED-tapering commencement and at 6 months/SR time. RESULTS: Among 129 enrolled PWE (levetiracetam [n = 52], valproate [n = 34], carbamazepine [n = 29], and phenytoin [n = 14]), SR occurred in 23.3% during follow-up (range 12-44 months). PWE with subtherapeutic serum AED level at the onset of tapering had higher SR (P = 0.004) than those with therapeutic or higher levels. Levetiracetam-treated PWEs with SR have significantly low AED levels than PWE with no-SR (P < 0.001). PWE had significantly raised inflammatory biomarkers (interleukin [IL]-1 ß, tumor necrosis factor [TNF]-α, IL-6, and high-mobility group box protein 1) and decreased IL-10 than healthy control subjects. SR and no-SR groups did not differ significantly in inflammatory markers except for higher IL-1 ß and TNF-α levels in SR group (P = 0.001, 0.02, respectively). Improvement in LAEP score was observed in follow-up visits without any difference between SR and no-SR groups. CONCLUSION: Low serum AED levels (especially levetiracetam) and raised levels of TNF-α and IL-1 ß during tapering commencement had a higher association with SR following AED-tapering.

Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (CA) is commonly used herbal medicine for treatment of epilepsy. CA has CYP2C9, CYP2D6 and CYP3A4 enzymes inhibition property and used as an adjuvant therapy with conventional antiepileptic drugs (AEDs). That may be responsible for herb-drug interaction. AIM OF THE STUDY: The present study was planned to evaluate interactions profile of hydroalcoholic extract Centella asiatica (HECA) with antiepileptic drugs in experimental models of epilepsy in rats. MATERIALS AND METHODS: Wistar rats (175-200 g) were used. In the pharmacodynamic interaction study, seizures were induced using pentylenetetrazole (PTZ) (60 mg/kg, i.p.) and maximal electroshock seizure (MES) (70 mA for 0.2 s). The therapeutic and sub-therapeutic doses of valproate (VPA) and phenytoin (PHT) were co-administrated with HECA in PTZ and MES model of seizures respectively. Behavioural parameters were assessed using elevated plus maze test and passive avoidance paradigm. Rat brain oxidative stress parameters were also assessed. In the pharmacokinetic interaction study, the serum levels of the VPA and PHT were estimated at different time intervals by HPLC and pharmacokinetic parameters were analyzed by WinNonlin software. RESULTS: The VPA and PHT produced complete protection against seizures in their therapeutic doses but not with sub-therapeutic doses. However, co-administration of HECA with a sub-therapeutic dose of VPA and PHT enhanced the protection of seizures and significantly (p < 0.001) attenuated the seizure induced oxidative stress and cognitive impairment. It also significantly increased (p < 0.001) serum levels of VPA and PHT. The alterations in pharmacokinetic parameters (maximum serum concentration, area under the curve, clearance) of AEDs were also found with co-administration of HECA. CONCLUSION: The results suggested that co-administration of HECA could improve the therapeutic efficacy of VPA and PHT. But, alteration in pharmacokinetic parameters revel that needs critical medical supervision to avoid any toxic reactions.

SARS-CoV-2 Infections among Recent Organ Recipients, March-May 2020, United States.

We conducted public health investigations of 8 organ transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 infection. Findings suggest the most likely source of transmission was community or healthcare exposure, not the organ donor. Transplant centers should educate transplant candidates and recipients about infection prevention recommendations.

Adjuvant role of Ocimum sanctum hydroalcoholic extract with carbamazepine and phenytoin in experimental model of acute seizures.

PURPOSE: This study assessed adjuvant potential of Ocimum sanctum hydroalcoholic extract (OSHE) with antiepileptic drugs (AEDs) carbamazepine (CBZ) and phenytoin (PHT) in maximal electroshock seizure (MES) model in male Wistar rats. MATERIAL AND METHODS: Pharmacodynamic effect of OSHE (1000 mg/kg) was assessed through seizure protection potential, neurobehavioral tests and oxidative stress estimation in MES model after 14 days administration of OSHE alone or combination with maximal (M) and sub-maximal (SM) dose of CBZ or PHT. Pharmacokinetic interaction of OSHE with AEDs was also assessed after 14 days of drug treatment. RESULTS: OSHE per se showed 50% protection against MES-induced seizures. Combination of OSHE with AEDs' SM dose enhanced its seizure protection potential. Significant reduction in duration of tonic hind limb extension was observed in CBZ-SM + OSHE as compared to control group (p = 0.006). Among neurobehavioral tests in Morris water maze test rats of CBZ-M + OSHE took significantly less time to reach the platform (p = 0.022) and spent more time in target quadrant (p = 0.016) as compared to other groups. Similarly, rats of PHT-SM + OSHE group spent significantly more time in the target quadrant (p = 0.013). In elevated plus maze test, CBZ-M + OSHE had significantly decreased transfer latency compared to other groups (p = 0.013). OSHE alone treated group had significantly lower oxidative stress as compared to other groups. No significant pharmacokinetic interaction was observed between OSHE and AEDs (CBZ, PHT). CONCLUSION: Ocimum's potential of enhanced seizure protection and neuroprotection along with minimal drug interaction with AEDs substantiate its adjuvant role in the management of epilepsy.

Primary lung carcinoma in cystic fibrosis: A case report and literature review.

Patients with cystic fibrosis (CF) have increased life span because of improved care over last 50 years. With increasing survival, predisposition of cancer may become evident. We have observed increase risk of gastrointestinal tract cancer, testicular cancer and lymphoid leukemia. Lung cancer in patients with CF is rare. Our patient developed chronic respiratory failure due to CF related bronchiectasis. Patient had progressive disease despite optimum treatment, requiring lung transplantation. Pathology of explant lung showed focus of invasive adenocarcinoma of lung origin. Patient had no evidence of lung carcinoma recurrence in one year. To our knowledge this is the fourth reported lung cancer case in a patient with CF.

Postoperative Horner Syndrome After Lung Transplantation.

BACKGROUND: Horner syndrome arises from a disruption along the oculosympathetic efferent chain and can be caused by a variety of pathological and iatrogenic etiologies. We present 3 cases of postoperative Horner syndrome after bilateral lung transplantation. METHODS: The electronic health records of 3 patients with iatrogenic Horner syndrome after lung transplantation were examined, including notes from each patient's medical history, operative and postoperative records, and ophthalmology consultation results. A literature review was performed. RESULTS: All 3 of our patients displayed anisocoria and ptosis, symptoms consistent with Horner syndrome, and the patients from Cases 1 and 2 showed reversal of anisocoria after an application of topical apraclonidine. CONCLUSIONS: Ophthalmologists should be aware of the risk of Horner syndrome after lung transplantation.

An interaction study of Ocimum sanctum L. and levetiracetam in pentylenetetrazole kindling model of epilepsy.

ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum sanctum L. commonly known as tulsi (synonym of Ocimum tenuiflorum L.) is widely used in Ayurveda medicine and is having multitude neuromodulatory effect including the anticonvulsant effect in acute seizure models as per previous studies. In India, it is used for the treatment of epilepsy as traditional medicine. However, its role in chronic seizure model and interaction with newer antiepileptic drugs has not been investigated, which will enhance its translational value. AIM OF THE STUDY: Current study investigated the effect of Ocimum on chronic seizure model and its interaction with levetiracetam (LEV), a newer antiepileptic drug. MATERIALS AND METHODS: The adjuvant role of Ocimum sanctum hydroalcoholic extracts (OSHE) 1000 mg/kg along with LEV 300 mg/kg was studied in adult male Wistar rats with mean weight of 227.84 ± 21.68 g using pentylenetetrazole (30 mg/kg, i.p.) kindling (K) (with maximum 24 injections on alternate days and challenge on 7th-day). Along with seizure score, neurobehavioral, brain tissue oxidative stress and histopathology status were assessed. Pharmacokinetic interaction was assessed between LEV and OSHE after 14 days of drug treatment. RESULTS: K-LEV + OSHE had least seizure score during kindling and on the pentylenetetrazole-challenge test (p=0.031) than other kindling groups. Seizure protection was more in K-LEV + OSHE (85.72%) than others (K-LEV-42.86%, K-OSHE-42.86%, and K-Control-28.58%). Ocimum treated groups had better memory retention potential as evident from Morris water maze (MWM), passive avoidance test but not in an elevated plus maze test. Oxidative-stress was lower in Ocimum treated groups than K-Control group. As per histopathology, K-LEV + OSHE group had the least neuronal degeneration among kindling groups. There was no significant pharmacokinetic interaction between LEV and OSHE, except increased Tmax in LEV + OSHE group than LEV alone (p=0.009). CONCLUSIONS: Ocimum per se and combination with levetiracetam treatment exerted better seizure control, memory retention, oxidative stress reduction, and neuronal structure preservation than kindling control group. There was a very minimal drug interaction between Ocimum and LEV. So, Ocimum as an adjuvant to LEV may be shelpful in enhancing the antiepileptic effect and also in minimizing the adverse effects.

The Houston Methodist Lung Transplant Risk Model: A Validated Tool for Pretransplant Risk Assessment.

BACKGROUND: Lung transplantation is the gold standard for a carefully selected patient population with end-stage lung disease. This study sought to create a risk stratification model using only preoperative recipient data to predict 1-year postoperative mortality during the pretransplant assessment. METHODS: Data of lung transplant recipients at Houston Methodist Hospital in Houston, Texas from January 2009 to December 2014 were extracted from the United Network for Organ Sharing (UNOS) database. Patients were randomly divided into development and validation cohorts. Cox proportional-hazards models were conducted. Variables associated with 1-year mortality after transplantation were assigned weights on the basis of the beta coefficients, and risk scores were derived. Patients were stratified into low-, medium- and high-risk categories. The model was validated using the validation data set and data from other US transplant centers in the UNOS database. RESULTS: The study randomized 633 lung recipients from Houston Methodist Hospital into development (n = 317 patients) and validation cohorts (n = 316). The 1-year survival after transplantation was significantly different among risk groups: 95% (low risk), 84% (medium risk), and 72% (high risk) (P < .001), with a C-statistic of 0.74. Patient survival in the validation cohort was also significantly different among risk groups (85%, 77%, and 65%, respectively; P < .001). Validation of the model with the UNOS data set included 9920 patients and found 1-year survival to be 91%, 86%, and 82%, respectively (P < .001). CONCLUSIONS: Using only recipient data collected at the time of the prelisting evaluation, this simple scoring system was found to have good discrimination power and could be a practical tool in the assessment and selection of potential lung transplant recipients.

Retransplantation Outcomes at a Large Lung Transplantation Program.

BACKGROUND: With the increase of primary lung transplantation across major centers worldwide, over the last several years the need of lung retransplant (ReTX) is likely to increase. Therefore, characterization of ReTX patients is prudent and necessary. Our study aimed to investigate and characterize the covariates and outcomes associated with lung ReTX survival in a single large U.S. transplant center. METHODS: Demographic, clinical diagnoses, and comorbidities were analyzed. Kaplan-Meier statistics were used to calculate and predict survival for 30 days and up to 3 years. Cox proportional modeling was used to determine the variables associated with mortality. RESULTS: Of included 684 lung transplants performed at the Houston Methodist Hospital between January 2009 and December 2015, 49 were lung ReTX. Median age of primary lung transplant (non-ReTX) and ReTx recipients was 62 and 49 years, respectively. Chronic graft rejection in the form of restrictive chronic lung allograft dysfunction and bronchiolitis obliterans syndrome was the main indications for ReTX. Compared with non-ReTX patients, ReTX patients had higher median lung allocation score (46.2 vs 37.0, respectively) and higher mortality after 6 months posttransplant. ReTX, older age, female sex, hospitalization 15 days or longer, estimated glomerular filtration rate less than 60, 6-minute walk distance less than 400 ft, and donor/recipient height ratio less than 1 were significantly associated with decreased 1-year patient and graft survival. Chronic graft rejection was still the major cause of death in the long-term follow-up recipients. CONCLUSIONS: Our findings suggested that lung ReTX recipients have poor long-term survival outcomes. Lung ReTX should only be offered to carefully selected patients.

Association of methacholine challenge test with diagnosis of chronic lung allograft dysfunction in lung transplant patients.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a complication of lung transplantation. We sought to determine whether bronchial hyperresponsiveness detected by the methacholine challenge test (MCT) at 3 months after lung transplant (LT) predicts the development of CLAD. METHODS: We performed a retrospective cohort study of 140 LT patients between 1/2008 and 6/2014 who underwent MCT at 3 months after LT. Pearson's chi-squared test and Kruskal-Wallis test were used to compare categorical and continuous variables, respectively. Cox proportional hazards modeling was used to evaluate the association between CLAD and MCT. RESULTS: Methacholine challenge test+ was associated with the development of overall CLAD (adjusted hazards ratio [aHR]: 3.47; 95% confidence interval [95% CI]: 1.71, 7.03; P = 0.001) and CLAD within 3 years (aHR: 4.98; 95%CI: 1.84, 13.48; P = 0.002). Subgroup analysis showed that MCT (+) is associated with overall CLAD in single lung transplant (SLT) (aHR: 8.18; 95% CI: 2.22, 30.09; P = 0.002), double lung transplant (DLT) (aHR: 3.27; 95% CI: 1.22, 8.78; P = 0.02) and CLAD within 3 years in DLT patients (aHR: 6.76; 95% CI: 1.71, 26.74; P = 0.01). CONCLUSION: Methacholine challenge test+ at 3 months after LT is associated with the development of overall CLAD. Positive MCT could predict the development of early CLAD within 3 years in DLT patients.

A rare case of pulmonary cement embolism in a lung transplant patient.

Pulmonary cement embolism (PCE) is a complication of percutaneous vertebral augmentation techniques. PCE in lung transplant patient population has not been reported. We report a case 57-year-old male patient with double lung transplant secondary to idiopathic pulmonary fibrosis presented with shortness of breath after vertebroplasty. CTA chest showed thin dense opacities within the bilateral pulmonary arteries consistent with pulmonary cement embolism. The patient was treated with therapeutic enoxaparin and remained stable at one year follow up.

Long-Term Survival in Bilateral Lung Transplantation for Scleroderma-Related Lung Disease.

BACKGROUND: Lung disease is the leading cause of morbidity and death in scleroderma patients, but scleroderma is often considered a contraindication to lung transplantation because of concerns for worse outcomes. We evaluated whether 5-year survival in scleroderma patients after lung transplantation differed from other patients with restrictive lung disease. METHODS: This was a single-center, retrospective cohort study of all patients undergoing bilateral lung transplantation for scleroderma-related pulmonary disease between January 2006 and December 2014. This cohort was compared with patients undergoing bilateral lung transplantation for nonscleroderma group D restrictive disease. Primary outcomes reported were 1-year and 5-year survival. Diagnoses were identified by United Network of Organ Sharing listing and were confirmed by clinical examination and prelisting workup. RESULTS: We compared 26 patients who underwent BLT for scleroderma and 155 patients who underwent BLT for group D restrictive disease. Overall, the nonscleroderma cohort was younger, with lower lung allocation score but no difference in functional status. Donor characteristics were not different between the cohorts. Survival at 1 year was not different (73.1% vs 80.0%, p = 0.323). Long-term survival at 5 years was also not significantly different (65.4% vs 66.5%, p = 0.608). Multivariate Cox proportional hazards analysis found no differences in survival between scleroderma and nonscleroderma group D restrictive disease (hazard ratio, 2.19; p = 0.122). CONCLUSIONS: Despite being at high risk for extrapulmonary complications, patients undergoing bilateral lung transplantation for scleroderma have similar 1-year and 5-year survival as those with restrictive lung disease. Transplantation is a reasonable treatment option for a carefully selected population of candidates.

Pharmacokinetic and pharmacodynamic interaction of hydroalcoholic extract of Ocimum sanctum with valproate.

For effective control of seizures, antiepileptic drugs (AEDs) are administered at higher dose which is associated with several adverse effects. This study envisaged antiepileptic and neuroprotective potential of Tulsi, a commonly used herb for its immunomodulatory property. The optimal dose of Ocimum sanctum hydroalcoholic extract (OSHE) was determined using maximal electroshock seizure (MES)- and pentylenetetrazol (PTZ)-induced seizure models in Wistar rats (200-250g) after administering OSHE (200-1000mg/kg) orally for 14days. For interaction study, OSHE optimal dose in combination with maximum and submaximal therapeutic doses of valproate was administered for 14days. Serum levels of valproate were estimated using HPLC for pharmacokinetic study. For pharmacodynamic interaction, antiepileptic effect on above seizure models, neurobehavioral effect using Morris water maze, passive avoidance and elevated plus maze tests, and antioxidant capacity were assessed. Ocimum sanctum hydroalcoholic extract 1000mg/kg was found to be optimal providing 50% protection against both MES- and PTZ-induced seizures. Combination of OSHE with valproate did not alter antiepileptic efficacy of valproate significantly. However, the combination showed better memory retention potential in neurobehavioral tests and protection against oxidative stress compared with valproate-alone-treated groups. Pharmacokinetic parameters did not reveal any significant change in combination group compared with valproate alone. Ocimum, although having per se antiepileptic action, did not affect antiepileptic action of valproate in combination. However, combination treatment has an edge over valproate alone-better neurobehavioral function and reduced oxidative stress-predicting adjuvant potential of Ocimum in epilepsy treatment.

Early clearance vs persistence of de novo donor-specific antibodies following lung transplantation.

BACKGROUND: The natural history of de novo donor-specific antibodies (dnDSA) after lung transplantation is not well-described. We sought to determine the incidence and risk factors associated with dnDSA and compare outcomes between recipients with transient (or isolated) vs persistent dnDSA after transplantation. METHODS: A single-center review of all lung transplants from 1/2009-7/2013. DSAs were tested eight times in the first year and every 4 months thereafter. Outcomes examined included acute rejection and graft failure. RESULTS: Median follow-up was 18 months (range: 1-61 months), and 24.6% of 333 first-time lung-only transplant recipients developed a dnDSA. Ethnicity, HLA-DQ mismatches, post-transplantation platelet transfusion and Lung Allocation Score >60 were associated with dnDSA (P<.05). Overall graft survival was worse for dnDSA-positive vs negative recipients (P=.025). Of 323 recipients with 1-year follow-up, 72 (22.2%) developed dnDSA, and in 25 (34.7%), the dnDSA was transient and cleared. Recipients with transient dnDSA were less likely to develop acute rejection than those with persistent dnDSA (P=.007). CONCLUSIONS: Early post-lung transplantation, dnDSA occurred in 1/4 of recipients, was associated with peri-transplant risk factors and resulted in decreased survival. Spontaneous clearance of dnDSA, seen in one-third of recipients, was associated with a lower risk of acute rejection.