Correction to: Treatment of adults with intracranial hemorrhage on apixaban or rivaroxaban with prothrombin complex concentrate products

Journal of Thrombosis and Thrombolysis - In the original publication of the article, unfortunately the given name and family name of the author’s in the author group were inadvertently...     

In-Situ Molecular Vapor Composition Measurements During Lyophilization

Purpose

Monitoring process conditions during lyophilization is essential to ensuring product quality for lyophilized pharmaceutical products. Residual gas analysis has been applied previously in lyophilization applications for leak detection, determination of endpoint in primary and secondary drying, monitoring sterilization processes, and measuring complex solvents. The purpose of this study is to investigate the temporal evolution of the process gas for various formulations during lyophilization to better understand the relative extraction rates of various molecular compounds over the course of primary drying.

Methods

In this study, residual gas analysis is used to monitor molecular composition of gases in the product chamber during lyophilization of aqueous formulations typical for pharmaceuticals. Residual gas analysis is also used in the determination of the primary drying endpoint and compared to the results obtained using the comparative pressure measurement technique.

Results

The dynamics of solvent vapors, those species dissolved therein, and the ballast gas (the gas supplied to maintain a set-point pressure in the product chamber) are observed throughout the course of lyophilization. In addition to water vapor and nitrogen, the two most abundant gases for all considered aqueous formulations are oxygen and carbon dioxide. In particular, it is observed that the relative concentrations of carbon dioxide and oxygen vary depending on the formulation, an observation which stems from the varying solubility of these species. This result has implications on product shelf life and stability during the lyophilization process.

Conclusions

Chamber process gas composition during lyophilization is quantified for several representative formulations using residual gas analysis. The advantages of the technique lie in its ability to measure the relative concentration of various species during the lyophilization process. This feature gives residual gas analysis utility in a host of applications from endpoint determination to quality assurance. In contrast to other methods, residual gas analysis is able to determine oxygen and water vapor content in the process gas. These compounds have been shown to directly influence product shelf life. With these results, residual gas analysis technique presents a potential new method for real-time lyophilization process control and improved understanding of formulation and processing effects for lyophilized pharmaceutical products.

     

Spondylodiscitis by drug-multiresistant bacteria: a single-center experience of 25 cases

Background contextAlthough the incidence of pyogenic spinal infections is increasing, the ideal treatment of spondylodiscitis is still a controversially discussed issue. Furthermore, the proportion of multiresistant bacteria in spondylodiscitis is increasing, and treatment recommendations or reported results are missing for this especially difficult subset of patients.PurposeThe aim of this study is to evaluate the surgical outcome and the postoperative antibacterial treatment regime.Study designRetrospective case series.Patient samplePatients treated for a spondylodiscitis from multiresistant bacteria at our department between 2006 and 2011.MethodsData were gathered through review of patients' case notes, relevant imaging, and electronic records. Magnetic resonance imaging of the whole spine including gadolinium (Gd)-enhanced T1 sequences and computed tomography scans of the affected regions were obtained in all cases.Outcome measuresC-reactive protein (CRP) and complete blood cell count were analyzed in all cases using routine laboratory techniques. Neurologic deficits were classified according to the American Spinal Injury Association (ASIA) impairment scale.ResultsTwenty-five patients were identified (15 gram-positive and 10 gram-negative drug-multiresistant bacteria). The mean age at presentation was 66 years, and 14 patients were male (56%). All patients presented with pain, and a neurologic deficit was present in 11 (44%) cases. An epidural abscess was found in 11 (44%) cases. At admission, CRP was elevated in all cases with a mean of 13±9.2 mg/dL. The main source of infection was previous spine surgery (36%). All patients in this series underwent surgical debridement of the infection and instrumentation of the spine. Postoperative intravenous antibiotics were administered for 19±8.6 days followed by 3±0.3 months of oral antibiotic therapy. Eradication of the infection was achieved ultimately in all surviving patients. Out of 11 patients with neurologic deficits, 4 had a full recovery, 4 improved incompletely, and 3 remained unchanged after surgery.ConclusionsStaged surgical immobilization and instrumentation and optimal debridement at the interdiscal space and spinal canal is a reliable approach to achieve complete healing of spinal infection with multiresistant bacteria. A period of intravenous antibiotic therapy of 2 to 3 weeks followed by a 3-month oral antibiotic therapy seems appropriate for most cases.     

Impact of Chemoradiotherapy on CSF Leak Repair after Skull Base Surgery

Background Transnasal endoscopic resection (TER) has become the treatment of choice for many skull base tumors. A major limitation of TER is the management of large dural defects and the need for repair of cerebrospinal fluid (CSF) leaks, particularly among patients who are treated with chemotherapy (CTX) or radiotherapy (RT). The objective of this study is to determine the impact of CTX and RT on the success of CSF leak repair after TER. Methods We performed a retrospective chart review of a single-institution experience of TER from 1992 to 2011. Results We identified 28 patients who had endoscopic CSF leak repair after resection of malignant skull base tumors. Preoperative RT was utilized in 18 patients, and 9 had undergone CTX. All patients required CSF leak repair with rotational flaps after cribriform and/or dural resection. CSF leak repair failed in three patients (11%). A history of RT or CTX was not associated with failed CSF leak repair. Conclusion Adjuvant or neoadjuvant CTX or RT is not associated with failed CSF leak repair. Successful CSF leak repair can be performed in patients with malignant skull base tumors with an acceptable risk profile.     

A retrospective study of 113 consecutive cases of surgically treated spondylodiscitis patients. A single-center experience

Background

Recommendations for the operative treatment of spondylodiscitis are still a controversial issue.

Methods

A retrospective review identified 113 consecutive patients who underwent surgical debridement and instrumentation for spondylodiscitis between 2006 and 2010 at our department.

Results

The mean age at presentation was 65 years; 78 patients were male (69 %). Distribution of the inflammation was lumbar in 68 (60 %), thoracic in 19 (17 %) and cervical in 20 (18 %) cases. Six patients (5 %) had two concomitant non-contiguous spondylodiscitis foci in different segments of the spine. Epidural abscess was found in 33 patients (29 %). One hundred four patients (92 %) had pain. Neurological deficit was found in 40 patients (35 %). In the thoracic and lumbar cases, dorsal instrumentation alone was considered sufficient in 26 cases; additional interbody fusion from the posterior was performed in 44 cases. A 360° instrumentation was performed in 22 cases. In the cervical cases, only ventral spondylodesis and plating were performed in eight cases, only dorsal instrumentation in five and 360° instrumentation in seven. Postoperative intravenous antibiotics were administered for 14.4?±?9.3 (mean ± SD) days followed by 3.2?±?0.8 (mean ± SD) months of oral antibiosis. Complete healing of the inflammation was achieved in 111 (98 %) cases. Two patients died because of septic shock, both with fulminant endocarditis. Pain resolved in all cases. Neurological deficits were completely resolved in 20 patients, and 14 patients had a partial recovery.

Conclusion

The results of our retrospective study show that surgical treatment of spondylodiscitis with a staged surgical approach (if needed) and a short 1-2-week period of intravenous antibiotics followed by 3 months of oral antibiotics is appropriate for most patients in whom conservative treatment has failed or is not advisable. Furthermore, surgical treatment of newly diagnosed spondylodiscitis might be recommended as an initial treatment option in many cases. Thereby the choice of fusion material (autologous bone, titanium, PEEK) seems less important.