A biopsy-integrated algorithm for determining Gleason 6 upgrading risk stratifies risk of active surveillance failure in prostate cancer.

INTRODUCTION: A significant proportion of patients that fail active surveillance (AS) for prostate cancer management do so because of cancer upgrading. A previously validated upgrading nomogram generates a score that predicts risk of biopsy Gleason 6 upgrading following radical prostatectomy in lower-risk populations that are candidates for Active Surveillance (Cancer, 2013). OBJECTIVES: We hypothesize that the upgrading risk (UR) score generated by this nomogram at diagnosis improves the ability to predict patients that will subsequently fail AS. METHODS: To evaluate the nomogram, retrospective data from several institutional cohorts of patients who met AS criteria, group 1 (n = 75) and group 2 (n = 1230), were independently examined. A UR score was generated using the coefficients from the nomogram consisting of PSA density (PSAD), BMI, maximum % core involvement (MCI), and number of positive cores. AS failure was defined as Gleason score (GS) >6, >50 % maximum core involvement, or >2 positive cores on biopsy. Univariate and multivariate Cox proportional-hazards regression models, upgrading risk score, and other clinicopathologic features were each assessed for their ability to predict AS failure. RESULTS: Clinicopathologic parameters were similar in both groups with the exception of mean PSAD (0.13 vs. 0.11, p < 0.01) and follow-up (2.1 vs. 3.2 years, p = 0.2). Most common cause of AS failure was GS > 6 (group 1) compared to >2 positive cores (group 2). On univariate analysis in both populations, features at diagnosis including PSAD and the UR score were significant in predicting AS failure by upgrading (Gleason > 6) and any failure. Multivariate analysis revealed the UR score predicts AS failure by GS upgrading (HR 1.8, 95 % CI 1.12-2.93; p = 0.01) and any failure criteria (HR 1.7, 95 % CI 1.06-2.65); p = 0.02) for group 1. Likewise, the UR score in group 2 predicts AS failure with GS upgrading (HR 1.3, 95 % CI 1.15-1.42; p < 0.0001) and any failure criteria (HR 1.18, 95 % CI 1.18-1.38; p < 0.0001). An ROC generated an AUC of 0.66. Decision curve analysis demonstrated a high net benefit for the UR score across a range of threshold probabilities. Based on these outcomes, at 3 years, patients in the lowest risk quartile have a 15 % risk of AS failure versus a 46 % risk in the highest quartile (p < 0.0001). CONCLUSIONS: The UR score was predictive of pathologic AS failure on multivariate analysis in several AS cohorts. It outperformed single clinicopathologic criteria and may provide a useful adjunct using clinicopathologic data to stratify patients considering AS.

Primary cutaneous adenosquamous carcinoma of the penis: the first characterization of HPV status in this rare and diagnostically challenging entity with review of glandular carcinomas of the penis.

Glandular and pseudoglandular tumors of the penile skin are extremely uncommon and can present diagnostic challenges. Primary adenosquamous carcinoma of the penis is an extremely rare tumor, composed of distinct areas of malignant squamous and glandular cells, making it a diagnostically challenging entity. The World Health Organization (WHO) recognizes several subtypes of squamous cell carcinoma (SCC), each with its own distinctive pathologic appearance, clinical associations and prognosis. Among these variants is the exceedingly uncommon adenosquamous carcinoma (ASC), representing 1%-2% of all SCC of the penis. Recent large studies have interrogated the presence of human papillomavirus (HPV) in malignant penile tumors and have shown specific morphologic patterns and clinical presentations to associate with HPV status. However, given the rarity of the adenosquamous variant of SCC, it has largely been excluded from these studies. The glandular components of these lesions can present a confusing appearance, particularly when a large tumor is represented on a small biopsy. Here we describe a difficult histologic presentation of this rare tumor, with the first published characterization of the HPV status of this subtype. This case represents a distinctly unusual case of metastatic HPV-positive primary cutaneous adenosquamous carcinoma of the penis.

Polymorphisms in the promoter region of myostatin gene are associated with carcass traits in pigs.

Higher average daily gain, more lean meat yield and less fat yield of porcine carcass increase selling profits for animal producers. Myostatin (MSTN), previously called GDF8, is a member of transforming growth factor-ß (TGF-ß) superfamily. It is a negative regulator for both embryonic development and adult homeostasis of skeletal muscle. In this study, the genotypes of the previously described SNPs MSTN g.435G>A and g.447A>G SNPs in 66 Duroc pigs, 33 Landrace pigs, 180 Duroc × Landrace (DL) pigs and 155 Duroc × Yorkshire × Landrace (DYL) pigs were determined by Taqman SNP Genotyping Assays. For Duroc and Landrace pigs, MSTN g.435GG/g.447AA individual had greater backfat thickness (p < 0.05) than g.435AA/g.447GG individual, whereas MSTN g.435AA/g.447GG had greater meat (p < 0.05) and meat percentage (p < 0.05) than g.435GA/g.447AG individual. For DL and DYL pigs, the MSTN g.435GG/g.447AA animals were greater in backfat at ultrasound 10th rib (p < 0.05) and carcass 10th rib (p < 0.01) than g.435AA/g.447GG individual. The MSTN g.435AA/g.447GG individual also had higher values than g.435GG/g.447AA for anterior-end meat (p < 0.05), posterior-end meat (p < 0.01), total meat weight (p < 0.01) and meat percentage (p < 0.01). This study confirmed evidence that MSTN g.435G>A and g.447A>G affected carcass traits in pigs. The effects of the mutated alleles were additive with the maximal effects resulting from two copies of the mutated allele. Selection for MSTN g.435A/g.447G allele is expected to increase muscle of limb and total meat production and decrease backfat thickness.

Long-term survival after hand-assisted laparoscopic approach of primary retroperitoneal mucinous cystadenocarcinoma in male: case report and review of literature.

BACKGROUND: Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is a rare disease and mostly occurs in females, and there are only three male cases described in the literatures without long-term follow-up. CASE REPORT: A 59-year-old male presented with a left retroperitoneal cystic mass (7.5 ´ 7 ´ 3 cm) that upwardly displaced the left kidney and caused abdominal discomfort. The tumor was totally excised by the hand-assisted laparoscopic method without complications or recurrence in a follow-up period of 79 months. The etiology from coelomic metaplasia of peritoneal epithelium was proved by a spectrum of diverse cells (benign, borderline malignant, and malignant cells) during pathological examination. RESULTS: This is the fourth male case of PRMC in the world with a favorable outcome after hand-assisted laparoscopic excision, and this is also distinct by the longest follow-up period in this disease entity. CONCLUSIONS: Because of its low-malignant potential and recurrence rate, surgical excision is still the best choice of treatment, but the least invasion method should be adopted in front.

Does the ratio and thickness of prevertebral soft tissue provide benefit in blunt cervical spine injury?

PURPOSE: Although many reports advocate computed tomography (CT) as the initial surveillance tool for occult cervical spine injury (CSI) at the emergency department (ED), the role of a lateral cervical spine radiograph (LCSX) has still not been replaced. We hypothesized that the increased width of the prevertebral soft tissue on an LCSX provides helpful information for selecting the high-risk patients who need to be evaluated with more accurate diagnostic tools. METHODS: This was a retrospective and consecutive series of injured patients requiring cervical spine evaluation who were first imaged with three-view plain films at the ED. The prevertebral soft tissue thickness (PVST) and ratio of prevertebral soft tissue thickness to the cervical vertebrae diameter (PVST ratio) were calculated on the LCSX. Suspicion of CSI was confirmed by either CT or magnetic resonance imaging (MRI) scans. RESULTS: A total of 826 adult trauma patients requiring cervical spine evaluation were enrolled. The C3 PVST and PVST ratio were significantly different between patients with or without upper cervical area injury (UCAI, 8.64 vs. 5.49 mm, and 0.394 vs. 0.276, respectively), and, likewise, the C6 PVST and PVST ratio for patients with or without lower cervical area injury (LCAI, 16.89 vs. 14.66 mm, and 0.784 vs. 0.749, respectively). The specificity was greater than 90 % in predicting UCAI and LCAI when combining these two parameters. CONCLUSIONS: This method maximizes the usefulness of LCSX during the initial assessment of a conscious patient with blunt head and neck injury, especially for the identification of high-risk patients requiring prompt CT or MRI; on the other hand, it prevents the overuse of these high-cost imaging studies as initial diagnostic tools.

Prostate atypia: clinical and pathological variables associated with cancer diagnosis on repeat biopsy.

The clinical significance of atypical glands suspicious for malignancy (atypia) on prostate biopsy is unclear. We studied a cohort of 139 patients with atypia who underwent repeat prostate biopsy. We analyzed clinical and pathological variables that may be associated with cancer on repeat biopsy. Cancer was diagnosed in 41 (29%) of patients with atypia: 26 of 41 (66%) were Gleason 6, 20% were Gleason 7 and 7% were Gleason 8 (Gleason < 6 not reported). There were no significant associations of age, race, family history, PSA, PSA density (PSAd), number of previous biopsies or time to repeat biopsy with cancer diagnosis. In multivariate regression, histological inflammation was associated with an 85% decreased probability of cancer on repeat biopsy (odds ratio; OR 0.15; 95% confidence interval; CI 0.04-0.57; P=0.04). Radical prostatectomy was performed in 14 of 41 (34%) patients with cancer; 6 (43%) were Gleason sum ≥7, 3 (21%) were pT3a and 1 (7%) had lymph node metastases. In conclusion, inflammation was independently associated with a significantly decreased risk of cancer on repeat biopsy. However, some patients with initial atypia have higher-risk prostate cancer. Additional studies are needed to elucidate these associations.

Establishment of the long-term in vitro culture system for chicken primordial germ cells.

The objective of this study was to establish the long-term in vitro culture system for chicken gonadal primordial germ cells (gPGCs). Primitive gonads collected from 5.5-day-old chicken embryos were dissociated and explanted onto plates pre-coated with 0.1% gelatin. Each of the four different conditioned media from proliferating and mitotically inactivated chicken embryonic fibroblast (CEF) cells and murine embryonic fibroblasts (STO cells, CRL-1053, ATCC, USA), respectively, was supplemented with growth factors and used to support the growth of gPGCs. The result showed that all the conditioned media could promote the growth and colony formation of gPGCs in vitro, in particular the medium conditioned by inactivated CEF cells. The gPGC-derived colonies maintained in inactivated CEF cells-conditioned medium up to 281 days were positively stained by periodic acid Schiff reaction and antibodies specific to anti-SSEA-1, SSEA-3, SSEA-4, integrin alpha6 and integrin beta1. Their capacities of migration via vascular system and taking up residence in the primary gonadal ridge were further demonstrated by transferring to the dorsal aorta of stage 17 recipient embryos. These results suggested that our culture system is able to maintain chicken gPGCs for long-term in vitro culture without losing their capacity to express pluripotent markers and to integrate into the gonads.

Characterization of an H5N1 avian influenza virus from Taiwan.

In 2003, an avian influenza (AI) virus of H5N1 subtype (A/Duck/China/E319-2/03; Dk/CHN/E319-2/03) was isolated from a smuggled duck in Kinmen Island of Taiwan. Phylogenetic analysis and pairwise comparison of nucleotide and amino acid sequences revealed that the virus displayed high similarity to the H5N1 viruses circulating in Asia during 2004 and 2005. The hemagglutinin (HA) protein of the virus contained multiple basic amino acid residues (-RERRRKR-) adjacent to the cleavage site between the HA1 and HA2 domains, showing the highly pathogenic (HP) characteristics. The HP phenotype was confirmed by experimental infection of chickens, which led up to 100% mortality within 24-72h postinfection. The virus replicated equally well in the majority of organs of the infected chickens with titers ranging from 10(7.5) to 10(4.7) 50% embryo lethal dose (ELD50) per gram of tissue. In a mouse model the virus exhibits low pathogenic characteristics with a lethal infection observed only after applying high inoculating dose (>or=10(7.6) ELD50) of the virus. The infectious virus particles were recovered only from the pulmonary system including trachea and lungs. Our study suggests that ducks infected with H5N1 AIV of HPAI pathotype showing no disease signs can carry the virus silently and that bird smuggling represent a serious risk for H5N1 HPAI transmission.

The effect of electrical field strength on activation and development of cloned caprine embryos.

The activation procedure used in nuclear transfer (NT) is one of the critical factors affecting the efficiency of animal cloning. The purpose of this study was to compare the effect of two electrical field strengths (EFS) for activation on the developmental competence of caprine NT embryos reconstructed from ear skin fibroblasts of adult Alpine does. The NT embryos were obtained by transfer of the quiescent fibroblasts at the fourth passage into the enucleated metaphase II (M II) oocytes. Four to five hours after electrical fusion, the NT-embryos were activated by EFS either at 1.67 or at 2.33 kV/cm and immediately incubated in 6-DMAP (2 mM) for 4 h. The cleavage rate of the NT-embryos activated with 2.33 kV/cm was greater than that activated with 1.67 kV/cm after in vitro culture for 18 h (65.6% versus 19.6%, p < 0.001). No pregnancy was found in 14 recipient does after transferring 51 NT embryos at 1-2 cell stages activated with 1.67 kV/cm. In contrast, two of the seven recipients were pregnant and gave birth to three kids after transferring 61 NT embryos at 1-2 cell stages activated by 2.33 kV/cm. The birth weights of three cloned kids were within the normal range of Alpine goats. However, one kid died 1h after birth while the remaining two are still healthy. DNA analysis by polymerase chain reaction (single-strand conformation polymorphism, SSCP) confirmed that the three kids were genetically identical to the nuclear donor.

Adjunctive use of endoscopy during posterior fossa surgery to treat cranial neuropathies.

OBJECTIVE: The objective of this study was to determine the utility and safety of rigid endoscopy as an adjunct during posterior fossa surgery to treat cranial neuropathies. METHODS: A suboccipital craniotomy was performed for 19 patients with non-neoplastic processes involving the Vth, VIIth, and/or VIIIth cranial nerves. Ten patients with trigeminal neuralgia (n = 8), hemifacial spasm (n = 1), or intractable tinnitus (n = 1) underwent primarily microvascular decompression procedures. One patient with geniculate neuralgia underwent nervus intermedius sectioning combined with microvascular decompression. Eight patients underwent unilateral vestibular nerve neurectomies for treatment of Meniere's disease. A 0- or 30-degree rigid endoscope was used in conjunction with the standard microscopic approach for all procedures. RESULTS: All patients experienced resolution or significant improvement of their preoperative symptoms after posterior fossa surgery. The endoscope allowed improved definition of anatomic neurovascular relationships without the need for significant cerebellar or brainstem retraction. Cleavage planes between the cochlear and vestibular nerves entering the internal auditory canal and sites of vascular compression could not be microscopically observed for several patients; however, endoscopic identification was possible for all patients. There were no complications related to the use of the endoscope. CONCLUSION: The rigid endoscope can be used safely during posterior fossa surgery to treat cranial neuropathies, and it allows improved observation of the cranial nerves, nerve cleavage planes, and vascular anatomic features without significant cerebellar or brainstem retraction.

Mice immunized with DNA encoding a modified Pseudomonas aeruginosa exotoxin A develop protective immunity against exotoxin intoxication.

A recombinant plasmid, which contains the Pseudomonas aeruginosa exotoxin A (PE) gene with a C-terminal deletion, was inserted into expression vector pSecTag Xpress. The expression of this bacterial exotoxin in an animal cell was first demonstrated in 3T3 cell by transient transfection and western blot assay. Recombinant plasmid DNA was then injected intramuscularly to BALB/c mice, anti-PE specific antibodies were found in all animals vaccinated with plasmid containing the PE gene and with 'detoxicated' recombinant PE protein. Mice vaccinated with DNA were protected from the intoxication of lethal dosage of P. aeruginosa exotoxin A. Our results indicated that mice vaccinated with DNA encoding the PE gene could express PE protein in vivo, induced specific immune response, and provided sufficient protective immunity that safeguarded mice from the injection of lethal dosage of PE toxin.

Adsorption isotherms of phenols from water onto macroreticular resins.

The amounts of equilibrium adsorption of phenol and 4-chlorophenol from water on non-ionic macroreticular resins were measured in the temperature range 288-318 K. It was shown that the isotherm data could not be fit by any conventional two- or three-parameter equation including the Langmuir, Freundlich, BET, and Redlich-Peterson equations over the entire range of concentration (1-32 mol m(-3)). They were well fit by combined BET equation or its modified form with the Freundlich or Langmuir equation, depending on the types of solutes and the resins. Such different fitting results could be related to the solute-resin interactions owing to the relatively wide pore size distribution of the resins. The effect of temperature on adsorption equilibrium was also discussed.

The ineffectiveness of immunosuppressive therapy in lymphocytic myocarditis: an overview.

BACKGROUND: The use of immunosuppressive therapy for myocarditis is controversial. PURPOSE: To review the literature on the effectiveness of immunosuppressive therapy in biopsy-proven lymphocytic myocarditis. DATA SOURCES: Two authors independently searched MEDLINE and other medical databases from 1980 to 26 June 1997. STUDY SELECTION: Randomized, controlled trials; matched-cohort studies; and case-control studies of patients with biopsy-proven myocarditis (Dallas criteria or a mean of > or = 2.5 lymphocytes per high-power field) for which any form of immunosuppressive treatment was used. The outcomes of interest were mortality and change in left ventricular ejection fraction. DATA EXTRACTION: 6 of 374 studies satisfied the selection criteria. DATA SYNTHESIS: In survivors, left ventricular function in myocarditis improved approximately 10% over 6 months without immunosuppressive treatment. Prednisone alone did not improve survival (P >0.2) or left ventricular function (P >0.11). Prednisone combined with azathioprine or cyclosporine did not improve survival (P >0.2) or left ventricular function (P >0.2) in three studies. However, one small matched-cohort study showed improvement in children (P <0.01). Neither interferon nor thymic hormone improved survival or left ventricular function. CONCLUSIONS: Immunosuppressive therapy is ineffective in lymphocytic myocarditis. Current therapy in lymphocytic myocarditis seems to be limited to supportive measures or transplantation.

Combination of bupivacaine scalp circuit infiltration with general anesthesia to control the hemodynamic response in craniotomy patients.

BACKGROUND: Sudden and overwhelming increases in blood pressure (BP) and heart rate (HR) during incision of the scalp may give rise to morbidity or mortality in patients with intracranial pathology undergoing neurosurgery. A modification of the method proposed by Labat to abate this circumstantiality was applied in a group of patients receiving craniotomy. The modified method was to combine scalp circuit infiltration of local anesthetic with general anesthesia to control the hemodynamic response to craniotomy. METHODS: Twenty-six patients scheduled to undergo craniotomy were randomly divided into two groups. Patients whose conditions or their current medication that might affect the stability of hemodynamics were excluded. In group A patients (N = 16) 25-30 ml of 0.25% bupivacaine was used for scalp circuit infiltration on the operation side, while in those of group B (N = 10) the same volume of 0.9% normal saline was used. After induction, anesthesia was maintained with 0.6% to 1.2% end-tidal isoflurane (ET-Iso) and 50% N2O in oxygen (N2O:O2 = 2 l/min:2 l/min). The end-tidal CO2 was kept within the range of 25-30 mmHg. BP and HR were recorded every five min before incision and then every two min after incision until one hour after induction. ET-Iso was also recorded every two min throughout a period of sixty min. If the BP and HR increased above 20% of the baseline (10 min before incision), thiopental 2.5 mg/kg and fentanyl 2 micrograms/kg were administered. If hypertension became sustained, the isoflurane concentration was adjusted until an acceptable level was obtained. RESULTS: The mean BP during the surgery was 92 +/- 1 mmHg in group A and 92 +/- 7 mmHg in group B. The difference in BP between incision to 6 min after incision was statistically significant (P < 0.05). The mean HR during surgery was 101 +/- 5 beats/min in group B and 91 +/- 2 beats/min in group A, the difference of which was not statistically significant. All of the patients in group B required a deepened anesthesia to keep the BP and HR within the normal range, but no patient in group A had such need. The average concentration of ET-Iso during the 60 min period was 0.95 +/- 0.12% in group B and 0.41 +/- 0.01% in group A, respectively. The difference was statistically significant (P < 0.05). CONCLUSIONS: Our results showed that scalp circuit infiltration with 0.25% bupivacaine significantly improved the cardiovascular stability and reduced the requirement of isoflurane during craniotomy. The routine use of bupivacaine scalp circuit infiltration in patients undergoing craniotomy should be considered.

Long-term effects of neuromuscular rehabilitation of chronic facial paralysis.

Although chronic facial dysfunction can be improved with neuromuscular biofeedback therapy, it is uncertain whether this improvement is maintained after such therapy ends, or whether post-therapy, home exercise programs optimize this improvement. We aimed to clarify these issues. Post-therapy facial function, in 38 previously treated patients, was blindly assessed using the House grading system, 1 to 41 months after ending therapy. Results were compared with pre-therapy function. It was found that post-therapy function was better than pre-therapy function in most patients (40%), it was worse in some (26%), and was unchanged in the rest. This surprising result occurred because, although most patients who recently stopped therapy (1 to 6 mo) had improved significantly, the longer other patients were out of therapy, the more they had tended to deteriorate, particularly those who had been practicing. Results suggested that unsupervised, post-therapy, home exercise programs may be detrimental, and that new post-therapy programs may be required to maintain the benefits of regular therapy.

An accurate impression method for implant prosthesis fabrication.

The long-term success of an implant prosthesis depends not only on the development of osseointegration, but also on the maintenance of osseointegration after the prosthetic phase. To achieve this, a passive superstructure must be fabricated. Errors that result from the impression transfer method of implant position during the impression procedures often made it necessary to section and solder metal frameworks repeatedly. This article presents a modified impression technique intended to deal with the problems of more traditional impressions with the aim of achieving a more accurate master cast.

Analysis of the "shear" bond strength of pretreated aged composites used in some indirect bonding techniques.

Investigations of the repair of composites have shown that bond strengths can be significantly reduced at an interface involving an aged composite. Brackets placed by some indirect bonding techniques also have an interface involving an aged composite. This study investigated some of the properties of sealant-composite interfaces and parameters affecting these properties independent of other regions and interfaces found in the total enamel-sealant-composite-bracket system using a shear bond-strength test and fractographic analysis. The effects of various pretreatments of 7-day-old composite surfaces on the bond strength and contact angle of a mixed sealant on these pretreated surfaces were determined. Fractured specimens with adhesive failure closest to the point of force application had low bond strengths (17.62 MPa), which could be correlated with surface pretreatment. Preliminary tests showed that acetone pretreatment produced the most consistently strong interfaces with the fewest adhesive failures of this type. Specimens with adhesive failure only in other regions had higher bond strengths (23.41 MPa), which showed no dependence on pretreatment. There was no statistical relationship between contact angle and bond strength. The data coupled with fracture path analysis suggest that: first, the critical region for fracture analysis is that part of the adhesive interface which is closest to the point of force application; second, failure during some dental shear bond strength tests probably occurs as a consequence of tensile stress induced by a bending moment rather than by shear stress; and third, specifying bond strength as breaking load/area may be incorrect.

Bond strength of aged composites found in brackets placed by an indirect technique.

The "Thomas" indirect technique for bracket attachment produces an interface not present in direct techniques, that is, an aged composite-sealant interface. Our primary goal was to determine if a weakened interface was produced by a modified (sealant was mixed prior to placement of brackets) Thomas indirect technique when the composite was aged for 7 days. The enamel-bracket system was investigated in vitro by comparison of shear bond strengths for metal and ceramic brackets bonded to bovine teeth by a direct and indirect method. Nearly all specimens failed at the bracket-composite interface and, subsequently, no difference was found between specimens placed by direct or indirect methods. No evidence was found to suggest that an aged composite would predispose the enamel-bracket system to fail at the sealant-composite interface. The ceramic brackets used in this investigation had lower bond strengths then metal ones, but the breaking loads were similar.

Adult bacteremic pneumonia: bacteriology and prognostic factors.

Bacteremic pneumonia is a highly specified subgroup of pneumonia that is potentially life-threatening. In order to find out the prognostic factors in this subgroup of pneumonia, we conducted a 40-month retrospective analysis of 70 cases in our hospital. The male to female ratio was 54:16. Forty-one cases were community-acquired bacteremic pneumonia (CABP), and 29 cases were nosocomial bacteremic pneumonia (NBP). Both CABP and NBP were predominated by gram-negative bacteria. Klebsiella pneumoniae was the most common microorganism isolated in both CABP and NBP. The overall mortality was 62.9% (44/70). There was no significant difference in the mortality between CABP (61.0%) and NBP (65.5%). After univariate analysis of all possible prognostic factors, 10 variables were found to have significantly poor prognostic values. They were: 1) the presence of septic shock; 2) the use of ventilatory support; 3) the presence of radiologic spread; 4) treatment in an intensive care unit; 5) male gender; 6) the development of adult respiratory distress syndrome; 7) Klebsiella bacteremic pneumonia in patients with an alcohol habit; 8) patients with ultimately fatal underlying diseases; 9) an initial AaDO2 > 200 mmHg; and 10) an initial arterial pH < 7.25.