A prospective study of predictors of poststroke depression.

OBJECTIVE: To investigate the association between early depressive behavior after stroke onset and occurrence of poststroke depression (PSD) at 3- and 12-month follow-up evaluations. METHODS: The study prospectively included 273 patients with first-ever single uncomplicated ischemic stroke. In the stroke unit, nurses scored crying, overt sadness, and apathy daily using an observational method to include patients with comprehension deficits. The Barthel Index was used to assess disability. Follow-up evaluation at months 3 and 12 included psychiatric assessment based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. RESULTS: Crying (19.8%), overt sadness (50.5%), and apathy (47.6%) were observed. Of the patients observed crying, 4 showed pathologic crying, 19 emotionalism, and 12 catastrophic reactions. Crying and overt sadness, but not apathy, were associated with a subjective experience of depression (p < 0.05). Thirty of 52 (58%) patients observed crying, 12 of 19 (63%) patients with emotionalism, and 5 of 12 (41%) patients with catastrophic reactions developed PSD within the first year. Multiple logistic regression analysis showed that only severe functional disability (odds ratio [OR], 4.31; 95% CI, 2.41 to 7.69), crying behaviors (OR, 2.66; 95% CI, 1.35 to 5.27), and an age <68 years (OR, 2.32; 95% CI, 1.30 to 4.13) were (p < 0.05) predictors of late PSD development (13% of the variance). CONCLUSIONS: In the stroke unit, crying and overt sadness are more reliable indicators of depressed mood than apathy. In patients with first-ever stroke, crying behaviors soon after stroke, a younger age, and severe disability are predictors of poststroke depression occurrence within the first year after stroke onset.

Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab.

Metastatic melanoma has a poor prognosis with high resistance to chemotherapy and radiation. Recently, the anti-CTLA-4 antibody ipilimumab has demonstrated clinical efficacy, being the first agent to significantly prolong the overall survival of inoperable stage III/IV melanoma patients. A major aim of patient immune monitoring is the identification of biomarkers that predict clinical outcome. We studied circulating myeloid-derived suppressor cells (MDSC) in ipilimumab-treated patients to detect alterations in the myeloid cell compartment and possible correlations with clinical outcome. Lin(-) CD14(+) HLA-DR(-) monocytic MDSC were enriched in peripheral blood of melanoma patients compared to healthy donors (HD). Tumor resection did not significantly alter MDSC frequencies. During ipilimumab treatment, MDSC frequencies did not change significantly compared to baseline levels. We observed high inter-patient differences. MDSC frequencies in ipilimumab-treated patients were independent of baseline serum lactate dehydrogenase levels but tended to increase in patients with severe metastatic disease (M1c) compared to patients with metastases in skin or lymph nodes only (M1a), who had frequencies comparable to HD. Interestingly, clinical responders to ipilimumab therapy showed significantly less lin(-) CD14(+) HLA-DR(-) cells as compared to non-responders. The data suggest that the frequency of monocytic MDSC may be used as predictive marker of response, as low frequencies identify patients more likely benefitting from ipilimumab treatment. Prospective clinical trials assessing MDSC frequencies as potential biomarkers are warranted to validate these observations.

Skew deviation [Skew deviation]

BACKGROUND: Skew deviation is a vertical ocular misalignment of prenuclear origin. Although well described in the literature, it is still probably underdiagnosed. Natural history of skew deviation is not well described in the literature. PURPOSE: To describe the clinical presentations, etiologies and follow-up of skew deviation. METHODS: Retrospective study of 29 patients diagnosed with skew deviation between 1993 and 1996. RESULTS: The commonest cause was cerebrovascular accident (12/29) and the commonest localisation was mesencephalic (9/29). Other causes included surgery (7/29), tumor (4/29), trauma (3/29), degeneration (3/29), inflammatory (2/29), increased intracranial pressure (1/29). Other localisations included cerebellum (5/29), ponto-mesencephalic (3/29), and medulla (2/29). Vertical diplopia was always accompanied by other neuro-ophthalmologic abnormalities. 69.2% (18/26) patients were totally asymptomatic after 7.5 months. 30.8% (8/26) were still symptomatic (diplopia). One patient required surgery, three patients were relieved with prisms, one patient needed monocular occlusion. One patient died during follow-up and precise data were lacking in two symptomatic patients. CONCLUSION: Skew deviation is not so rare, 10% of the cases referred to us for diplopia in 3 years. The diagnosis of skew deviation should be entertained when vertical diplopia cannot be explained by pathology of extraocular muscles, peripheral or central cranial nerve III or IV palsies, myasthenia, or orbital pathology. Prognosis for recovery in patients with skew deviation is good. 70% will recover, after a median time of 7.5 months. Surgery should be postponed at least for 12 months.

The cervical spine in calcium pyrophosphate dihydrate deposition disease. A prevalent case-control study.

OBJECTIVE: To test the hypothesis that calcium pyrophosphate dihydrate (CPPD) deposition disease is a risk factor for neck pain. METHODS: A prevalent case-control study was conducted to assess cervical calcifications and neck pain between patients with and without known peripheral CPPD deposition disease. CPPD cases were included if diagnosed with CPPD deposition disease of peripheral joints, and excluded if their chief complaint was neck pain. Controls were randomly selected among consecutive patients, hospitalized for conditions unrelated to CPPD deposition disease or neck pain, and matched to CPPD cases by age and sex. Cervical calcifications were assessed by lateral cervical radiographs and computed tomography scans of the upper cervical spine; neck pain and cervical function were appraised by a validated questionnaire. RESULTS: Cervical calcifications were found in 24 out of 35 patients (69%) in the CPPD group compared to 4 out of 35 patients (11%) in the control group (p < 0.001). Patients with CPPD deposition disease reported significantly more neck pain and discomfort than controls (p < 0.001), and were 5 times more likely to report any neck pain (odds ratio 5.5; 95% confidence interval: 1.9, 21.9). Among male patients, more extensive cervical calcified deposits correlated with more severe neck pain (rs = 0.58, p = 0.03). CONCLUSION: These results suggest that CPPD deposition disease frequently involves the cervical spine and may be associated with the development of neck pain.

Hydrokolloid bei diabetischen Fussulzera: besser als herkömmliche Wundverbände

Sie betreuen einen 82-jährigen Typ-2-Diabetiker mit einer 1 cm grossen Wunde an der Grosszehe. Der Patient hat sich geschnitten, als er Hornhaut entfernte. Die Wunde vergrössert sich seither stetig und sondert Flüssigkeit ab. Die Wundumgebung ist hyperkeratotisch, aufgeweicht, leicht fibrinös und feucht. Weder ist Kontakt zum darunterliegenden Knochen vorhanden noch gibt es Infektionszeichen. Der Patient ist für eine Neuropathie und Veneninsuffizienz bekannt; die Fusspulse sind spürbar. Seine Blutzuckerwerte sind stabil, der HbA1c-Wert liegt bei 7,5%. Er möchte die Wunde selbst weiter versorgen und sich regelmässig duschen können.

Nouveautés en médecine ambulatoire [Innovations in ambulatory care]

During 2008, we selected 8 studies of interest. It seems important to continue to treat high tension for old patients. To give a good medication against pain, to maintain activity and to reassure patient is the treatment for acute back pain; surgery for spinal stenosis has better results than other treatments at two years of evolution. Pregabalin seems to provide clinically benefit to patients with fibromyalgia. Helicobacter pylori test and treat has the same results than proton pomp inhibitor in initial management of dyspepsia; extending triple therapy beyond 7 days is unlikely to be a clinical useful strategy. Syphilis testing algorithms using treponemal tests for initial screening could be inversed. Finally, selective reporting of clinical trials results for antidepressant are relatively frequent.

Patterns of extraocular muscle weakness in vasculopathic pupil-sparing, incomplete third nerve palsy.

OBJECTIVE: To determine the pattern of extraocular muscle (EOM) paresis in incomplete vasculopathic third nerve palsies (3NP) that have normal pupillary function. METHODS: A retrospective study in a private practice and academic neuro-ophthalmic practice. Patients diagnosed with vasculopathic 3NP within 4 weeks of symptom onset were identified. The chart of each patient was reviewed to determine pupillary function and the pattern and degree of EOM and levator palpebrae paresis at the time of presentation. RESULTS: Of 55 patients with vasculopathic 3NP, 42 (76%) had normal pupillary function. Of these 42, 23 (55%) demonstrated an incomplete EOM palsy, defined as partially reduced ductions affecting all third nerve-innervated EOMs and levator (diffuse pattern) or partially reduced ductions that involved only some third nerve-innervated EOMs and levator (focal pattern). Twenty (87%) of these 23 patients showed a diffuse pattern of paresis; only three (13%) showed a focal pattern of paresis, one that affected only the superior rectus and levator muscles (superior division weakness). CONCLUSIONS: Based on our series, most patients with EOM/levator involvement in pupil-sparing, incomplete 3NP of vasculopathic origin have a diffuse pattern of paresis. In contrast, our review of the literature suggests that pupil-sparing 3NP of aneurysmal origin usually have a focal pattern of paresis. We propose that distinguishing these two patterns of EOM paresis may be helpful in differentiating between vasculopathic and aneurysmal 3NP. Future studies will be needed to confirm the clinical utility of this hypothesis.

Cefuroxime prophylaxis is effective in noninstrumented spine surgery: a double-blind, placebo-controlled study.

STUDY DESIGN: Double-blind, placebo-controlled randomized clinical trial. OBJECTIVE: To assess the efficacy of 1 preoperative 1.5 g dose of cefuroxime in preventing surgical site infection after surgery for herniated disc. SUMMARY OF BACKGROUND DATA: Antibiotic prophylaxis was only tested in nonconclusive trials in this setting. METHODS: The study was conducted in 2 university hospitals in Switzerland. Patients were assessed for occurrence of surgical site infection (defined by the criteria of the Centers for Diseases Control and Prevention), other infections, or adverse events up to 6 months after surgery. Outcome measures were compared in a univariate, per-protocol analysis. RESULTS: Baseline characteristics were similar in patients allocated to cefuroxime (n = 613) or placebo (n = 624). Eight (1.3%) patients in the cefuroxime group and 18 patients (2.8%) in the placebo group developed a surgical site infection (P = 0.073). A diagnosis of spondylodiscitis or epidural abscess was made in 9 patients in the placebo group, but none in the cefuroxime group (P < 0.01), which corresponded to a number necessary to treat of 69 patients to prevent one of these infections. There were no significant adverse events attributed to either cefuroxime or placebo. CONCLUSION: A single, preoperative dose of cefuroxime significantly reduces the risk of organ-space infection, most notably spondylodiscitis, after surgery for herniated disc.

Ex vivo characterization of allo-MHC-restricted T cells specific for a single MHC-peptide complex.

Alloreactive T cells are thought to be a potentially rich source of high-avidity T cells with therapeutic potential since tolerance to self-Ags is restricted to self-MHC recognition. Given the particularly high frequency of alloreactive T cells in the peripheral immune system, we used numerous MHC class I multimers to directly visualize and isolate viral and tumor Ag-specific alloreactive CD8 T cells. In fact, all but one specificities screened were undetectable in ex vivo labeling. In this study, we report the occurrence of CD8 T cells specifically labeled with allo-HLA-A*0201/Melan-A/MART-1(26-35) multimers at frequencies that are in the range of 10(-4) CD8 T cells and are thus detectable ex vivo by flow cytometry. We report the thymic generation and shaping of tumor Ag-specific, alloreactive T cells as well as their fate once seeded in the periphery. We show that these cells resemble their counterparts in HLA-A*0201-positive individuals, based on their structural and functional attributes.

Routine therapeutic drug monitoring in patients treated with 10-360 mg/day citalopram

From data collected during routine TDM, plasma concentrations of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were measured in 345 plasma samples collected in steady-state conditions. They were from 258 patients treated with usual doses (20-60 mg/d) and from patients medicated with 80-360 mg/d CIT. Most patients had one or several comedications, including other antidepressants, antipsychotics, lithium, anticonvulsants, psychostimulants and somatic medications. Dose-corrected CIT plasma concentrations (C/D ratio) were 2.51 +/- 2.25 ng mL-1 mg-1 (n = 258; mean +/- SD). Patients >65 years had significantly higher dose-corrected CIT plasma concentrations (n = 56; 3.08 +/- 1.35 ng mL-1 mg-1) than younger patients (n = 195; 2.35 +/- 2.46 ng mL-1 mg-1) (P = 0.03). CIT plasma concentrations in the generally recommended dose range were [mean +/- SD, (median)]: 57 +/- 64 (45) ng/mL (10-20 mg/d; n = 64), 117 +/- 95 (91) ng/mL (21-60 mg/d; n = 96). At higher than usual doses, the following concentrations of CIT were measured: 61-120 mg/d CIT, 211 +/- 103 (190) ng/mL (n = 93); 121-200 mg/d: 339 +/- 143 (322) ng/mL (n = 70); 201-280 mg/d: 700 +/- 408 (565) ng/mL (n = 18); 281-360 mg/d: 888 +/- 620 (616) ng/mL (n = 4). When only one sample per patient (at the highest daily dose if repeated dosages) is considered, there is a linear and significant correlation (n = 48, r = 0.730; P < 0.001) between daily dose (10-200 mg/d) and CIT plasma concentrations. In experiments with dogs, DDCIT was reported to affect the QT interval when present at concentrations >300 ng/mL. In this study, DDCIT concentration reached 100 ng/mL in a patient treated with 280 mg/d CIT. Twelve other patients treated with 140-320 mg/d CIT had plasma concentrations of DDCIT within the range 52-73 ng/mL. In a subgroup comprised of patients treated with > or =160 mg/d CIT and with CIT plasma concentrations < or =300 ng/mL, and patients treated with < or =200 mg/d CIT and CIT plasma concentrations > or = 600 ng/mL, the enantiomers of CIT and DCIT were also analyzed. The highest S-CIT concentration measured in this subgroup was 327 ng/mL in a patient treated with 140 mg/d CIT, but the highest S-CIT concentration (632 ng/mL) was measured in patient treated with 360 mg/d CIT. In conclusion, there is a highly linear correlation between CIT plasma concentrations and CIT doses, well above the usual dose range.

Healthcare utilization of elderly persons hospitalized after a noninjurious fall in a Swiss academic medical center.

OBJECTIVES: To determine the risk of hospital readmission, nursing home admission, and death, as well as health services utilization over a 6-month follow-up, in community-dwelling elderly persons hospitalized after a noninjurious fall. DESIGN: Prospective cohort study with 6-month follow-up. SETTING: Swiss academic medical center. PARTICIPANTS: Six hundred ninety persons aged 75 and older hospitalized through the emergency department. MEASUREMENTS: Data on demographics and medical, physical, social, and mental status were collected upon admission. Follow-up data were collected from the state centralized billing system (hospital and nursing home admission) and proxies (death). RESULTS: Seventy patients (10%) were hospitalized after a noninjurious fall. Fallers had shorter hospital stays (median 4 vs 8 days, P<.001) and were more frequently discharged to rehabilitation or respite care than nonfallers. During follow-up, fallers were more likely to be institutionalized (adjusted hazard ratio=1.82, 95% confidence interval=1.03-3.19, P=.04) independent of comorbidity and functional and mental status. Overall institutional costs (averaged per day of follow-up) were similar for both groups ($138.5 vs $148.7, P=.66), but fallers had lower hospital costs and significantly higher rehabilitation and long-term care costs ($55.5 vs $24.1, P<.001), even after adjustment for comorbidity, living situation, and functional and cognitive status. CONCLUSION: Elderly patients hospitalized after a noninjurious fall were twice as likely to be institutionalized as those admitted for other medical conditions and had higher intermediate and long-term care services utilization during follow-up, independent of functional and health status. These results provide direction for interventions needed to delay or prevent institutionalization and reduce subsequent costs.

Percutaneous retrograde screwing for stabilisation of acetabular fractures.

OBJECTIVES: To evaluate the results of retrograde percutaneous screw fixation (PSF) in minimally or undisplaced acetabular fractures in a geriatric population. PATIENTS AND METHODS: Between July 1998 and July 2001, 21 consecutive patients with an acetabular fracture underwent fluoroscopic guided percutaneous fixation. The mean age was 81 years (range 67--90 years). In all cases, the fracture was minimally or undisplaced (<2mm). Two cannulated cancellous 7.3mm screws were inserted in a retrograde fashion to stabilise the posterior and the anterior column. Bed to chair transfer began after 24h. Weight bearing as tolerated was allowed at 4 weeks. RESULTS: Eighteen patients were reviewed at a mean of 3.5 years (range 2--5 years). Soft tissue dissection was minimal. There were no intraoperative or postoperative complications. At the latest follow-up there was no radiographical evidence of secondary displacement of fragments, degenerative changes, or screw failure. Fractures healed at a mean time of 12 weeks (range 8--15 weeks). Clinical results were satisfactory in 17 patients. CONCLUSION: Our results show that percutaneous screw fixation under fluoroscopic control is a safe technique to treat some pattern of acetabular fracture.

Oral pregabalin as an add-on treatment for status epilepticus.

Oral antiepileptic drugs (AEDs) represent possible add-on options in refractory status epilepticus (SE). In this setting, pregabalin (PGB) has not been reported before. Over the last 42 months, we identified 11 SE episodes (10 patients) treated with PGB in our hospital. Its use was prompted by the favorable pharmacokinetic profile, devoid of drug-drug interactions. The patients mostly had refractory, partial SE. Only two patients were managed in the intensive care unit (ICU). We found a definite electroclinical response in 5 of 11, already evident 24 h after PGB introduction, and a possible response (concomitantly with other AEDs) in 3 of 11 of the episodes; 3/11 did not respond. The treatment was well tolerated. Partial SE appeared to better respond than generalized convulsive SE. PGB appears to be an interesting option as add-on treatment in refractory partial SE.

Transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: results from the global valve-in-valve registry.

BACKGROUND: Transcatheter aortic valve-in-valve implantation is an emerging therapeutic alternative for patients with a failed surgical bioprosthesis and may obviate the need for reoperation. We evaluated the clinical results of this technique using a large, worldwide registry. METHODS AND RESULTS: The Global Valve-in-Valve Registry included 202 patients with degenerated bioprosthetic valves (aged 77.7±10.4 years; 52.5% men) from 38 cardiac centers. Bioprosthesis mode of failure was stenosis (n=85; 42%), regurgitation (n=68; 34%), or combined stenosis and regurgitation (n=49; 24%). Implanted devices included CoreValve (n=124) and Edwards SAPIEN (n=78). Procedural success was achieved in 93.1% of cases. Adverse procedural outcomes included initial device malposition in 15.3% of cases and ostial coronary obstruction in 3.5%. After the procedure, valve maximum/mean gradients were 28.4±14.1/15.9±8.6 mm Hg, and 95% of patients had ≤+1 degree of aortic regurgitation. At 30-day follow-up, all-cause mortality was 8.4%, and 84.1% of patients were at New York Heart Association functional class I/II. One-year follow-up was obtained in 87 patients, with 85.8% survival of treated patients. CONCLUSIONS: The valve-in-valve procedure is clinically effective in the vast majority of patients with degenerated bioprosthetic valves. Safety and efficacy concerns include device malposition, ostial coronary obstruction, and high gradients after the procedure.

Polymorphisms in tumor necrosis factor-α increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients*.

OBJECTIVES: To evaluate the influence of genetic polymorphisms on the susceptibility to Candida colonization and intra-abdominal candidiasis, a blood culture-negative life-threatening infection in high-risk surgical ICU patients. DESIGN: Prospective observational cohort study. SETTING: Surgical ICUs from two University hospitals of the Fungal Infection Network of Switzerland. PATIENTS: Eighty-nine patients at high risk for intra-abdominal candidiasis (68 with recurrent gastrointestinal perforation and 21 with acute necrotizing pancreatitis). MEASUREMENTS AND MAIN RESULTS: Eighteen single-nucleotide polymorphisms in 16 genes previously associated with development of fungal infections were analyzed from patient's DNA by using an Illumina Veracode genotyping platform. Candida colonization was defined by recovery of Candida species from at least one nonsterile site by twice weekly monitoring of cultures from oropharynx, stools, urine, skin, and/or respiratory tract. A corrected colonization index greater than or equal to 0.4 defined "heavy" colonization. Intra-abdominal candidiasis was defined by the presence of clinical symptoms and signs of peritonitis or intra-abdominal abscess and isolation of Candida species either in pure or mixed culture from intraoperatively collected abdominal samples. Single-nucleotide polymorphisms in three innate immune genes were associated with development of a Candida corrected colonization index greater than or equal to 0.4 (Toll-like receptor rs4986790, hazard ratio = 3.39; 95% CI, 1.45-7.93; p = 0.005) or occurrence of intra-abdominal candidiasis (tumor necrosis factor-α rs1800629, hazard ratio = 4.31; 95% CI, 1.85-10.1; p= 0.0007; β-defensin 1 rs1800972, hazard ratio = 3.21; 95% CI, 1.36-7.59; p = 0.008). CONCLUSION: We report a strong association between the promoter rs1800629 single-nucleotide polymorphism in tumor necrosis factor-α and an increased susceptibility to intra-abdominal candidiasis in a homogenous prospective cohort of high-risk surgical ICU patients. This finding highlights the relevance of the tumor necrosis factor-α functional polymorphism in immune response to fungal pathogens. Immunogenetic profiling in patients at clinical high risk followed by targeted antifungal interventions may improve the prevention or preemptive management of this life-threatening infection.