Neuromuscular complications of the lower extremity after thrombectomy in a patient with superficial femoral artery occlusion: Case series.

BACKGROUND: Ischemia reperfusion (IR) injury may result in rhabdomyolysis and compartment syndrome when blood supply returns after thrombectomy for patients with acute limb ischemia. OBJECTIVE: We highlight the value of early diagnosis and treatment in post-thrombectomy patients with IR injuries in their lower legs. CASE DESCRIPTION: Two patients received thrombectomy due to left superficial femoral artery occlusion. Both patients complained of left calf pain during ambulation at the 1- and 3-day follow up post-thrombectomy, as well as a heating sensation, swelling, weakness, and sensory changes in the affected leg. For early diagnosis musculoskeletal ultrasounds were performed and in both cases revealed swelling and change of echogenicity in the left calf. To further diagnosis, magnetic resonance imaging of the left leg revealed limb IR-induced muscular injury and rhabdomyolysis, respectively. In both cases, an electrodiagnostic study revealed peripheral nerve injury in the left leg. Medications were provided for neuropathic pain control and early rehabilitation was performed to improve function. In both cases, patients reported during their follow-up that their pain and muscle weakness had improved. CONCLUSION: When post-thrombectomy calf pain occurs early evaluation and treatment should be performed to identify any potential IR injury.

Effect of Voice and Articulation Parameters of a Home-Based Serious Game for Speech Therapy in Children With Articulation Disorder: Prospective Single-Arm Clinical Trial.

BACKGROUND: Articulation disorder decreases the clarity of language and causes a decrease in children's learning and social ability. The demand for non-face-to-face treatment is increasing owing to the limited number of therapists and geographical or economic constraints. Non-face-to-face speech therapy programs using serious games have been proposed as an alternative. OBJECTIVE: The aim of this study is to investigate the efficacy of home therapy on logopedic and phoniatric abilities in children with articulation disorder using the Smart Speech game interface. METHODS: This study is a prospective single-arm clinical trial. Children with articulation disorders, whose Urimal Test of Articulation and Phonology (U-TAP) was -2 SDs or less and the Receptive and Expressive Vocabulary Test score was -1 SD or more, were enrolled. A preliminary evaluation (E0) was conducted to check whether the children had articulation disorders, and for the next 4 weeks, they lived their usual lifestyle without other treatments. Prior to the beginning of the training, a pre-evaluation (E1) was performed, and the children trained at home for ≥30 minutes per day, ≥5 times a week, over 4 weeks (a total of 20 sessions). The Smart Speech program comprised oral exercise training, breathing training, and speech training; the difficulty and type of the training were configured differently according to the participants' articulation error, exercise, and vocal ability. After the training, postevaluation (E2) was performed using the same method. Finally, 8 weeks later, postevaluation (E3) was performed as a follow-up. A voice evaluation included parameters such as maximum phonation time (MPT), fundamental frequency (F0), jitter, peak air pressure (relative average perturbation), pitch, intensity, and voice onset time. Articulation parameters included a percentage of correct consonants (PCC; U-TAP word-unit PCC, U-TAP sentence-unit PCC, and three-position articulation test) and alternate motion evaluation (diadochokinesis, DDK). Data obtained during each evaluation (E1-E2-E3) were compared. RESULTS: A total of 13 children with articulation disorders aged 4-10 years were enrolled in the study. In voice parameters, MPT, jitter, and pitch showed significant changes in repeated-measures ANOVA. However, only MPT showed significant changes during E1-E2 (P=.007) and E1-E3 (P=.004) in post hoc tests. Other voice parameters did not show significant changes. In articulation parameters, U-TAP, three-position articulation test (TA), and DDK showed significant changes in repeated-measures ANOVA. In post hoc tests, U-TAP (word, sentence) and TA showed significant changes during E1-E2 (P=.003, .04, and .01) and E1-E3 (P=.001, .03, and .003), and DDK showed significant changes during E1-E2 only (P=.03). CONCLUSIONS: Home-based serious games can be considered an alternative treatment method to improve language function. TRIAL REGISTRATION: Clinical Research Information Service KCT0006448; https://cris.nih.go.kr/cris/search/detailSearch.do/20119.

Ipsilateral Motor Evoked Potentials in a Preschool-age Child With Traumatic Brain Injury: A Case Report.

To the best of our knowledge, the upper age limit at which post-neonatal cerebral palsy (CP) can manifest remains uncertain. This uncertainty is attributed to the lack of objective parameters for assessing the developing brain. In a previous study, we reported that an ipsilateral corticospinal projection associated with brain injury, as manifested in the paretic hand of a CP patient, had never been observed in individuals aged > 2 years. In this case report, we present an instance of ipsilateral motor evoked potential (iMEP) in a girl whose traumatic brain injury occurred at the age of 4 years. This case is the oldest in which brain injury occurred and iMEP was maintained. In conclusion, iMEP can be a valuable indicator of motor system plasticity in the developing brain.

Photoswitchable Microgels for Dynamic Macrophage Modulation.

Dynamic manipulation of supramolecular self-assembled structures is achieved irreversibly or under non-physiological conditions, thereby limiting their biomedical, environmental, and catalysis applicability. In this study, microgels composed of azobenzene derivatives stacked via π-cation and π-π interactions are developed that are electrostatically stabilized with Arg-Gly-Asp (RGD)-bearing anionic polymers. Lateral swelling of RGD-bearing microgels occurs via cis-azobenzene formation mediated by near-infrared-light-upconverted ultraviolet light, which disrupts intermolecular interactions on the visible-light-absorbing upconversion-nanoparticle-coated materials. Real-time imaging and molecular dynamics simulations demonstrate the deswelling of RGD-bearing microgels via visible-light-mediated trans-azobenzene formation. Near-infrared light can induce in situ swelling of RGD-bearing microgels to increase RGD availability and trigger release of loaded interleukin-4, which facilitates the adhesion structure assembly linked with pro-regenerative polarization of host macrophages. In contrast, visible light can induce deswelling of RGD-bearing microgels to decrease RGD availability that suppresses macrophage adhesion that yields pro-inflammatory polarization. These microgels exhibit high stability and non-toxicity. Versatile use of ligands and protein delivery can offer cytocompatible and photoswitchable manipulability of diverse host cells.

Submolecular Ligand Size and Spacing for Cell Adhesion.

Cell adhesion occurs when integrin recognizes and binds to Arg-Gly-Asp (RGD) ligands present in fibronectin. In this work, submolecular ligand size and spacing are tuned via template-mediated in situ growth of nanoparticles for dynamic macrophage modulation. To tune liganded gold nanoparticle (GNP) size and spacing from 3 to 20 nm, in situ localized assemblies of GNP arrays on nanomagnetite templates are engineered. 3 nm-spaced ligands stimulate the binding of integrin, which mediates macrophage-adhesion-assisted pro-regenerative polarization as compared to 20 nm-spaced ligands, which can be dynamically anchored to the substrate for stabilizing integrin binding and facilitating dynamic macrophage adhesion. Increasing the ligand size from 7 to 20 nm only slightly promotes macrophage adhesion, not observed with 13 nm-sized ligands. Increasing the ligand spacing from 3 to 17 nm significantly hinders macrophage adhesion that induces inflammatory polarization. Submolecular tuning of ligand spacing can dominantly modulate host macrophages.

Manipulating Nanoparticle Aggregates Regulates Receptor-Ligand Binding in Macrophages.

The receptor-ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor magnetic nanoparticle aggregates of tunable sizes over the cell-adhesive RGD ligand (Arg-Gly-Asp)-active material surface while maintaining the density of dispersed ligands accessible to macrophages at constant. Lowering the accessible ligand dispersity by increasing the aggregate size at constant accessible ligand density facilitates the binding of integrin receptors to the accessible ligands, which promotes the adhesion of macrophages. In high ligand dispersity, distant magnetic manipulation to lift the aggregates (which increases ligand accessibility) stimulates the binding of integrin receptors to the accessible ligands available under the aggregates to augment macrophage adhesion-mediated pro-healing polarization both in vitro and in vivo. In low ligand dispersity, distant control to drop the aggregates (which decreases ligand accessibility) repels integrin receptors away from the aggregates, thereby suppressing integrin receptor-ligand binding and macrophage adhesion, which promotes inflammatory polarization. Here, we present "accessible ligand dispersity" as a novel fundamental parameter that regulates receptor-ligand binding, which can be reversibly manipulated by increasing and decreasing the ligand accessibility. Limitless tuning of nanoparticle aggregate dimensions and morphology can offer further insight into the regulation of receptor-ligand binding in host cells.

Efficacy of preoperative percutaneous cholecystostomy in the management of acute cholecystitis according to severity grades.

BACKGROUND/AIMS: The aim of this retrospective study was to assess the efficacy of percutaneous cholecystostomy (PC) for patients with acute cholecystitis (AC) according to severity. METHODS: A total of 325 patients who underwent cholecystectomy between January 2008 and October 2010 were enrolled. Patients were classified into three groups based on severity grade according to the Tokyo guidelines for AC: grade I (mild), grade II (moderate), and grade III (severe). These groups were further classified into two subgroups based on whether or not they underwent preoperative PC. RESULTS: A total of 184 patients were classified into the grade I group (57%), 135 patients were classified into the grade II group (42%), and five patients were classified into the grade III group (1%). In the grade I and II groups, the mean length of hospital stay was significantly shorter in the patients who did not undergo PC than in those who received PC (10.7 ± 4.4 vs. 13.7 ± 5.8, p < 0.001; 11.8 ± 6.5 vs. 16.9 ± 12.5, p = 0.003, respectively). The mean length of preoperative hospital stay was significantly shorter in the patients without PC than in those with PC in the grade I and II groups (5.8 ± 3.3 vs. 8.2 ± 4.6, p = 0.001; 6.0 ± 4.4 vs. 8.8 ± 5.2, p = 0.002). In addition, the operative time was shorter in patients without PC, especially in the grade I group (94.6 ± 36.4 vs. 107.3 ± 33.5, p = 0.034). CONCLUSIONS: Preoperative PC should be reserved for only selected patients with mild or moderate AC. No significant benefit of preoperative PC was identified with respect to clinical outcome or complications.

Discrepancy between self-awareness and actual diagnosis and treatment of the conditions among adolescent with scoliosis in middle-school age.

[Purpose] The purpose of this research was to determine the awareness of the actual conditions of the diagnosis and treatment of scoliosis by focusing on middle-school students in order to provide a basis for active education and treatment of scoliosis. [Subjects and Methods] The survey was conducted among 4,782 students. The students performed Adam's forward bend test, and some of the students who showed predictive features of scoliosis were further examined for the spine structure with rasterstereography. [Results] The proportion of students with awareness about scoliosis appeared to be 71.47%. Among the students, 50.84% knew the definition of scoliosis and 4.37% were diagnosed as having scoliosis, of whom 46.37% underwent treatment. It was a significant difference between to get a diagnosis and the predictive scoliosis or the scoliosis. [Conclusion] The results showed that the students in the second grade of middle school had high awareness levels, but about 50% of them did not know the definition of scoliosis. More than 50% of them did not receive treatment after diagnosed as having scoliosis. Therefore, active education and school screening for scoliosis should be provided to adolescent students.

Cytokine secreted by S100A9 via TLR4 in monocytes delays neutrophil apoptosis by inhibition of caspase 9/3 pathway.

Dysregulation of neutrophil apoptosis causes pathogenesis and aggravation of allergy. S100A9 exists as one of the proteins in the neutrophils, triggering inflammatory responses by activating the immune cells. In this study, we investigated whether S100A9 affects constitutive neutrophil apoptosis by activating the monocytes in normal and allergic subjects. Supernatant from human monocytic THP-1 cells after treatment with S100A9 suppressed normal neutrophil apoptosis by inhibiting the activations of caspase 9 and caspase 3. S100A9 upregulated the release of MCP-1, IL-6, and IL-8 in THP-1 cells. An increase in cytokine was suppressed by CLI-095, a Toll-like receptor (TLR) 4 inhibitor, PP2, a Src inhibitor, rottlerin, a PKCδ inhibitor, MAP kinase inhibitors, including PD98059, SB202190, and SP600125, and BAY-11-7085, an NF-κB inhibitor. Src, PKCδ, ERK1/2, p38 MAPK, and JNK were phosphorylated by S100A9. The phosphorylation of Src and PKCδ was suppressed by CLI-095, and the activation of ERK1/2, p38 MAPK, and JNK was inhibited by CLI-095, PP2, and rottlerin. S100A9 induced NF-κB activity, and the activation was suppressed by CLI-095, PP2, rottlerin, and MAPK kinase inhibitors. In normal and allergic subjects, supernatant from normal and allergic monocytes after stimulation with S100A9 suppressed normal and allergic neutrophil apoptosis, respectively; MCP-1, IL-6, and IL-8 in the supernatant was increased by S100A9. The cytokine secretion induced by S100A9 is related to TLR4, Src, PKCδ, ERK1/2, p38 MAPK, JNK, and NF-κB. Taken together, S100A9 induces anti-apoptotic effect on normal and allergic neutrophils by increasing cytokine secretion of monocytes. These findings may help us to better understand neutrophil apoptosis regulated by S100A9 and pathogenesis of allergic diseases.

[A Study on the Classification of Nursing Management Competencies and Development of related Behavioral Indicators in Hospitals].

PURPOSE: The aim of this study was to classify nursing management competencies and develop behavioral indicators for nurse managers in hospitals. Also, levels of importance and performance based on developed criteria were to be identified and compared. METHODS: Using expert survey we classified nursing management competencies and behavioral indicators with data from 34 nurse managers and professors. Subsequently, data from a survey of 216 nurse managers in 7 cities was used to analyze the importance-performance comparison of the classified nursing management competencies and behavioral indicators. RESULTS: Forty-two nursing management competencies were identified together with 181 behavioral indicators. The mean score for importance of nursing management competency was higher than the mean score for performance. According to the importance-performance analysis, 5 of the 42 nursing management competencies require further development: vision-building, analysis, change management, human resource development, and self-management competency. CONCLUSION: The classification of nursing management competencies and behavioral indicators for nurse managers in hospitals provides basic data for the development and evaluation of programs designed to increase the competency of nurse managers in hospitals.

Effect of duration of smartphone use on muscle fatigue and pain caused by forward head posture in adults.

[Purpose] The effect of duration of smartphone use on neck and shoulder muscle fatigue and pain was investigated in adults with forward head posture. [Subjects and Methods] Thirty-four adults with forward head posture were classified into groups by duration of smartphone use: 11 used a smartphone for 10 minutes each (group 1), 12 for 20 minutes each (group 2), and 11 for 30 minutes each (group 3). Fatigue cervical erector spinae and upper trapezius muscles was measured by electromyography, and pain before and after the experiment was evaluated using Visual Analog Scale (VAS) scores. [Results] There was a significant difference in the degree of fatigue in the left upper trapezius muscles in group 2 and left cervical erector spinae and bilateral upper trapeziuses group 3. There was a significant difference in fatigue in the left upper trapezius in groups 1 and 3. The VAS showed significant differences in all groups before and after the experiment and between groups 1 and 3. [Conclusion] Pain and fatigue worsened with longer smartphone use. This study provided data on the proper duration of smartphone use. Correct posture and breaks of at least 20 minutes are recommend when using smartphones.

Effects of kinesio tape compared with non-elastic tape on hand grip strength.

[Purpose] Many assumptions have been made about taping and several studies have considered tape application methods; however, the true effect of taping on muscle strength remains unclear. Most previous studies compared application techniques using Kinesio tape (KT), but studies that compared muscle strength using non-elastic tape (NT) are limited. Moreover, no studies have applied KT and NT in the same way to assess grip strength in normal subjects. The purpose of this study was to evaluate the immediate effect of application of two tapes with different elastic properties on maximal grip strength in healthy adults. [Subjects and Methods] Twenty healthy adults were divided into two groups (KT and NT). Maximal grip strength was measured with a dynamometer. Forearm extensor muscles of the dominant hand were then taped and subjects were immediately asked to perform hand grip movement with maximum strength in the same standardized manner. [Results] In the KT group, maximal grip strength was significantly increased compared to the initial value; however, in the NT group, there was no significant difference in maximal grip strength. [Conclusion] This study suggests that only Kinesio tape can increase maximal grip strength immediately after application on the extensor region of the forearm.

Effects of proprioceptive neuromuscular facilitation stretching and deep-breathing exercises on upper extremity lymphedema in stroke patients.

[Purpose] The purpose of this study was to determine the effects of deep-breathing and proprioceptive neuromuscular facilitation stretching exercises on upper limb lymphedema in stroke patients. [Subjects and Methods] The study consisted of 10 patients with lymphedema that had occurred after stroke. Neurodevelopmental treatment was applied in the same manner as that used for the existing treatment. The subjects performed deep-breathing and stretching exercises three times per week for 4 weeks (12 sessions total). Body water volume in the upper limbs was measured before and after exercise by using an InBody S10 analyzer. [Results] Performance of deep-breathing and stretching exercises significantly reduced body water volume in both the affected and unaffected arms. The extracellular-to-total cellular fluid volume ratio in the affected arm improved to 0.379 after exercise, although this change was not significant. [Conclusion] The results of the present study show that deep-breathing and proprioceptive neuromuscular facilitation stretching exercises reduce upper extremity lymphedema in stroke patients.

Preparation of nano/macroporous polycaprolactone microspheres for an injectable cell delivery system using room temperature ionic liquid and camphene.

The nano/macroporous polycaprolactone (PCL) microspheres with cell active surfaces were developed as an injectable cell delivery system. Room temperature ionic liquid (RTIL) and camphene were used as a liquid mold and a porogen, respectively. Various-sized spheres of 244-601µm with pores of various size and shape of 0.02-100µm, were formed depending on the camphene/RTIL ratio (0.8-2.6). To give cell activity, the surface of porous microspheres were further modified with nerve growth factors (NGF) containing gelatin to give a thin NGF/gelatin layer, to which the neural progenitor cells (PC-12) attached and extended their neurites on to the surface layers of the microspheres. The developed microspheres may be potentially applicable as a neuronal cell delivery scaffold for neuron tissue engineering.

House dust mite allergen suppresses neutrophil apoptosis by cytokine release via PAR2 in normal and allergic lymphocytes.

House dust mite (HDM) is an essential allergen in allergic diseases such as allergic rhinitis and asthma. The pathogenic mechanism of allergy is associated with cytokine release of lymphocytes and constitutive apoptosis of neutrophils. In this study, we examined whether HDM induces cytokine release of lymphocytes and whether the secretion of cytokines is involved in modulation of neutrophil apoptosis. In normal and allergic subjects, extract of Dermatophagoides pteronyssinus (DP) increased IL-6, IL-8, MCP-1, and GM-CSF secretion in a time-dependent manner. This secretion was suppressed by PAR2i, an inhibitor of PAR2, in a dose-dependent manner, as well as by LY294002, an inhibitor of PI3K, AKTi, an inhibitor of Akt, PD98059, an inhibitor of ERK, and BAY-11-7085, and an inhibitor of NF-κB. DP induced ERK and NF-κB activation in a time-dependent manner. ERK activation was suppressed by PAR2i, LY294002, and AKTi, and NF-κB activation was blocked by PAR2i, LY294002, AKTi, and PD98059. Supernatants collected from normal and allergic neutrophils after DP treatment inhibited the apoptosis of normal and allergic neutrophils through suppression of caspase 9 and caspase 3 cleavage. DP inhibited neutrophil apoptosis in coculture of normal neutrophils with normal lymphocytes, similar to the anti-apoptotic effects of DP on neutrophils alone. DP more strongly inhibited apoptosis of allergic neutrophils cocultured with allergic lymphocytes than allergic neutrophils without lymphocytes. In summary, DP induces the release of cytokines through the PAR2/PI3K/Akt/ERK/NF-κB pathway, which has anti-apoptotic effects on neutrophils of normal and allergic subjects. These results will facilitate elucidation of the pathogenic mechanism of allergic diseases.

Multi-walled carbon nanotubes change morpho-functional and GABA characteristics of mouse cortical astrocytes.

BACKGROUND: Multi-walled carbon nanotubes (MW-CNTs) have been extensively explored for their possible beneficial use in the nervous system. CNTs have shown to modulate neuronal growth and electrical properties, but its effect that varying length of MW-CNTs on primary astrocyte roles have not been clearly demonstrated yet. RESULTS: We investigate here the effect of MW-CNTs on astrocytic morphology, cell-cell interaction and the distribution of intracellular GABA (gamma-amino butyric acid). Primary cultured cortical astrocytes on MW-CNT-coated glass coverslips grow rounder and make more cell-cell interactions, with many cell processes, compared to astrocytes on poly-D-lysine (PDL) coverslips. In addition, intracellular GABA spreads into the cell processes of astrocytes on MW-CNT coverslips. When this GABA spreads into cell processes from the cell body GABA can be released more easily and in larger quantities compared to astrocytes on PDL coverslips. CONCLUSIONS: Our result confirm that MW-CNTs modulate astrocytic morphology, the distribution of astrocytic GABA, cell-cell interactions and the extension of cell processes. CNTs look to be a promising material for use neuroprosthetics such as brain-machine interface technologies.

Production of CNT-taxol-embedded PCL microspheres using an ammonium-based room temperature ionic liquid: as a sustained drug delivery system.

We describe a one-pot method for the mass production of polymeric microspheres containing water-soluble carbon-nanotube (w-CNT)-taxol complexes using an ammonium-based room temperature ionic liquid. Polycaprolactone (PCL), trioctylmethylammonium chloride (TOMAC; liquid state from -20 to 240°C), and taxol were used, respectively, as a model polymer, room temperature ionic liquid, and drug. Large quantities of white colored PCL powder without w-CNT-taxol complexes and gray colored PCL powders containing w-CNT-taxol (1:1 or 1:2 wt/wt) complexes were produced by phase separation between the hydrophilic TOMAC and the hydrophobic PCL. Both microsphere types had a uniform, spherical structure of average diameter 3-5µm. The amount of taxol embedded in PCL microspheres was determined by HPLC and (1)H NMR to be 8-12µg per 1.0mg of PCL (loading capacity (LC): 0.8-1.2%; entrapment efficiency (EE): 16-24%). An in vitro HPLC release assay showed sustain release of taxol without an initial burst over 60days at an average rate of 0.003-0.0073mg per day. The viability patterns of human breast cancer cells (MCF-7) for PCTx-1 and -2 showed dose-dependent inhibitory effects. In the presence of PCTx-1 and -2, the MCF-7 cells showed high viability in the concentration level of, respectably, <70 and <5µg/mL.

Improvement of H2S sensing properties of SnO2-based thick film gas sensors promoted with MoO3 and NiO.

The effects of the SnO2 pore size and metal oxide promoters on the sensing properties of SnO2-based thick film gas sensors were investigated to improve the detection of very low H2S concentrations (<1 ppm). SnO2 sensors and SnO2-based thick-film gas sensors promoted with NiO, ZnO, MoO3, CuO or Fe2O3 were prepared, and their sensing properties were examined in a flow system. The SnO2 materials were prepared by calcining SnO2 at 600, 800, 1,000 and 1,200 °C to give materials identified as SnO2(600), SnO2(800), SnO2(1000), and SnO2(1200), respectively. The Sn(12)Mo5Ni3 sensor, which was prepared by physically mixing 5 wt% MoO3 (Mo5), 3 wt% NiO (Ni3) and SnO2(1200) with a large pore size of 312 nm, exhibited a high sensor response of approximately 75% for the detection of 1 ppm H2S at 350 °C with excellent recovery properties. Unlike the SnO2 sensors, its response was maintained during multiple cycles without deactivation. This was attributed to the promoter effect of MoO3. In particular, the Sn(12)Mo5Ni3 sensor developed in this study showed twice the response of the Sn(6)Mo5Ni3 sensor, which was prepared by SnO2(600) with the smaller pore size than SnO2(1200). The excellent sensor response and recovery properties of Sn(12)Mo5Ni3 are believed to be due to the combined promoter effects of MoO3 and NiO and the diffusion effect of H2S as a result of the large pore size of SnO2.

Timing of chemotherapy-induced neutropenia is a prognostic factor in patients with metastatic non-small-cell lung cancer: a retrospective analysis in gemcitabine-plus-platinum-treated patients.

PURPOSE: Chemotherapy-induced neutropenia (CIN) has been associated with better therapeutic results in studies of various tumors. Herein, we explored the relationship between timing (onset) of CIN and clinical outcomes of patients with metastatic non-small-cell lung cancer (NSCLC). METHODS: Patients with stage IV NSCLC receiving at least two cycles of first-line doublet chemotherapy (gemcitabine plus platinum) were reviewed retrospectively. Subjects were stratified by onset of CIN into two groups: early-onset (lowest neutrophil count of cycles 1-2 <2.0 × 10(9)/L) and non-early-onset. The non-early-onset group was further subdivided into late-onset (lowest neutrophil count of cycles 3-6 <2.0 × 10(9)/L) and absence of neutropenia. RESULTS: A total of 123 patients were studied. Significantly better disease control rate, progression-free survival (PFS), and overall survival (OS) were observed in early-onset versus non-early-onset patients. Median PFS of 5.1 and 3.8 months (p = 0.0016) and median OS of 16.7 and 11.2 months (p = 0.0004) were achieved for these groups, respectively. Patient subsets with late-onset and absence of neutropenia showed similarly poor clinical outcomes, with 4.8 and 3.8 months median PFS (p = 0.5067) and 13.0 and 11.2 months median OS (p = 0.6304), respectively. CONCLUSIONS: Timing of CIN is predictive of prognosis in patients with metastatic NSCLC receiving gemcitabine/platinum doublet chemotherapy. Better clinical outcomes were achieved when onset of neutropenia was early versus late or absent altogether. Further research is warranted to determine whether above findings are applicable to other chemotherapeutic regimens.