Partial pressure of carbon dioxide/pH interaction and its association with mortality among patients mechanically ventilated in the emergency department.

OBJECTIVES: There is currently conflicting data as to the effects of hypercapnia on clinical outcomes among mechanically ventilated patients in the emergency department (ED). These conflicting results may be explained by the degree of acidosis. We sought to test the hypothesis that hypercapnia is associated with increased in-hospital mortality and decreased ventilator-free days at lower pH, but associated with decreased in-hospital mortality and increased ventilator-free days at higher pH, among patients requiring mechanical ventilation in the emergency department (ED). METHODS: Secondary analysis of patient level data from prior clinical trials and cohort studies that enrolled adult patients who required mechanical ventilation in the ED. Patients who had a documented blood gas while on mechanical ventilation in the ED were included in these analyses. The primary outcome was in-hospital mortality, and secondary outcome was ventilator-free days. Mixed-effects logistic, linear, and survival-time regression models were used to test if pH modified the association between partial pressure of carbon dioxide (pCO2) and outcome measures. RESULTS: Of the 2348 subjects included, the median [interquartile range (IQR)] pCO2 was 43 (35-54) and pH was 7.31 (7.22-7.39). Overall, in-hospital mortality was 27%. We found pH modified the association between pCO2 and outcomes, with higher pCO2 associated with increased probability of in-hospital mortality when pH is below 7.00, and decreased probability of in-hospital mortality when pH is above 7.10. These results remained consistent across multiple sensitivity and subgroup analyses. A similar relationship was found with ventilator-free days. CONCLUSIONS: Higher pCO2 is associated with decreased mortality and greater ventilator-free days when pH is >7.10; however, it is associated with increased mortality and fewer ventilator-free days when the pH is below 7.00. Targeting pCO2 based on pH in the ED may be a potential intervention target for future clinical trials to improve clinical outcomes.

Spontaneous Cerebrospinal Fluid Leak in a Patient with Asymptomatic Idiopathic Intracranial Hypertension.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks occur when there is a tear in the dura mater. Spontaneous CSF leaks are rare, and often associated with conditions like intracranial hypertension, connective tissue disorders, or congenital defects in the dura mater. CASE REPORT: The patient was a 66-year-old woman who presented to the Emergency Department with clear, positional nasal discharge from her left nostril for 1 week. She had a history of chronic headaches, which seemed to have been relieved around the time of onset of her rhinorrhea. Diagnostic imaging, including computed tomography and magnetic resonance imaging scans, confirmed the presence of a CSF leak and a left temporal meningoencephalocele. The patient subsequently underwent surgical repair of the leak and ventriculoperitoneal shunt placement, and was discharged home in stable condition. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early detection of CSF leaks require a thorough history and physical examination, and is crucial in preventing potentially life-threatening complications such as meningitis and intracranial abscesses.

Mycobacterium leprae Infection in Ticks and Tick-Derived Cells.

Leprosy is a zoonosis in the southern United States involving humans and wild armadillos. The majority of patients presenting with zoonotic strains of Mycobacterium leprae note extensive outdoor activity but only rarely report any history of direct contact with wild armadillos. Whether M. leprae is transmitted to new vertebrate hosts through the environment independently or with the aid of other organisms, e.g., arthropod vectors, is a fundamental question in leprosy transmission. The objectives of this study were to assess the potential for ticks to transmit M. leprae and to test if viable M. leprae can be maintained in tick-derived cells. To evaluate tick transmission, nymphal Amblyomma maculatum ticks were injected with isolated M. leprae. Infection and transmission were assessed by qPCR. Ticks infected as nymphs harbored M. leprae through vertical transmission events (nymph to adult and adult to progeny); and, horizontal transmission of M. leprae to a vertebrate host was observed. Mycobacterium leprae DNA was detected in multiple tick life cycle stages. Likewise, freshly isolated M. leprae (Thai-53) was used to infect a tick-derived cell line, and enumeration and bacterial viability were assessed at individual time points for up to 49 days. Evaluations of the viability of long-term cultured M. leprae (Thai-53 and Br4923) were also assessed in a mouse model. Tick-derived cells were able to maintain viable M. leprae over the 49-day course of infection and M. leprae remained infectious within tick cells for at least 300 days. The results of this study suggest that ticks themselves might serve as a vector for the transmission of M. leprae and that tick cells are suitable for maintenance of viable M. leprae for an extended period of time.

Regression of Keratoconus After Gastric Sleeve Surgery.

PURPOSE: To report a case of regression of keratoconus by corneal topography after gastric sleeve surgery. METHODS: Case report. RESULTS: A patient with a history of bilateral progressive keratoconus was observed before and after bariatric surgery for morbid obesity. His left eye had a history of penetrating keratoplasty for advanced keratoconus, and his right eye had active progression of keratoconus in the years before sleeve gastrectomy. After the surgery, the right eye showed significant corneal flattening over a period of 2 years. This was especially pronounced at the apex of the cone (∼5 D). The patient's best spectacle-corrected visual acuity also improved along with management of his obesity and type 2 diabetes mellitus. CONCLUSIONS: This is the first report of regression of keratoconus after bariatric surgery.

Pediatric keratoprosthesis.

OBJECTIVE: To describe the authors' experience using keratoprosthesis to treat pediatric corneal opacity. DESIGN: Nonrandomized, consecutive, retrospective interventional series. PARTICIPANTS: Twenty-two eyes of 17 children with opaque corneas as a result of primary congenital disease and or previous failed keratoplasty. METHODS: A retrospective review of pediatric patients with a history of corneal opacification treated with keratoprosthesis surgery. MAIN OUTCOME MEASURES: Intraocular pressure, inflammation, clarity of the visual axis, visual acuity, refraction, complications, and retention of the prosthesis. RESULTS: Twenty-two eyes of 17 patients 1.5 to 136 months of age underwent 23 keratoprosthesis procedures. The follow-up period was 220 patient months (range, 1-37 months; mean, 9.7 months). In both cases implanted with the AlphaCor (Argus Biomedical Pty. Ltd., Perth, Australia), the keratoprosthesis was not retained. In one instance, the prosthesis sustained traumatic dislocation and was replaced with a cadaver cornea. In the second instance, the intralamellar implant began to extrude and was replaced with a Boston keratoprosthesis. In all 21 Boston cases, the prosthesis was retained without dislocation or extrusion. The visual axis remained clear in 100% of cases, although retroprosthetic membranes were removed in 5 eyes. Reoperation was necessitated for management of concurrent glaucoma (n = 3) or retinopathy (n = 2). There were no instances of surface infection or endophthalmitis. In 7 instances where patient age was 4 years or more, visual acuity ranged from counting fingers to 20/30. In the remaining cases, all infants were able to follow light, fingers, and objects. Intraocular pressure was controlled in all cases. CONCLUSIONS: Implantation of the Boston keratoprosthesis rapidly establishes and maintains a clear optical pathway and does not prejudice management of concurrent glaucoma or retinopathy. The device is retained without extrusion or rejection and is appropriate for the management of pediatric corneal opacity.

Paraproteinemic keratopathy in monoclonal gammopathy of undetermined significance treated with primary keratoprosthesis: Case report, histopathologic findings, and world literature review.

RATIONALE: We report a case of paraproteinemic keratopathy associated with monoclonal gammopathy of undetermined significance, treated with keratoprosthesis as a primary penetrating procedure. Histopathological findings and a world literature review are presented. PATIENT CONCERNS: A 74 year old female recently diagnosed with monoclonal gammopathy undetermined significance presented with progressive blurry vision bilaterally. DIAGNOSES: Examination revealed corneal opacities consistent with paraproteinemic keratopathy. INTERVENTIONS: Corneal transplantation with the Boston Type I keratoprosthesis was performed on the right and, a year later, on the left. OUTCOMES: Visual outcomes were good. Histopathological staining of host corneal buttons were consistent with monoclonality, and electron microscopy revealed fibrillar extracellular aggregates within intervening normal stroma. LESSONS: Corneal deposits may be the only manifestation of monoclonal gammopathy of undetermined significance in patients who are otherwise systemically asymptomatic. Ophthalmologists who encounter corneal opacities may order the appropriate diagnostic studies to determine the presence of occult systemic disease. Risk of graft failure after penetrating keratoplasty from recurring opacities is high, so keratoprosthesis as a primary penetrating procedure may afford superior long-term outcomes. Host corneal buttons retrieved from penetrating keratoplasty or corneal biopsy may be sent for histopathological examination to confirm the diagnosis.

Keratoprosthesis: current techniques.

PURPOSE: To compare and contrast the techniques and results of keratoprosthesis (KPro) using the Cardona device (1975-1985) with those related to the use of the Dohlman-Doane type 1 device (2003-2005). METHODS: We conducted a retrospective review of 31 cases of Cardona KPro implanted between 1975 and 1981 and a review of 25 cases of Dohlman-Doane type 1 KPro implanted between 2003 and 2005. Procedures were limited to eyes with a poor prognosis for traditional penetrating keratoplasty. RESULTS: In the Cardona cases, 39% (12/31) of patients achieved a visual acuity of 20/40 or better at some point postoperatively, degrading to 16% (5/31) at the end of the observation period. Fifty percent (15/31) required subsequent surgical revision of the KPro. Sixteen percent of cases (5/31) developed endophthalmitis, and 58% (18/31) developed retroprosthetic membranes. There were 5 dislocations of the prosthesis and an additional 3 frank extrusions (26%). Of the 25 Dohlman-Doane cases, there have been no reoperations, endophthalmitis, dislocations, or extrusions to date (8/15/05). Forty-eight percent (12/25) achieved 20/200 acuity or better, and 12% (3/25) achieved 20/40 or better. Retroprosthetic membranes formed in 3 cases. CONCLUSION: Although KPro remains a technique to be used in poor prognosis keratoplasty, improvements in the design of the device and surgical technique over the past 30 years have reduced the overall morbidity and severity of complications and improved the prognosis for visual rehabilitation.

Higher-order aberrations in eyes with irregular corneas after laser refractive surgery.

PURPOSE: To investigate the distribution of the eye's higher-order aberrations in postoperative laser refractive surgery patients with visual complaints and highly irregular corneal shapes. DESIGN: Retrospective case-control study. PARTICIPANTS: Thirty-three symptomatic postoperative LASIK and/or photorefractive keratectomy eyes with subjective visual complaints not corrected by spectacles more than 6 months after surgery are compared with 46 normal preoperative and 46 asymptomatic successful postoperative conventional LASIK eyes. METHODS: Postoperative wave aberrations were measured for each patient using a Shack-Hartmann wavefront sensor (Zywave, Bausch & Lomb, Rochester, NY) over a 6-mm pupil. These measurements were averaged across patients with similar corneal topographic diagnoses (central islands, decentered ablations, a new group termed baby bowties, and irregularly irregular corneas). MAIN OUTCOME MEASURES: Higher-order aberrations and corneal topography. RESULTS: The average (+/-1 standard deviation) higher-order root-mean-square (rms) wavefront error values (third, fourth, and fifth orders) for the symptomatic patients was 1.31+/-0.58 microm. This was an average of 3.46 times greater than the average magnitude of normal preoperative eyes (mean rms, 0.38+/-0.14 microm), and an average of 2.3 times greater than the average magnitude of asymptomatic successful postoperative conventional LASIK eyes (mean rms, 0.58+/-0.21 microm) over a 6-mm pupil. Higher-order rms wavefront error increased with pupil size, roughly doubling for every millimeter of increasing pupil diameter. On average, eyes with central islands (n = 6) had the most vertical coma (Z3(-1); mean, -1.35+/-0.43 microm). Eyes with central islands and decentered ablations (n = 2) also had elevated amounts of spherical aberration (Z4(0); means of 0.83+/-0.11 microm and 0.69+/-0.29 microm, respectively) compared with successful postoperative LASIK eyes (mean of 0.42+/-0.20 microm). Eyes with a topographic central baby bowtie demonstrated the most secondary astigmatism (Z4(2) and Z4(-2); mean rms, 0.56+/-0.17 microm; n = 3), despite the lowest average higher-order rms (mean, 0.84+/-0.05 microm) among symptomatic topographic subgroups. Eyes with irregularly irregular corneas had a mean higher-order rms of 1.10+/-0.39 mum. CONCLUSIONS: Symptomatic postoperative laser refractive surgery patients with irregular corneas have higher-order aberrations that are 2.3 to 3.5 times greater than asymptomatic postoperative LASIK and normal preoperative eyes, respectively. The higher-order aberrations seem to correlate with corneal topography.

Keratoprosthesis: the Dohlman-Doane device.

PURPOSE: To determine the usefulness of the Dohlman-Doane type I keratoprosthesis for visual rehabilitation in cases of poor prognosis for traditional penetrating keratoplasty. DESIGN: A retrospective, noncomparative interventional series of 25 patients who had sustained multiple graft failure or who were otherwise deemed poor candidates for conventional keratoplasty. METHODS: Candidates were evaluated for potential acuity, intraocular pressure, inflammation, the quality of the ocular surface, and overall prognosis for penetrating keratoplasty. The keratoprosthesis was assembled and mounted on an 8.5- or 9.0-mm diameter donor corneal button and sutured into an 8.0- or 8.5-mm diameter recipient bed with 12 to 16 9-0 nylon sutures. Patients were examined on the first day and subsequently in 1 week and 1 month and then at 3-month intervals. RESULTS: All devices were retained without dislocation or extrusion. There were no instances of endophthalmitis or surface infection. Fundus details were visible on the first postoperative day. Patients achieved their best acuity in an average of 2 months (range, 1 to 180 days). Improvement in acuity was observed in an average of 13 days (range, 1 to 60 days). Retroprosthetic membranes occurred in three cases, with multiple recurrences in one instance. Visual acuity ranged from no light perception to 20/25. CONCLUSION: We conclude that this prosthesis can be implanted routinely and maintained with minimal complications in poor prognosis keratoplasty, which presents the potential for visual rehabilitation.

Idiopathic peripheral necrotizing keratitis after femtosecond laser in situ keratomileusis.

UNLABELLED: We report a case of necrotizing peripheral keratitis after laser in situ keratomileusis (LASIK) using the low-energy Femto LDV femtosecond laser in a 31-year-old helicopter pilot with no history of medical or ocular disease. The severe peripheral flap inflammation resulted in stromal necrosis that was unresponsive to intensive topical steroid but improved rapidly on oral prednisone. The uncorrected distance visual acuity was maintained at 20/15 in both eyes, and the flaps were left undisturbed rather than attempting a more aggressive intervention such as a flap lift with culture and antibiotic irrigation. Identification of sterile corneal infiltration must be distinguished from infectious etiologies as the treatment is distinctly different. Although increased corneal infiltration has been reported with increasing femtosecond laser energy level for flap creation, to our knowledge this is the first report of necrotizing sterile corneal infiltration after LASIK with the low-energy femtosecond laser. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.

A new model for studying the effects of Mycobacterium leprae on Schwann cell and neuron interactions.

Millions of patients with leprosy suffer from nerve damage resulting in disabilities as a consequence of Mycobacterium leprae infection. However, mechanisms of nerve damage have not been elucidated because of the lack of a model that maintains M. leprae viability and mimics disease conditions. A model was developed using viable M. leprae, rat Schwann cells, and Schwann cell-neuron cocultures incubated at 33 degrees C. M. leprae retained 56% viability in Schwann cells for 3 weeks after infection at 33 degrees C, compared with 3.6% viability at 37 degrees C. Infected Schwann cells had altered morphology and expression of genes encoding cellular adhesion molecules at 33 degrees C but were capable of interacting with and myelinating neurons. Cocultures, infected after myelination occurred, showed no morphological changes in myelin architecture after 1 month of incubation at 33 degrees C, and M. leprae retained 53% viability. This article describes a new model for studying the effects of M. leprae on Schwann cells.

IL-10 treatment of macrophages bolsters intracellular survival of Mycobacterium leprae.

In these studies, metabolically active Mycobacterium leprae were maintained for as long as 8 weeks in monolayer cultures of mouse peritoneal macrophages (MPhi). Supplemental IL-10, but not TGF-beta, bolstered, directly or indirectly, M. leprae metabolism in mouse MPhi. In the cell culture system temperature setting is extremely important and 31 to 33 degrees C incubation temperature was more permissive than 37 degrees C. Acid fast staining and transmission electron microscopy (TEM) of intracellular M. leprae revealed visible elongation of bacilli cultured under the above ideal conditions.

Intracellular parasitism of parenchymal cells by Mycobacterium leprae

The liver, skeletal muscle, and adrenal gland obtained from two nine-banded armadillos infected with Mycobacterium leprae were studied using an electron microscope. M. leprae were found in varying numbers inside hepatocytes, Kupffer's cells, striated muscle cells, adrenal cortical and adrenal medullary cells, endothelial cells, and macrophages. There was evidence to suggest that M. leprae were actively phagocytosed by the liver and skeletal muscle cells. The inert nature of M. leprae and its behavior as an almost ideal parasite of parenchymal cells are emphasized. The question of whether this unique parasitism of parenchymal cells and the possible processing and presentation of M. leprae antigens by these cells could be responsible for aberrant immune responses is raised

A new model for studying the effects of Mycobacterium leprae on Schwann cell and neuron interactions

Millions of patients with leprosy suffer from nerve damage resulting in disabilities as a consequence of Mycobacterium leprae infection. However, mechanisms of nerve damage have not been elucidated because of the lack of a model that maintains M. leprae viability and mimics disease conditions. A model was developed using viable M. leprae, rat Schwann cells, and Schwann cell-neuron cocultures incubated at 33 degrees C. M. leprae retained 56% viability in Schwann cells for 3 weeks after infection at 33 degrees C, compared with 3.6% viability at 37 degrees C. Infected Schwann cells had altered morphology and expression of genes encoding cellular adhesion molecules at 33 degrees C but were capable of interacting with and myelinating neurons. Cocultures, infected after myelination occurred, showed no morphological changes in myelin architecture after 1 month of incubation at 33 degrees C, and M. leprae retained 53% viability. This article describes a new model for studying the effects of M. leprae on Schwann cells.

A new model for studyng the effects of Mycobacterium leprae on Schwann cell and neuron interactions

Millions of patients with leprosy suffer from nerve damage resulting in disabilities as a consequence of Mycobacterium leprae infection. However, mechanisms of nerve damage have not been elucidated because of the lack of a model that maintains M. leprae viability and mimics disease conditions. A model was developed using viable M. leprae, rat Schwann cells, and Schwann cell-neuron cocultures incubated at 33 degrees C. M. leprae retained 56 per cente viability in Schwann cells for 3 weeks after infection at 33 degrees C, compared with 3.6 per cente viability at 37 degrees C. Infected Schwann cells had altered morphology and expression of genes encoding cellular adhesion molecules at 33 degrees C but were capable of interacting with and myelinating neurons. Cocultures, infected after myelination occurred, showed no morphological changes in myelin architecture after 1 month of incubation at 33 degrees C, and M. leprae retained 53 per cente viability. This article describes a new model for studying the effects of M. leprae on Schwann cells.