Ventricular arrhythmias in adult patients following surgical repair of tetralogy of Fallot (TOF) may be challenging to manage and life-threatening. Ventricular tachycardia (VT) is the leading cause ...of sudden cardiac death in this patient population. Radiofrequency catheter ablation (RFCA) constitutes an important treatment modality for VT.
The present study summarizes the outcomes of repaired TOF patients undergoing RFCA for resistant VT.
A systematic literature search of the PubMed and Cochrane databases was performed with respect to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
Eight studies including 106 patients were analyzed. Mean patient age at the time of RFCA was 39.0 ± 15.9 years, male:female ratio was 1.97:1. Programmed ventricular stimulation induced sustained VT in 81.6% (95%CI: 72.7–88.1) of patients. VT recurred shortly after the procedure in 16% (95%CI: 10.2–24.3) and during follow-up in 12.2% (95%CI: 6.3–21.7). The post-procedural use of amiodarone and beta-blockers therapy was decreased from 40% (95%CI: 30.3–51.1) to 20% (95%CI: 8.4–39.6) and from 58% (95%CI: 44.2–70.6) to 28% (95%CI: 14.1–47.8) of patients, respectively. A repeat RFCA procedure was required in 17.5% (95%CI: 11.1–26.4). No in-hospital deaths occurred, while overall mortality rate during a mean follow-up of 73.5 ± 61.4 months was 3% (95%CI: 0.2–10.9).
RFCA can control ventricular dysrhythmias in over 80% of the cases, with zero in-hospital and low overall mortality, while substantially reducing the need for antiarrhythmic drugs.
Background/Aim: Germline copy number variation (CNV) is a type of genetic variant that predisposes significantly to inherited cancers. Today, next-generation sequencing (NGS) technologies have ...contributed to multi gene panel analysis in clinical practice. Materials and Methods: A total of 2,163 patients were screened for cancer susceptibility, using a solution-based capture method. A panel of 52 genes was used for targeted NGS. The capture-based approach enables computational analysis of CNVs from NGS data. We studied the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and of the non-commercial tool panelcn.MOPS. Additionally, we tested the performance of digital multiplex ligation-dependent probe amplification (digitalMLPA). Results: Pathogenic/likely pathogenic variants (P/LP) were identified in 464 samples (21.5%). CNV accounts for 10.8% (50/464) of pathogenic variants, referring to deletion/duplication of one or more exons of a gene. In patients with breast and ovarian cancer, CNVs accounted for 10.2% and 6.8% of pathogenic variants, respectively. In colorectal cancer patients, CNV accounted for 28.6% of pathogenic/likely pathogenic variants. Conclusion: In silico CNV detection tools provide a viable and cost-effective method to identify CNVs from NGS experiments. CNVs constitute a substantial percentage of P/LP variants, since they represent up to one of every ten P/LP findings identified by NGS multigene analysis; therefore, their evaluation is highly recommended to improve the diagnostic yield of hereditary cancer analysis.
IntroductionSo far, investigations in patients with rotator cuff diseases have used pain measurement tools such as visual analog scale (VAS) for nociceptive pain as well as neuropathic pain (NeuP) ...specialized ones like Douleur Neuropathique 4 Question (DN4) and Pain Detect. The study’s goal was to look at the existence of NeuP in patients with chronic shoulder pain, as well as variables that may be predictive of its progression.MethodsThere were 112 outpatients in all. Current and previous pain intensity levels were documented with the numerical rating scale (NRS), the Shoulder Pain and Disability Index (SPADI) was used to assess pain and disability levels, and the S-LANSS (self-completed Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale) was used to diagnose NeuP. The Pearson Chi-Square test was employed to check for any relationships between variables. The Mann-Whitney U test was also employed to check for between-group differences (with or without NeuP). To investigate factors that may be utilized as a prognostic for NeuP, logistic regression was performed, with those components (from the univariate analysis) that were statistically significant being included.ResultsAccording to the S-LANSS questionnaire for NeuP diagnosis, 21 patients had NeuP. According to S-LANSS, chi-square test findings revealed that NeuP is independent of sex, smoking, size, and location or rotator cuff tear. Univariate analysis with Mann-Whitney U test revealed statistically significant differences in SPADI and NRS scores between the two patient groups (p < 0.001). Α multivariate analysis using S-LANSS as the binary dependent variable and NRS currently, NRS average last month and SPADI total score as independent variables (with statistical significance) revealed that total SPADI score may be considered as an independent prognostic factor for NeuP (odds ratio = 1.189, p < 0.001).LimitationsDue to the limited number of patients who participated in the study, the findings were deemed insufficient in terms of statistical power. In particular, the power analysis of the study (type I error probability being a = .05) was less than 80% (for the total SPADI score), hence relatively small. As a result, there is a limited probability of a type I error.ConclusionsUsing S-LANSS, we discovered that 18.8% of patients with rotator cuff tears had NeuP. The SPADI scores (pain and disability) in the NeuP group were substantially greater than in the nociceptive pain group. As previous studies have suggested utilizing certain levels of the VAS for pain assessment and specialized questionnaires for NeuP evaluation, we recommend that SPADI be included as a tool for emphasizing the neuropathic features of shoulder pain.
To evaluate the effect of immunotherapy on response, survival, and certain immune markers in patients with small cell lung cancer (SCLC) who are receiving chemotherapy.
Patients with SCLC (n = 164) ...were assigned to receive either chemotherapy alone (group A) or a combination of chemotherapy and immunotherapy as follows: interferon α (IFN-α; 3 million IU) 3 times per week (group B); IFN-γ (3 million IU) 3 times per week (group C); and IFN-α and IFN-γ (1.5 million IU of each) 3 times per week (group D). Chemotherapy was the same for all groups and consisted of eight cycles with carboplatin 5.5 mg/m(2) intravenously on day 1, ifosfamide 3.5 mg/m(2) intravenously on day 1, and etoposide 200 mg/m(2) total dose taken orally on days 1 through 3, every 28 days. Patients completing chemotherapy were restaged, and those who were found to have limited disease received primary site and prophylactic cranial irradiation. Immunotherapy was continued throughout these treatments and during the follow-up period. Blood was taken before each course of chemotherapy and during follow-up to measure CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, natural killer cells, and natural killer T cells.
Differences in response and survival were not significantly different when all patients were considered. However, among patients with limited disease, Kaplan-Meier analysis disclosed a survival benefit for group B (P , 0.05). The analysis of immunologic measurements revealed that the improvement of immune markers was always accompanied by clinical improvement, whereas deterioration of all markers was accompanied by disease progression (result not statistically significant except for group C; P , 0.05).
Among cytokines used in the study, only IFN-α seems to confer a survival benefit to patients with SCLC with limited disease. However, immunotherapy remains a challenge in the treatment of lung neoplasms and should be further explored.
During the last years, translational research has contributed in many advances in the treatment of non-small cell lung cancer (NSCLC) discovering genetic alternations or recognizing the immuno-escape ...and neo-angiogenesis of lung cancer. Although the majority of these advances took place in the non-squamous histological subtype, therapeutic options for patients diagnosed with advanced squamous cell lung cancer (SqCLC) have been also enriched significantly with the addition of nab-paclitaxel in the conventional chemotherapy; the introduction of necitumumab, afatinib and erlotinib in the inhibition of epidermal growth factor receptor (EGFR) axis and of ramucirumab in the inhibition of VEGF-induced angiogenesis and last with the approvals of nivolumab, pembrolizumab atezolizumab and durvalumab soon in the promising field of immunotherapies. Agents targeted various other pathways including FGFR, IGF-1, PI3K, CDK4/6, MET and PARP inhibitors are under investigation in order to open new prospects in the treatment of SqCLC. In this review, we present all published data that led to recent approvals for the treatment of advanced SqCLC and all ongoing clinical trials that keep searching for new molecular targets following a more-personalized approach.
Carfilzomib (CFZ) is a non-reversible proteasome inhibitor approved for the treatment of patients with relapsed or refractory myeloma (RRMM), either in combination with dexamethasone (Kd) or with ...lenalidomide and dexamethasone (KRd). CFZ has been associated with a risk of cardiovascular toxicity but although a signal of clinically significant renal complications has also been identified, renal toxicity is less extensively investigated. Thus, we analyzed the data of 114 consecutive patients who received CFZ for RRMM in our center (Department of Clinical Therapeutics, Athens, Greece) for renal outcomes and complications.
Detailed baseline characteristics and medical history (demographics, history of renal and cardiovascular diseases, diabetes, medication use) and detailed data on myeloma status, proteinuria and urine electrophoresis, serum free light chains (sFLC), serum creatinine and cardiovascular complications were available in all patients for the duration of CFZ therapy.
Median age was 70 years (range 36-86, 25% were ≥75) and 60.5% were men. Median number of prior therapies was 2 (range 1-7): 78% had prior bortezomib, 73% prior IMiDs, 27% prior anthracyclines and 46.5% prior ASCT. CFZ dose was 20/27 in 30%, 20/36 in 11% and 20/56 in 59%; 75% received Kd, 14% received KRd and 11% other CFZ-based combinations. Median follow up from start of CFZ is 27 months, median duration of CFZ therapy is 5.5 months (IQR 3.2 to 11.5) and 28 (24.5%) patients continue on CFZ therapy at the time of analysis.
During CFZ therapy, 19 (17%) patients developed renal complications, not related to MM progression: 6 (5%) developed thrombotic microangiopathy (TMA), 7 (6%) developed albuminuria > 1gr/day (in all with very low amounts of light chains or with negative urine immunofixation) and 6 (5%) developed acute kidney injury/ acute renal failure (AKI/ARF) at least grade 3, which was not otherwise explained. Median time to development of renal complications was 62 days (~2 months) (IQR 35 to 272) and in 15/19 patients CFZ was discontinued due to renal complications. Median time from CFZ start to TMA was 3 months (0.3-19.5). At diagnosis of TMA, median platelet counts were 20x109/L (range 11-30), median hemoglobin 8 gr/dl, median LDH 449 IU/L (ULN<225, range 371-619) and median blood schistocytes were 2.5% (range 2%-6.5%). All received plasmapheresis: 5 recovered renal function and platelet counts while one died of sepsis. In 2 patients in whom ADAMTS13 was measured, no deficiency was found. No patient was re-exposed to CFZ after TMA. Median time to proteinuria >1 gr/d was 6 months (range 2-59 months), median proteinuria was 3.7 gr/d (range 1 - 4.5) and in all cases >90% of urine protein was albumin; all patients were in disease remission (VGPR or CR); median eGFR was 53 ml/min/1.73 m2 (range 41-92). Only one patient had proteinuria before CFZ which was mainly Bence Jones proteinuria. Following interruption of CFZ, proteinuria decreased in 2/7 patients and in one patient CFZ was resumed at a reduced dose.
A renal biopsy was performed in 5/6 patients with albuminuria and one with AKI: none had immunoglobulin mediated pathology (cast nephropathy, MIDD or amyloidosis) or pathology related to the alternative complement activation pathway. The most constant finding (in all patients with albuminuria), was a pattern of focal segmental glomerulosclerosis (FSGS) of various subtypes. Coexistent with the previous lesions, a pattern of TMA with intraglomerular and/or arteriolar fibrin microthrombi and/or mucoid degeneration of arteriolar/arterial wall and/or reduplication of glomerular basement membranes with endothelial cells' swelling, was seen in 4 biopsies.
We found no association between CFZ dose with renal complications or of baseline proteinuria (immunoglobulin or albumin), sFLC or myeloma type, age, prior history of cardiovascular disease or hypertension or baseline eGFR. Among 33 patients with baseline eGFR < 60 ml/min, 18 (54.5%) patients improved their eGFR to >60 ml/minafter CFZ therapy.
We conclude that renal complications during CFZ therapy are common, occur mostly early and are essentially unpredictable. Albuminuria associated with FSGS and TMA developed in 6% and 5% of our patients respectively and warrant further investigation. A potential effect of CFZ on the renal endothelium could be implicated in the pathogenesis of these complications and may also share common pathophysiology with cardiovascular effects of CFZ.
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Kastritis:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees. Terpos:Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; BMS: Consultancy; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of DMC, Research Funding; Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding; Novartis: Consultancy. Dimopoulos:Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria.
The pan-cancer presence of microsatellite instability (MSI)-positive tumors demonstrates its clinical utility as an agnostic biomarker for identifying immunotherapy-eligible patients. Additionally, ...MSI is a hallmark of Lynch syndrome (LS), the most prevalent cancer susceptibility syndrome among patients with colorectal and endometrial cancer. Therefore, MSI-high results should inform germline genetic testing for cancer-predisposing genes. However, in clinical practice, such analysis is frequently disregarded.
A next-generation sequencing (NGS)-based technique was used for MSI analysis in 4,553 patients with various tumor types. Upon request, somatic
gene analysis was conducted. In addition, hereditary testing of cancer-associated genes was performed in MSI-high cases using a capture-based NGS protocol.
promoter methylation analysis was conducted retrospectively in patients with colorectal and endometrial cancer to further investigate the origin of MSI at the tumor level.
The MSI positivity rate for the entire cohort was 5.27%. Endometrial, gastric, colorectal, urinary tract, and prostate cancers showed the highest proportion of MSI-high cases (15.69%, 8.54%, 7.40%, 4.55%, and 3.19%, respectively). A minority of 45 patients (22.73%) among the MSI-high cases underwent germline testing to determine whether the mismatch repair pathway deficiency was inherited. 24.44% of those who performed the genetic test carried a pathogenic variant in an LS-associated gene. Three MSI-high individuals had non-LS gene alterations, including
,
, and
pathogenic variants, indicating the presence of non-LS-associated gene alterations among MSI-high patients.
Although MSI analysis is routinely performed in clinical practice, as many as 77% of MSI-high patients do not undergo LS genetic testing, despite international guidelines strongly recommending it.
and
methylation analysis could shed light on the somatic origin of MSI in 42.50% of the MSI-high patients; however,
analysis is barely ever requested in clinical practice.
Introduction
Obstructive sleep apnea (OSA) in children has been associated with systemic inflammation and oxidative stress. Limited evidence indicates that pediatric OSA is associated with oxidative ...stress and inflammation in the airway.
Objective
The objective of this study is to assess the hypothesis that levels of oxidative stress and inflammatory markers in the exhaled breath condensate (EBC) of children with OSA are higher than those of control subjects.
Methods
Participants were children with OSA and control subjects who underwent overnight polysomnography. Morning levels of hydrogen peroxide (H
2
O
2
) and sum of nitrite and nitrate (NO
x
) in EBC of participants were measured.
Results
Twelve subjects with moderate-to-severe OSA (mean age ± standard deviation: 6.3 ± 1.7 years; apnea–hypopnea index—AHI, 13.6 ± 10.1 episodes/h), 22 subjects with mild OSA (6.7 ± 2.1 years; AHI, 2.8 ± 1 episodes/h) and 16 control participants (7.7 ± 2.4 years; AHI, 0.6 ± 0.3 episodes/h) were recruited. Children with moderate-to severe OSA had higher log-transformed H
2
O
2
concentrations in EBC compared to subjects with mild OSA, or to control participants: 0.4 ± 1.1 versus −0.9 ± 1.3 (
p
= 0.015), or versus −1.2 ± 1.2 (
p
= 0.003), respectively. AHI and % sleep time with oxygen saturation of hemoglobin <95% were significant predictors of log-transformed H
2
O
2
after adjustment by age and body mass index
z
score (
p
< 0.05). No significant differences were demonstrated between the three study groups in terms of EBC NO
x
levels.
Conclusions
Children with moderate-to-severe OSA have increased H
2
O
2
levels in morning EBC, an indirect index of altered redox status in the respiratory tract.
Inadequate treatment of severe burn injury often results in scar contractures with subsequent functional impairment and cosmetic deformities depending on the body area involved. Arm-thorax synechia ...is a rare but devastating complication of burns. The authors report a case of a 17-year-old boy with subtotal arm-thorax synechia, secondary to burn contracture. Reconstruction was accomplished, in two stages, with the use of tissue expanders and a latissimus dorsi muscle flap. The postoperative course was uneventful in both stages, with complete survival of both the expanded skin and the muscle flap. Early initiation of intensive rehabilitation resulted in excellent functional outcome, while significant aesthetic improvement was also ensured. In conclusion, the combined use of tissue expansion and latissimus dorsi transfer may prove to be a very good option in the treatment of complex postburn axillary contractures. The main advantages of the suggested method are the best quality of skin provided by tissue expansion and the safe coverage of any vital structures exposed with the use of the muscle flap.
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