Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

Bat Red Blood Cells Express Nucleic Acid-Sensing Receptors and Bind RNA and DNA.

RBCs demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. However, little is known about bat RBCs, and no studies have examined the immune function of bat erythrocytes. In this study, we show that bat RBCs express the nucleic acid-sensing TLRs TLR7 and TLR9 and bind the nucleic acid ligands, ssRNA, and CpG DNA. Collectively, these data suggest that, like human RBCs, bat erythrocytes possess immune function and may be reservoirs for nucleic acids. These findings provide unique insight into bat immunity and may uncover potential mechanisms by which virulent pathogens of humans are concealed in bats.

DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia.

Red blood cells (RBCs) are essential for aerobic respiration through delivery of oxygen to distant tissues. However, RBCs are currently considered immunologically inert, and few, if any, secondary functions of RBCs have been identified. Here, we showed that RBCs serve as critical immune sensors through surface expression of the nucleic acid­sensing Toll-like receptor 9 (TLR9). Mammalian RBCs expressed TLR9 on their surface and bound CpG-containing DNA derived from bacteria, plasmodia, and mitochondria. RBC-bound mitochondrial DNA was increased during human and murine sepsis and pneumonia. In vivo, CpG-carrying RBCs drove accelerated erythrophagocytosis and innate immune activation characterized by increased interferon signaling. Erythroid-specific deletion of TLR9 abrogated erythrophagocytosis and decreased local and systemic cytokine production during CpG-induced inflammation and polymicrobial sepsis. Thus, detection and capture of nucleic acid by TLR9-expressing RBCs regulated red cell clearance and inflammatory cytokine production, demonstrating that RBCs function as immune sentinels during pathologic states. Consistent with these findings, RBC-bound mitochondrial DNA was elevated in individuals with viral pneumonia and sepsis secondary to coronavirus disease 2019 (COVID-19) and associated with anemia and severity of disease. These findings uncover a previously unappreciated role of RBCs as critical players in inflammation distinct from their function in gas transport.

Erythrocytes identify complement activation in patients with COVID-19.

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and preclinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in patients with COVID-19 using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.

The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent.

Interferon alpha/beta (IFN-α/ß) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/ß after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/ß receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/ß response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/ß and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/ß and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/ß-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/ß efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.IMPORTANCE The interferon alpha/beta (IFN-α/ß) response is a first-line innate defense against arthropod-borne viruses (arboviruses). Arboviruses, such as chikungunya virus (CHIKV), can infect cells and replicate across a wide temperature range due to their replication in both mammalian/avian and arthropod hosts. Accordingly, these viruses can cause human disease in tissues regularly exposed to temperatures below the normal mammalian core temperature, 37°C. We questioned whether temperature variation could affect the efficacy of IFN-α/ß responses against these viruses and help to explain some aspects of human disease manifestations. We observed that IFN-α/ß efficacy was dramatically lower at subnormal temperatures and modestly enhanced at febrile temperatures, with the effects involving altered IFN-α/ß response gene transcription but not IFN-α/ß pathway signaling. These results provide insight into the functioning of the IFN-α/ß response in vivo and suggest that temperature elevation may represent an immune-enhancing therapeutic modality for a wide variety of IFN-α/ß-sensitive infections and pathologies.

Gamma-interferon exerts a critical early restriction on replication and dissemination of yellow fever virus vaccine strain 17D-204.

Live attenuated viruses are historically among the most effective viral vaccines. Development of a safe vaccine requires the virus to be less virulent, a phenotype that is historically arrived by empirical evaluation often leaving the mechanisms of attenuation unknown. The yellow fever virus 17D live attenuated vaccine strain has been developed as a delivery vector for heterologous antigens; however, the mechanisms of attenuation remain elusive. The successful and safe progress of 17D as a vaccine vector and the development of live attenuated vaccines (LAVs) to related flaviviruses requires an understanding of the molecular mechanisms leading to attenuation. Using subcutaneous infection of interferon-deficient mouse models of wild type yellow fever virus (WT YFV) pathogenesis and 17D-mediated immunity, we found that, in the absence of type I IFN (IFN-α/ß), type II interferon (IFN-γ) restricted 17D replication, but not that of WT YFV, by 1-2 days post-infection. In this context, IFN-γ responses protected 17D-infected animals from mortality, largely restricted the virus to lymphoid organs, and eliminated viscerotropic disease signs such as steatosis in the liver and inflammatory cell infiltration into the spleen. However, WT YFV caused a disseminated infection, gross liver pathology, and rapid death of the animals. In vitro, IFN-γ treatment of myeloid cells suppressed the replication of 17D significantly more than that of WT YFV, suggesting a direct differential effect on 17D virus replication. Together these data indicate that an important mechanism of 17D attenuation in vivo is increased sensitivity to IFN-γ stimulated responses elicited early after infection.

Ribbon scanning confocal for high-speed high-resolution volume imaging of brain.

Whole-brain imaging is becoming a fundamental means of experimental insight; however, achieving subcellular resolution imagery in a reasonable time window has not been possible. We describe the first application of multicolor ribbon scanning confocal methods to collect high-resolution volume images of chemically cleared brains. We demonstrate that ribbon scanning collects images over ten times faster than conventional high speed confocal systems but with equivalent spectral and spatial resolution. Further, using this technology, we reconstruct large volumes of mouse brain infected with encephalitic alphaviruses and demonstrate that regions of the brain with abundant viral replication were inaccessible to vascular perfusion. This reveals that the destruction or collapse of large regions of brain micro vasculature may contribute to the severe disease caused by Venezuelan equine encephalitis virus. Visualization of this fundamental impact of infection would not be possible without sampling at subcellular resolution within large brain volumes.

The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells.

A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines.

Host translation shutoff mediated by non-structural protein 2 is a critical factor in the antiviral state resistance of Venezuelan equine encephalitis virus.

Most previous studies of interferon-alpha/beta (IFN-α/ß) response antagonism by alphaviruses have focused upon interruption of IFN-α/ß induction and/or receptor signaling cascades. Infection of mice with Venezuelan equine encephalitis alphavirus (VEEV) or Sindbis virus (SINV) induces serum IFN-α/ß, that elicits a systemic antiviral state in uninfected cells successfully controlling SINV but not VEEV replication. Furthermore, VEEV replication is more resistant than that of SINV to a pre-existing antiviral state in vitro. While host macromolecular shutoff is proposed as a major antagonist of IFN-α/ß induction, the underlying mechanisms of alphavirus resistance to a pre-existing antiviral state are not fully defined, nor is the mechanism for the greater resistance of VEEV. Here, we have separated viral transcription and translation shutoff with multiple alphaviruses, identified the viral proteins that induce each activity, and demonstrated that VEEV nonstructural protein 2-induced translation shutoff is likely a critical factor in enhanced antiviral state resistance of this alphavirus.

Reduction of benzoquinones to hydroquinones via spontaneous reaction with glutathione and enzymatic reaction by S-glutathionyl-hydroquinone reductases.

S-Glutathionyl-hydroquinone reductases (GS-HQRs) are a new class of glutathione transferases, widely present in bacteria, halobacteria, fungi, and plants. They catalyze glutathione (GSH)-dependent reduction of GS-trichloro-p-hydroquinone to trichloro-p-hydroquinone. Since GS-trichloro-p-hydroquinone is uncommon in nature, the extensive presence of GS-HQRs suggests they use common GS-hydroquinones. Here we demonstrate that several benzoquinones spontaneously reacted with GSH to form GS-hydroquinones via Michael addition, and four GS-HQRs from yeast and bacteria reduced the GS-hydroquinones to the corresponding hydroquinones. The spontaneous and enzymatic reactions led to the reduction of benzoquinones to hydroquinones with the concomitant oxidation of GSH to oxidized glutathione (GS-SG). The enzymes did not use GS-benzoquinones or other thiol-hydroquinones, for example, S-cysteinyl-hydroquinone, as substrates. Apparent kinetic parameters showed the enzymes preferred hydrophobic, bulky substrates, such as GS-menadiol. The broad substrate range and their wide distribution suggest two potential physiological roles: channeling GS-hydroquinones back to hydroquinones and reducing benzoquinones via spontaneous formation of GS-hydroquinones and then enzymatic reduction to hydroquinones. The functions are likely important in metabolic pathways with quinone intermediates.

A comparison of the effectiveness between Western medicine and Chinese medicine outpatient consultations in primary care.

BACKGROUND: Traditional Chinese medicine (TCM) plays an important role in the primary care system in many places, but research evidence on its effectiveness is largely lacking. The aim of the present study was to compare the effectiveness between TCM and Western medicine (WM) consultations in primary care. OBJECTIVES: To evaluate whether medical consultations could improve the quality of life and health condition of patients in primary care and to find out whether there was any difference in the effectiveness bewteen TCM and WM. DESIGN, SETTING AND SUBJECTS: This was a prospective, longitudinal study on 290 patients of one TCM public and 841 patients of two WM general outpatient clinics (GOPC) in Hong Kong when they consulted for an episodic illness. METHODS: All patients attending a TCM GOPC in TWH, and the two WM GOPC (TWH and ALC), who fullfilled the inclusion criteria were invited to participate. Each patient answered a structured questionnaire on the presenting complaint, socio-demography, chronic morbidity and service utilization, the Chinese Quality of Life instrument (ChQOL) and the SF-36V2 Health Survey immediately before and two weeks after the doctor consultation. The Global Rating on change Scale (GRS) was also administered in the week 2 assessment. OUTCOME MEASURES: The primary outcomes were changes in the ChQOL and SF-36V2 HRQOL scores. Secondary outcomes included the GRS score. The significance of the change within individual were tested by paired t-tests. The differences in change in scores between WM and TCM were tested by independent sample-t-tests or chi-square, as appropriate. Multivariate regresions were used to determine the independent effect of type of medicine on the change in HRQOL scores. RESULTS: Mean ChQOL and SF-36V2 scores of subjects improved significantly two weeks after TCM or WM consultations in all domains except for the Physical form domain of ChQOL. The greatest improvements were found in the SF-36V2 physical-health related domains. 78% TCM clinics and 71% of subjects WM clinics reported an improvement in GRS. The proportion of subjects who had improvement in HRQOL scores were lower among subjects consulting the WM clinic (72.3%) than those consulting TCM clinics (100%) but the difference was not significant after correction for baseline scores. CONCLUSIONS: Both TCM and WM consultations were associated with significant improvement in HRQOL in over 90% of patients. There was no singificant difference between the effectiveness of TCM and WM consultations. The results support the role of TCM as an alternative primary care service in Hong Kong.

Biochemical characterization of ethanol-dependent reduction of furfural by alcohol dehydrogenases.

Lignocellulosic biomass is usually converted to hydrolysates, which consist of sugars and sugar derivatives, such as furfural. Before yeast ferments sugars to ethanol, it reduces toxic furfural to non-inhibitory furfuryl alcohol in a prolonged lag phase. Bioreduction of furfural may shorten the lag phase. Cupriavidus necator JMP134 rapidly reduces furfural with a Zn-dependent alcohol dehydrogenase (FurX) at the expense of ethanol (Li et al. 2011). The mechanism of the ethanol-dependent reduction of furfural by FurX and three homologous alcohol dehydrogenases was investigated. The reduction consisted of two individual reactions: ethanol-dependent reduction of NAD(+) to NADH and then NADH-dependent reduction of furfural to furfuryl alcohol. The kinetic parameters of the coupled reaction and the individual reactions were determined for the four enzymes. The data indicated that limited NADH was released in the coupled reaction. The enzymes had high affinities for NADH (e.g., K ( d ) of 0.043 µM for the FurX-NADH complex) and relatively low affinities for NAD(+) (e.g., K ( d ) of 87 µM for FurX-NAD(+)). The kinetic data suggest that the four enzymes are efficient "furfural reductases" with either ethanol or NADH as the reducing power. The standard free energy change (ΔG°') for ethanol-dependent reduction of furfural was determined to be -1.1 kJ mol(-1). The physiological benefit for ethanol-dependent reduction of furfural is likely to replace toxic and recalcitrant furfural with less toxic and more biodegradable acetaldehyde.

Cupriavidus necator JMP134 rapidly reduces furfural with a Zn-dependent alcohol dehydrogenase.

Ethanol is a renewable biofuel, and it can be produced from lignocellulosic biomass. The biomass is usually converted to hydrolysates that consist of sugar and sugar derivatives, such as furfural. Yeast ferments sugar to ethanol, but furfural higher than 3 mM is inhibitory. It can take several days for yeast cells to reduce furfural to non-inhibitory furfuryl alcohol before producing ethanol. Bioreduction of furfural to furfuryl alcohol before fermentation may relieve yeast from furfural toxicity. We observed that Cupriavidus necator JMP134, a strict aerobe, rapidly reduced 17 mM furfural to less than 3 mM within 14 min with cell turbidity of 1.0 at 600 nm at 50°C. The rapid reduction consumed ethanol. The "furfural reductase" (FurX) was purified, and it oxidized ethanol to acetaldehyde and reduced furfural to furfuryl alcohol with NAD(+) as the cofactor. The protein was identified with mass spectrometry fingerprinting to be a hypothetical protein belonging to Zn-dependent alcohol dehydrogenase family. The furX-inactivation mutant of C. necator JMP134 lost the ability to rapidly reduce furfural, and Escherichia coli producing recombinant FurX gained the ability. Thus, an alcohol dehydrogenase enabled bacteria to rapidly reduce furfural with ethanol as the reducing power.

Lymphadenopathy of IgG4-related sclerosing disease.

IgG4-related sclerosing disease is a recently recognized syndrome characterized by mass-forming lesions in exocrine glands or extranodal tissues due to lymphoplasmacytic infiltrates and sclerosis, a raised serum IgG4 level and increased IgG4+ plasma cells in the involved tissues. We report the morphologic features of the enlarged regional (n=3) and nonregional lymph nodes (n=3) in patients with this syndrome. The patients presented with autoimmune pancreatitis, lymphoplasmacytic sclerosing cholangitis, chronic sclerosing dacryoadenitis, or chronic sclerosing sialadenitis. The histologic features of the lymph nodes could be categorized into 3 patterns: Castleman diseaselike, follicular hyperplasia, and interfollicular expansion by immunoblasts and plasma cells. The percentage of IgG4+/IgG+ plasma cells was markedly elevated (mean 62% vs. 9.9% in 54 control lymph nodes comprising a wide variety of reactive conditions). We also report 6 cases of primary lymphadenopathy characterized by increased IgG4+/IgG+plasma cells (mean 58%). These cases share many clinical and pathologic similarities with IgG4-related sclerosing disease. In fact, 2 of these patients developed lymphoplasmacytic sclerosing cholangitis or lacrimal and submandibular gland involvement during the clinical course. These cases therefore probably represent primary lymph node manifestation of the disease. The importance of recognition of the lymphadenopathic form of IgG4-related sclerosing disease lies in the remarkable response to steroid therapy, and the potential of mistaking the disease for lymphoma either clinically or histologically.

Pharyngolaryngoesophagectomy using the thoracoscopic approach.

BACKGROUND: Thoracoscopic mobilization of the esophagus for pharyngolaryngoesophagectomy allows dissection under direct vision, and therefore it potentially results in fewer complications than conventional transhiatal mobilization. In this article we report our experience with this approach. It was also hypothesized that a learning curve existed and that results have improved over time. PATIENTS AND METHODS: From July 1994 until January 2004, 57 patients underwent pharyngolaryngoesophagectomy in our institution. Intraoperative events and postoperative outcome were prospectively documented, and long-term follow-up data were also studied. Results were compared between the first 30 patients and the last 27 patients. RESULTS: There were no significant differences between the two groups with respect to the various clinicopathological characteristics. There was no difference in the median thoracoscopic time between the first 30 and last 27 patients at 90 and 75 min, respectively, p = 0.18. For the complete procedure there was significantly less blood loss in the later group; median (range) blood loss 700 (164-3000) ml versus 400 (100-1200) ml, p = 0.002. Overall pulmonary complications occurred in 12 patients (40%) in the first group versus 13 (48%) in the second group, p = 0.6. The incidence of atrial arrhythmia was also similar, affecting 6 (20%) patients and 3 (11%), respectively, p = 0.47. Hospital mortality rates were 13.3% and 7.4%, p = 0.67. Two-year survival rates were no different (46% versus 45% p = 0.85). CONCLUSIONS: Although, subjectively, operating skills have improved over time, better results in the second half of this series could not be demonstrated clearly, likely because the operating surgeons had prior extensive experience in esophageal and thoracoscopic procedures.

The use of pulsed dye laser for the prevention and treatment of hypertrophic scars in chinese persons.

BACKGROUND: Pulse dye laser has been used with variable degrees of success in the treatment of hypertrophic scars, and although earlier reports suggested a significant degree of improvement, more recent studies have raised concern about its effectiveness. Furthermore, most previous studies examined its use in patients with light skin types, and the use of pulse dye laser in dark-skinned patients for the treatment of hypertrophic scars is not well established. OBJECTIVE: The objective was to assess the role of pulsed dye laser therapy in the treatment and prevention of hypertrophic scars in Chinese persons. METHODS: Twenty-nine patients (35 scars) who had scars for less than 6 months were recruited into the prevention group, and 27 patients (36 scars) who had scars for more than 6 months were recruited into the treatment arm of the study. Each received pulse dye laser treatment (585 nm, 1.5-msec pulse duration, 5-mm spot size, 7-8 J/cm(2)) for three to six treatments at 8-week intervals. Half of the scar was treated with the laser and the other half was used as a control. All patients were assessed for subjective improvement with the use of a structured questionnaire and objectively with ultrasonography for thickness and a cutometer for viscoelasticity. Scars were marked on every patient and mapped with a translucent paper at the first appointment to ensure the consistency of location. At the end of the study, 15 patients from the prevention group (15 scars) and 23 patients from the treatment group (34 scars) agreed to return for spectrophotometer assessment. RESULTS: Fifty-four percent of patients in the prevention group and 66% of patients in the treatment group considered their scars to be better or much better. For both groups of patients, there was significant improvement in term of pruritics after laser treatment. For objective assessment, although scar thickness reduced significantly compared to baseline in the treatment group, such change was not significant when changes in the control side were taken into consideration. There was insignificant change in viscoelasticity. Spectrophometer assessment indicated a significant degree of lightening in the treatment group. CONCLUSION: Our study indicated that although there was significant symptomatic improvement, there was an insignificant degree of objective improvement in terms of scar thickness and viscoelasticity in the prevention group compared to the control group. Our findings are in line with several previous controlled studies and contradict the results of several others. Such differences can be due to differences in assessment methodology, laser settings, skin type, and scar location. Suprapurpuric pulsed dye laser should not be considered as the standard of practice for the treatment and prevention of hypertrophic surgical scars especially in the chest in Asians patients.

Microvascular free tissue reconstruction following extirpation of head and neck tumour: experience towards an optimal outcome.

Familiarity with four types of free tissues transfers allows appropriate reconstruction of most defects in the head and neck region functionally and aesthetically. These include jejunal graft, radial forearm, rectus abdominus myocutaneous and fibula osteocutaneous flaps. Free colonic and gastric patches were used occasionally. We report our experience of 215 free tissue transfers for reconstruction of defects in the head and neck region after tumour extirpation. The overall success rate was 94 per cent. The commonest cause of failure was related to arterial inflow (70 per cent). Three patients died in hospital, but their mortality was not related to the tissue transfers. Complications due to free tissue transfer at both the donor and recipient sites were few and manageable. The co-operation between the two surgical teams, together with the timely application of suitable salvage procedures, contribute to an optimal outcome.

A retrospective study on the efficacy and complications of Q-switched alexandrite laser in the treatment of acquired bilateral nevus of Ota-like macules.

BACKGROUND: Acquired bilateral nevus of Ota-like macules (ABNOM), or Hori's macules, is a common Asian condition that is characterized by bluish hyperpigmentation in the bilateral malar regions. Unlike nevus of Ota, ABNOM is an acquired condition that often develops after 20 years of age and involves both sides of the face, but there is no mucosal involvement. Recently Q-switched (QS) 1064 nm Nd:YAG lasers have been effective in clearing this condition. The effectiveness of QS alexandrite lasers has not yet been studied. OBJECTIVE: To retrospectively assess the efficacy and complications of QS alexandrite lasers in the treatment of ABNOM. METHODS: Thirty-two Chinese women with ABNOM ranging in age from 28 to 66 years were involved in the study. All underwent QS alexandrite laser treatment (755 nm, spot size 3 mm, 8 J/cm(2)). Topical hydroquinone and tretinoin cream were given to those with hyperpigmentation after the laser surgery. Clinical photographs were taken before and after laser surgery and assessed by two independent observers. The degree of clearing was scored and complications, including hypopigmentation, hyperpigmentation, scarring, and erythema, were assessed. RESULTS: The mean number of treatment sessions was 7 (range 2-11) and the mean treatment interval was 33 days. Both observers identified more than 80% of the patients as having more than a 50% degree of clearing, and complete clearance was seen in more than 28% of patients. Although most patients had postlaser hyperpigmentation and were on depigmentary regimes, the hyperpigmentation was seen in only 12.5% of the patients during photographic evaluation. Hypopigmentation was seen in 50% of patients and erythema in 41%. CONCLUSION: QS alexandrite appears to be effective in the treatment of ABNOM. Postoperative pigmentary changes were frequent and the use of topical depigmentary agents was necessary to achieve a satisfactory result. Transient hypopigmentation risk was high, affecting up to 50% of the patients. Further study is warranted to compare the efficacy and complications of different laser systems in the treatment of this condition.