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Abstract Background The prevalence of knee osteoarthritis (KOA), a progressive degenerative disease, is gradually increasing, and it is a progressive degenerative disease. In patients with mild-to-moderate KOA, intra-articular hyaluronic acid (IA-HA) has been shown to be an effective non-operative treatment option that can provide significant pain relief and symptom improvement by increasing intra-articular viscoelasticity. This study aimed to evaluate the efficacy of IA-HA injections in delaying total knee arthroplasty (TKA) and the safety of IA-HA according to IA-HA type and combination with intra-articular corticosteroid (IA-CS) using a large health insurance claim database. Methods For this retrospective cohort study, the study population included patients aged ≥ 50 years with a first diagnosis of KOA between 2009 and 2014, who underwent TKA by 2020, using the Health Insurance Review and Assessment Service claim database in Republic of Korea. IA-HA injections were categorized as single or multiple injection regimen agents. Cox proportional hazard models estimated hazard ratios (HR) for TKA risk, adjusted for covariates. Logistic regression assessed the occurrence of adverse events after IA-HA administration. Results In all, 36,983 patients were included. Patients who received IA-HA injections had a significantly longer time to TKA compared to those who did not (mean delay of approximately 1 year). The IA-HA group had a significantly lower risk of TKA (HR: 0.61, 95% CI: 0.60–0.62) than non-IA-HA group after adjusting for covariates, which included age, sex, medical history, number of hospital beds, and CS injection. Single injection IA-HA regimen agents showed the longest time to TKA and lowest risk (HR: 0.56, 95% CI: 0.53–0.59). TKA risk decreased with the number of IA-HA cycles. Adverse events occurred in 6.7% of IA-HA cases without CS, with very low incidence of infection. Multiple injection regimen agents (multiple injection regimen 7.0% vs. single injection regimen 3.6%) and concurrent IA-CS use (concurrent IA-CS use 13.9% vs. IA-HA only 6.7%) were associated with higher infection risk. Conclusion IA-HA injections were associated with a significant delay in TKA among patients with KOA. Single-injection regimen agents had the lowest TKA risk. Infection risk increased with multiple injections and concurrent IA-CS use. These findings could suggest the use of IA-HA as an effective non-operative intervention option for managing KOA and delaying TKA. Careful selection of IA-HA type and consideration of concurrent IA-CS use could play a role in delaying the time to TKA and reducing complications.

Abstract This study aimed to compare functional outcomes sequentially up to 1 year after combined anterior cruciate ligament reconstruction (ACLR) and anterolateral ligament reconstruction (ALLR) and isolated ACLR. Fifty patients who underwent ACLR with versus without ALLR were analyzed at four different time points (preoperatively and 3, 6, and 12 months postoperatively). For the functional outcomes, muscle strength and acceleration time (AT) were measured using an isokinetic dynamometer. Proprioception was evaluated using joint position sense and dynamic postural stability. Patient-reported outcomes were measured using the Tampa Scale for Kinesiophobia (TSK-11) scores. Functional performance was assessed using single-leg hop distance (SLHD) and Limb Symmetry Index. In the operated knees, quadriceps (at 6 months postoperatively, p = 0.003) and hamstring (at 6 and 12 months postoperatively, p

Background and Objectives: Remodeling and healing of the graft are crucial processes for long-term graft survival after anterior cruciate ligament reconstruction (ACLR). However, few studies have objectively evaluated the differences in graft healing between autografts and allografts. This study aimed to compare the status of the anterior cruciate ligament (ACL) grafts between hamstring tendon (HT) autografts and tibialis anterior tendon (TAT) allografts using second-look arthroscopy. Materials and Methods: The outcomes of 193 consecutive patients (153 males and 40 females, with an average age of 30.38 and BMI of 25.43 kg/m2) who underwent second-look arthroscopy following primary ACLR were retrospectively reviewed. Prior to participating in this study, all patients provided written informed consent. The patients were divided into two groups: those with HT autografts and those with TAT allografts. Confounding factors were matched between the two groups using propensity score matching (PSM). ACL graft status was assessed during second-look arthroscopy using a numeric scale system based on the degree of four parameters: graft tension, continuity, synovium coverage, and vascular marking. Clinical outcomes were assessed using the Lysholm and International Knee Documentation Committee (IKDC) scores. Graft status and clinical outcomes were compared between the two groups. Additionally, a subgroup analysis based on the timing of the second-look arthroscopy (12–24 months vs. >24 months after the initial ACLR) was conducted. Results: After PSM, 62 patients were included in each group. The second-look arthroscopy was conducted at 23.6 ± 6.6 months for the HT group and at 24.0 ± 7.9 months for the TAT group (p = 0.749). The continuity and tension of the ACL graft were not significantly different between the two groups (p = 0.146 and 0.075, respectively). However, the TAT group exhibited significantly inferior synovial coverage and vascular marking of the ACL graft compared with the HT group (p = 0.021 and 0.007, respectively). These findings were consistent regardless of the timing of the second-look arthroscopy. Clinical outcomes, according to the Lysholm and IKDC scores, significantly improved in both groups with no significant differences (p = 0.386 and 0.733, respectively). Conclusions: Although there were no differences in graft tension and continuity between HT autografts and TAT allografts, the biological healing of ACL grafts, in terms of synovialization and vascularization, was superior in HT autografts compared to TAT allografts.

Abstract Subchondral insufficiency fracture of the knee (SIFK) causes acute knee pain in adults and often requires surgical management. Unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) are the two most common surgical treatments for SIFK. While both UKA and TKA have their advantages, there is no consensus for SIFK localized on the medial compartment. We hypothesized that patients with SIFK treated with UKA would show superior patient-reported outcomes compared to those who underwent TKA. A total of 90 patients with SIFK located medially were included in the TKA (n = 45) and UKA (n = 45) groups. Size of SIFK lesions were measured on MR images. Patient reported outcomes in the form of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Hospital Special Surgery (HSS) scores, and Knee Society Scores (KSS) were assessed preoperatively, postoperative 6, 12 months, and at the final follow-up. There were no differences in the size of the SIFK lesion between two groups. At 6 months, WOMAC score was better in the UKA group than the TKA group (p

This study aimed to compare functional outcomes including knee muscle strength in the quadriceps and hamstrings, and proprioception, assessed through dynamic postural stability (overall stability index [OSI]) and self-reported outcomes in the operated and non-operated knees between anterior cruciate ligament reconstruction (ACLR) with meniscal repair for unstable (root and radial tears) and stable (longitudinal, horizontal, and bucket handle tears) meniscal tears. A total of 76 patients were randomly selected (41 with ACLR with meniscal repair for unstable meniscal tears and 35 with ACLR with meniscal repair for stable meniscal tears) at three different time points (preoperative, 6 months, and 12 months). Repeated measures analysis of variance was used to investigate the differences in outcomes for between-subject and within-subject factors. In the operated knees, there were no significant differences for functional outcomes between the two groups (all p > 0.05). In the non-operated knees, a significant difference was observed for the OSI between the two groups, which was significantly higher in ACLR with meniscal repair for unstable meniscal tears than for stable meniscal tears at 6 months (p < 0.001). Multiple linear regression analysis showed that age (p = 0.027), preoperative OSI in the operated knees (p = 0.005), and postoperative OSI in the operated knees at 6 months (p = 0.002) were significant and independent predictors for OSI in the non-operated knees at 6 months postoperatively. Therefore, while no differences were observed in functional outcomes between the two groups in the operated knees, dynamic postural stability was poorer at 6 months postoperatively in the non-operated knees of patients with ACLR with meniscal repair for unstable meniscal tears. Furthermore, a significant correlation was observed between preoperative/postoperative dynamic postural stability in the operated knees and postoperative dynamic postural stability in the non-operated knees. Hence, we recommend incorporating balance exercises for both knees in post-surgical rehabilitation, particularly for patients with unstable meniscal tears.

Abstract Background Postoperative pneumonia (POP) is a devastating complication that can frequently occur after hip fracture surgery. This study aimed to quantitatively and comprehensively summarize the risk factors for POP following hip fracture surgery. Methods PubMed, Embase, and Cochrane Library were systematically searched for studies assessing risk factors for POP following hip fracture surgery. The pooled odds ratio (OR) and standardized mean difference (SMD) between patients with and without POP were calculated. Evidence was assessed using the Newcastle–Ottawa scale. Results Ten studies including 37,130 patients with hip fractures were selected. POP occurred in 1768 cases with an accumulated incidence of 7.8% (95% confidence interval [CI]: 0.061–0.094). Advanced age (SMD: 0.50, 95% CI: 0.10–0.90), male sex (OR: 1.50, 95% CI: 1.12–2.01), American Society of Anesthesiologists physical status scale ≥3 (OR: 3.17, 95% CI: 1.25–8.05), chronic obstructive pulmonary disease (OR: 2.05, 95% CI: 1.43–2.94), coronary heart disease (OR: 1.82, 95% CI: 1.27–2.60), arrhythmia (OR: 1.49, 95% CI: 1.04–2.15), congestive heart failure (OR: 1.41, 95% CI: 1.14–1.75), chronic kidney disease (OR: 2.09, 95% CI: 1.28–3.41), and cerebrovascular accident (OR: 2.14, 95% CI: 1.60–2.85) were risk factors for POP. Hemoglobin (SMD: -0.14, 95% CI: − 0.25 to − 0.03), albumin (SMD: -0.97, 95% CI: − 1.54–-0.41), blood urea nitrogen (SMD: 0.20, 95% CI: 0.03–0.37), alanine aminotransferase (SMD: 0.27, 95% CI: 0.10–0.44), arterial oxygen pressure (SMD: -0.49, 95% CI: − 0.71–-0.27), time from injury to surgery (SMD: 0.13, 95% CI: 0.08–0.17), and surgery within 48 h (OR: 3.74, 95% CI: 2.40–5.85) were associated with the development of POP. Conclusion Patients with the aforementioned risk factors should be identified preoperatively, and related prophylaxis strategies should be implemented to prevent POP following hip fracture surgery.

Background One in five patients with mechanical alignment (MA) after total knee arthroplasty (TKA) was reportedly dissatisfied. As constitutional varus knees are common, restoring the patients’ natural residual varus (RV) alignment is as an appealing alternative to neutral MA. This meta-analysis aimed to evaluate the effects of RV alignment on the functional outcomes compared with those of MA in TKA for the knees with varus osteoarthritis. Methods The MEDLINE/PubMed, Cochrane Library, and EMBASE databases were comprehensively searched for papers comparing the effects of RV alignment and MA on the functional outcomes from the time of inception of the databases to July 2020. Studies comparing the functional outcomes in the knees subjected to TKA with RV alignment (case group) and MA (control group) were included. The Knee Society knee and functional scores (KSKS and KSFS, respectively), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Oxford knee score (OKS), and forgotten joint score (FJS) were compared. Results Seven studies were finally included; all studies showed a low risk of selection bias and provided detailed demographic data. The pooled mean difference in the KSKS (0.06, 95% confidence interval [CI]: −0.14 to 0.27; p = 0.55) and KSFS (0.08, 95% CI: −0.08 to 0.35; p = 0.56) between RV alignment and MA did not significantly differ. The pooled mean differences in the WOMAC (−0.25, 95% CI: −0.57 to 0.07; p = 0.12), OKS (0.06, 95% CI: −0.15 to 0.27; p = 0.56), and FJS (0.41, 95% CI: −0.18 to 1.00; p = 0.18) between the groups were not significant. Conclusion The beneficial effects of RV alignment on the functional outcomes are limited compared to those of MA in TKA for varus osteoarthritis to date. Currently, TKA with neutral MA should be considered as the gold standard.

Abstract This study aimed to evaluate (1) the overall reasons for first revision in CoC THAs; (2) whether the reasons for revision differ between third-generation and fourth-generation CoC THAs; and (3) the specific factors associated with bearing-related problems as the reason for revision. We retrospectively reviewed 2045 patients (2194 hips) who underwent first revision THA between 2004 and 2013, among which 146 hips with CoC bearings underwent revision. There were 92 hips with third-generation ceramic bearings and 54 hips with fourth-generation ceramic bearings. The major reasons for CoC THA revisions were ceramic fracture and loosening of the cup or stem. When ceramic fracture, squeaking, incorrect ceramic insertion, and unexplained pain were defined as directly related or potentially related to ceramic use, 28.8% (42/146) of CoC revisions were associated with bearing-related problems. Among the third-generation ceramic bearings, revision was performed in 41.3% (38/92) of cases owing to bearing-related problems whereas revisions were performed for only 7.4% (4/54) of cases with fourth-generation ceramic bearings owing to bearing-related problems (p

Background and Objectives: The medial collateral ligament (MCL) is one of the major supporting ligaments of the knee joint, and MCL injuries are common where excessive valgus loading is applied to the knee joint. Although most MCL injuries can be treated conservatively, healing of the MCL can take several weeks to months. Furthermore, once injured, the biomechanical properties of the healed MCL differ from those of the native MCL, resulting in an increased risk of re-injury and chronic remnant symptoms. Mesenchymal stem cells (MSCs), owing to their therapeutic potential, have been investigated in various musculoskeletal injuries, and some preclinical studies regarding MSC-based approaches in MCL injuries have shown promising results. Despite satisfactory results in preclinical studies, there is still a lack of clinical studies in the orthopedic literature. This article describes the basic knowledge of the MCL, standard treatments for MCL injuries, and recent studies regarding the application of MSCs for enhanced healing of the MCL. MSC-based approaches are expected to be a potential therapeutic option for enhanced healing of the MCL in the future.

Abstract Background Unnecessary costs and complications can be reduced by increasing hemoglobin (Hb) levels and minimizing blood transfusions in patients who underwent total knee arthroplasty (TKA). This study aimed to determine the effects of intravenous iron monotherapy before TKA on preoperative iron deficient anemia and postoperative transfusion rates. Methods This prospective cohort study included 45 patients scheduled for TKA in the experimental group (Group I) and 221 patients who underwent TKA in 2015 and 2018 in the control group (Group C). One thousand milligrams of ferric carboxymaltose was administrated 1 month before TKA in group I. Intergroup comparison of the rate and total volume of transfusion, perioperative changes in Hb and analysis of iron metabolism variables in group I were performed. Subgroup analysis of Group I was conducted according to the response to iron monotherapy. Results Although Hb levels increased after intravenous iron monotherapy in Group I, postoperative transfusion rates in Groups I and C were 17.8% and 18.6%, respectively, without significant intergroup differences in the rate and total units of transfusion. Ferritin level and transferrin saturation were corrected in both subgroups of Group I. Only 17 patients (37.78%) showed response to iron monotherapy, with an Hb increase of 1.0 g/dL or more. Subgroup analysis showed lower proportions of coexisting chronic diseases, including chronic kidney disease in responders. Conclusion IV iron monotherapy was shown to be insufficient in successfully treating preoperative iron-deficient anemia to reduce postoperative allogenic blood transfusion in patients who underwent TKA. As preoperative anemia should be managed due to the high rates of postoperative transfusion for this surgery, clinicians should consider the complex interplay among the causal factors of anemia, apart from ID, in patients with preoperative anemia who are scheduled for TKA.

Abstract Background Hip fracture in elderly patients is a serious health concern due to the associated morbidity and mortality. Although acute kidney injury after hip fracture is known to be a significantly poor prognostic factor for morbidity and mortality, the literature regarding the risk factors for acute kidney injury after hip fracture is insufficient. This study aimed to investigate the incidence and associated risk factors for acute kidney injury in patients with femoral neck fracture. Methods A total of 248 patients who underwent an operation for femoral neck fracture between January 2011 and January 2015 were retrospectively analyzed. Acute kidney injury was defined according to the Kidney Disease: Improving Global Outcomes guidelines. Results The incidence of acute kidney injury was 17.7% (n = 44). Risk factors for acute kidney injury included diabetes mellitus, pre-existing renal disease, preoperative blood urea nitrogen (BUN), preoperative estimated glomerular filtration rate (eGFR), preoperative haemoglobin (Hb) level, type of operation, postoperative creatinine level and intraoperative hypotension (P

Clinical outcomes after anterior cruciate ligament reconstruction (ACLR) have improved remarkably. However, residual rotational instability of the knee joint remains a major concern. The anterolateral ligament (ALL) has recently gained interest as a secondary stabilizer of knee joint rotatory instability, and this has led to the attempt of ALL reconstruction (ALLR) in combination with ACLR to restore rotational stability in patients with anterior cruciate ligament (ACL) injury. Although several techniques for ALLR have recently been introduced, the ideal graft type and surgical technique for combined ACLR and ALLR are yet to be established. This technical note therefore aimed at introducing a novel surgical procedure involving the use of a single Achilles tendon allograft as a relatively simple and minimally invasive procedure for combined ALL and ACL reconstruction.

Despite remarkable advances in the clinical outcomes after anterior cruciate ligament reconstructions (ACLRs), residual rotational instability of the knee joint remains a major concern. Since the anterolateral ligament (ALL) on the knee joint has been “rediscovered”, the role of anterolateral structures, including ALL and deep iliotibial band, as secondary stabilizers of anterolateral rotatory instability has gained interest. This interest has led to the resurgence of anterolateral procedures combined with ACLRs to restore rotational stability in patients with anterior cruciate ligament (ACL) deficiencies. However, the difference in concepts between anterolateral ligament reconstructions (ALLRs) as anatomical reconstruction and lateral extra-articular tenodesis (LETs) as non-anatomical reinforcement has been conflicting in present literature. This study aimed to review the anatomy and biomechanics of anterolateral structures, surgical techniques, and the clinical outcomes of anterolateral procedures, including LET and ALLR, in patients with ACL deficiencies.

Background: During total knee arthroplasty (TKA) for osteoarthritis, the sagittal gap imbalance (SGI) with a relatively large extension gap is an important surgical challenge. We determined the predictors of SGI with a relatively large extension gap and evaluated the surgical outcomes of knees with SGI. Methods: 551 consecutive cases of primary TKA for osteoarthritis were retrospectively reviewed. The cohort was divided into two groups according to the SGI and statistically matched according to baseline characteristics via the inverse probability of treatment weighting method. Multiple linear and logistic regression analyses were performed to determine the predictors of sagittal gap difference (SGD) and SGI. Intergroup differences in clinical and radiological outcomes were analyzed. Results: Of all the knees included, 8.5% (n = 45) presented with SGI with a relatively large extension gap and required femoral sagittal balancing to manage SGI. The hyperextension angle (HA), preoperative joint line convergence angle (JLCA), and the change in posterior tibial slope (PTS) significantly correlated to SGD and predicted SGI with a relatively large extension gap. SGI group showed significant changes in femoral posterior condylar offset and joint line height compared to those without SGI (1.48 vs −0.45, 1.37 vs −0.51, respectively). Postoperative ROM and knee society knee scores were lower in SGI group. Conclusion: Knees requiring sagittal balancing to manage SGI with a relatively large extension gap is not uncommon in TKA for osteoarthritic knees. The change in PTS is an independent and modifiable predictor of SGI.

Many studies have found associations between unicompartmental knee arthroplasty (UKA) and implant survival, but controversy still exists regarding the relative survival of medial versus lateral UKA over mid-to long-term follow-up. The purpose of this study was to compare survival and clinical outcomes of medial and lateral UKAs. In this meta-analysis, we reviewed studies that assessed implant survival in patients who underwent medial or lateral UKA with short- to mid-term (10years) follow-up, and that used assessments, such as pain and function scores, to compare postoperative scores on knee outcome scales. A total of eight studies (33,999 knees with medial UKA and 2,853 with lateral UKA) met the inclusion criteria and was analyzed in detail. There were no significant differences between medial and lateral UKA in pain score (95% CI: -0.37 to 0.88; P = 0.42), function score (95% CI: -0.19 to 0.60; P = 0.31), short- to mid-term survival (medial, 32,083/33,483; lateral, 2,636/2,726; OR 0.98, 95% CI: 0.64 to 1.48;P = 0.91), or long-term survival (medial, 479/516; lateral, 110/127; OR 2.51, 95% CI:0.67 to 9.43; P = 0.17). In addition, both groups had substantial proportions of knees with short- to mid-term survival (95.6% by medial UKA and 94.6% by lateral UKA) and long-term survival (92.8% by medial UKA and 86.6% by lateral UKA). This meta-analysis found no significant differences in short- to mid-term and long-term survival of medial and lateral UKAs. Similarly, patients treated with medial UKA showed no difference in pain relief or functional improvement compared to patients treated with lateral UKA. These results suggest that both UKA techniques are viable treatment options for patients with unicompartmental knee osteoarthritis over long-term follow-up, although further high-quality studies are needed to address some remaining uncertainties regarding the clinical benefits of these procedures.

IntroductionAt present, information about clinical efficacy and adverse events of controlled release (CR) form of pelubiprofen, a prodrug of 2-arylopropionic acid with relatively selective effects on cyclooxygenase-2 activity, remains scarce. In this study, we sought to determine non-inferiority of pelubiprofen CR 90 mg/day compared to aceclofenac 200 mg/day regarding clinical efficacy and adverse events after a 4-week course of medication in the patients with symptomatic knee osteoarthritis.Materials and methodsA total of 191 patients were randomly assigned to take either pelubiprofen CR 90 mg (n = 95) or aceclofenac 200 mg (n = 96). The primary outcome variable was non-inferiority of pain reduction between baseline and week 4 when assessed using a 100 mm pain visual analogue scale (VAS). Pelubiprofen was considered non-inferior to aceclofenac if the upper limit of the one-sided 97.5% confidence interval for the difference in terms of pain VAS was above 15 mm (the average change of pain VAS in the pelubiprofen group-pain VAS reduction in the aceclofenac group). Secondary outcome variables were the changes in 100 mm pain VAS at week 2 versus baseline, K-Western Ontario, and McMaster University Arthritis Index (K-WOMAC) changes at weeks 2 and 4 as compared to baseline, patient global assessment at weeks 2 and 4. The frequency and amount of rescue medicine usage at weeks 2 and 4 were also evaluated as the secondary outcome variable. For safety analysis, adverse events, clinical laboratory tests, vital signs, and physical examinations were assessed and conducted at each follow-up visit.ResultsAt week 4, the pain VAS values were significantly reduced in both groups receiving either pelubiprofen CR 90 mg or aceclofenac 200 mg as compared to the baseline. However, the pelubiprofen group and the aceclofenac group respectively showed the pain VAS changes of -22 and -21.9 in the pre-protocol set and -20.8 and -21.7 in the full analysis set, confirming non-inferiority. The pelubiprofen CR 90 mg showed a reduced incidence of adverse events compared to the aceclofenac 200 mg (p = 0.005).ConclusionsPelubiprofen CR 90 mg is as effective as aceclofenac 200 mg with reduced adverse events for the treatment of symptomatic knee osteoarthritis.

This study aimed to determine the subjects for bacterial multiplex polymerase chain reaction (mPCR) testing and to interpret the mPCR test results based on patients’ clinical symptoms and diagnoses. The medical records of 710 pediatric patients who underwent a bacterial mPCR test were retrospectively reviewed. Clinical characteristics and mPCR test results were compared between patients with positive (n = 199) and negative mPCR test results (n = 511) and between patients with invasive pathogens (n = 95) and toxigenic pathogens (n = 70). Positive mPCR test results were significantly associated with older age (p < 0.001), diagnosis of acute gastroenteritis (p = 0.021), presence of hematochezia (p < 0.001), and absence of cough (p = 0.004). The diagnosis of acute gastroenteritis (p = 0.003), presence of fever (p = 0.027) and diarrhea (p = 0.043), and higher C-reactive protein levels (p = 0.025) were significantly associated with the identification of invasive pathogens in patients with positive mPCR test results. Thus, selective bacterial mPCR testing should be performed based on the patients’ clinical symptoms and diagnoses, and the results should be interpreted in consideration with identified pathogens.

The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), such as proportion and multilineage potential, can be affected by donor age. However, the qualitative and quantitative features of ACL MSCs isolated from younger and older individuals have not yet been compared directly. This study assessed the phenotypic and functional differences in ACL-MSCs isolated from younger and older donors and evaluated the correlation between ACL-MSC proportion and donor age. Torn ACL remnants were harvested from 36 patients undergoing ACL reconstruction (young: 29.67 ± 10.92 years) and 33 undergoing TKA (old: 67.96 ± 5.22 years) and the proportion of their MSCs were measured. The mean proportion of MSCs was slightly higher in older ACL samples of the TKA group than of the younger ACL reconstruction group (19.69 ± 8.57% vs. 15.33 ± 7.49%, p = 0.024), but the proportions of MSCs at passages 1 and 2 were similar. MSCs from both groups possessed comparable multilineage potentiality, as they could be differentiated into adipocytes, osteocytes, and chondrocytes at similar level. No significant correlations were observed between patient age and MSC proportions at passages 0-2 or between age and MSC proportion in both the ACL reconstruction and TKA groups. Multiple linear regression analysis found no significant predictor of MSC proportion including donor age for each passage. Microarray analysis identified several genes that were differentially regulated in ACL-MSCs from old TKA patients compared to young ACL reconstruction patients. Genes of interest encode components of the extracellular matrix (ECM) and may thus play a crucial role in modulating tissue homeostasis, remodeling, and repair in response to damage or disease. In conclusion, the proportion of freshly isolated ACL-MSC was higher in elderly TKA patients than in younger patients with ACL tears, but their phenotypic and multilineage potential were comparable.

Febrile seizure (FS), which occurs in febrile children without underlying health problems, is the most common type of seizure disorder in children. The suggested pathogenesis of FS derived from several animal and human studies is multifactorial and debatable. Neuronal hyperexcitability, which develops during inflammatory responses that accompany fever, provokes seizures. However, the exact role of each inflammatory mediator (e.g., cytokines) is undefined in terms of the connection between systemic or local inflammation and the central nervous system, and the mechanisms by which cytokines increase neuronal excitability remain unclear. In contrast, the cause of fever in most children with FS is usually mild respiratory virus infection (e.g., rhinovirus, influenza virus, adenovirus, and enterovirus) rather than severe bacterial infections. In temperate regions, the major causative respiratory viruses seem to mirror seasonally prevalent respiratory viruses in the community. Therefore, vigorous efforts to identify the causative pathogen of fever may not be necessary in children with FS. Genetic factors seem to play a role in neuronal hyperexcitability, and some types of genetic variation have been identified in several genes encoding ion channels of neurons that participate in neuronal excitation. Although most children with FS have benign outcomes, some characteristics such as complex FS, febrile status epilepticus, consecutive afebrile seizures, and the presence of neurodevelopmental disabilities may require further genetic and neurologic evaluations. [ABSTRACT FROM AUTHOR]

Infections with Haemophilus influenzae type b have been decreasing due to widespread use of conjugate vaccines thereto, and there has been an increasing trend in the relative proportion of invasive infections by non-typeable H. influenzae (NTHi). NTHi commonly colonizes the upper respiratory tract and causes recurrent infections of the adjacent organs. There is a rapid development of antibiotic resistance in NTHi strains, and therefore it is important to select appropriate antibiotics for treatment. We report a case of recurrent NTHi meningitis in a 5-year-old girl with a previous history of recurrent otitis media. The patient presented with fever accompanying recurrent vomiting, and β-lactamase-positive amoxicillin/clavulanate-resistant NTHi was isolated in cerebrospinal fluid culture. Antibiotic resistance testing revealed penicillin-binding protein 3 mutation, which is an important emerging mechanism of antibiotic resistance of NTHi. Cystic cochleovestibular malformation was also identified, which may be the predisposing condition for recurrent otitis media, and invasive NTHi infection. Acute symptoms resolved with antibiotic therapy (cefotaxime, 200 mg/kg per day). After surgical revision, the patient has been in good health without recurrence. In children with recurrent respiratory tract infections, or invasive NTHi infection, it is important to consider the presence of underlying diseases and infections due to antibiotic resistant pathogens, in order to select an appropriate antibiotic agent for treatment. [ABSTRACT FROM AUTHOR]

Febrile seizure (FS) is a common benign seizure disorder of young children. Although upper respiratory tract infection is the cause of fever in most episodes of FS, studies to identify respiratory viruses using a multiplex polymerase chain reaction (mPCR) test have rarely been performed for children with FS. Medical records of children presenting with FS between January 2015 and December 2019 were retrospectively reviewed. Respiratory viruses identified by a rapid influenza detection test and mPCR test were investigated, and their seasonal distribution and the association between viral identification and seizure characteristics were determined. A total of 607 episodes of FS were analyzed: 81.1% of cases were generalized tonic-clonic seizures, 81.5% occurred within 24 h after fever onset, and 87.3% continued for 5 min. Complex FS occurred in 17.5% of FS episodes, and epilepsy was diagnosed in 2.5% of tracked cases. Of the 138mPCRtests performed in 235 hospitalized episodes of FS, 112 (81.2%) tested positive for respiratory viruses: rhinovirus, enterovirus, adenovirus, and influenza virus were most frequently identified. The identified respiratory viruses showed similar seasonal distributions as were observed in community-acquired respiratory tract infections. The identification of a specific respiratory virus was not significantly associated with seizure characteristics or the development of complex FS. In conclusion, respiratory viruses, showing similar seasonal distributions with community-acquired respiratory tract infections and no significant association with the severity and outcomes of FS, should not be rigorously tested for in children with FS. [ABSTRACT FROM AUTHOR]

Splenic abscess occurs very rarely in healthy children. Although typhoid fever was the leading cause of splenic abscess in the pre-antibiotic era, Salmonella spp. remain to be the major pathogens causing splenic abscess, with an increasing worldwide frequency of splenic abscess due to non-typhoidal Salmonella infection. Here, we report the case of a 12-year-old boy, who was presumably diagnosed with acute gastroenteritis on admission and eventually diagnosed with a large splenic abscess (maximum diameter, 14.5 cm) caused by non-typhoidal Salmonella. Although splenectomy has been considered in cases of large splenic abscesses, the patient was treated with antibiotics and ultrasonography-guided percutaneous drainage. A detailed physical examination and appropriate imaging studies are necessary for the early diagnosis of extra-intestinal complications of non-typhoidal Salmonella enteritis. For treatment, percutaneous drainage, rather than splenectomy, can be used in large splenic abscesses. [ABSTRACT FROM AUTHOR]

Purpose: There are limited population-based data regarding herpes zoster in children. Thus we conducted a multi-institutional epidemiological analysis of herpes zoster in children and comparative analysis according to their immune status. Materials and Methods: The study included 126 children under the age of 18 years who were hospitalized for herpes zoster at 8 hospitals in South Korea, between July 2009 and June 2015. The subjects were divided into 2 groups according to their immune status, and medical records were reviewed. Results: There were 61 cases (48.4%) in the immunocompetent group and 65 cases (51.6%) in the immunocompromised group. Median age was older in immunocompromised group (11.4 vs. 8.6) (p<0.001). The mean duration of hospitalization was longer in immunocompromised group (11.0 vs. 6.6) (p<0.001). Patients were treated with oral or intravenous antiviral agents. A total of 12 in immunocompetent group were cured only by oral acyclovir. No treatment failure was found in both groups. Six immunocompromised patients had postherpetic neuralgia and 1 case was in immunocompetent group. In immunocompetent children, herpes zoster was likely caused by early varicella infection. There was no increase in progression of severity in both groups due to appropriate treatment. Conclusion: Early initiation of therapy is necessary for those in immunocompromised conditions. And inactivated herpes zoster vaccination may be considered in immunocompromised adolescents in the future. [ABSTRACT FROM AUTHOR]

This retrospective study was performed to determine the seroprevalence of hepatitis A virus (HAV) in children and adolescents with hematologic malignancies after the completion of chemotherapy and hematopoietic cell transplantation (HCT). Of 97 enrolled patients, 60 (61.9%) were seropositive for HAV. The seroprevalences in patients undergoing chemotherapy and HCT were 60.3% (41/68) and 65.5% (19/29), respectively (P = 0.628). No significant factors associated with seropositivity for HAV after chemotherapy and HCT were identified. Anti-HAV tests and HAV re-vaccinations can be considered in children and adolescents with underlying hematologic malignancies after chemotherapy and HCT based on the anti-HAV results. [ABSTRACT FROM AUTHOR]

Background: Despite the introduction of a polymerase chain reaction (PCR) test for the diagnosis of respiratory viral infection (RVI), guidance on the application of this test and the management of RVI in immunocompromised children is lacking. This study evaluated the clinical characteristics of RVI and established strategies for the PCR test in children and adolescents with hematological malignancies. Methods: This study included children and adolescents with underlying hematological malignancies and respiratory symptoms, in whom a multiplex PCR test was performed. Patients in whom RVI was identified and not identified were categorized into Groups I and II, respectively. Group I was sub-divided into patients with upper and lower respiratory infections. The medical records of the enrolled patients were retrospectively reviewed. Results: A total of 93 respiratory illnesses were included. Group I included 46 (49.5%) cases of RVI, including 31 (67.4%) upper and 15 (32.6%) lower respiratory infections. Rhinovirus (37.0%) was the most common viral pathogen. Significantly more patients in Group I had community-acquired respiratory illnesses (p=0.003) and complained of rhinorrhea (p<0.001) and sputum (p=0.008) than those in Group II. In Group I, significantly more patients with lower respiratory infections had uncontrolled underlying malignancies (p=0.038) and received reinduction or palliative chemotherapy (p=0.006) than those with upper respiratory infections. Conclusions: A multiplex PCR test should be considered for RVI diagnosis in immunocompromised children and adolescents with respiratory symptoms, especially in those with rhinorrhea or sputum prominent over a cough. The early application of the PCR test in patients with uncontrolled underlying malignancies may improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose: There is no standard method for confirming the immunogenicity of acellular pertussis vaccines. We tried to develop a local standard method for evaluating the immunogenicity of the three-component of acellular pertussis vaccines which was developed by a Korean local company. Materials and Methods: The developed pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) were evaluated by in-house enzyme-linked immunosorbent assay (ELISA) using 189 negative sera, 25 positive sera, and 73 paired sera (pre- and post-Tdap [tetanus, diphtheria, and acellular pertussis] vaccinated sera). ELISA units were calculated by the reference line method, compared with World Health Organization reference sera, and the cutoff value was calculated using negative sera. Results: When compared to National Institute for Biological Standards and Control control antigen (NIBSC) control antigens, the developed pertussis toxin (PT) and filamentous haemagglutinin (FHA) antigens were 203.48 and 61.60 IU/μg, respectively. Each in-house ELISA was established by validating the coefficients of variation % (PT, 11.53%; FHA, 8.60%; pertactin [PRN], 9.86%) obtained from the results of inter- and intra-assay variation. Also, the cut-off values of PT, FHA, and PRN were 11.65, 38.95, and 5.66 EU/mL, respectively. The distributions of antibody levels in paired showed that 93.15% (68/73) in anti-PT IgG, 97.26% (72/73) in anti-FHA IgG, and 100% in anti-PRN IgG were higher than a 100% increase after vaccination. Additionally, the values of 89.04% (65/73) in anti-PT IgG, 97.26% (72/73) in anti-FHA IgG, and 100% in anti-PRN IgG were below each cut-off point. Conclusion: We established an in-house ELISA method using self-developed antigens, and these immunoassays have provided a way to standardize measuring the immunogenicity of newly developed vaccines, through single- and dual-serology. [ABSTRACT FROM AUTHOR]

Purpose: Although the DTaP and Tdap vaccines used to prevent pertussis have been used for a long time, there is no standard method for measuring pertussis antigens. Therefore, this preliminary study was conducted to develop an enzyme-linked immunosorbent assay method using an animal model for measuring antibodies against pertussis toxin, the most important pertussis pathogenic antigen, in the sera of vaccinated mice. Materials and Methods: Bordetella pertussis Tohama phase I was cultured for 24-30 hours, and then pertussis toxin was purified from the culture medium by chromatography. Purified pertussis toxin was diluted in phosphate-buffered saline-coating buffer, and 100 μL of diluted pertussis toxin was added to each well and reacted at room temperature for 4 hours. Positive serum was diluted to 1/1,250-1/80,000 and negative serum was diluted to 1/50 to determine the coating concentration with the optimal signal/noise ratio. Optimal test conditions were confirmed from the dilution factors of the secondary antibody and streptavidin horseradish peroxidase (SA-HRP). Results: Optimal conditions were as follows: 4 μg/mL for coating antigen; 1/40,000 for secondary antibody; and 1/1,000 for the SA-HRP dilution factor. Comparison of the sera obtained from mice treated with a developing vaccine and commercial vaccine with National Institute for Biological Standard and Control standard serum under the established conditions showed the following results: 1,300.62, 534.94, and 34.85, respectively. Conclusion: The method developed in this study is suitable for measuring anti-pertussis toxin antibodies and may be applicable for clinical sample analysis or indirect diagnosis of pertussis. [ABSTRACT FROM AUTHOR]

Long-term trends in global sea spray aerosol (SSA) emissions and dimethyl sulfide (DMS) fluxes from sea to air during the recent global warming hiatus (2000–2015) were analyzed using satellite observations and modelling data. The SSA emissions were estimated using a widely used whitecap method with sea surface temperature (SST) dependence. In addition, sea-to-air DMS fluxes were also used to quantify the secondary contributions of DMS through its sequential oxidation and gas-to-particle conversion. Aerosol optical depth (AOD) was estimated by an aerosol optical model using the number concentration of SSA and non-sea-salt sulfate from DMS. The estimated AOD, which was derived from the SSA and DMS emitted from the sea surface, was compared with satellite-derived AOD to quantify its (primary and secondary) contribution to atmospheric aerosol loading (i.e., observed AOD). Yearly global mean anomalies in DMS fluxes and AOD derived from SSA showed statistically significant downward trends during the recent global warming hiatus, whereas SSA emissions and AOD derived from DMS oxidation did not. In terms of regional trends, the decreases in SSA emissions during 2000–2015 occurred over the central Pacific Ocean, the Indian Ocean, and the Caribbean Sea, whereas upward trends in SSA emissions occurred over the tropical southeastern Pacific Ocean, the Southern Ocean, and the North Atlantic Ocean. DMS fluxes during the study period showed a clear downward trend over most regions of the global ocean. The estimates of the contributions of SSA (primary) and DMS (secondary) to atmospheric aerosol loading were 23–62% and 26–38%, respectively, with the largest primary contribution (~90%) over the Southern Ocean. [ABSTRACT FROM AUTHOR]

Background: Although Escherichia coli is a common cause of bacterial enteritis in Korea, reports on community-acquired E. coli enteritis in Korean children are scarce. This study aimed to determine the clinical characteristics and pathotype distribution of community- acquired E. coli enteritis diagnosed by a multiplex polymerase chain reaction (PCR) assay in Korean children. Materials and Methods: The medical records of children aged 18 years or less who were diagnosed with acute gastroenteritis by the attending physician between 2013 and 2016 were retrospectively reviewed. The clinical characteristics of children diagnosed with E. coli enteritis were investigated and compared with those diagnosed with Salmonella enteritis. E. coli and Salmonella infections were diagnosed by a stool PCR assay. Results: Among 279 children, in whom PCR assays for E. coli and Salmonella spp. were performed, Salmonella enteritis and E. coli enteritis were diagnosed in 43 (15.4%) and 39 (14.0%) children, respectively. Among the 39 children with E. coli enteritis, enteropathogenic E. coli (n=21, 53.8%) and enteroaggregative E. coli (n=15, 38.4%) were the most common causative agents. Empirical antibiotics were administered to 33 (84.6%) children. A total of 31 (79.5%) children developed fever, and 25 (80.6%) of them had the fever for 3 days or less, which resolved a median of 1 day (range 0-3 days) after hospitalization. The most frequent gastrointestinal symptom was diarrhea (n=36, 92.3%). Significantly more children with E. coli enteritis were aged 2 years or less as compared with those with Salmonella enteritis (41.0% vs. 21.9%, P = 0.021). Children with Salmonella enteritis more frequently complained of fever (97.7% vs. 79.5%, P = 0.012), abdominal pain (90.7% vs. 64.1%, P = 0.004), and hematochezia (46.5% vs. 10.3%, P <0.001) than those with E. coli enteritis. Erythrocyte sedimentation rate and C-reactive protein levels were significantly higher in children with Salmonella enteritis than those with E. coli enteritis (P <0.001). Conclusion: Enteropathogenic E. coli was the most frequent pathotype in Korean children with E. coli enteritis that caused mild clinical symptoms. A stool PCR assay for E. coli may be useful for epidemiological purpose and for an early diagnosis of E. coli enteritis. [ABSTRACT FROM AUTHOR]

Background: Although the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients.Methods: Thirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P. aeruginosa bacteremia between 2011 and 2016 were enrolled in the study. Their medical records were retrospectively reviewed to evaluate the demographic and clinical characteristics. Antibiotic susceptibility rates of the isolated P. aeruginosa to eight antibiotic categories (anti-pseudomonal penicillin, anti-pseudomonal penicillin and β-lactamase inhibitor combination, anti-pseudomonal cephalosporin, monobactam, carbapenem, aminoglycoside, fluoroquinolone, and colistin) were also determined. Among the investigated factors, risk factors for mortality and infections by a multidrug-resistance (MDR) strain were determined.Results: Thirty-six episodes of P. aeruginosa bacteremia were identified. The mean age of the enrolled patients was 9.5 ± 5.4 years, and 26 (72.2%) episodes occurred in boys. Acute myeloid leukemia (41.7%) and acute lymphoblastic leukemia (33.3%) were the most common underlying disorders. The 30-day mortality was 38.9%, and 36.1% of the episodes were caused by MDR strains. The deceased patients were more likely to experience breakthrough infection (P = 0.036) and bacteremia (P = 0.005) due to MDR strains when compared with the patients who survived. The survived patients more likely received appropriate empirical antibiotic therapy (P = 0.024) and anti-pseudomonal β-lactam and aminoglycoside combination therapy (P = 0.039) compared with the deceased patients. The antibiotic susceptibility rates of the isolated P. aeruginosa strains were as follows: piperacillin/tazobactam, 67.6%; meropenem, 72.2%; and amikacin, 100%.Conclusions: Mortality due to P. aeruginosa bacteremia remained at 38.9% in this study, and more than one-third of the isolated strains were MDR. In this context, empirical antibiotic combination therapy to expand the antibiotic spectrum may be a strategy to reduce mortality due to P. aeruginosa bacteremia in febrile neutropenic patients. [ABSTRACT FROM AUTHOR]

The volume of hip arthroplasty is stiffly increasing because of excellent clinical outcomes, however it has not been shown to decrease the incidence of transfusions due to bleeding related to this surgery. This is an important consideration since there are concerns about the side effects and social costs of transfusions. First, anemia should be assessed at least 30 days before elective hip arthroplasty, and if the subject is diagnosed as having anemia, an additional examination of the cause of the anemia should be carried and steps taken to address the anemia. Available iron treatments for anemia take 7 to 10 days to facilitate erythropoiesis, and preoperative iron supplementation, either oral or intravenous, is recommended. When using oral supplements for iron storage, administer elemental iron 100 mg daily for 2 to 6 weeks before surgery, and calculate the dose using intravenous supplement. Tranexamic acid (TXA) is a synthetic derivative of the lysine component, which reduces blood loss by inhibiting fibrinolysis and clot degradation. TXA is known to be an effective agent for reducing postoperative bleeding and reducing the need for transfusions in primary and revision total hip arthroplasties. Patient blood management has improved the clinical outcome after hip arthroplasty through the introduction and research of various agents, thereby reducing the need for allogeneic blood transfusions and reducing the risk of transfusionrelated infections and the duration of hospitalizations. [ABSTRACT FROM AUTHOR]

Background: Tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccination during adolescence was introduced in response to the resurgence of pertussis in various countries. A new Tdap vaccine was manufactured in Korea as a countermeasure against a predicted Tdap vaccine shortage. This study was performed to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model.Methods: Four-week-old BABL/c mice were used for assessment of immunogenicity and protection efficacy. A single dose of primary diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered, followed by a single dose of Tdap booster vaccine after a 12-week interval. Anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), and anti-pertactin (PRN) IgG titers were measured before primary vaccination, and before and after booster vaccination. An intranasal challenge test was performed after booster vaccination to determine protection efficacy. To assess safety, mouse weight gain test and leukocytosis promotion test were performed using 4-week-old ddY female mice.Results: Anti-PT and anti-FHA IgG titers after booster vaccination were significantly higher than those before booster vaccination with either the new vaccine or a commercially available Tdap vaccine (P = 0.01 for all occasions). After booster vaccination, no significant difference was observed between the two vaccines in antibody titers against pertussis antigens (P = 0.53 for anti-PT IgG, P = 0.91 for anti-FHA IgG, P = 0.39 for anti-PRN IgG). In the intranasal challenge test, inoculated B. pertussis was eradicated 7 days after infection. On days 4 and 7 after infection, colony counts of B. pertussis were not significantly different between the new and positive control vaccine groups (P = 1.00). Mean body weight changes and leukocyte counts of the new vaccine, positive control, and negative control groups were not significantly different 7 days after vaccination (P = 0.87 and P = 0.37, respectively). All leukocyte counts in the new vaccine group were within a mean ± 3 standard deviations range.Conclusions: A murine model involving a single dose primary DTaP vaccination followed by a single dose Tdap booster vaccination can be used for non-clinical studies of Tdap vaccines. The new Tdap vaccine manufactured in Korea exhibited comparable immunogenicity, protection efficacy, and safety with a commercially available Tdap vaccine. [ABSTRACT FROM AUTHOR]

Background: Tunnel widening (TW) after anterior cruciate ligament (ACL) reconstruction can be a serious complication, and there is controversy over how to prevent it. This study aimed to suggest surgical approaches to prevent TW using an allo-Achilles tendon graft, and then to evaluate TW after these surgical tips were applied. Materials and Methods: Sixty two patients underwent ACL reconstruction with an allo-Achilles tendon graft. Four surgical approaches were used: Making a tibial tunnel by bone impaction, intraarticular reamer application, bone portion application for the femoral tunnel, and an additional bone plug application for the tibial tunnel. After more than 1-year, followup radiographs including anteroposterior and lateral views were taken in 29 patients encompassing thirty knees. The diameter of the tunnels at postoperation day 1 (POD1) and at followup was measured and compared. Results: In 18 knees (60%), there were no visible femoral tunnel margins on the radiographs at POD1 or followup. In the other 12 cases, which had visible femoral tunnel margins on followup radiographs, the mean femoral tunnel diameter was 8.6 mm. In the tibial tunnel, the mean diameters did not increase on all three levels (proximal, middle, and distal), and there was no statistically significant difference between the diameters at POD1 and followup. Conclusion: The suggested tips for surgery involving an allo-Achilles tendon graft can effectively prevent TW after ACL reconstruction according to this case series. These surgical tips can prevent TW. [ABSTRACT FROM AUTHOR]

Background: Although adenovirus (ADV) infection occurs steadily all year round in Korea and the identification of respiratory viral coinfections has been increasing following the introduction of multiplex real-time polymerase chain reaction tests, the clinical impact of viral coinfection in children with ADV infection has rarely been reported. Materials and Methods: Medical records of children diagnosed with ADV infection were retrospectively reviewed. The enrolled children were divided into two groups based on the identified respiratory viruses: ADV group and coinfection group. Clinical and laboratory parameters were compared between the two groups. Results: In total, 105 children (60 males and 45 females) with a median age of 29 months (range: 0-131 months) diagnosed with an ADV infection were enrolled. Fever (99.0%) was by far the most frequent symptom, followed by respiratory (82.9%), and gastrointestinal (22.9%) symptoms. Upper and lower respiratory tract infections were diagnosed in 56 (53.3%), and 32 (30.5%) children, respectively. Five (4.8%) children received oxygen therapy, and no child died due to ADV infection. Coinfection was diagnosed in 32 (30.5%) children, with rhinovirus (46.9%), and respiratory syncytial virus (21.9%) being the most frequent. The proportions of children younger than 24 months (P <0.001), with underlying medical conditions (P = 0.020), and diagnosed with lower respiratory tract infection (P = 0.011) were significantly higher in the coinfection group than in the ADV group. In a multivariate analysis, only the younger age was significantly associated with coinfection (P <0.001). Although more children in the coinfection group received oxygen therapy (P = 0.029), the duration of fever and hospitalization was not significantly different between the two groups. Conclusion: Respiratory viral coinfection with ADV occurred more frequently in children younger than 24 months of age compared with children aged 24 months or older. Respiratory viral coinfection may increase the severity of ADV infection, however, appropriate therapy prevented prolonged hospitalization and poor prognosis due to coinfection. [ABSTRACT FROM AUTHOR]