The diagnostic value of image guided percutaneous fine needle aspiration biopsy in equivocal mediastinal masses

Background and aims The aim of this study was to assess the diagnostic value of image guided percutaneous fine needle aspiration (FNA) biopsy in equivocal mediastinal masses.Patients Sixty-six patients with an equivocal mediastinal mass who underwent FNA biopsy between 1993 and 2003 were eligible for final analysis. The cytological and definitive diagnosis of masses were grouped as primary 22 (33%)−30 (46%) and secondary (metastatic) neoplasms 18 (27%)−18 (27%) and nonneoplastic lesions 20 (30%)−18 (%27) respectively.Results The diagnostic accuracy (%95 C.I.) of FNA biopsy for primary mediastinal neoplasms, secondary neoplasms and nonneoplastic lesions were found to be 93.3 (83.8–98.2)%, 100 (95.1–100)%, 93.3 (83.8–98.2)%, respectively.Conclusion Image guided percutaneous FNA biopsy is a safe and highly accurate diagnostic method for equivocal mediastinal masses.     

Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1−CD8+ Tumor-Infiltrating T Cells

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Grandparental genotyping enhances exome variant interpretation

Trio exome sequencing is a powerful tool in the molecular investigation of monogenic disorders and provides an incremental diagnostic yield over proband‐only sequencing, mainly due to the rapid identification of de novo disease‐causing variants. However, heterozygous variants inherited from unaffected parents may be inadvertently dismissed, although multiple explanations are available for such scenarios including mosaicism in the parent, incomplete penetrance, imprinting, or skewed X‐inactivation. We report three probands, in which a pathogenic or likely pathogenic variant was identified upon exome sequencing, yet was inherited from an unaffected parent. Segregation of the variants (in NOTCH1, PHF6, and SOX10) in the grandparent generation revealed that the variant was de novo in each case. Additionally, one proband had skewed X‐inactivation. We discuss the possible genetic mechanism in each case, and urge caution in data interpretation of exome sequencing data. We illustrate the utility of expanding segregation studies to the grandparent generation and demonstrate the impact on exome interpretation strategies, by showing that objective genotype data can overcome subjective parental report of lack of symptoms.     

Childhood Cancer and the Risk of ESKD

BackgroundIncreasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.MethodsTo assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.ResultsOf the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).ConclusionsChildhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.     

Effects of diclofenac and intra-articular morphine/bupivacaine on postarthroscopic pain control

BACKGROUND: This study was undertaken to compare analgesic effects and requirements for supplemental analgesic therapy after knee arthroscopy in patients given intraarticular morphine/bupivacaine, diclofenac i.m., or both compared with placebo. METHOD: In a randomised, double-blind controlled trial 40 patients were divided into four groups. Patients received 25 ml of 0.25% bupivacaine and 2 mg of morphine intraarticularly in group I, 75 mg of diclofenac i.m. in group III, the combination of 75 mg of diclofenac i.m. and 25 ml of 0.25% bupivacaine and 2 mg of morphine intraarticularly in group II, and placebo in group IV. Postoperative analgesia was provided with fentanyl in the recovery room and acetaminophen was given for subsequent pain relief. RESULTS: In the postoperative period, VAS scores for pain were highest in the placebo group, whereas they were lowest in the combination group. VAS scores were significantly lower in group I and II than group IV at the postoperative 2nd hour (p < 0.05). VAS score was significantly lower in group II than groups III and IV at the postoperative 3rd hour (p < 0.01). VAS scores were significantly lower in group I, II and III than group IV at the postoperative 6th hour (p < 0.05). Fentanyl consumption was significantly lower in group II than group IV (p < 0.05). Acetaminophen consumption in groups II and III were significantly lower than group IV (p < 0.05). CONCLUSION: The combination of diclofenac i.m. and intraarticular morphine/bupivacaine appears to be the most beneficial analgesic combination due to its lower VAS scores and supplemental analgesic requirements in the postoperative period.     

Midterm angiographic assessment of coronary artery bypass grafting without cardiopulmonary bypass

BACKGROUND: Coronary bypass surgery that provides good long-term graft patency can be performed on the beating heart as a viable alternative to conventional coronary artery bypass grafting (CABG). METHODS: From September 1993 to December 1996, 696 patients underwent CABG on the beating heart at the Ko?uyolu Heart and Research Hospital in Istanbul. Among them, 70 patients were chosen randomly for angiographic assessment of off-pump coronary artery bypass grafting. RESULTS: The interval from operation to angiography varied from 24 to 61 months (mean, 36.1+/-10.9 months). The patency rate of left internal mammary-left anterior descending artery anastomoses was 95.59% (patency achieved in 65 of 68 patients) and of vein grafts was 47.06% (patency achieved in 16 of 34 patients) (p < 0.0001). The patency rates of grafts anastomosed to the left anterior descending artery were significantly higher than the rates of the grafts anastomosed to the other coronary arteries (95.71% versus 45.45%, p < 0.0001). Multivariate analysis showed that graft type (p < 0.0001) and hyperlipidemia (p = 0.023) were significant predictors for graft occlusion. Left ventricular function improved significantly after CABG (p = 0.04). Reintervention (using percutaneous transluminal cardiac angioplasty) and reoperation rates were 0.97% and 1.4%, respectively. CONCLUSIONS: Off-pump coronary artery bypass grafting appears to produce midterm and long-term patency rates that are comparable to those of conventional techniques; that is especially true in cases of arterial conduits and of conduits anastomosed to the left anterior descending artery.     

Inositol-Related Gene Knockouts Mimic Lithium's Effect on Mitochondrial Function

The inositol-depletion hypothesis proposes that lithium attenuates phosphatidylinositol signaling. Knockout (KO) mice of two genes (IMPA1 or Slc5a3), each encoding for a protein related to inositol metabolism, were studied in comparison with lithium-treated mice. Since we previously demonstrated that these KO mice exhibit a lithium-like neurochemical and behavioral phenotype, here we searched for pathways that may mediate lithium''s/the KO effects. We performed a DNA-microarray study searching for pathways affected both by chronic lithium treatment and by the KO of each of the genes. The data were analyzed using three different bioinformatics approaches. We found upregulation of mitochondria-related genes in frontal cortex of lithium-treated, IMPA1 and Slc5a3 KO mice. Three out of seven genes differentially expressed in all three models, Cox5a, Ndufs7, and Ndufab, all members of the mitochondrial electron transfer chain, have previously been associated with bipolar disorder and/or lithium treatment. Upregulation of the expression of these genes was verified by real-time PCR. To further support the link between mitochondrial function and lithium''s effect on behavior, we determined the capacity of chronic low-dose rotenone, a mitochondrial respiratory chain complex I inhibitor, to alter lithium-induced behavior as measured by the forced-swim and the amphetamine-induced hyperlocomotion paradigms. Rontenone treatment counteracted lithium''s effect on behavior, supporting the proposition suggested by the bioinformatics analysis for a mitochondrial function involvement in behavioral effects of lithium mediated by inositol metabolism alterations.The results provide support for the notion that mitochondrial dysfunction is linked to bipolar disorder and can be ameliorated by lithium. The phenotypic similarities between lithium-treated wild-type mice and the two KO models suggest that lithium may affect behavior by altering inositol metabolism.     

Semantic memory recognition is supported by intrinsic recollection-like processes: “The butcher on the bus” revisited

Dual-process models suggest that recognition memory is independently supported by recollection and familiarity. Current theories attribute recollection solely to hippocampally mediated episodic memory (EM), and familiarity to both episodic and semantic memory (SM) supported by medial temporal lobe cortex (MTLC) and prefrontal cortex. We tested whether, contrary to this view, recollection-like processes also intrinsically support SM recognition and whether MTL structures are involved in their execution. A semantic Process Dissociation Procedure (PDP) with famous and non-famous names was used in three experiments. Experiment 1 revealed that recollection-like processes in semantic memory were not associated with episodic memory for the public events, were predicted by performance on standard SM tasks and were independent of EM tasks, suggesting they are intrinsic to SM. Experiment 2 demonstrated the independence of the two process estimates by showing only familiarity was affected by shifting response criterion while only recollection estimates were significantly altered under divided-attention. Finally experiment 3 tested amnesic patients with varying degrees of hippocampal and MTLC damage. Despite normal overall fame recognition performance, recollection estimates were specifically affected by MTL damage. When damage was primarily hippocampal, only retrograde recollection estimates were reduced, while more extensive MTLC damage led to both retrograde and anterograde recollection deficits. We conclude that recognition of semantic information is supported by at least two independent processes akin to the ones that support EM recognition. Recollection-like processes are intrinsic to SM and likely do not reflect EM contribution to SM performance. Together with previous studies of recollection in remote memory, these data suggest that recollection is not a unitary phenomenon. In EM it involves autonoetic re-experiencing, and is supported by interaction of fronto-temporal networks; in EM and SM it supports retrieval of contextual/associative information regardless of consciousness type, and is dependent on intact MTL function. Familiarity processes and neural substrates may also differ between lifetime familiarity and within-session familiarity.