Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma

AbstractDevelopment of anti-drug antibodies (ADAs) can interfere with therapeutic monoclonal antibodies and may lead to drug neutralisation and clinical disease progression. Measurement of circulating drug levels and development of ADAs in the setting of anti-programmed cell death-1 agent pembrolizumab has not been well-studied. Enzyme-linked immunosorbent assays were used to measure pembrolizumab drug level and ADAs in 41 patients with melanoma at baseline, Time-point 1 (3 weeks) and Time-point 2 (21 weeks). Assay results were related to patient demographics and clinical outcome data at 6 months. The median pembrolizumab drug level at 3 weeks was 237 ng/μL and did not correlate with age, sex or body surface area.17/41 patients had an ADA detected at any timepoint, with the highest prevalence at Timepoint 1 (median concentration = 17 ng/μL). The presence of an ADA did not correlate with clinical progression at 6 months. 3/41 (7%) of patients displayed a falling pembrolizumab drug level and rising ADA titre between Timepoint 1 and 2 suggestive of a neutralising ADA. Pembrolizumab drug levels and ADAs can be readily measured. The rates of total and treatment-emergent ADAs may be higher in “real-word” settings than those previously reported. Larger studies are needed to determine effect of neutralising ADAs on long-term clinical outcome.

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Immunosuppressive Drug Levels in Liver Transplant Recipients: Impact in Decision Making

Seminars in Liver Disease ◽

10.1055/s-0039-1688443 ◽

2019 ◽

Vol 39 (04) ◽

pp. 414-421

Author(s):

Themistoklis Kourkoumpetis ◽

Josh Levitsky

Keyword(s):

Side Effects ◽

Liver Transplant ◽

Graft Function ◽

Drug Level ◽

Immunosuppressive Drug ◽

Clinical Impression ◽

Drug Levels ◽

Monitoring Strategies ◽

Liver Transplant Recipients

AbstractTo prevent rejection, liver transplant providers largely base their management decisions on their clinical impression and pharmacokinetics. Clinical impression relies on assessing graft function, liver enzymes, and biopsy. High immunosuppressive drug levels, although minimizing rejection, are related to significant side effects such as nephrotoxicity and metabolic syndrome, contributing to long-term morbidity and mortality. Similarly, levels that are lower than necessary can decrease the rate of side effects with a potential toll on rejection and graft survival. Herein, the authors present an update on immunosuppressive drug level monitoring and manipulation strategies according to different scenarios and time from transplant. They also provide a brief overview of next level immunosuppression monitoring strategies that aim to properly balance rejection rates with drug side effect profiles.

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Re-Appraisal Learning Curve of Laparoscopic Roux-En Y Gastric Bypass: Results of One Hundred and Eight Cases From A Low Volume Unit

10.21203/rs.3.rs-103556/v1 ◽

2020 ◽

Author(s):

Hung Chieh Lo ◽

Sheng-Mao Wu

Keyword(s):

Gastric Bypass ◽

Learning Curve ◽

Operation Time ◽

Outcome Data ◽

Patient Demographics ◽

Group A ◽

Volume Unit ◽

Group B ◽

Modern Era

Abstract Background The study aim was to reevaluate the learning curve of laparoscopic Roux-en Y gastric bypass (LRYGB) in the modern era considering a single surgeon’s experience.Methods Except those with body mass index (BMI) >50 kg/m2 needs further discussion; all other patients who met the regional criteria and underwent primary LRYGB were retrospectively enrolled. Those who underwent surgery in 2016-17, 2018 and 2019 by a single surgeon with 10+ years of laparoscopic experience were assigned to groups A, B and C, respectively. Patient demographics and 30-day outcome data, including operation time, length of stay (LOS), emergency room visits, readmission, and reoperation, were compared between groups.Results One hundred and eight patients met the inclusion criteria; 36, 38, and 34 patients were assigned to groups A, B and C, respectively. There were no differences in age, sex distribution or common comorbidities between groups, except group B had a lower BMI (35.1 kg/m2 vs. 37.0 kg/m2) and a higher rate of hypertension (44.7% vs. 22.2%) than group A. The operation time was markedly reduced (96.1 min and 114.9 min, respectively), and the LOS was shortened (2.2 days and 2.9 days, respectively) in group B compared to group A and remained stationary in group C, with no further reduction in 30-day complications.Conclusion The learning process for LRYGB can be shortened to approximately 30 cases if conducted selectively and by experienced laparoscopic surgeons. Further follow-up is required to verify the long-term safety and its applicability to other patient subgroups.

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Reappraisal learning curve of laparoscopic Roux-en Y gastric bypass: retrospective results of one hundred and eight cases from a low-volume unit

BMC Surgery ◽

10.1186/s12893-021-01058-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hung-Chieh Lo ◽

Sheng-Mao Wu

Keyword(s):

Gastric Bypass ◽

Learning Curve ◽

Operation Time ◽

Outcome Data ◽

Patient Demographics ◽

Group A ◽

Volume Unit ◽

Group B ◽

Modern Era

Abstract Background This study aimed to reevaluate the learning curve of laparoscopic Roux-en Y gastric bypass (LRYGB) in the modern era while considering a single surgeon’s experience. Methods From the beginning of our LRYGB practice, all patients who met the regional criteria and underwent primary LRYGB were retrospectively enrolled. Patients with a body mass index (BMI) > 50 kg/m2 were excluded. Those who underwent surgery in 2016–17, 2018 and 2019 by a single surgeon with 10 + years of laparoscopic experience were assigned to groups A, B and C, respectively. The patient demographics and 30-day outcome data, including the operation time, length of stay (LOS), emergency room visits, readmission, and reoperation, were compared among the groups. Results One hundred and eight patients met the inclusion criteria; 36, 38, and 34 patients were assigned to groups A, B and C, respectively. There were no differences in age, sex distribution or common comorbidities among the groups; however, B had a lower BMI (35.1 kg/m2 vs. 37.0 kg/m2) and a higher rate of hypertension (44.7% vs. 22.2%) than group A. The operation time was markedly reduced (96.1 min and 114.9 min, p < 0.001), and the LOS was shortened (2.2 days and 2.9 days, p < 0.001) in group B compared to group A and remained stationary in group C, with no further reduction in 30-day complications. Conclusion The learning process of LRYGB can be shortened to approximately 30 cases if conducted selectively by experienced laparoscopic surgeons. Further follow-up is required to verify the long-term safety and applicability in other patient subgroups.

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Life Interrupted: The Nature and Consequences of Cryostasis

Seminars in Reproductive Medicine ◽

10.1055/s-0038-1676850 ◽

2018 ◽

Vol 36 (05) ◽

pp. 273-279

Author(s):

Henry Malter

Keyword(s):

Clinical Outcome ◽

Assisted Reproduction ◽

Basic Science ◽

Large Body ◽

Outcome Data ◽

Cryogenic Temperatures ◽

Clinical Protocols ◽

And Storage ◽

Established Technique

AbstractCryopreservation and associated cryostorage has become a well-established technique in both basic and clinical science. When the potentially lethal consequences of freezing itself are ameliorated, existence at cryogenic temperatures seems to be a form of true viable stasis that can persist for long periods of time. Natural cryopreservation and revival after long-term periods in cryostasis is reality in many species. While some evidence exists for imperfections in artificial cryopreservation protocols and storage, these protocols are for the most part successful and compatible with efficient restoration of vitality in a variety of biomaterial after freezing. Clinical protocols in use for cryopreserving and storing gametes and embryos in human-assisted reproduction are similarly well proven and supported by a large body of basic science and clinical outcome data.

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An enzymatic assay to measure long-term adherence to pre-exposure prophylaxis and antiretroviral therapy

10.1101/832410 ◽

2019 ◽

Cited By ~ 1

Author(s):

Ayokunle O. Olanrewaju ◽

Benjamin P. Sullivan ◽

Jane Y. Zhang ◽

Andrew T. Bender ◽

Derin Sevenler ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Reverse Transcriptase ◽

Fluorescent Dyes ◽

Antiviral Drug ◽

Drug Level ◽

Poor Adherence ◽

Standard Drug ◽

Drug Levels ◽

Exposure Prophylaxis

AbstractPoor adherence to pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) can lead to human immunodeficiency virus (HIV) acquisition and emergence of drug resistant infections, respectively. Measurement of antiviral drug levels provides objective adherence information that may help prevent adverse health outcomes. Gold standard drug-level measurement by liquid chromatography/mass spectrometry is centralized, heavily instrumented, and expensive and is thus unsuitable and unavailable for routine use in clinical settings. We developed the REverse TranscrIptase Chain Termination (RESTRICT) assay as a rapid and accessible measurement of drug levels indicative of long-term adherence to PrEP and ART. The assay uses designer single stranded DNA templates and intercalating fluorescent dyes to measure complementary DNA (cDNA) formation by reverse transcriptase in the presence of nucleotide reverse transcriptase inhibitor drugs. We developed a probabilistic model for the RESTRICT assay by calculating the likelihood of incorporation of inhibitors into cDNA as a function of the relative concentrations of inhibitors and nucleotides. We validated the model by carrying out the RESTRICT assay using aqueous solutions of tenofovir diphosphate (TFV-DP), a measure of long-term adherence to PrEP and ART. We used dilution in water as a simple sample preparation strategy to detect TFV-DP spiked into blood. The RESTRICT assay accurately distinguishes TFV-DP drug levels within the clinical range for adherence and has the potential to be a useful test to identify patients with poor adherence to ART and PrEP.

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Microsurgical Treatment of Basilar Apex Aneurysms: Perioperative and Long-term Clinical Outcome

Neurosurgery ◽

10.1227/01.neu.0000103222.13642.00 ◽

2004 ◽

Vol 54 (2) ◽

pp. 286-299 ◽

Cited By ~ 56

Author(s):

Alan P. Lozier ◽

Grace H. Kim ◽

Robert R. Sciacca ◽

E. Sander Connolly ◽

Robert A. Solomon

Keyword(s):

Subarachnoid Hemorrhage ◽

Clinical Outcome ◽

Giant Aneurysm ◽

Outcome Data ◽

Surgical Morbidity ◽

Detachable Coil ◽

Entire Cohort ◽

Guglielmi Detachable Coil

Abstract OBJECTIVE We sought to analyze the perioperative and long-term clinical outcome data for patients with microsurgically treated basilar apex aneurysms. METHODS We identified 98 consecutively treated basilar apex aneurysms in patients prospectively enrolled in a cerebral aneurysm database. RESULTS Fifty patients presented with subarachnoid hemorrhage, and 19 aneurysms were giant. Eighty-four of 98 aneurysms were directly clipped. Surgical morbidity was 19.4% for the entire cohort and 8.8% for the unruptured, nongiant subgroup. The most common complication resulting in long-term morbidity was perforator injury. Sixty-seven percent of patients with clipped aneurysms were independent at discharge; this fraction increased to 79.0% at the 3-month follow-up examination. Good long-term outcomes (modified Rankin Scale score ≤2) were achieved in 56 (70%) of 80 cases. The mean Barthel Index of surviving patients was 95.8 ± 15.0 (median = 100, n = 66). Patients with unruptured, nongiant lesions fared considerably better than patients in other cohorts. Ninety-three percent of this subgroup was independent at discharge; this fraction increased to 100% at the 3-month follow-up examination (n = 27). In univariate analyses, poor clinical grade, giant aneurysm size, major operative complications, and operations performed early in the series were associated with worse outcomes. In the multivariate analysis, unruptured giant aneurysm status was found to confer a tremendous risk for poor outcome (risk ratio, 80.0; 95% confidence interval, 8.0–800.7; P < 0.01). Surviving patients were observed for a mean clinical follow-up period of 7.4 ± 3.7 years. The annual rate of postoperative subarachnoid hemorrhage was 0.18% for all clipped aneurysms and 0% for completely clipped lesions. CONCLUSION In comparison to data from the existing literature regarding Guglielmi detachable coil embolization of basilar apex aneurysms, the data presented suggest that surgical clipping should be an important component of a multimodality approach to the treatment of patients with basilar apex aneurysms.

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Predictors of short – and long-term clinical outcome in schizophrenic psychosis – the Northern Finland 1966 Birth Cohort study

European Psychiatry ◽

10.1016/j.eurpsy.2011.11.001 ◽

2013 ◽

Vol 28 (5) ◽

pp. 263-268 ◽

Cited By ~ 21

Author(s):

P. Juola ◽

J. Miettunen ◽

J. Veijola ◽

M. Isohanni ◽

E. Jääskeläinen

Keyword(s):

Clinical Practice ◽

Clinical Outcome ◽

Birth Cohort ◽

Population Based ◽

Outcome Data ◽

Birth Cohort Study ◽

Term Outcome ◽

Long Term Outcome ◽

Insidious Onset

AbstractObjective:Since the outcome in schizophrenia is heterogeneous and often poor, identification of specific predictors of outcome would be useful in clinical practice.Methods:Subjects with schizophrenic psychoses (n = 103) included in the Northern Finland 1966 Birth Cohort (n = 12,058), representing the general population, were followed-up for an average of 16.4 years. Predictor and outcome data were collected from the nationwide Finnish Hospital Discharge Register, hospital records and interviews.Results:Insidious onset of illness predicted a rehospitalization due to psychosis in the 2 years after the initial discharge. Being single, having an early onset, insidious onset, suicidal ideations upon the first admission, a rehospitalization and a high number of treatment days due to psychosis in the early stages of the illness all predicted a poorer clinical outcome in the longer term, after a minimum follow-up of 10 years.Conclusions:This population-based study indicates that clinical and sociodemographic factors around the onset of illness have significance for the long-term outcome in schizophrenia. These prognostic factors should be taken into account in clinical practice.

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