Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study

Background:

Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world.

Objectives:

The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years.

Materials and Methods:

In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded.

Results:

The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI.

Conclusions:

Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.     

Three-dimensional directional nerve guide conduits fabricated by dopamine-functionalized conductive carbon nanofibre-based nanocomposite ink printing

A potential issue in current nerve guides is that they do not transmit electrical nerve impulses between the distal and proximal end of an injured nerve, i.e. a synapse. Conductivity is a desirable property of an ideal nerve guide that is being considered for peripheral nerve regeneration. Most conductive polymers reported for the fabrication of tissue engineering scaffolds, such as polypyrrole and polyaniline, are non-biodegradable and possess weak mechanical properties, and thus cannot be fabricated into 3D structures. Herein, we have designed a new nanocomposite material composed of dopamine, carbon nanofibers (CNF) and polycaprolactone (PCL) for the fabrication of nerve conduits, which facilitates the growth and migration of neurons toward the targeted end of an injured nerve. This support and navigation of the scaffold leads to better sensory and motor function. The results showed that the mechanical properties of the printed PCL increased by 30% in comparison with the pure PCL film, which is comparable with human nerves. The in vitro cell study of human glioma cells showed that the printed lines provided support for neural cell attachment, migration and differentiation toward the targeted end. In contrast, in the absence of printed lines in the scaffold, the cells attach and grow in random directions, forming a flower shape (cell cluster) on the surface of PCL. Thus, the proposed scaffold is a promising candidate for nerve guide application based on its signal transmission and navigating neurons in a correct pathway towards the targeted end.

Directional growth induced by dopamine-functionalized CNF-based nanocomposite ink printing.     

Incidence of Low Back Pain After Lumbar Discectomy for Herniated Disc and Its Effect on Patient-reported Outcomes

Background

Long-term postdiscectomy degenerative disc disease and low back pain is a well-recognized disorder; however, its patient-centered characterization and quantification are lacking.

Questions/purposes

We performed a systematic literature review and prospective longitudinal study to determine the frequency of recurrent back pain after discectomy and quantify its effect on patient-reported outcomes (PROs).

Methods

A MEDLINE search was performed to identify studies reporting on the frequency of recurrent back pain, same-level recurrent disc herniation, and reoperation after primary lumbar discectomy. After excluding studies that did not report the percentage of patients with persistent back or leg pain more than 6 months after discectomy or did not report the rate of same level recurrent herniation, 90 studies, which in aggregate had evaluated 21,180 patients, were included in the systematic review portion of this study. For the longitudinal study, all patients undergoing primary lumbar discectomy between October 2010 and March 2013 were enrolled into our prospective spine registry. One hundred fifteen patients were more than 12 months out from surgery, 103 (90%) of whom were available for 1-year outcomes assessment. PROs were prospectively assessed at baseline, 3 months, 1 year, and 2 years. The threshold of deterioration used to classify recurrent back pain was the minimum clinically important difference in back pain (Numeric Rating Scale Back Pain [NRS-BP]) or Disability (Oswestry Disability Index [ODI]), which were 2.5 of 10 points and 20 of 100 points, respectively.

Results Systematic Review

The proportion of patients reporting short-term (6–24 months) and long-term (> 24 months) recurrent back pain ranged from 3% to 34% and 5% to 36%, respectively. The 2-year incidence of recurrent disc herniation ranged from 0% to 23% and the frequency of reoperation ranged from 0% to 13%.

Prospective Study

At 1-year and 2-year followup, 22% and 26% patients reported worsening of low back pain (NRS: 5.3 ± 2.5 versus 2.7 ± 2.8, p < 0.001) or disability (ODI%: 32 ± 18 versus 21 ± 18, p < 0.001) compared with 3 months.

Conclusions

In a systematic literature review and prospective outcomes study, the frequency of same-level disc herniation requiring reoperation was 6%. Two-year recurrent low back pain may occur in 15% to 25% of patients depending on the level of recurrent pain considered clinically important, and this leads to worse PROs at 1 and 2 years postoperatively.     

The Diagnostic Dilemma of a Parasympathetic Schwannoma in the Submandibular Gland

Schwannomas are benign soft tissue tumours that arise from nerve sheath cells. They are rare in the salivary glands and are thought to arise from the parasympathetic nerves. We report the case of a 69-year-old man who presented with a painless right submandibular mass that appeared to resemble a pleomorphic adenoma on ultrasonography and, on this basis, proceeded to surgical excision of the gland. We review the relevant literature and highlight the diagnostic pitfalls.     

Mutant G protein alpha subunit activated by Gbeta gamma: a model for receptor activation?

How receptors catalyze exchange of GTP for GDP bound to the Galpha subunit of trimeric G proteins is not known. One proposal is that the receptor uses the G protein's betagamma heterodimer as a lever, tilting it to pull open the guanine nucleotide binding pocket of Galpha. To test this possibility, we designed a mutant Galpha that would bind to betagamma in the tilted conformation. To do so, we excised a helical turn (four residues) from the N-terminal region of alpha(s), the alpha subunit of G(S), the stimulatory regulator of adenylyl cyclase. In the presence, but not in the absence, of transiently expressed beta(1) and gamma(2), this mutant (alpha(s)Delta), markedly stimulated cAMP accumulation. This effect depended on the ability of the coexpressed beta protein to interact normally with the lip of the nucleotide binding pocket of alpha(s)Delta. We substituted alanine for an aspartate in beta(1) that binds to a lysine (K206) in the lip of the alpha subunit's nucleotide binding pocket. Coexpressed with alpha(s)Delta and gamma(2), this mutant, beta(1)-D228A, elevated cAMP much less than did beta(1)-wild type; it did bind to alpha(s)Delta normally, however, as indicated by its unimpaired ability to target alpha(s)Delta to the plasma membrane. We conclude that betagamma can activate alpha(s) and that this effect probably involves both a tilt of betagamma relative to alpha(s) and interaction of beta with the lip of the nucleotide binding pocket. We speculate that receptors use a similar mechanism to activate trimeric G proteins.     

A physical basis for protein secondary structure

A physical theory of protein secondary structure is proposed and tested by performing exceedingly simple Monte Carlo simulations. In essence, secondary structure propensities are predominantly a consequence of two competing local effects, one favoring hydrogen bond formation in helices and turns, the other opposing the attendant reduction in sidechain conformational entropy on helix and turn formation. These sequence specific biases are densely dispersed throughout the unfolded polypeptide chain, where they serve to preorganize the folding process and largely, but imperfectly, anticipate the native secondary structure.     

Calibration and optimization of 3D digital breast tomosynthesis guided near infrared spectral tomography

Calibration of a three-dimensional multimodal digital breast tomosynthesis (DBT) x-ray and non-fiber based near infrared spectral tomography (NIRST) system is challenging but essential for clinical studies. Phantom imaging results yielded linear contrast recovery of total hemoglobin (HbT) concentration for cylindrical inclusions of 15 mm, 10 mm and 7 mm with a 3.5% decrease in the HbT estimate for each 1 cm increase in inclusion depth. A clinical exam of a patient’s breast containing both benign and malignant lesions was successfully imaged, with greater HbT was found in the malignancy relative to the benign abnormality and fibroglandular regions (11 μM vs. 9.5 μM). Tools developed improved imaging system characterization and optimization of signal quality, which will ultimately improve patient selection and subsequent clinical trial results.OCIS codes: (120.3890) Medical optics instrumentation, (170.0110) Imaging systems, (170.3830) Mammography     

Compression screw fixation without bone grafting for scaphoid fibrous nonunion

Purpose

Bone graft is often recommended as an adjuvant for treatment of scaphoid nonunions. However, recent literature has suggested that fibrous nonunion may be suited to treatment with rigid fixation without bone grafting. This work reported on outcomes of compression screw fixation for established scaphoid fibrous nonunions without bone graft.

Methods

Fourteen patients underwent surgical compression screw fixation without bone grafting of scaphoid fibrous nonunion between January 1, 2000, and December 31, 2012, with minimum follow-up until the time of clinical and radiographic healing. Fibrous nonunion of the scaphoid was defined as a scaphoid fracture with all of the following features: (1) persistent tenderness, (2) incomplete trabecular bridging on three X-ray views, (3) injury that had occurred at a minimum of 6 months prior to surgery, and (4) identification of fibrous union at the time of surgery. Outcomes were assessed with range of motion assessment, Disability of the Arm, Shoulder and Hand (DASH) scores, and plain radiographs.

Results

Twelve of the 14 patients healed successfully, while two patients required secondary vascularized bone grafting. Both unhealed patients sustained proximal pole fractures and had a duration of ≥1 year from injury to surgery. Average time to healing was 4.4 ± 2.0 months. Average flexion was 73 ± 22° and average extension was 66 ± 22° postoperatively. Average grip strength was 90 ± 25 lbs on the operative side. Mean postoperative pain score was 1.4 (range, 0 to 7). Mean postoperative DASH score was 10.2 (range, 0 to 52). Increasing age and an interval from injury to surgery of >1 year correlated with worse DASH and pain scores.

Conclusions

Patients with fibrous scaphoid nonunion demonstrated good results with rigid fixation without bone grafting. Increasing age and >1-year interval between injury and surgery resulted in lower self-assessed outcomes.

Level of Evidence

Therapeutic Level IV, retrospective case series     

Risk factors in early life as predictors of adult heart disease: the Bogalusa Heart Study

The adult heart diseases, coronary artery disease and essential hypertension, are now clearly recognized to begin in childhood. The evidence comes from autopsy studies of cardiovascular-renal changes in the first two decades of life. Cardiovascular risk factors can be identified in children just as in adults and these have a high correlation with the anatomic disease. This relationship underscores the importance of risk factor screening of children. Of interest is that clinical risk factors tend to persist within a rank (track) so that studies in childhood can be predictive of future levels. Behavior and lifestyle of eating, cigarette smoking, alcohol intake, and use of oral contraceptive pills influence risk factors in children. Familial aggregation of risk factors are also noted. Studies of apolipoproteins, B and A-I, have identified subsets of children that have a greater frequency of paternal myocardial infarction. The findings from the Bogalusa Heart Study and other epidemiological studies of children show the need to begin prevention of adult heart disease in early life. Approaches to prevention should include high risk families and children and a public health or population approach. Cardiovascular health education for elementary school children should be directed to children in the general population in an effort to encourage them to adopt healthy life styles.