Fracture gap and working length are important actionable factors affecting bone union after minimally invasive plate osteosynthesis for the treatment of simple diaphyseal or distal metaphyseal tibia fractures.

INTRODUCTION: Indirect reduction of minimally invasive plate osteosynthesis (MIPO) can often result in delayed union in tibia fractures. This study evaluated several factors in MIPO in relation to bone union. HYPOTHESIS: We hypothesized that the fracture gap, plate - tibia distance, or working length would have a substantial effect on the tibia union rate. MATERIALS AND METHODS: Forty-one patients with simple diaphyseal or distal metaphyseal tibia fractures who underwent internal fixation surgery using the MIPO technique were divided into two groups: patients with delayed union and patients without delayed union. Non-actionable factors involving AO/OTA classification, fibula fracture and actionable factors including postoperative fracture gap, plate - tibia distance, working length in relation to parameters of bone union were compared between the two groups. Also cumulative rates of bone union and risk factors of delayed union according to variables of interest were investigated. RESULTS: AO/OTA classification, site of fibula fracture, postoperative fracture gap, working length, and bone union rate of the two groups significantly differed (p<0.05). The cumulative rate of bone union during 1-year follow-up according to 43A tibia fracture, distal fibula fracture, fracture gap, and working length significantly differed between the two groups (p<0.05). By univariate Cox proportional hazards model, 43A tibia fracture, distal fibula fracture, facture gap, and short working length were risk factors for delayed union (p<0.05). DISCUSSION: Non-actionable factors involving AO/OTA classification, distal fibula fracture and actionable factors including postoperative fracture gap, working length were significant factors affecting bone union after MIPO. The present study indicated that small fracture gap and long working length during MIPO might facilitate bone healing in tibia fracture. LEVEL OF EVIDENCE: IV; single-center retrospective cohort study.

Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication.

Viral replication often depends on RNA maturation and degradation processes catalyzed by viral ribonucleases, which are therefore candidate targets for antiviral drugs. Here, we synthesized and studied the antiviral properties of a novel nitrocatechol compound (1c) and other analogs that are structurally related to the catechol derivative dynasore. Interestingly, compound 1c strongly inhibited two DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 3'-to-5' exoribonuclease (ExoN). While 1c inhibited SARS-CoV-2 ExoN activity, it did not interfere with the mRNA methyltransferase activity of nsp14. In silico molecular docking placed compound 1c in the catalytic pocket of the ExoN domain of nsp14. Finally, 1c inhibited SARS-CoV-2 replication but had no toxicity to human lung adenocarcinoma cells. Given its simple chemical synthesis from easily available starting materials, these results suggest that 1c might be a lead compound for the design of new antiviral compounds that target coronavirus nsp14 ExoN and other viral ribonucleases.

Risk Factors for Contralateral Tendon Rupture in Patients With Acute Achilles Tendon Rupture.

The present study was performed to determine the incidence and risk factors of contralateral Achilles tendon rupture after an initial tendon rupture, and to identify the associated patient characteristics. Medical records of 181 adult patients with acute Achilles tendon rupture were reviewed. We investigated the risk factors for contralateral Achilles tendon rupture and calculated the incidence density (per 100 person-years), survival rate, hazard ratios, and 95% confidence intervals. The risk factors were extracted, including blood type, age, body mass index (BMI), occupation, underlying comorbidities, history of alcohol intake or smoking, injury mechanism, and fluoroquinolone antibiotic or steroid use. Military personnel and manual laborers, including farmers and firefighters were considered to have an occupation involving physical activity. Ten patients (5.5%) were identified as having nonsimultaneous, contralateral Achilles tendon rupture a mean of 3.3 years (range 1.0-8.3 years) after the initial tendon rupture. The incidence density of contralateral tendon rupture was 0.89 per 100 person-years. The 8-year survival rate of contralateral tendon rupture was 92.2%. Unadjusted and adjusted hazard ratios (with 95% confidence intervals, p value) of blood type O were 3.71 (1.07-12.82, p = .038) and 2.90 (0.81-10.32, p = .101), respectively, and those of occupations involving physical activity were 5.87 (1.64-20.98, p = .006) and 4.69 (1.27-17.28, p = .02), respectively. Based on the present data, blood type O and occupations involving physical activity are significantly associated with an increased risk of contralateral tendon rupture in adult patients who have sustained Achilles tendon rupture.

Efficacy of Lavage by Tube under Local Anesthesia versus Arthroscopic Treatment of Acute Septic Arthritis of Native Knee.

Although arthroscopic treatment is a minimally invasive surgery that effectively treats septic arthritis of the knee joint, it requires general or regional anesthesia. This study aimed to compare the clinical results of lavage after tube insertion versus arthroscopic treatment. Patients treated with arthroscopic treatment were included in group I (n = 76), while those treated with lavage by tube were included in group II (n = 34). We investigated the following in all patients: demographics, underlying disorders, initial serum white blood cell (WBC) count, C-reactive protein (CRP) level, synovial fluid WBC and polymorphonuclear cell counts, causative organism, initial Kellgren-Lawrence grade, lavage number, interventional delay, hospitalization days, CRP normalization time, and Western Ontario McMaster Universities Osteoarthritis index scores for clinical outcomes at 3 months postoperative. The mean interventional delay was significantly greater in group I (23.6 ± 15.6 h vs. 8.7 ± 9.3 h, p < 0.001). The lavage by tube featured a significantly shorter interventional delay time than arthroscopy, while the CRP decrease rate did not differ between groups. Moreover, lavage by tube showed no significant differences in outcomes, including laboratory results and functional outcomes at 3 months postoperative.

Expression of the cytokinesis regulator PRC1 results in p53-pathway activation in A549 cells but does not directly regulate gene expression in the nucleus.

Protein regulator of cytokinesis 1 (PRC1) is a microtubule-binding protein with essential roles in mitosis and cytokinesis. PRC1 is frequently overexpressed in cancer cells where it could contribute to chromosomal instability. Due to its nuclear localization in interphase, it has been speculated that PRC1 has additional functions that are involved in its pro-tumorigenic functions. In this study we investigated the potential nuclear functions of PRC1 in a lung cancer cell line. Genome wide expression profiling by RNA sequencing revealed that the expression of PRC1 results in activation of the p53 pathway and inhibition of the pro-proliferative E2F-dependent gene expression. A mutant of PRC1 that is unable to enter into the nucleus regulated the same gene sets as wildtype PRC1, suggesting that PRC1 has no nuclear-exclusive functions in A549 cells. Instead, induction of p53 by PRC1 correlates with multinucleation and depends on the localization of PRC1 to the midbody, suggesting that the induction of p53 is a consequence of overexpressed PRC1 to interfere with the normal function of PRC1 during cytokinesis. Activation of p53 by PRC1 results in cellular senescence but not in apoptosis. In conclusion, while PRC1 is frequently overexpressed in many cancers, the p53 pathways may initially protect cancer cells from the negative effects of PRC1 overexpression on cytokinesis. Because depletion of PRC1 also results in p53-pathway activation and senescence, levels of PRC1 need to be tightly regulated to allow unperturbed proliferation. Targeting the expression or function of PRC1 could create a therapeutic vulnerability for the treatment of cancer.

Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro).

Starting from the MLPCN probe compound ML300, a structure-based optimization campaign was initiated against the recent severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (3CLpro). X-ray structures of SARS-CoV-1 and SARS-CoV-2 3CLpro enzymes in complex with multiple ML300-based inhibitors, including the original probe ML300, were obtained and proved instrumental in guiding chemistry toward probe compound 41 (CCF0058981). The disclosed inhibitors utilize a noncovalent mode of action and complex in a noncanonical binding mode not observed by peptidic 3CLpro inhibitors. In vitro DMPK profiling highlights key areas where further optimization in the series is required to obtain useful in vivo probes. Antiviral activity was established using a SARS-CoV-2-infected Vero E6 cell viability assay and a plaque formation assay. Compound 41 demonstrates nanomolar activity in these respective assays, comparable in potency to remdesivir. These findings have implications for antiviral development to combat current and future SARS-like zoonotic coronavirus outbreaks.

Reverse shoulder arthroplasty with os acromiale.

Function and strength of the deltoid muscle are important in reverse shoulder arthroplasty (RSA). Moreover, location and shape of the acromion, clavicle, and scapular spine, which are origins of the deltoid muscle, are also important. The frequency of os acromiale is 5% to 15%; however, it is rare in the Asian population, affecting approximately 0.7% of Koreans. RSA has rarely been reported in patients with os acromiale. We present a case series of two patients with cuff tear and arthropathy combined with os acromiale who underwent RSA. From 2016 to 2018, two patients with os acromiale who presented with pain and limited range of motion (ROM) underwent RSA with cuff tear arthropathy using the subscapularis-sparing deltopectoral approach. Their ROM, visual analog scale (VAS), and satisfaction were evaluated before and after surgery. In both patients, VAS decreased, ROM increased, and postoperative satisfaction increased. There were no specific complications due to os acromiale. The VAS, ROM, and satisfaction of patients improved after surgery compared with values before surgery. However, careful attention must be given during surgery to ensure optimal repair and recovery.

Additional fixation using a metal plate with bioresorbable screws and wires for robinson type 2B clavicle fracture.

Simple clavicle fractures can achieve satisfactory results through conservative treatment, and the less frequency of nonunion. Non-union or malunion can occur in displaced clavicle fractures or comminuted shaft fractures. Treatment of displaced comminuted clavicle shaft fractures is performed by holding together the free fragments with interfragmentary screws or wires and fixing them to the clavicle with a plate. Therefore, we performed interfragmentary fixation using open reduction and internal fixation with bioresorbable screws (Mg-Ca alloy, Resomet bioresorbable bone screw; U&I Corp.) and bioresorbable wires (Mg-Ca alloy, Resomet bioresorbable K-wire and pin, U&I Corp.) for displaced comminuted clavicle fractures (Robinson type 2B) and additionally used a metal plate. We expected decreased irritation and infection due to absorption after surgery. We report four cases that were treated in this way.

Efficient Inhibition of Human Papillomavirus Infection by L2 Minor Capsid-Derived Lipopeptide.

The amino (N)-terminal region of human papillomavirus (HPV) minor capsid protein (L2) is a highly conserved region which is essential for establishing viral infection. Despite its importance in viral infectivity, the role of the HPV N-terminal domain has yet to be fully characterized. Using fine mapping analysis, we identified a 36-amino-acid (aa) peptide sequence of the L2 N terminus, termed L2N, that is critical for HPV infection. Ectopic expression of L2N with the transmembrane sequence on the target cell surface conferred resistance to HPV infection. Additionally, L2N peptide with chemical or enzymatic lipidation at the carboxyl (C) terminus efficiently abrogated HPV infection in target cells. Among the synthetic L2N lipopeptides, a stearoylated lipopeptide spanning aa 13 to 46 (13-46st) exhibited the most potent anti-HPV activity, with a half-maximal inhibitory concentration (IC50) of ∼200 pM. Furthermore, we demonstrated that the 13-46st lipopeptide inhibited HPV entry by blocking trans-Golgi network retrograde trafficking of virion particles, leading to rapid degradation. Fundamentally, the inhibitory effect of L2N lipopeptides appeared to be evolutionarily conserved, as they showed cross-type inhibition among various papillomaviruses. In conclusion, our findings provide new insights into the critical role of the L2N sequence in the HPV entry mechanism and identify the therapeutic potential of L2N lipopeptide as an effective anti-HPV agent.IMPORTANCE HPV is a human oncogenic virus that causes a major public health problem worldwide, which is responsible for approximately 5% of total human cancers and almost all cases of cervical cancers. HPV capsid consists of two structure proteins, the major capsid L1 protein and the minor capsid L2 protein. While L2 plays critical roles during the viral life cycle, the molecular mechanism in viral entry remains elusive. Here, we performed fine mapping of the L2 N-terminal region and defined a short 36-amino-acid peptide, called L2N, which is critical for HPV infection. Specifically, L2N peptide with carboxyl-terminal lipidation acted as a potent and cross-type HPV inhibitor. Taken together, data from our study highlight the essential role of the L2N sequence at the early step of HPV entry and suggests the L2N lipopeptide as a new strategy to broadly prevent HPV infection.

Severe fever with thrombocytopenia syndrome phlebovirus non-structural protein activates TPL2 signalling pathway for viral immunopathogenesis.

Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the World Health Organization Prioritized Pathogens, is an emerging phlebovirus with a high fatality1-4. Owing to the lack of therapies and vaccines5,6, there is a pressing need to understand SFTSV pathogenesis. SFSTV non-structural protein (NSs) has been shown to block type I interferon induction7-11 and facilitate disease progression12,13. Here, we report that SFTSV-NSs targets the tumour progression locus 2 (TPL2)-A20-binding inhibitor of NF-κB activation 2 (ABIN2)-p105 complex to induce the expression of interleukin-10 (IL-10) for viral pathogenesis. Using a combination of reverse genetics, a TPL2 kinase inhibitor and Tpl2-/- mice showed that NSs interacted with ABIN2 and promoted TPL2 complex formation and signalling activity, resulting in the marked upregulation of Il10 expression. Whereas SFTSV infection of wild-type mice led to rapid weight loss and death, Tpl2-/- mice or Il10-/- mice survived an infection. Furthermore, SFTSV-NSs P102A and SFTSV-NSs K211R that lost the ability to induce TPL2 signalling and IL-10 production showed drastically reduced pathogenesis. Remarkably, the exogenous administration of recombinant IL-10 effectively rescued the attenuated pathogenic activity of SFTSV-NSs P102A, resulting in a lethal infection. Our study demonstrates that SFTSV-NSs targets the TPL2 signalling pathway to induce immune-suppressive IL-10 cytokine production as a means to dampen the host defence and promote viral pathogenesis.

Prognostic factors for outcome of surgical treatment in medication-related osteonecrosis of the jaw.

OBJECTIVES: The number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing, but treatment remains controversial. Published papers and systematic reviews have suggested that surgical treatment is effective in patients with MRONJ. The purpose of this study was to determine whether preoperative University of Connecticut Osteonecrosis Numerical Scale (UCONNS), other serologic biomarkers, and size of necrosis are prognostic factors for outcome of surgical treatment in MRONJ. MATERIALS AND METHODS: From January 2008 to December 2016, 65 patients diagnosed with MRONJ at the Department of Oral and Maxillofacial Surgery in College of Dentistry, Dankook University who required hospitalization and surgical treatment were investigated. Patient information, systemic factors, and UCONNS were investigated. In addition, several serologic values were examined through blood tests one week before surgery. The size of osteolysis was measured by panoramic view and cone-beam computed tomography in all patients. With this information, multivariate logistic regression analysis with backward elimination was used to examine factors affecting postoperative outcome. RESULTS: In multivariate logistic analysis, higher UCONNS, higher C-reactive protein (CRP), larger size of osteolysis, and lower serum alkaline phosphate were associated with higher incidence of incomplete recovery after operation. This shows that UCONNS, CRP, serum alkaline phosphate, and size of osteolysis were statistically significant as factors for predicting postoperative prognosis. CONCLUSION: This study demonstrated that CRP, UCONNS, serum alkaline phosphate, and size of osteolysis were statistically significant factors in predicting the prognosis of surgical outcome of MRONJ. Among these factors, UCONNS can predict the prognosis of MRONJ surgery as a scale that includes various influencing factors, and UCONNS should be used first as a predictor. More aggressive surgical treatment and more definite surgical margins are needed when the prognosis is poor.

Nail Plate and Bed Reconstruction for Pincer Nail Deformity.

Pincer nail deformity is a severe condition in which the nail bed becomes compressed and the nail shows an overcurvature. We retrospectively analyzed 13 pincer nail deformities treated using our nail plate and bed reconstruction technique. Visual analogue scale scores, the width of nail root, width of nail tip, height of nail tip, width index, and height index were assessed before and after surgery. The overcurvature was corrected after detachment of the nail plate. The nail fold was pushed underneath the nail plate and then fixed. The width of nail tip significantly increased after surgery (p < 0.05) and was maintained during follow-up. The height of nail tip decreased after surgery (p < 0.05). This nail plate and bed reconstruction technique is a simple and quick surgical method for correcting deformities and reduces risks of complications such as skin necrosis and infection compared to other existing surgical techniques. We recommend this efficient surgical technique for the treatment of pincer nails.

Surgical Treatment With Closing-Wedge Distal Femoral Osteotomy for Recurrent Patellar Dislocation With Genu Valgum.

BACKGROUND: Closing-wedge distal femoral osteotomy (CWDFO)-combined with medial reefing and lateral release, if necessary- has been used to treat recurrent patellar dislocation (RPD) with genu valgum. PURPOSE: To evaluate the clinical and radiologic outcomes of surgical treatment with CWDFO for treatment of RPD with genu valgum. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Fourteen consecutive patients (23 knees) with RPD and genu valgum were treated with CWDFO. Patients with a minimum 2-year follow-up period were eligible for this study. Patients with prior failed surgery were also eligible. Radiographic evaluation was performed with mechanical femorotibial and lateral distal femoral angle. The radiographic parameters presenting patellar positions and pathologic abnormalities associated with RPD were evaluated. Chondral lesion changes in second-look arthroscopic examination were examined, and clinical outcomes (eg, occurrence of redislocation, range of motion, and clinical scores) were assessed pre- and postoperatively at a minimum of 2 years. RESULTS: At a mean follow-up of 30.7 months (range, 25-62 months), the mean mechanical femorotibial and mechanical lateral distal femoral angles changed significantly from valgus 5° (range, 2°-11°) to varus 3° (2°-11°; P < .001) and from 83° (range, 78°-86°) to 89° (84°-92°; P < .001), respectively. The mean patellar congruence angle improved from 40° lateral (range, 20°-53° lateral) to 4° medial (23° medial to 21° lateral; P < .001), as did the lateral patellofemoral angle from 26° (range, 8°-62°) to 9° (0°-15°; P < .001). Computed tomography scans showed that the mean distance of patellar lateral shift decreased from 13.5 mm (range, 4-22 mm) to 2.0 mm (-4 to 5 mm; P < .001). The mean tibial tubercle to trochlear groove distance significantly decreased from 20.4 to 13.5 mm ( P < .001), while the Caton-Deschamps ratio did not change significantly after surgery ( P = .984). Chondral lesions of the patella and trochlear groove significantly improved or were maintained. None of the patients experienced subluxation or redislocation after surgery. Patellar instability symptoms also improved, as validated by radiographic and other clinical outcomes. CONCLUSION: CWDFO combined with medial reefing and lateral release successfully treated RPD with genu valgum for a minimum follow-up of 2 years, with improved patellar alignment and stability.

Anatomical Relationships between Muscles Overlying Distal Transverse Carpal Ligament and Thenar Motor Branch of the Median Nerve.

BACKGROUND: The purpose of the current study is to investigate anatomical relationships between the muscle overlying the distal transverse carpal ligament (TCL) and the thenar motor branch of the median nerve. METHODS: Of the 192 wrists that underwent open carpal tunnel release, a muscle belly overlying the TCL was observed on the distal margin of TCL in 25 wrists and ligament exposure could not be achieved without transection of it. We recorded surgical findings of these 25 wrists. The origin of the recurrent motor branch arising from the major median nerve was marked on the axial and coronal section diagrams of the wrist. RESULTS: The presence of muscle overlying the TCL was seen in 25 wrists (21 patients, 13%). The locations of origin were distributed not only on the radial side but anterior or ulnar side of the major median nerve. Abnormal branches originated from the unusual side in 14 cases (56% of those with a muscle overlying the TCL): central-anterior side in eight cases, ulnar-anterior side in five cases, and ulnar side in one case. These anomalous branches were frequently associated with the muscle belly overlying the TCL in our study regardless of the origin site. The branches were prone to cut if careless midline incision along the third web space was performed. Unusual origin and aberrant pathway of the recurrent thenar motor branch were associated with the presence of a muscle overlying the TCL. CONCLUSIONS: A thorough knowledge of the standard and variant anatomy of the muscle belly and recurrent motor branch in the carpal tunnel is fundamental to prevention of complications such as muscle wasting or atrophy by iatrogenic motor branch injury during carpal tunnel release.

Osteonecrosis of Femoral Head Treated with Extracorporeal Shock Wave Therapy: Analysis of Short-term Clinical Outcomes of Treatment with Radiologic Staging.

PURPOSE: To evaluate clinical results of extracorporeal shock wave therapy (ESWT) with radiographic staging on patients with avascular necrosis of femoral head (AVNFH). MATERIALS AND METHODS: We evaluated 24 patients diagnosed with AVNFH (32 hip joints) who were treated with ESWT from 1993 to 2012. Average follow-up period was 27 months, and the average age of patients was 47.8 years. The Association Research Circulation Osseous (ARCO) system was used to grade radiographic stage prior to treatment. For this study patients were divided into two groups based on their ARCO stage, group 1 (ARCO stages I and II) and group 2 (ARCO stage III). Comparative analyses were done between the two groups using the visual analogue scale (VAS) score and the Harris hip score (HHS) at pre-treatment and 3, 6, 12, and 24 months after treatment. Failure was defined when radiographic stage progressed or arthroplasty surgery was needed due to clinical exacerbation. RESULTS: Both groups showed clinical improvements with VAS scoring at final follow-up (group 1: median 7 to 1.5, P<0.001; group 2: mean 7 to 4, P=0.056). Using HHS, group 1 showed a significant improvement (from 65.5 to 95 [P<0.001]), while no significance was observed for group 2 (P=0.280). At final follow-up, 3 hips from group 1 and one hip from group 2 showed radiographic improvement; however, two patients underwent total hip arthroplasty due to persistent pain and dysfunction. CONCLUSION: ESWT can be considered as an interventional option before surgical treatment in patients with not only early stage AVNFH but also with mid stage.

Carbon isotope fractionation of benzene and toluene by progressive evaporation.

Evaporation is one of the key attenuation processes for near-surface volatile organic compounds (VOCs) in the upper soil zone. Evaporation experiments were performed to investigate the carbon isotope fractionation of benzene and toluene during progressive and non-equilibrium evaporation at room temperature. Considerable carbon isotope fractionation occurred during evaporative enrichment of benzene and toluene. The carbon isotope compositions of residual compounds increased exponentially with increasing evaporation. Thus, the remaining liquids become isotopically heavier, and the process follows a Rayleigh trend. This result is compatible with the direction of isotopic changes associated with both microbial degradation and volatilization of hydrocarbons previously observed in soil columns, but shows exactly the opposite behavior to previous equilibrium volatilization findings.