Venous thromboembolism in the trauma patient

Deep vein thrombosis (DVT) is a common complication amongst patients who sustain major trauma. Whilst DVT may result in long-term morbidity, it is the potential for the fatal consequences of acute pulmonary embolism (PE) that remain a significant cause for concern in the severely injured patient. The incidence and risk factors for venous thromboembolism (VTE) are discussed. The aetiology of thrombus formation in trauma is reviewed in depth.Multiple methods of thromboprophylaxis exist, both pharmacological and mechanical. Inferior venal caval filters, on the other hand, aim to prevent the emboli from DVTs that have already formed lodging within the pulmonary vasculature. All modalities have potential advantages and disadvantages.The likelihood of DVT can potentially be predicted by scoring systems, whilst numerous methods of DVT detection can be employed. Once DVT has been diagnosed, treatment should be commenced.Major trauma patients may sustain a vast array of injuries, and prevention and treatment of VTE in specific injury patterns are reviewed. However, further evidence in the form of multi-centre, randomized controlled trials must be obtained before a standardized protocol for thromboprophylaxis in major trauma can be produced.     

The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13

Dendritic cells (DCs) are indispensable for defense against pathogens but may also contribute to immunopathology. Activation of DCs upon the sensing of pathogens by Toll-like receptors (TLRs) is largely mediated by pattern recognition receptor/nuclear factor-κB (NF-κB) signaling and depends on the appropriate ubiquitination of the respective signaling molecules. However, the ubiquitinating and deubiquitinating enzymes involved and their interactions are only incompletely understood. Here, we reveal that the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) is upregulated in DCs upon murine Toxoplasma gondii infection and lipopolysaccharide challenge. Stimulation of DCs with the TLR11/12 ligand T. gondii profilin and the TLR4 ligand lipopolysaccharide induced an increase in NF-κB activation in OTUB1-competent cells, resulting in elevated interleukin-6 (IL-6), IL-12, and tumor necrosis factor (TNF) production, which was also observed upon the specific stimulation of TLR2, TLR3, TLR7, and TLR9. Mechanistically, OTUB1 promoted NF-κB activity in DCs by K48-linked deubiquitination and stabilization of the E2-conjugating enzyme UBC13, resulting in increased K63-linked ubiquitination of IRAK1 (IL-1 receptor-associated kinase 1) and TRAF6 (TNF receptor-associated factor 6). Consequently, DC-specific deletion of OTUB1 impaired the production of cytokines, in particular IL-12, by DCs over the first 2 days of T. gondii infection, resulting in the diminished production of protective interferon-γ (IFN-γ) by natural killer cells, impaired control of parasite replication, and, finally, death from chronic T. encephalitis, all of which could be prevented by low-dose IL-12 treatment in the first 3 days of infection. In contrast, impaired OTUB1-deficient DC activation and cytokine production by OTUB1-deficient DCs protected mice from lipopolysaccharide-induced immunopathology. Collectively, these findings identify OTUB1 as a potent novel regulator of DCs during infectious and inflammatory diseases.     

Evaluation of dental age and associated developmental anomalies in subjects with impacted mandibular canines

Objectives:To assess the null hypothesis that there is no difference in the rate of dental development and the occurrence of selected developmental anomalies related to shape, number, structure, and position of teeth between subjects with impacted mandibular canines and those with normally erupted canines.Materials and Methods:Pretreatment records of 42 subjects diagnosed with mandibular canines impaction (impaction group: IG) were compared with those of 84 subjects serving as a control reference sample (control group: CG). Independent t-tests were used to compare mean dental ages between the groups. Intergroup differences in distribution of subjects based on the rate of dental development and occurrence of selected dental anomalies were assessed using χ² tests. Odds of late, normal, and early developers and various categories of developmental anomalies between the IG and the CG were evaluated in terms of odds ratios.Results:Mean dental age for the IG was lower than that for the CG in general. Specifically, this was true for girls (P < .05). Differences in the distribution of the subjects based on the rate of dental development and occurrence of positional anomalies also reached statistical significance (P < .05). The IG showed a higher frequency of late developers and positional anomalies compared with controls (odds ratios 3.00 and 2.82, respectively; P < .05).Conclusions:The null hypothesis was rejected. We identified close association of female subjects in the IG with retarded dental development compared with the female orthodontic patients. Increased frequency of positional developmental anomalies was also remarkable in the IG.     

CTLA‐4 (CD152) enhances the Tc17 differentiation program

Although CD8⁺ T cells that produce IL‐17 (Tc17 cells) have been linked to host defense, Tc17 cells show reduced cytotoxic activity, which is the characteristic function of CD8⁺ T cells. Here, we show that CTLA‐4 enhances the frequency of IL‐17 in CD8⁺ T cells, indicating that CTLA‐4 (CD152) specifically promotes Tc17 differentiation. Simultaneous stimulation of CTLA‐4^+/+ and CTLA‐4^?/? T cells in cocultures and agonistic CTLA‐4 stimulation unambiguously revealed a cell‐intrinsic mechanism for IL‐17 control by CTLA‐4. The quality of CTLA‐4‐induced Tc17 cells was tested in vivo, utilizing infection with the facultative intracellular bacterium Listeria monocytogenes (LM). Unlike CTLA‐4^+/+ Tc17 cells, CTLA‐4^?/? were nearly as efficient as Tc1 CTLA‐4^+/+ cells in LM clearance. Additionally, adoptively transferred CTLA‐4^?/? Tc17 cells expressed granzyme B after rechallenge, and produced Tc1 cytokines such as IFN‐γ and TNF‐α, which strongly correlate with bacterial clearance. CTLA‐4^+/+ Tc17 cells demonstrated a high‐quality Tc17 differentiation program ex vivo, which was also evident in isolated IL‐17‐secreting Tc17 cells, with CTLA‐4‐mediated enhanced upregulation of Tc17‐related molecules such as IL‐17A, RORγt, and IRF‐4. Our results show that CTLA‐4 promotes Tc17 differentiation that results in robust Tc17 responses. Its inactivation might therefore represent a central therapeutic target to enhance clearance of infection.     

Intrapericardial Immature Teratoma with Successful Treatment in a Neonate

Intra-pericardial teratoma, most often a benign tumor, is an extremely rare condition in a newborn. It can be a diagnostic and therapeutic challenge if it presents with massive pericardial effusion. Complete surgical excision of the tumor is necessary because of its association with tissues of malignant potential. A 16-d-old newborn was diagnosed with intra pericardial immature teratoma (IT) and managed successfully with multidisciplinary team approach by prompt referral for complete surgical resection followed by adjuvant chemotherapy with carboplatin, etoposide and bleomycin (JEB) to prevent recurrence. The infant is now on close follow up with monitoring of serum alpha fetoprotein (AFP) levels and imaging studies for early diagnosis of recurrence of tumor and chemotherapy related complications.     

Clinical Efficacy of Subgingivally Delivered 1.2% Atorvastatin in Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: Atorvastatin (ATV) is a specific competitive inhibitor of 3‐hydroxy‐2‐methyl‐glutaryl coenzyme A reductase. Recently, statins have shown pleiotropic effects such as anti‐inflammation and bone stimulation. The aim of the present study is to investigate the effectiveness of 1.2% ATV as an adjunct to scaling and root planing (SRP) in the treatment of intrabony defects (IBDs). Methods: Sixty individuals were randomized into two treatment groups: SRP plus 1.2% ATV and SRP plus placebo gel. At baseline and 3, 6, and 9 months, clinical parameters, which included modified sulcus bleeding index, plaque index, probing depth (PD), and clinical attachment level (CAL), were recorded at baseline. Radiologic assessment of IBD fill was done using computer‐aided software at baseline and 6 and 9 months. Results: Mean PD reduction and mean CAL gain were greater in the ATV group than the placebo group at 3, 6, and 9 months. A significantly greater mean percentage of radiographic bone fill was found in the ATV group (35.49% ± 5.50%) compared to the placebo group (1.82% ± 1.32%) after 9 months. Conclusion: ATV as an adjunct to SRP can provide a new direction in the management of IBDs.     

Locally Delivered 1% Metformin Gel in the Treatment of Smokers with Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: Metformin (MF) (1,1‐dimethylbiguanide HCl) is one of the most commonly used oral antihyperglycemic agents for the treatment of type 2 diabetes mellitus. Recently, MF has been shown to have bone‐sparing properties. The present study is designed to investigate the effectiveness of MF 1% in an indigenously prepared, biodegradable, controlled‐release gel, as an adjunct to scaling and root planing (SRP) in treatment of vertical defects in smokers with generalized chronic periodontitis (CP). Methods: Fifty patients were categorized into two treatment groups: SRP plus 1% MF and SRP plus placebo. Clinical parameters were recorded at baseline and at 3 and 6 months; they included plaque index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). At baseline and after 6 months, intrabony defect (IBD) fill was radiologically assessed using computer software. Results: Mean PD reduction and mean CAL gain were found to be greater in the MF group than the placebo group at all visits. Furthermore, a significantly greater mean percentage of bone fill was found in the MF group (26.17% ± 6.66%) than the placebo sites (3.75% ± 8.06%) (P <0.001). Conclusion: There was greater decrease in mSBI and PD and more CAL gain with significant IBD fill at vertical defect sites treated with SRP plus locally delivered MF, versus SRP plus placebo, in smokers with generalized CP.     

Efficacy of Subgingivally Delivered Simvastatin in the Treatment of Patients With Type 2 Diabetes and Chronic Periodontitis: A Randomized Double‐Masked Controlled Clinical Trial

Background: Simvastatin (SMV) is a specific competitive inhibitor of 3‐hydroxy‐2‐methyl‐glutaryl coenzyme A reductase. Recently, it has been reported that statins promote bone formation. The present study is designed to investigate the effectiveness of 1.2% SMV in an indigenously prepared, biodegradable, controlled‐release gel as an adjunct to scaling and root planing (SRP) in the treatment of patients with type 2 diabetes and chronic periodontitis (CP). Methods: Thirty‐eight patients were categorized into two treatment groups: SRP plus 1.2% SMV and SRP plus placebo. Clinical parameters were recorded at baseline before SRP and at 3, 6, and 9 months; they included modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). At baseline and after 6 and 9 months, radiologic assessment of intrabony defect (IBD) fill was done using computer‐aided software. Results: Mean PD reduction and mean CAL gain were found to be greater in the SMV group than the placebo group at 3, 6, and 9 months. Furthermore, significantly greater mean percentage of bone fill was found in the SMV group (32.64% ± 12.90%) compared to the placebo group (4.22% ± 9.75%) after 9 months. Conclusion: There was a greater decrease in mSBI and PD and more CAL gain with significant IBD fill at sites treated with SRP plus locally delivered SMV in patients with type 2 diabetes and CP.     

Bilateral gluteal compartment syndrome after total hip arthroplasty under epidural anesthesia

The gluteal compartment syndrome is uncommon and is discussed in only a few published case reports. The simultaneous bilateral gluteal compartment syndrome is exceptionally rare and is tackled in only 4 case reports to date. We report a case of bilateral gluteal compartment syndrome after total hip arthroplasty under epidural anesthesia and discuss its management.