Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial.

BACKGROUND: Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression. METHOD: We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point. RESULTS: The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period. CONCLUSIONS: The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.

Interleukin-2 induction of T-cell G1 progression and c-myb expression.

In studies to determine the biochemical mechanisms responsible for cell proliferation, synchronized T cells were used as a model for cellular growth control. By metabolic and morphologic criteria, it was found that activation of the T-cell antigen receptor rendered the cells responsive to interleukin-2 (IL-2), but did not move them through the cell cycle. Instead, IL-2 stimulated G1 progression to S phase, or lymphocyte "blastic transformation." During IL-2-promoted G1 progression, expression of the cellular proto-oncogene c-myb was induced transiently at six to seven times basal levels, maximal levels occurring at the midpoint of G1.

[The role of electromagnetic navigation bronchoscopy in the diagnosis of peripheral pulmonary lesions]. / Place de la navigation électromagnétique endobronchique pour le diagnostic de lésions pulmonaires périphériques.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a recent, minimally invasive procedure utilized to guide endoscopic diagnostic tools to peripheral pulmonary nodules. The place of this technology among other diagnostic procedures remains uncertain. METHOD: We analyzed our 30 first months of ENB used in the diagnosis of 106 lesions in 101 patients, from June 2016 to December 2018. Follow-up and final diagnosis was completed for 95 lesions (90%). RESULTS: ENB was performed for 3.5% of all patients referred for abnormal findings on pulmonary imaging, and represented 19% of second line procedures for peripheral pulmonary lesions. Procedures were performed under general anesthesia, with a mean duration of 35min. The sensitivity of ENB was 64% (95%CI: 52-74%) for lesions with a mean diameter of 21mm, with an improvement over time (sensitivity 69% in the last 18 months). The presence of a bronchus within the lesion (bronchus sign) was associated with an increased sensitivity of 74%. Pneumothorax occurred in 5 patients (5%) of which 4 required drainage. There was no hemoptysis, and no death related to the procedure. CONCLUSION: ENB is a minimally invasive procedure reaching acceptable sensitivity in the most difficult patients. ENB can be recommended for the diagnosis of peripheral pulmonary nodules when no other procedure is successful or possible. Its use as a first choice procedure is, for the moment, limited by the cost, but must be weighed against that of non-diagnostic procedures, and the cost of complications of trans-thoracic lung biopsies.

[Full thoracoscopic lobectomy and segmentectomy for benign or metastatic conditions]. / Lobectomies et segmentectomies par thoracoscopie exclusive pour pathologie bénigne ou métastatique.

INTRODUCTION: Several techniques for video-assisted pulmonary lobectomy have been reported. However full thoracoscopic lobectomy, i.e., without the help of a utility incision has seldom been performed. We report our results based on a series of resections for benign or metastatic conditions where mediastinal lymphadenectomy is not indicated. PATIENTS AND METHODS: Fifty-six patients (29 males and 27 females) with a mean age of 46 years (range: 8-82 years) had an attempted major pulmonary resection (54 lobectomies and 2 segmentectomies) via thoracoscopy alone for either a benign lesion (30 cases) or a metastasis (26 cases). RESULTS: There was no operative mortality. Six patients required conversion to thoracotomy (11%). In the 50 remaining patients who underwent an exclusively thoracoscopic operation, there was 1 intra-operative complication that was managed thoracoscopically. The duration of the procedure ranged from 65 to 230 minutes (mean: 157 minutes). Intra-operative blood loss was 55 cc (range: 0 to 200 cc) in the "metastasis group" and 109 cc (range: 0 to 280 cc) in the "benign lesion group". There were 5 postoperative complications (10%). Postoperative duration of stay ranged from 3 to 15 days (Mean: 6.7 days). All patients were seen at the first postoperative month and no clinical or radiological complication was noticed. CONCLUSION: Full thoracoscopic lobectomies are feasible and safe provided appropriate equipment is used and the surgical team is experienced in endoscopic surgery.

Experimental chemotherapy-induced skin necrosis in swine. Mechanistic studies of anthracycline antibiotic toxicity and protection with a radical dimer compound.

The reactivity of antitumor anthracycline and mitomycin C antibiotics with the oxomorpholinyl radical dimers, bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM3) and bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3), was studied in vitro. The oxomorpholinyl radical reduced daunorubicin to a quinone methide intermediate that reacted with solvent to form 7-deoxydaunorubicinone. The solvolysis reaction followed first order kinetics, and the reactivity rate constants (k2) measured for seven anthracycline analogues ranged from 2 X 10(-2) s-1 to 8.0 X 10(-4) s-1. The chemical reactivity of each anthracycline quinone methide correlated with the total skin toxicity caused by the respective parent anthracycline following injection into swine skin. Microscopic examination of experimental lesions in swine skin resemble those observed in humans after inadvertant chemotherapy extravasation. Hydrocortisone sodium succinate was not effective for the treatment of doxorubicin-induced skin necrosis, whereas DHM3 was effective for the treatment of skin necrosis caused by all seven anthracyclines and by the quinone containing antibiotic, mitomycin C.

[Pleural diffusion of amoxicillin 1 and vancomycin in patients treated for post-surgical empyema]. / Empyème après chirurgie d'exérèse pulmonaire: étude de la diffusion pleurale de l'amoxicilline et de la vancomycine.

INTRODUCTION: Treatment of post surgical thoracic empyema consists of chest tube drainage, antibiotic administration, and in some cases surgical lavage of infected spaces. Data in human on the diffusion of antibiotics in pleural cavity after post surgical empyema are lacking. METHODS: We studied on 9 patients with post surgical thoracic empyema (including 6 pneumonectomy) the diffusion of 2 antibiotics commonly used in this situation: amoxicillin (for 7 patients) and vancomycin (for 2 patients). Antibiotics concentrations were measured after at least 3 days of treatment (3-12 days), in order to reach a plateau concentration in the pleural space. RESULTS: The ratio pleural/plasma antibiotic concentration was 1.96 (range: 0.6-4.9). The pleural infection was cured for 8 on 9 patients. The last patients required thoracostomy, and the outcome was favorable after this procedure. CONCLUSION: That the penetration of amoxicillin and vancomycin in pleural space after post surgical empyema is good. Pleural antibiotics concentrations are in the majority of cases higher than plasmatic concentrations.

Thoracoscopic palliative treatment of malignant pleural effusions: results in 273 patients.

BACKGROUND: The aim of this study was to analyze the results of pleurodesis for malignant pleural effusion performed by surgeons. PATIENTS AND METHODS: A series of 273 patients with malignant pleural effusion underwent thoracoscopy with the aim of performing a palliative pleurodesis. There were 94 males (34.4%) and 175 females (64.1%), ranging in age from 15 to 94 years (mean age: 60.6 years). The effusion was on the right side in 136 patients (49.8%), on the left side in 110 (40.3%), and bilateral in 27 (9.9%). Thoracoscopy was performed under general anaesthesia in all patients. Pleural biopsy was performed in two thirds of the patients (70.7%). Pleurodesis was produced by instillation of 5g of sterile asbestos-free talc; the chest tube was left in place a minimum of 3 days. It was removed when fluid drainage was less than 200 ml/24 h. Patients were usually discharged the day after chest tube removal. RESULTS: There was no intraoperative mortality. Two patients (0.7%) had intraoperative complications; 17 (6.2%) underwent a bilateral pleurodesis, and 10 (3.7%) had a pericardiopleural window. In 32 patients (11.7%) no pleurodesis was done, either because the lung did not properly re-expand (5.2%), or because of suspected infection, e.g., false membranes (1.9%), or because of multiple adhesions (4.6%). Finally, only 241 patients (88.3%) had a talc poudrage at the time of thoracoscopy. Duration of postoperative pleural drainage ranged between 1 and 11 days (mean: 3.64 days). The postoperative hospital stay ranged from 2 to 21 days (mean: 7.1 days). Pleural empyema occurred in 4 patients (1.5%) and was lethal in one patient. The mean follow-up period was 8.39 (7.2 months, and 172 patients had regular follow up. In this group, there were 24 recurrences (14%), 12 of which were treated by repeat pleurodesis. The results were very good in 133 patients (77.3%), acceptable in 35 patients (20.3%), and there was a failure in 4 patients (2.4%). CONCLUSIONS: Results of surgical thoracoscopy for malignant pleural effusion are good, with low morbidity. However, in debilitated patients, bedside talc slurry may be preferable.

[Cystic mediastinal schwannoma appended to the vagus nerve]. / Schwannomes kystiques du médiastin développés au dépend du nerf vague.

INTRODUCTION: Schwannomas are a form of rare tumor, arising from neural tissue and representing 2 % of mediastinal tumors. They are usually located in the posterior mediastinum, most often in the paravertebral gutters and typically appended to intercostal nerves. CASE REPORTS: We report two cases of unusual mediastinal schwannomas, appended to the vagus nerve. The schwannoma was located in the subcarinal region in the first case and in the right para-tracheal region in the second case. The lesions were thought to be bronchogenic cysts preoperatively in both cases because of a cystic appearance on preoperative CT scan and endobronchial ultrasonography. A surgical approach was adopted to remove the tumors. Video-assisted thoracoscopy was used in one case and robotic-assisted surgery in the second case, without any complication, allowing for complete resection and to establish a certain pathological diagnosis. CONCLUSION: Despite this location and cystic presentation being unusual, schwannoma should be considered as a possible cause of cystic lesions in the mediastinum. Minimally invasive surgery allows for complete resection and definitive pathological diagnosis.

[Endobronchial ultrasonography (EBUS) for the internist]. / Écho-endoscopie bronchique (EBUS) pour l'interniste.

Endobronchial ultrasonography (EBUS) is a recent mini-invasive technique allowing transbronchial needle aspiration (TBNA) of mediastinal lymph nodes as well as peribronchial lesions. EBUS was initially developed for lung cancer mediastinal staging. Over the years, indications for EBUS have been progressively extended to the scope of inflammatory disorders, mediastinal lymphomas, and infectious diseases. Particularly in immunosuppressed patients, including HIV-infected patients, EBUS allows the diagnosis of several diseases that involve the mediastinum, avoiding invasive surgical explorations such as mediastinoscopy or thoracoscopy. This review aims at discussing the technical aspects, and specifies indications, results, and limits of EBUS for the internist.

Pagetoid melanocytosis. Histologic features in benign and malignant lesions.

Pagetoid melanocytosis (PM), the upward discontinuous extension of melanocytes into the superficial epidermis, although generally considered a histologic feature of malignancy, may be seen in certain benign melanocytic lesions. To formulate the histologic criteria for distinction between benign and malignant PM, we examined 218 melanocytic tumors, including melanomas, Spitz nevi, nevi of palms and soles, pigmented spindle cell nevi, recurrent nevi, vulvar nevi, nevi of infancy and early childhood, and ordinary acquired nevi. We found PM to be present in 96% of melanomas, 38% of Spitz nevi, 61% of nevi of palms and soles, 20% of pigmented spindle cell nevi, 60% of recurrent nevi, 80% of vulvar nevi, and none of the ordinary acquired nevi. All the nevi of infancy and early childhood showed PM, but they had been selected for that feature. In melanomas, PM showed significant cellular atypia (81%), which was extensive and diffuse, and in 13% it extended laterally beyond the underlying junctional component. In the benign lesions, cellular atypia was generally absent, nor was lateral extension present, and PM was usually focal or multifocal rather than diffuse and not extensive. Although PM should be considered a tocsin for malignant melanoma, it may also occur in certain benign melanocytic lesions. Accurate interpretation depends on evaluation of all of the pertinent histologic and clinical findings.

Reexcision perineural invasion. Not a sign of malignancy.

Perineural invasion has been reported to occur in both benign and malignant neoplasms. We describe two cases in which perineural invasion by epithelial cells was present in reexcision skin specimens removed because of melanocytic lesions in the original biopsy material. Because of the absence of a primary epithelial neoplasm, this phenomenon was interpreted as a reactive or reparative process, most probably resulting from regenerating traumatized sweat gland ducts. On the basis of this study alone, it may not be possible to distinguish between reexcision perineural invasion and perineural invasion from a primary epithelial neoplasm. For such cases, the following histologic features serve as provisional guidelines favoring an interpretation of reexcision perineural invasion: absence of perineural spread beyond the immediate previous biopsy site, benign appearance of the perineural epithelial cells different from the appearance of the original tumor, and absence of residual epithelial tumor in the vicinity of the involved perineurium.

Basal cell carcinoma: clues to its presence in histologic sections when the initial slide is nondiagnostic.

Initial sections of skin biopsies may not be diagnostic of basal cell carcinoma (BCC). Are there histologic predictors of BCC that should prompt deeper sections? Ninety-four cases in which the clinical diagnosis was BCC or "rule-out BCC," and the initial histologic slides were nondiagnostic, were submitted for deeper sections on three additional slides. Of the 94 cases, 50 (53%) demonstrated BCC on deeper sections. This relatively high incidence suggests that deeper sections should be taken in all cases of clinically suspected BCCs unless alternate histologic findings adequately account for the clinical lesion. The results of this study suggest that additional sections are more likely to yield BCC when the initial nondiagnostic slide demonstrates focal epidermal atypia, equivocal adnexae, stromal fibrosis, empty dermal space, and microcalcifications, criteria which may be useful in determining the need to do deeper sections in cases in which BCC is not clinically suspected.

Cutaneous pathology in Wegener's granulomatosis. A clinicopathologic study of 75 biopsies in 46 patients.

While no cutaneous lesion is specific for Wegener's granulomatosis (WG), several histopathologic entities, including leukocytoclastic vasculitis and necrotizing granulomatous inflammation, are characteristic. This report details the histopathologic features of 75 cutaneous biopsies from 46 patients with WG. Biopsies were subdivided into histologic groups that included leukocytoclastic vasculitis (31%), granulomatous inflammation (GI) (19%), nonspecific ulceration (4%), superficial dermal and epidermal necrosis without inflammation (2.7%), erythema nodosum (2.7%), granuloma annulare (1%), chronic inflammation (31%), and acute inflammatory lesions without vasculitis (9%). No convincing example of granulomatous vasculitis was observed. The histopathologic subgroups were correlated with clinical features, and the results were compared with those from a control group of 82 WG patients with no skin involvement. We found that the histopathologic subgroups of leukocytoclastic vasculitis and granulomatous inflammation correlated with different clinical courses. Patients with leukocytoclastic vasculitis developed WG at an earlier age (median age, 30 years) than did the control group (median age, 45 years). Leukocytoclastic vasculitis developed shortly after onset of WG (median, 15 months vs. 35 months for patients with nonspecific chronic inflammation). All lesions occurred during active disease. Active disease with leukocytoclastic vasculitis was associated with a mean erythrocyte sedimentation rate twice that of active disease in the same patient when leukocytoclastic vasculitis was absent. The patients with leukocytoclastic vasculitis had more rapidly progressive and widespread WG than patients with granulomatous skin lesions or patients without skin lesions. A marked excess of joint and musculoskeletal symptoms and renal disease was seen in patients with leukocytoclastic vasculitis. Patients with granulomatous inflammation also developed WG at an early age (median age, 30 years) when compared with the control group. Cutaneous granulomatous lesions also developed shortly after presentation (median, 12 months). Only 64% of granulomatous biopsies were from patients with active disease. These patients frequently had neither renal nor pulmonary manifestations of WG, and their disease progressed at a slower rate than that of the patients with leukocytoclastic vasculitis. These findings suggest that the cutaneous lesions characteristic of WG may correlate with the activity, distribution, and course of the disease.

Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features.

Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive Epstein-Barr virus-associated B-cell lymphoproliferative disorder (EBV-BLPD), varying widely from an indolent process to an aggressive large cell lymphoma. The skin is the extrapulmonary organ most commonly involved in LYG. We studied 32 skin lesions from 20 patients with known pulmonary LYG, using immunohistochemistry, in situ hybridization for EBV, and polymerase chain reaction for the presence of antigen receptor gene rearrangements (IgH and TCR) to better define both the clinicopathologic spectrum and pathogenesis of the cutaneous lesions. We describe two distinct patterns of cutaneous involvement. Multiple erythematous dermal papules and/or subcutaneous nodules, with or without ulceration, were present in 17 patients (85%). These lesions demonstrate a marked angiocentric lymphohistiocytic infiltrate, composed predominantly of CD4-positive T-cells, with a high propensity for involving the subcutaneous tissues, and exhibiting angiodestruction, necrosis, and cytologic atypia. EBV-positive B-cells were detected in the nodules from five patients; clonal immunoglobulin heavy chain gene (IgH) rearrangements were detected by polymerase chain reaction in two patients. Multiple indurated, erythematous to white plaques were present in three patients (15%). The plaque lesions were negative for EBV and clonal IgH gene rearrangements in all cases studied. The clinical course of overall disease was variable, ranging from spontaneous regression without treatment (1 of 13; 7%), resolution with chemo/immunomodulatory therapy (8 of 13; 62%), and progression (4 of 13; 31%). The clinical and histopathologic features of cutaneous LYG are extremely diverse. However, the majority (85%) of the cutaneous lesions mirrors to some extent LYG in the lung, although EBV+ cells are less frequently identified. This subset of cases shows the histopathologic triad of angiodestruction with associated necrosis, panniculitis, and in some cases atypical lymphoid cells. The commonality of the histologic features in this group suggests a common pathophysiologic basis, possibly mediated by cytokines and chemokines induced by EBV. A small percentage of the lesions (15%) presented as indurated and atrophic plaques, and EBV was not identified in the small number of cases studied. The relationship of the plaque-like lesions to LYG remains uncertain. Whereas some cases of LYG regress spontaneously, most require therapy.

Preventive effect of inhaled nitric oxide and pentoxifylline on ischemia/reperfusion injury after lung transplantation.

BACKGROUND: The preventive effect of inhaled nitric oxide (NO) and pentoxifylline (PTX) administered during reperfusion has been demonstrated on experimental models of lung ischemia/reperfusion (I/R) injury but this strategy is not validated in clinical lung transplantation. The aim of this study was to assess retrospectively the protective effect of inhaled NO and PTX after lung transplantation. METHODS: Twenty-three consecutive patients who received inhaled NO (10 ppm) and PTX (NO-PTX group) at the time of reperfusion were compared retrospectively with (1) 23 consecutive patients transplanted just before the use of NO-PTX (control group 23); (2) 95 patients representing all the patients of the series who did not receive NO-PTX (control group 95), with respect to I/R injury related complications. In particular, the incidence of pulmonary reimplantation edema and early hemodynamic failure, the PaO2/FIO2 ratio as well as the duration of mechanical ventilation and the 2-month mortality rates were compared. RESULTS: Reimplantation edema was observed in 6/23 patients (26%) in the NO-PTX group vs. 13/23 patients (56%) in the control group 23 (P=0.035) and 48/95 patients (50%) in the control group 95 (P=0.035). The worst PaO2/FIO2 ratio during the first three postoperative days was 240-102 mmHg in the NO-PTX group vs. 162+/-88 mmHg (P=0.01) and 176+/-107 mmHg (P=0.01) in the control group 23 and the control group 95, respectively. The duration of mechanical ventilation was 2.1+/-2.4 days in the NO-PTX group vs. 7+/-9 days in the control group 23 (P=0.02) and 6+/-7 days in the control group 95 (P=0.01). The 2-month mortality rate was 4.3% in the NO-PTX group vs. 26% (P=0.04) and 21% (P=0.07) in the control group 23 and the control group 95, respectively. CONCLUSIONS: The marked decrease in the incidence of allograft dysfunction compared with two historical control groups suggests that PTX and inhaled NO given before and throughout reperfusion are protective against I/R injury in the setting of clinical transplantation.

Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure.

STUDY OBJECTIVE: To evaluate the beneficial effect of mechanical ventilation (MV) in patients with idiopathic pulmonary fibrosis (IPF) who develop acute respiratory failure (ARF), with special emphasis on prognosis. DESIGN: Retrospective study. SETTING: Ten-bed respiratory ICU that is a part of a respiratory department actively involved in lung transplantation (LTx). PATIENTS: From 1991 to 1999, 23 patients (mean age, 52.9 years; range, 21 to 82 years) with IPF required MV for ARF. At admission to the ICU, 16 patients were potential candidates for LTx, with 5 patients already on the waiting list. MEASUREMENTS AND RESULTS: Survival and gas exchange under MV were assessed. The precipitating cause of ARF was also analyzed. With the exception of 1 patient who successfully received a single-lung transplant 6 h after initiation of MV, all the remaining 22 patients died while receiving MV (median survival, 3 days; range, 1 h to 60 days). The duration of MV correlated positively with baseline vital capacity (percent predicted) (R = 0.54; p = 0.01) and baseline total lung capacity (percent predicted) (R = 0.71; p < 0.001), and correlated negatively with baseline PaCO(2) (R = - 0.47; p = 0.03) and the duration of evolution of IPF (R = -0.50; p = 0.01). Duration of MV did not correlate with the duration of immunosuppressive therapy (R = - 0.24; p = 0.27) or duration of oxygen therapy (R = - 0.32; p = 0.14) prior to admission. The precipitating cause of ARF was most often not identified. CONCLUSIONS: Our data support the general belief that MV does not benefit IPF patients presenting with ARF. Initiation of MV in IPF patients is thus questionable and should, in our opinion, be restricted to patients in whom LTx can be performed within a few days after initiation of MV.

Morbidity and mortality related to the native lung in single lung transplantation for emphysema.

It has been advocated that a major drawback of single lung transplantation (SLT) is the risk of serious complications arising from the native lung. The morbidity and mortality related to the native lung in 46 patients who underwent SLT for pulmonary emphysema in Clichy from 1988 to 1997 were reviewed retrospectively. In particular, infectious complications and native lung hyperinflation were searched. Complications arising from the native lung are not unusual after SLT for subjects with emphysema, and it was concluded they are not responsible for a substantial mortality.

Subcutaneous sacrococcygeal myxopapillary ependymoma. A clinicopathologic study of 32 cases.

A clinicopathologic investigation was performed on 32 cases of myxopapillary ependymoma occurring as a primary tumor of the skin and subcutaneous tissue of the sacrococcygeal area. The tumor usually presented as an asymptomatic mass at the base of the spine in young individuals. Pilonidal cyst was the most frequent clinical diagnosis. The excised tumors often "shelled out" easily and none was adherent to the vertebral column or spinal cord structures. The tumors were circumscribed and located in the subcutaneous tissue and deep dermis. Microscopically, ultramicroscopically, histochemically, and immunohistochemically, the cutaneous myxopapillary ependymomas showed distinct changes. Follow-up data were available for 23 patients with a median follow-up interval of 7 years. Six patients were followed for 15 years or longer. Metastases occurred in four patients, an incidence of 17%.

Unusual benign bladder tumor of Brunn nest origin.

An unusual bladder tumor consisting of proliferating benign Brunn nests is described. The tumor occurred in a forty-five-year-old man who presented with hematuria. The tumor recurred in the same location one and one-half years later and again caused hematuria. The tumor is distinguished from inverted papilloma of the bladder.