Prophylactic clipping using the over-the-scope clip (OTSC) system after complex ESD and EMR of large colon polyps.

BACKGROUND: Delayed bleeding is the most frequent complication after endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) of large colon polyps. Today, prophylactic clipping with through-the-scope clips (TTSCs) is commonly used to reduce the risk of bleeding. However, the over-the-scope clip (OTSC) system might be superior to TTSCs in achieving hemostasis. This study aims to evaluate the efficacy and safety of prophylactic clipping using the OTSC system after ESD or EMR of large colon polyps. METHODS: This is a retrospective analysis of a prospective collected database from 2009 until 2021 of three endoscopic centers. Patients with large (≥ 20 mm) colon polyps were enrolled. All polyps were removed by either ESD or EMR. After the resection, OTSCs were prophylactically applied on parts of the mucosal defect with a high risk of delayed bleeding or/and perforation. The main outcome measurement was delayed bleeding. RESULTS: A total of 75 patients underwent ESD (67%, 50/75) or EMR (33%, 25/75) in the colorectum. The mean resected specimen diameter was 57 mm ± 24.1 (range 22-98 mm). The mean number of OTSCs placed on the mucosal defect was 2 (range 1-5). None of the mucosal defects were completely closed. Intraprocedural bleeding occurred in 5.3% (ESD 2.0% vs. EMR 12.0%; P = 0.105), and intraprocedural perforation occurred in 6.7% (ESD 8% vs. EMR 4%; P = 0.659) of the patients. Hemostasis was achieved in 100% of cases of intraprocedural bleeding, whereas two patients required surgical conversion due to intraprocedural perforation. Among the remaining 73 patients who received prosphylactic clipping, delayed bleeding occurred in 1.4% (ESD 0% vs. EMR 4.2%; P = 0.329), and delayed perforation occurred in 0%. CONCLUSIONS: The prophylactic partial closure of large post-ESD/EMR mucosal defects using OTSCs could serve as an effective strategy to reduce the risk of delayed bleeding and perforation. The prophylactic partial closure of large complex post-ESD/EMR mucosal defects using OTSCs could serve as an effective strategy to reduce the risk of delayed bleeding and perforation.

[Prevention and conservative therapy of diverticular disease]. / Prophylaxe und konservative Therapie der Divertikelkrankheit.

Diverticulosis and diverticular disease are a common problem in daily practice and one third of the patients with diverticulosis develop symptoms. Patients with uncomplicated diverticulitis are very often treated with antibiotics. There is growing evidence that antibiotics are not necessary in uncomplicated cases. One problem is the different classification of diverticulitis and diverticular disease. Therefore, it is not easy to compare different studies. The evidence for therapy with antibiotics, mesalamine, probiotics and fibers are initially discussed and secondly therapeutic recommendations are given for the various stages of diverticular disease.

Predictive factors for an uncomplicated long-term course of Crohn's disease: a retrospective analysis.

BACKGROUND: Predictive factors for a mild course of Crohn's disease (CD) may have therapeutic consequences, but as yet have not been identified. AIMS: To identify baseline factors that predict mild CD and design a predictive scoring system. METHODS: A retrospective, multicenter study of newly diagnosed CD patients allocated to mild CD (no therapy, mesalazine only, or mesalazine with a single initial short course of low-dose prednisone) or moderate CD (all other patients including resected patients). RESULTS: 162 patients (median follow-up 43 months) were analyzed: 47 mild CD and 115 moderate CD. For mild CD versus moderate CD, mean age at first diagnosis was higher (41.1 versus 33.9 years, p=0.02), mean C-reactive protein (CRP) concentration was lower (1.6 versus 3.6 mg/L, p<0.01), and perianal lesions were less frequent (0% versus 10.4%, p=0.02). The combined incidence of complications (stenosis, any type of fistula, extraintestinal complications or fever) was 21.3% in mild CD versus 35.7% in moderate CD (p=0.07). A scoring system based on age, CRP, endoscopic severity (adapted Rutgeert's score), perianal lesions and combined incidence of complications was developed which can predict a mild prognosis at the initial diagnosis, giving patients the chance of simplified therapy and accelerated step-up in the event of treatment failure. CONCLUSIONS: Approximately a third of CD patients experience a mild disease course and require only basic therapy. A possible scoring system to predict mild CD which may avoid overtreatment and unnecessary risks for the patient and costs is suggested.

Conservative management.

Treatment of diverticulitis comprises at least two options: conservative or surgical management. There is a recent trend to limit surgical treatment of acute diverticulitis and to favor conservative management. This review addresses general aspects of conservative patient care with special focus on the treatment of patients with a first attack of diverticulitis. The presentation does not include a discussion of specific drugs which is given in other sections of this issue.

[Current management of toxic megacolon]. / Management des toxischen Megakolons.

Toxic megacolon is a rare and life-threatening complication of severe colitis, defined as a dilatation of the colon > 6 cm in the absence of distal obstruction in combination with signs of systemic toxicity (major criteria: fever, tachycardia, leukocytosis, anaemia). Various triggers are known and the most common causes are underlying ulcerative colitis and Clostridium difficile. Diagnosis can easily be made by clinical examination, routine laboratory parameters and a plain X-ray of the abdomen. Much more difficult is to decide between non-surgical treatment including intensive care treatment or surgery (mostly subtotal colectomy with terminal ileostomy). Non-surgical therapy includes balancing of electrolytes and fluid volumes, broad-spectrum antibiotics including metronidazole, positioning of patients and probably careful intermittent decompression. In case of ulcerative colitis immunosuppression should be started with corticosteroids and potentially with calcineurin inhibitors. In pseudomembranous colitis vancomycin should be given orally and metronidazole should be given intravenously. As far as possible the patient should be treated in a centre with experience in the field.

Successful non-invasive treatment of stricturing fibrosing colonopathy in an adult patient.

OBJECTIVE: Fibrosing colonopathy (FC) is a rare entity associated with cystic fibrosis (CF). Until now, patients with stricturing FC have usually been treated surgically. In this instance, we aimed at avoiding surgery by applying a new conservative approach. - METHODS: Case report on an adult with CF who developed persistent abdominal pain due to a non-passable stricture in the right transverse colon. Histology confirmed fibrosing colonopathy. - RESULTS: Initially we treated the patient with prednisolone pulse therapy and additive antibiotic therapy. For maintenance therapy we administered budesonide. The patient underwent clinical, laboratory and endoscopic follow-up over a three-year period. The stricture healed and was easy to pass. A relapse in the cecum at the ileocecal valve again improved under steroid and antibiotic therapy. - CONCLUSIONS: We present a novel therapeutic approach for advanced stricturing FC in an adult patient which successfully avoided surgery (right hemicolectomy) over a three year follow up.

Mesalazine granules are superior to Eudragit-L-coated mesalazine tablets for induction of remission in distal ulcerative colitis - a pooled analysis.

BACKGROUND: Different oral formulations of 'mesalazine (mesalamine)' may have different efficacy in distal ulcerative colitis. AIM: To evaluate the efficacy of mesalazine granules (Salofalk granules) vs. mesalazine tablets (Salofalk tablets) as induction therapy in patients with distinct extensions of ulcerative colitis. METHODS: A pooled analysis of 705 patients from four prospective, randomised, double-blind phase III trials was performed. The efficacy of 8 weeks' induction with 3 g/day mesalazine granules [3 g once daily (o.d.) or 1 g three times daily (t.d.s)] vs. 3 g/day mesalazine tablets (1 g t.d.s.) was compared in terms of clinical remission (CR: CAI ≤ 4) and endoscopic remission (ER: EI ≤ 3) (both according to Rachmilewitz) in subgroups with pancolitis, left-sided colitis, or proctosigmoiditis. RESULTS: Mesalazine granules were equipotent to mesalazine tablets in pancolitis regarding CR (72% vs. 71%, P = 0.909) and ER (58% vs. 49%, P = 0.338). In left-sided colitis, both mesalazine formulations were equipotent regarding CR (66% vs. 67%; P = 0.843) but mesalazine granules were superior regarding ER (56% vs. 37%; P = 0.025). In proctosigmoiditis, mesalazine granules were significantly more effective than mesalazine tablets regarding CR (78% vs. 55% P < 0.001) and ER (67% vs. 43% P < 0.001). Furthermore, o.d. application of mesalazine granules was more effective than t.d.s. dosing in left-sided colitis (CR 73% vs. 62%, P = 0.181; ER 71% vs. 48% P = 0.005) and proctosigmoiditis (CR 86% vs. 73%, P = 0.020; ER 75% vs. 61%, P = 0.021), but not in pancolitis. CONCLUSION: This pooled analysis supports the hypothesis that mesalazine granules are superior to mesalazine tablets in induction of remission in distal colitis and should be taken once daily.

Keratin 18 provides resistance to Fas-mediated liver failure in mice.

BACKGROUND: Keratins are intermediate filament proteins of epithelial cells with pivotal functions for cell integrity. They comprise keratins 18 [K18] and 8 [K8] in hepatocytes. Keratins are of major importance for an intact cellular microarchitecture and have protective functions in human liver diseases. In mice, K8 has been demonstrated to protect against Fas-antibody-induced liver failure by direct interaction with apoptotic regulators, while the role of K18 remains unresolved. MATERIALS AND METHODS: We analysed effects of K18 deficiency on Fas-induced liver failure in mice. We determined survival and analysed induction of apoptosis after injection of the agonistic Fas antibody Jo2 into K18(-/-) and wild-type control mice by TUNEL assay and fluorometrically analysed caspase-3, -8 and -9 activities 1, 2 and 3 h after Jo2 injection. RESULTS: In K18(-/-) mice, survival of Fas-antibody treated mice was significantly shorter than that of wild-type controls (P = 0.02). However, shortened survival of K18(-/-) mice was caused by increased hepatic damage but was not correlated to enhanced induction of apoptotic pathways, as neither numbers of TUNEL positive apoptotic cells nor activities of caspases-3, -8 and -9 differed between K18(-/-) and K18(+/+) mice at any point of time. CONCLUSION: K18(-/-) mice are significantly more susceptible to Fas-antibody-induced liver failure. The cytoprotective effect of K18 is not explained by a differential activation of caspases-3, -8 and -9, suggesting that K18 does not directly interfere with apoptotic regulators. Importantly, however, K18 exerts significant protective functions by other mechanisms.

[Modern therapy of diverticular disease]. / Moderne Therapie der Divertikelkrankheit.

New concepts are developed in the therapy of diverticular disease. 5-aminosalicylates can be administered in patients with slight forms of diverticulitis. In moderate diverticulitis antibiotics should be applied alternatively or additionally. In cases of severe diverticulitis patients should be kept fasting with parenteral nutrition and intravenous broad spectrum antibiotics. Small abscesses can be treated conservatively while abscesses larger than 4 cm should be drained in a first step and than treated surgically. A free perforation is still an absolute indication for emergency operation. In recurring diverticulitis indication for resection of the affected segment of the bowel should be considered depending on the extent of former attacks.

Safety, feasibility, and tolerability of ileocolonoscopy in inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: Ileocolonoscopy including biopsies is the first-line investigation in the diagnosis, management, and monitoring of inflammatory bowel disease (IBD). However, data on its safety, feasibility, and tolerability, especially in patients with extensive or severe inflammation, are rare. The aim of this study was to assess prospectively the risks of ileocolonoscopy in relation to various disease patterns and to compare possible burdens of the procedure in the endoscopist's and the patient's perception. PATIENTS AND METHODS: We prospectively analyzed a total of 558 consecutive patients, 482 with a confirmed diagnosis of IBD and 76 with suspected IBD. Data were recorded regarding the indication for ileocolonoscopy, sedation, procedure time, completion rate, feasibility of the procedure, patient tolerance, and procedure-related and postprocedure complications. Endoscopic data included the region involved, the nature of the involvement, activity of the disease, and number of biopsies. RESULTS: In 558 endoscopic procedures performed by 14 gastroenterologists no procedure-related deaths occurred. Major complications, defined as bleeding (n = 1) or perforation (n = 3), occurred in 4/558 patients (0.7 %). Minor complications, which included intense flatulence, tachycardia, allergic reaction to a sedation drug, and autonomic symptoms such as nausea, vomiting, and intense perspiration, occurred in 22/558 patients (3.9 %). There was no relationship between the complication rate and the activity of the disease. Mean procedure time was 21.0 minutes and the completion rate, defined by intubation of the terminal ileum, was 94.6 %. We documented a high tolerability independent of the severity of the disease. CONCLUSIONS: Ileocolonoscopy is a safe and feasible procedure in patients with IBD and is well tolerated by patients when carried out by well-trained endoscopists.

Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience.

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.

Intrahepatic upregulation of RhoA and Rho-kinase signalling contributes to increased hepatic vascular resistance in rats with secondary biliary cirrhosis.

BACKGROUND AND AIMS: Portal hypertension in cirrhosis is mediated in part by increased intrahepatic resistance, reflecting an increased sensitivity of the hepatic microvasculature to vasoconstrictors. Activation of the RhoA/Rho-kinase pathway is essential for contraction of vascular smooth muscle. The aim of this study was to investigate RhoA/Rho-kinase mediated regulation of the intrahepatic vascular tone in cirrhotic rats. METHODS: Cirrhosis was induced by bile duct ligation (BDL). Hepatic RhoA and Rho-kinase expressions were studied by real time reverse transcription polymerase chain reaction and western blot analysis. Hepatic Rho-kinase activity in rat and human livers was assessed as phosphorylation of the Rho-kinase substrate moesin. The effect of the Rho-kinase inhibitor Y-27632 on hepatic perfusion pressure was measured in livers perfused at constant flow. The in vivo effect of intravenous application of Y-27632 was studied by haemodynamic measurements. RESULTS: Hepatic expressions of RhoA and Rho-kinase were increased at mRNA and protein level in BDL rats. Intrahepatic moesin phosphorylation was increased in livers from cirrhotic rats and patients with alcohol induced cirrhosis. Y-27632 reduced the basal perfusion pressure of in situ perfused livers in BDL rats but not in sham operated rats. Y-27632 reduced the sensitivity to methoxamine in isolated perfused livers in sham operated rats more than in BDL rats. In vivo, Y-27632 reduced portal pressure to a greater extent in BDL rats than in sham operated rats. Intrahepatic vascular resistance was decreased in response to bolus injection of Y-27632 in BDL rats but not in sham operated rats. CONCLUSIONS: Upregulation of RhoA and Rho-kinase contributes to increased intrahepatic resistance in cirrhotic rats and to an increased sensitivity of cirrhotic livers to vasoconstrictors.

Intrahepatic mRNA levels of interferon gamma and tumor necrosis factor alpha and response to antiviral treatment of chronic hepatitis C.

OBJECTIVES: The impact of intrahepatic messenger RNA (mRNA) levels of interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) on the outcome of antiviral treatment of chronic hepatitis C was evaluated. METHODS: Semiquantitative mRNA determination was performed on 36 pretreatment liver biopsies by reverse transcription/competitive polymerase chain reaction. RESULTS: Sustained response (normal aminotransferase levels and negative hepatitis C virus [HCV] RNA for more than 6 months) was achieved in 13 patients, whereas 23 of 36 patients did not achieve sustained response (12 partial responders, 11 complete nonresponders). In sustained responders, pretreatment intrahepatic mRNA levels of IFN-gamma and TNF-alpha were lower than in nonsustained responders (IFN-gamma, 0.23 +/- 0.10 vs. 0.35 +/- 0.07, respectively; p = 0.024 and TNF-alpha, 1.2 +/- 0.7 vs. 2.3 +/- 1.4, respectively; p= 0.009); similarly, HCV viral load was lower in sustained responders than in nonresponders (663,424 +/- 756,389 copies/mL vs. 1,656,713 +/- 1,517,683 copies/mL, respectively; p = 0.037). In addition, TNF-alpha mRNA levels were correlated to HCV viral load and liver fibrosis scores. CONCLUSIONS: Higher intrahepatic mRNA levels of IFN-gamma and TNF-alpha may reflect interferon resistance of HCV strains and may contribute to tissue damage in patients refractory to antiviral treatment.

Intrahepatic MxA expression is correlated with interferon-alpha expression in chronic and fulminant hepatitis.

Interferon-alpha (IFN-alpha) has potent pro-inflammatory and anti-viral functions. It exerts its effects by inducing intracellular proteins such as MxA. To analyse the role of intrahepatic interferon activation, IFN-alpha and MxA expression was studied by immunohistochemistry in explant livers of 20 patients with fulminant hepatic failure (FHF), 41 patients with chronic liver disease (CLD), and ten normal controls (NCs). In NCs only small numbers of Kupffer cells, but no hepatocytes, showed IFN-alpha and MxA expression. In contrast, significantly enhanced numbers of IFN-alpha- and MxA-positive Kupffer cells, along with small numbers of MxA-positive and larger numbers of IFN-alpha-positive lymphocytes, were found in CLD and in FHF. MxA protein was also expressed on hepatocytes and bile ducts in the vicinity of IFN-alpha-positive inflammatory infiltrates (hepatocytes: NCs: 0%, CLD: 8%, FHF: 68%; bile ducts: NCs: 19%, CLD: 46%, FHF: 83%). A significant correlation was found between the numbers of IFN-alpha- and MxA-positive cells (r=0.67, p<0.001). Thus, large amounts of IFN-alpha are released in the livers of patients with FHF, which is likely to contribute to immune-mediated liver cell damage. Intrahepatic MxA expression corresponds to IFN-alpha produced particularly by infiltrating inflammatory cells, rather than by hepatocytes themselves.

Tumor necrosis factor alpha in the pathogenesis of human and murine fulminant hepatic failure.

BACKGROUND & AIMS: The tumor necrosis factor (TNF)-alpha/TNF receptor system is critical for liver development because hepatocytes undergo apoptosis if the antiapoptotic cascades resulting in RelA NF-kappaB activation are not effective. Therefore, we studied the role of TNF-alpha in fulminant hepatic failure (FHF) and developed a new therapeutic strategy. METHODS: Serum levels and hepatic expression of TNF-alpha and both TNF receptors were determined by enzyme-linked immunosorbent assay and immunohistochemistry. Adenoviral vectors were constructed expressing dominant-negative proteins interfering with intracellular TNF-alpha-dependent pathways. The relevance of these constructs was studied in primary mouse hepatocytes and in a murine model of FHF. RESULTS: Serum levels of TNF-alpha and TNF receptors are significantly increased in FHF; this increase correlates with patient prognosis. In livers of patients with FHF, infiltrating mononuclear cells express high amounts of TNF-alpha and hepatocytes overexpress TNF receptor 1 (TNF-R1). Apoptotic hepatocytes are significantly increased in FHF, and there is a strong correlation with TNF-alpha expression, which is even more pronounced in areas of mononuclear infiltrates. In an in vivo FHF model, the Fas-associated death domain (FADD), adenovirus selectively blocked the intracellular pathway, leading to mitochondrial cytochrome c release, caspase-3 activation, and, thus, apoptosis of hepatocytes. CONCLUSIONS: The results show that the TNF-alpha/TNF-R1 system is involved in the pathogenesis of FHF in humans. Studies in this animal model indicate that FADD may serve as a molecular target to prevent liver cell death in vivo.

Semi-quantification of human C-C chemokine mRNAs with reverse transcription/real-time PCR using multi-specific standards.

A reverse transcription/real-time polymerase chain reaction (PCR) assay was established to semi-quantify the mRNA levels of the human C-C chemokines RANTES, MIP-1beta and MCP-1 relative to the housekeeping gene beta-actin. The assay showed a high sensitivity (below 60 cDNA molecules/10 microl reaction) and dynamic range (8 log units); both within-assay and inter-assay variability were below 0.06 log units and the accuracy was +/-0.06 log units for all four chemokines. Moreover, it is demonstrated that a multi-specific DNA fragment, which had previously been constructed for competitive PCR, can be used as a reliable external standard. This allows a direct semi-quantitative comparison of different chemokine mRNA levels and is a convenient alternative to the use of different sets of homologous external standards. The method was successfully applied to the semi-quantification of chemokines in human liver specimens and should be useful in further studies on steady state mRNA levels of C-C chemokines from low cell numbers or small tissue specimens.

T(H)1 to T(H)2 shift of cytokines in peripheral blood of HIV-infected patients is detectable by reverse transcriptase polymerase chain reaction but not by enzyme-linked immunosorbent assay under nonstimulated conditions.

BACKGROUND: Dysregulation of cytokines has been implicated in the pathogenesis of HIV infection. Therefore, we determined tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-4, IL-10, and interferon-gamma (IFN-gamma) mRNA and serum levels in HIV-infected patients under nonstimulated conditions. MATERIAL AND METHODS: Blood samples of 32 HIV-infected patients and 10 healthy HIV-negative controls were analyzed. Cytokine serum levels were quantified by enzyme-linked immunosorbent assay (ELISA). Cytokine mRNA levels were determined semiquantitatively by competitive reverse transcriptase polymerase chain reaction (RT-PCR) and expressed as ratios relative to those of beta-actin. RESULTS: Competitive RT-PCR was shown to be more sensitive than protein ELISA in analyzing cytokine production. We found a significant correlation between steady-state mRNA ratios and serum protein levels for TNF-alpha. Significantly higher cytokine mRNA ratios were found in those patients with IL-10 and IFN-gamma levels detectable by ELISA. Steady-state mRNA ratios of TNF-alpha, IL-4, and IL-10 were significantly increased in patients with highly replicative HIV-infection. Furthermore, elevated IL-4:IFN-gamma ratios were related to both high viral load and loss of CD4 cells. DISCUSSION: Determination of steady-state mRNA ratios by semiquantitative RT-PCR represents a sensitive method to analyze cytokines in peripheral blood of HIV-infected patients under nonstimulated conditions. The data obtained with this technique provide further evidence for a T(H)1 to T(H)2 cytokine shift with progressive HIV disease.

Indication, outcome and follow up of intensive care in patients with HIV-infection.

BACKGROUND/AIM: The admission to intensive care is controversially discussed in patients with HIV infection, since life expectancy is limited. Therefore, we analyzed indications, outcomes and follow up of all patients with confirmed HIV-infection and Aids defining symptoms who had been admitted to the intensive care unit (ICU) of our department between 1985-1996. RESULTS: 49 patients were admitted to the ICU, 42 of them with CDC stage C of HIV infection before admission. The leading indications were pneumonia (n = 15; PCP: 10, bacterial: 5), acute bleedings (n = 14), acute neurological diseases (n = 6), and gastrointestinal perforation (n = 5). Overall mortality was 39% (19/49) with a higher mortality seen in patients with respiratory disorders (53%) compared to non-respiratory disorders (22%, n.s.). The only significant predictor of mortality was the serum creatinine (p = 0.001), while differences in the APACHE II score between survivors and non-survivors did not reach statistical significance (22 +/- 7, 16 +/- 5; p = 0.14). During follow up no difference was seen in the life expectancy of HIV-infected survivors of intensive care as compared to those patients with AIDS who had never been admitted to ICU (8.4 months versus 9 months). DISCUSSION: The need for intensive care in HIV infected patients does not accelerate the progression of HIV infection to death, if the complications requiring ICU intervention can be managed successfully. Respiratory infections and impaired renal function are risk factors for a fatal outcome. Thus, HIV infected patients benefit from intensive care therapy.