Project description:The treatment of metastatic melanoma patients with autologous tumor-infiltrating lymphocytes (TIL) shows robust, reproducible, clinical responses in clinical trials executed in several specialized centers over the world. Even in the era of targeted therapy and immune checkpoint inhibition, TIL therapy can be an additional and clinically relevant treatment line. This review provides an overview of the clinical experiences with TIL therapy thus far, including lymphodepleting regimens, the use of interleukin-2 (IL-2) and the associated toxicity. Characteristics of the TIL products and the antigen recognition pattern will be discussed, as well as the current and upcoming production strategies, including the selective expansion of specific fractions from the cell product. In addition, the future potential of TIL therapy in melanoma and other tumor types will be covered.
Project description:IntroductionChoroideremia is an X-linked inherited retinal degeneration resulting from mutations in the CHM gene, encoding Rab escort protein-1 (REP1), a protein regulating intracellular vesicular transport. Loss-of-function mutations in CHM lead to progressive loss of retinal pigment epithelium (RPE) with photoreceptor and choriocapillaris degeneration, leading to progressive visual field constriction and loss of visual acuity. Three hundred and fifty-four unique mutations have been reported in CHM. While gene augmentation remains an ideal therapeutic option for choroideremia, other potential future clinical strategies may exist.Areas coveredThe authors examine the pathophysiology and genetic basis of choroideremia. They summarize the status of ongoing gene therapy trials and discuss CHM mutations amenable to other therapeutic approaches including CRISPR/Cas-based DNA and RNA editing, nonsense suppression of premature termination codons, and antisense oligonucleotides for splice modification. The authors undertook a literature search in PubMed and NIH Clinical Trials in October 2020.Expert opinionThe authors conclude that AAV-mediated gene augmentation remains the most effective approach for choroideremia. Given the heterogeneity of CHM mutations and potential risks and benefits, genome-editing approaches currently do not offer significant advantages. Nonsense suppression strategies and antisense oligonucleotides are exciting novel therapeutic options; however, their clinical viability remains to be determined.
Project description:Laparoscopic total adrenalectomy has become the standard treatment for adrenal mass. Meanwhile, there has been a growing trend toward laparoscopic adrenal-sparing surgery worldwide to avoid the risk and potential complications of adrenal insufficiency. The objectives of this study were to describe a retroperitoneoscopic adrenal tumor enucleation technique, to assess the clinical outcomes of this technique in the treatment of 20-40 mm nonsecreting adrenal tumor (NAT) with low potential of malignancy, and to provide a feasible choice for patients who have preference on resection. This study was a retrospective analysis of 61 patients with low potential of malignancy in 20-40 mm NAT identified at the first imaging examination or during follow-up. All patients were scheduled for planned enucleation adrenalectomy by a single surgeon between July 2016 and December 2020 in Xuanwu Hospital, Beijing, China. In all patients, retroperitoneoscopic surgery was performed via a retroperitoneoscopic process for all the patients. The crucial techniques of enucleation are presented in the video. Safety and feasibility factors of enucleation technique were measured for this study. No blood transfusion or organ injury was registered during the operation. The median operation time was 75 min, and the median blood loss was 35 mL. All operations were successfully performed without open conversion. A total of 58 patients received successful enucleation surgery. Three cases were converted to retroperitoneoscopic total adrenalectomy. In this study, surgical outcomes of retroperitoneoscopic enucleation adrenalectomy as a method to remove adrenal tumors were assessed. This procedure is a feasible and safe technique with the added benefit of preserving the remaining functional adrenal tissue.
Project description:Prospective identification of candidates for deferred therapy is not standardized and many patients receive immediate therapy regardless of risk. We conducted a retrospective, multi-center cohort analysis of MCL patients with comprehensive clinical data to examine the use and safety of deferred therapy for newly diagnosed patients. Previously untreated patients ≥18 years-old with MCL diagnosed in 1993-2015 at five academic sites were included. Of 395 patients, 72 (18%) received deferred therapy (defined as receipt of first treatment >90 days following initial diagnosis). Patients receiving deferred therapy were more likely to have an ECOG performance status of 0 (67 versus 44% p = .001), have no B symptoms (83 versus 65% p = .003) and have normal LDH levels at diagnosis (87 versus 55% p < .001). In multivariable analysis, deferred therapy was not associated with a significant difference in OS (HR 0.64: 95% CI 0.22-1.84, p = .407).
Project description:Cystic lesions of the spleen are a rare encounter in surgical practice and are broadly split into two categories: true and false, depending upon the presence of a defined epithelial lining. True cysts can further be broken down into parasitic and non-parasitic origins while false or pseudocysts tend to develop commonly after a traumatic event. We present here a 23-year-old female who came to the clinic with symptoms of abdominal fullness, early satiety and left flank pain which was diagnosed as a large splenic cyst after radiology confirmation. The patient was prepared and underwent laparoscopic splenic cyst fenestration successfully without any complications. Laparoscopic fenestration for benign uncomplicated splenic cysts is a viable alternative to splenectomy with low rates of recurrence and less patient morbidity along with the advantage of preservation of splenic function.
Project description:BackgroundThe purpose of this study was to determine demographic and psychosocial factors that influence the effectiveness of cooled radiofrequency genicular nerve ablation (C-RFA) and block in patients with chronic knee pain secondary to osteoarthritis (OA).MethodsA retrospective review was completed including patients with knee OA who underwent genicular nerve ablation or block or both. Patient information collected included opioid use, psychological comorbidities, smoking history, body mass index, and medical comorbidities. Success was defined using the Osteoarthritis Research Society International criterion of greater than or equal to 50% reported pain relief from the procedure. Patients without a diagnosis of knee OA and patients with ipsilateral total knee arthroplasty were excluded. Patient factors were compared between (1) those that did or did not respond to the initial block and (2) those that did or did not respond to C-RFA.ResultsOf the 176 subjects that underwent genicular nerve block, 31.8% failed to respond to the procedure. Subjects that failed the initial block were significantly more likely to have psychological comorbidities, smoking history, and diabetes. Of the subjects that proceeded to genicular nerve ablation, 53.7% reported less than 50% pain relief, and 46.3% reported pain relief greater than or equal to 50% at the first follow-up visit. While the presence of psychological comorbidities, smoking, and diabetes were associated with first-stage block failures, these patient factors were not associated with second-stage ablation failures.ConclusionsC-RFA may be an effective adjunct therapy as part of a multimodal pain regimen; however, individual patient characteristics must be considered.
Project description:Bacterial whole-genome sequencing in the clinical setting has the potential to bring major improvements to infection control and clinical practice. Sequencing instruments are not currently available in the majority of routine microbiology laboratories worldwide, but an alternative is to use external sequencing providers. To foster discussion around this we investigated whether send-out services were a viable option. Four providers offering MiSeq sequencing were selected based on cost and evaluated based on the service provided and sequence data quality. DNA was prepared from five methicillin-resistant Staphylococcus aureus (MRSA) isolates, four of which were investigated during a previously published outbreak in the UK together with a reference MRSA isolate (ST22 HO 5096 0412). Cost of sequencing per isolate ranged from £155 to £342 and turnaround times from DNA postage to arrival of sequence data ranged from 12 to 63 days. Comparison of commercially generated genomes against the original sequence data demonstrated very high concordance, with no more than one single nucleotide polymorphism (SNP) difference on core genome mapping between the original sequences and the new sequence for all four providers. Multilocus sequence type could not be assigned based on assembly for the two cheapest sequence providers due to fragmented assemblies probably caused by a lower output of sequence data per isolate. Our results indicate that external providers returned highly accurate genome data, but that improvements are required in turnaround time to make this a viable option for use in clinical practice.
Project description:BackgroundWe present a technique for mitral valve (MV) replacement that preserves the anterior mitral leaflet (AML) using complete chordal-sparing mitral valve replacement (CCS-MVR), which maintains the architecture of the left ventricle. This technique is beneficial for patients with functional, degenerative, and infective MV disease who were unable to undergo MV repair. The objective of this study is to ascertain the most efficacious treatment for MV disease. Furthermore, the study will contribute to international guidelines for this procedure and provide data on its efficacy in treating MV disease.MethodsWe performed MV replacement surgery on 161 patients, maintaining the integrity of the entire subvalvular chordae tendineae apparatus. Of these cases, 92 (57.1%) were degenerative, 58 (36.0%) were functional, 9 (5.6%) were infective, and 2 (1.2%) were rheumatic. Of the 93 patients with complicated MV disease, massive calcification was observed in 59 cases (36.6%) and mitral annular disjunction (MAD) was observed in 25 cases (15.5%) while endocarditis with posterior annular abscess was observed in 9 cases (5.6%). The anterior leaflet is detached from its connection to the annulus along the entire extent from the posterior commissure to the anterior commissure. In cases of excess tissue, a section of the free edge of the translocated leaflet must be removed. This must preserve a small section of the edge and the entire chordae tendineae unit. A CCS-MVR requires 24 to 28 individual sutures in routine cases. The AML was reinserted using 12 to 14 single sutures in this specific order: posterior annulus, posterior mitral leaflet, AML, and prosthetic valve.ResultsThe 30-day mortality rate was 8.7%, based on 14 cases. Ten patients, representing 5% of the total, required reoperation after the initial procedure. Out of 140 patients,74 (52.8%) experienced LV reverse remodeling at the six-month follow-up. Female patients exhibited a significantly higher rate of LV reverse remodeling (71% vs. 29%, P<0.001) compared to male patients. Patients with mitral annular calcification and MAD demonstrated significantly higher rates of left ventricular reverse remodeling compared to patients with coronary artery disease (CAD). We can conclude with certainty that male gender, CAD, atrial fibrillation, and preoperative left ventricular end-diastolic volume indexed (LVEDVI) are significant predictors of LV remodeling. We found that the median survival time after CCS-MVR was 39.5 months. The results of the multivariable analysis revealed that patients with MAD had significantly worse survival rates than those without.ConclusionsFor patients presenting with severely calcified posterior mitral annulus, complicated Barlow disease with MAD, or endocarditis involving the posterior annulus, the AML is consolidated with the posterior mitral leaflet to form a neo-annulus. This procedure is safe and effective for a wide range of simple and complex MV pathologies. Its efficacy is unquestionable. It preserves the complete architecture of the left ventricle, avoiding dilatation and promoting reverse remodeling.
Project description:Worldwide, the prevalence of obesity has doubled since 1980 in 70 countries. More than one in three adults now suffer from overweight or obesity. Health problems related to obesity include orthopedic problems, psychiatric conditions, metabolic and cardiovascular diseases, and of increasing concern, cancer. Thus, obesity has an enormous impact on the individual's wellbeing as well as on society's workforce and health care expenses. Medical efforts are ongoing to find safe and effective treatment options for obesity and its metabolic implications. At present, available treatment options include lifestyle interventions, pharmacotherapy, endoscopic applications, and bariatric surgery. Within the range of endoscopic treatment options, the intragastric balloon is the most widely used device. The idea is simple: the gastric volume is reduced by a balloon that is in most cases implanted by an endoscopic procedure similar to a gastroscopy. During the past decades, different models have been developed, which we will briefly introduce in this review. We aim at reviewing the pathophysiology underlying the effect of endoscopic intragastric balloon on weight loss and metabolic changes. We will assess expected short-term and long-term benefits for the patient, and we will discuss common side effects as well as rare complications. We will compare endoscopic intragastric balloon to conservative treatment options with or without pharmacological support on the one hand and to the spectrum of bariatric surgery on the other hand. In most patients, obesity must be considered a chronic disease that requires a lifelong treatment concept. In view of current treatment options for obesity, we will discuss whether endoscopic intragastric balloon is a viable treatment option, and who may be the right patient to benefit from it.