Computed tomography patterns of pulmonary and pleural involvement in lymphoma.

BACKGROUND: Pulmonary and pleural involvement is fairly common in patients with lymphoma, especially in the setting of progressive or recurrent disease. Pleuropulmonary involvement in lymphoma may occur as a single pattern or as a combination of multiple patterns which can often mimic unrelated pathologies. METHODS: Review of our institutional database from 01 Jan 2015 to 04 Oct 2017 revealed 90 patients with pulmonary and/or pleural lesions attributable to lymphoma. These lesions were classified into various categories, and the pattern of involvement was evaluated. RESULTS: Pulmonary involvement was seen in 17.6% of patients with Hodgkin lymphoma (HL) and in 10.5% of patients with non-Hodgkin lymphoma (NHL), whereas pleural involvement was seen in 6.5% of patients with NHL. Almost all the patients in our study had findings belonging to multiple categories. Pulmonary involvement in patients with HL was seen in the form of nodules (51.6%), masses (51.6%), and direct extension from a mediastinal/hilar mass (45.2%). Patients with NHL had pulmonary involvement in the form of nodules (42.4%), direct extension from a mediastinal/hilar mass (25.4%), pulmonary masses (18.6%), and interstitial pattern (2.4%). Pleural thickening (61.5%), masses (30.8%), and effusion (15.4%) were the three patterns of pleural involvement. CONCLUSION: Nodules and masses were the two commonest patterns of pulmonary involvement in patients with HL, whereas nodules were the commonest pattern noted in patients with NHL. Pulmonary masses were seen more commonly in patients with HL than in those with NHL. Pleural involvement was seen exclusively in patients with NHL.

Mitochondrial transcription factor A regulation of mitochondrial degeneration in experimental diabetic neuropathy.

Oxidative stress-induced mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage in peripheral neurons is considered to be important in the development of diabetic neuropathy. Mitochondrial transcription factor A (TFAM) wraps mtDNA and promotes mtDNA replication and transcription. We studied whether overexpression of TFAM reverses experimental peripheral diabetic neuropathy using TFAM transgenic mice (TFAM Tg) that express human TFAM (hTFAM). Levels of mouse mtDNA and the total TFAM (mouse TFAM + hTFAM) in the dorsal root ganglion (DRG) increased by approximately twofold in the TFAM Tg mice compared with control (WT) mice. WT and TFAM Tg mice were made diabetic by the administration of streptozotocin. Neuropathy end points were motor and sensory nerve conduction velocities, mechanical allodynia, thermal nociception, and intraepidermal nerve fiber density (IENFD). In the DRG neurons, mtDNA copy number and damage to mtDNA were quantified by qPCR, and TFAM levels were measured by Western blot. Mice with 16-wk duration of diabetes developed motor and sensory nerve conduction deficits, behavioral deficits, and intraepidermal nerve fiber loss. All of these changes were mostly prevented in diabetic TFAM Tg mice and were independent of changes in blood parameters. Mice with 16 wk of diabetes had a 40% decrease in mtDNA copy number compared with nondiabetic mice (P < 0.01). Importantly, the mtDNA copy number in diabetic TFAM Tg mice reached the same level as that of WT nondiabetic mice. In comparison, there was upregulation of mtDNA and TFAM in 6-wk diabetic mice, suggesting that TFAM activation could be a therapeutic strategy to treat peripheral neuropathy.

Clinical EEG slowing correlates with delirium severity and predicts poor clinical outcomes.

OBJECTIVE: To determine which findings on routine clinical EEGs correlate with delirium severity across various presentations and to determine whether EEG findings independently predict important clinical outcomes. METHODS: We prospectively studied a cohort of nonintubated inpatients undergoing EEG for evaluation of altered mental status. Patients were assessed for delirium within 1 hour of EEG with the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) and 3D-CAM severity score. EEGs were interpreted clinically by neurophysiologists, and reports were reviewed to identify features such as theta or delta slowing and triphasic waves. Generalized linear models were used to quantify associations among EEG findings, delirium, and clinical outcomes, including length of stay, Glasgow Outcome Scale scores, and mortality. RESULTS: We evaluated 200 patients (median age 60 years, IQR 48.5-72 years); 121 (60.5%) met delirium criteria. The EEG finding most strongly associated with delirium presence was a composite of generalized theta or delta slowing (odds ratio 10.3, 95% confidence interval 5.3-20.1). The prevalence of slowing correlated not only with overall delirium severity (R 2 = 0.907) but also with the severity of each feature assessed by CAM-based delirium algorithms. Slowing was common in delirium even with normal arousal. EEG slowing was associated with longer hospitalizations, worse functional outcomes, and increased mortality, even after adjustment for delirium presence or severity. CONCLUSIONS: Generalized slowing on routine clinical EEG strongly correlates with delirium and may be a valuable biomarker for delirium severity. In addition, generalized EEG slowing should trigger elevated concern for the prognosis of patients with altered mental status.

Radial endobronchial ultrasound for the diagnosis of bronchoscopically invisible lesions: First case series from India.

BACKGROUND: A peripheral, bronchoscopically invisible pulmonary lesion is a diagnostic challenge. Transthoracic needle aspiration has long been the investigation of choice but runs the risk of pneumothorax (up to 44%). Newer technologies like radial endobronchial ultrasound (R-EBUS) offer a safer approach. We present our results of R-EBUS in the diagnosis of bronchoscopically invisible lesions. This is the first large case series from India. AIMS: (1) To determine the yield of R-EBUS for the diagnosis of bronchoscopically invisible lesions. (2) To compare the yields of forceps versus cryobiopsies in the diagnosis of these lesions. SETTING: Tertiary care cancer center. DESIGN: Prospective study. METHODS: Consecutive patients presenting between January and October 2015 with bronchoscopically invisible peripheral pulmonary lesions were included. R-EBUS was used to localize and sample the lesion and the yields were analyzed. Yields of cryo and forceps biopsy were compared where both methods had been used. Data were analyzed using SPSS version 22. RESULTS: A definite diagnosis obtained in 67.3% (37/55) patients with no major complications. No significant difference was found in yield between: (1) small (<3 cm) and large (>3 cm) lesions: (46.2% versus 78.6%, P = 0.38). (2) central and adjacent lesions: 61.5% versus 70%. (3) forceps and cryobiopsy (n = 28, 75% versus 67.9% P = 0.562). CONCLUSIONS: R-EBUS is a safe procedure in our setting and its yield is comparable to that reported in literature. The yield of central and adjacent lesions and forceps or cryobiopsy appears similar. Further refinements in the technique could improve yield.

SIRT1 and NAD+ precursors: Therapeutic targets in multiple sclerosis a review.

Neurodegeneration is an important determinant of disability in multiple sclerosis (MS) but while currently approved treatments reduce inflammation, they have not been shown to reduce neurodegeneration. SIRT1, a NAD dependent protein deacetylase, has been implicated in the pathogenesis of neurodegeneration in neurological diseases including MS. We have studied the role of SIRT1 in experimental autoimmune encephalomyelitis (EAE) and found evidence for a neuroprotective role. In this review we summarize the most recent findings from the use of SIRT1 activators and SIRT1 overexpression in transgenic mice. These data support provide a rational for the use of SIRT1 activators in MS.

Evidence for a role for the dorsal anterior cingulate cortex in disengaging from an incorrect action.

Adjusting for an error requires both disengaging from the wrong course of action and initiating a corrective response. The dorsal anterior cingulate cortex (dACC) has been implicated in both these processes in the decision-making and action monitoring literatures. Here, we aimed to distinguish between these putative functions with a variant of the Eriksen flanker task that manipulated response requirements (i.e. one or two finger responses). We found that two event-related potentials originating from the dACC (error-related negativity (ERN) and anterior N2) only reflected the representation of the incorrect response: these waveforms were larger when the incorrect response involved two fingers rather than one finger. The increase in ERN magnitude was also accompanied by a reduction in spontaneous error corrections. These results argue that activity in the dACC reflects a process involved in disengaging from an ongoing incorrect action, clearing the way for the correct response.