Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

Non-arteritic Anterior Ischaemic Optic Neuropathy after Uneventful Cataract Extraction

We present the case of a 74-year-old Caucasian female who suffered sudden visual loss after routine phacoemulsification cataract surgery. The patient was subsequently diagnosed with non-arteritic anterior ischaemic optic neuropathy. The case is described in detail, and a concise review of the literature is presented together with the authors’ view on the subject outlined. This is a very rare complication after cataract surgery even in high-risk patients with associated systemic co-morbidities. We suspect that the previous history of obesity, coronary artery disease, and arteriosclerosis contributed to the development of this serious ocular complication. We suggest appropriate measures to reduce the risk of its occurrence.     

Rabs and axonal regeneration

Membrane trafficking processes are presumably vital for axonal regeneration after injury, but mechanistic understanding in this regard has been sparse. A recent loss-of-function screen had been carried out for factors important for axonal regeneration by cultured cortical neurons and the results suggested that the activity of a number of Rab GTPases might act to restrict axonal regeneration. A loss of Rab27b, in particular, is shown to enhance axonal regeneration in vitro, as well as in C. elegans and mouse central nervous system injury models in vivo. Possible mechanisms underlying this new finding, which has important academic and translational implication, are discussed.     

Surfactant

Surfactant, a complex substance containing specific proteins and phospholipids, is essential for gas exchange in the lungs. Research shows that surfactant not only lowers surface tension, but also plays a role in host defense. Surfactant replacement therapy is a cornerstone in the treatment of respiratory distress syndrome in premature infants. New information on endogenous surfactant composition including surfactant apoproteins has led to advances in the surfactant replacement products currently available. Because of the success of surfactant deficiency treatment in neonates, surfactant replacement therapy has been studied in both the pediatric and adult population for the treatment of other respiratory disorders. This article describes the composition, metabolism, and function of endogenous surfactant and other uses of surfactant replacement therapies in neonates.     

Acetabular blood flow during Bernese periacetabular osteotomy: an intraoperative study using laser Doppler flowmetry.

BACKGROUND: The blood flow to the acetabular fragment is of some concern in juxtaarticular pelvic osteotomies used for the treatment of hip dysplasia. No direct measurements have determined the effect of the Bernese periacetabular osteotomy (PAO) on acetabular perfusion. METHODS: Acetabular perfusion was measured by means of laser Doppler flowmetry in 10 patients undergoing a PAO for symptomatic acetabular dysplasia. During the surgical procedure, the intraosseous high energy laser Doppler reliably depicts dynamic changes of small vessel blood flow. Measurements were performed after defined surgical steps to obtain sequential information on the blood perfusion of the acetabular fragment. RESULTS: After complete separation of the acetabular fragment, nine out of 10 patients had pulsatile signals, but the blood flow (BF) significantly decreased by 77%. Corrective positioning of the fragment induced no further drop of the BF signal but a loss of pulsatility in six patients. After a recovery period of about 30 min following preliminary fixation of the fragment, reestablishment of the pulsatile signal and an increase of the BF signal was seen. At termination of the surgical procedure, five out of eight patients, who could be followed throughout the whole procedure, showed a clear pulsatile signal in the supraacetabular area. Bleeding of the supraacetabular cancellous surface could be observed in all acetabula. CONCLUSION: Despite careful preservation of soft tissues during the surgical procedure, a significant reduction of the blood flow in the supraacetabular region has been observed. Nevertheless, a pulsatile signal in more than 60% of the fragments after fragment correction and an increasing signal during the recovery period showed ongoing blood perfusion indicating reversible changes in the measured supraacetabular area. All osteotomies healed within eight weeks without showing signs of necrosis during a minimum follow up of 1 year.     

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.     

Facilitating Perinatal Grieving Between the Mother and the Father

Society often expects mothers and fathers to share equally in the perinatal grief process because the child was a common bond between them. Unfortunately, in perinatal grief, this is not always the case. The mother and the father can experience incongruent grieving and use discordant coping mechanisms. It is important to evaluate these differences to facilitate communication between the distraught parents. Improved communication can in turn facilitate the grieving process.