Surgical management of colovesical fistulas.

BACKGROUND: The most common etiology of colovesical fistulas is complicated diverticular disease and the treatment of choice is surgical resection. There are very few reports of the application of minimally invasive approaches for these surgeries. The aim of our study was to evaluate the role of laparoscopy in this challenging surgical setting. METHODS: A retrospective analysis of patients who underwent transabdominal surgery for colovesical fistula in 2008-2018 was performed. Patients were divided into 2 groups: patients who had open surgery and patients treated with laparoscopy. The postoperative course was reviewed for the length of stay, postoperative complications, readmission, emergency re-operation, and mortality RESULTS: Thirty-five patients were included (13 females [37%]; median age 68 [range 28-84] years) with a mean body mass index of 29 ± 7.19 kg/m2. The main fistula etiology was diverticulitis (91%). Seventeen patients (48.5%) had laparoscopic surgery and 2 patients in whom laparoscopy was attempted underwent conversion to laparotomy. The benefits of laparoscopy included significant reductions in morbidity including surgical site infections and medical complications following laparoscopy. CONCLUSIONS: Laparoscopic management of colovesical fistula is both safe and feasible in a high volume laparoscopic colorectal surgery center. Laparoscopy offers potential benefits including a decreased incidence of surgical site infections and medical complications.

Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus.

BACKGROUND: Prevention of rectal HIV transmission is a high-priority goal for vaccines and topical microbicides because a large fraction of HIV transmissions occurs rectally. Yet, little is known about the specific target-cell milieu in the human rectum other than inferences made from the colon. METHODS: We conducted a comprehensive comparative in situ fluorescence study of HIV target cells (CCR5-expressing T cells, macrophages, and putative dendritic cells) at 4 and 30 cm proximal of the anal canal in 29 healthy individuals, using computerized analysis of digitized combination stains. RESULTS: Most strikingly, we find that more than 3 times as many CD68 macrophages express the HIV coreceptor CCR5 in the rectum than in the colon (P = 0.0001), and as such rectal macrophages seem biologically closer to the HIV-susceptible CCR5 phenotype in the vagina than the mostly HIV-resistant CCR5 phenotype in the colon. Putative CD209 dendritic cells are generally enriched in the colon compared with the rectum (P = 0.0004), though their CCR5 expression levels are similar in both compartments. CD3 T-cell densities and CCR5 expression levels are comparable in the colon and rectum. CONCLUSIONS: Our study establishes the target-cell environment for HIV infection in the human distal gut and demonstrates in general terms that the colon and rectum are immunologically distinct anatomical compartments. Greater expression of CCR5 on rectal macrophages suggests that the most distal sections of the gut may be especially vulnerable to HIV infection. Our findings also emphasize that caution should be exercised when extrapolating data obtained from colon tissues to the rectum.

Are there benefits to starting antiretroviral therapy during primary HIV infection? Conclusions from the Seattle Primary Infection Cohort vary by control group.

It is controversial whether starting combination antiretroviral therapy (cART) during primary HIV infection (PHI) is beneficial. Subjects in this observational cohort began cART <30 days (group 1: acute treatment, n = 40), 31-180 days (group 2: early treatment, n = 82) or >180 days (group 3: delayed treatment, n = 35) after HIV infection, and were compared with 27 historical and 60 contemporary controls. Time to HIV-related diagnoses did not differ for group 1 (adjusted hazard ratio [aHR] 1.44, P = 0.3) or group 2 (aHR 1.17, P = 0.5) compared with contemporary controls, but it was delayed for both treated groups (aHR 0.38 for group 1, P = 0.01; and aHR 0.28 for group 2, P < 0.0001) compared with historical controls. Although rates of HIV-related diagnoses were similar in acutely treated subjects and contemporary controls, results were confounded by associations between higher CD4 counts, lower HIV RNA levels and delayed disease progression as reasons for deferring treatment. Randomized trials are needed to address benefits of cART during PHI.

Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators.

OBJECTIVE: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddl), or stavudine (d4T). DESIGN: Randomized, placebo-controlled, partially double-blinded multicenter study. SETTING: Adult AIDS Clinical Trials Units. PATIENTS: Treatment-naive HIV-infected adults with 200-600x10(6) CD4 T lymphocytes/l. INTERVENTIONS: Patients were openly randomized to a d4T or a ddl limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddl (400 mg/day), ddl plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos. After 24 weeks 3TC was added for patients assigned to the monotherapy arms. MAIN OUTCOME MEASURE: The reduction in plasma HIV-1 RNA level at weeks 24 and 48. RESULTS: Two hundred ninety-nine patients were enrolled. After 24 weeks the mean reduction in plasma HIV-1 RNA copies/ml from baseline was 0.49 log10 (d4T monotherapy) versus 1.03 log10 (d4T plus 3TC; P = 0.001), and 0.68 log10 (ddl monotherapy) versus 0.82 log10 (ddl plus 3TC; P>0.22). After 48 weeks the mean reduction was 1.08 log10 (d4T plus 3TC) versus 1.01 log10 (ZDV plus 3TC) in the d4T limb (P = 0.66), and 0.94 log10 (ddl plus 3TC) versus 0.88 log10 (ZDV plus 3TC; P = 0.70) in the ddl limb. CONCLUSIONS: 3TC added significantly to the virologic effects of d4T, but not ddl, in treatment-naive patients. 3TC plus d4T produced virologic changes comparable to those of 3TC plus ZDV. These results support the use of 3TC with either ZDV or d4 as a component of initial combination antiretroviral therapy.

Discontinuation of prophylaxis in HAART-responders.

AIDS: The 1997 U.S. Public Health Service/IDSA guidelines on preventing opportunistic infections stated that CD4 counts should be used to determine whether to initiate or continue prophylaxis. That recommendation did not take the effectiveness of HAART into account, and was a conservative approach. Substantial evidence now shows that HAART responders have a functional recovery of the immune system, enough to discontinue prophylaxis. As a result, the USPHS/IDSA Opportunistic Infection Guidelines for 1999 say that prophylaxis can be discontinued for M. avium infection, toxoplasmosis, and CMV retinitis under certain conditions. Contact information is provided for obtaining a full text of the draft document.^ieng

Combination antiretroviral therapy for HIV infection.

The primary goal of antiretroviral therapy for human immunodeficiency virus (HIV) infection is suppression of viral replication. Evidence indicates that the optimal way to achieve this goal is by initiating combination therapy with two or more antiretroviral agents. The agents now licensed in the United States for use in combination therapy include five nucleoside analog reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine and lamivudine), two nonnucleoside reverse transcriptase inhibitors (delavirdine and nevirapine) and four protease inhibitors (saquinavir, ritonavir, indinavir and nelfinavir). Current recommendations suggest that antiretroviral therapy be considered in any patient with a viral load higher than 5,000 to 20,000 copies per mL, regardless of the CD4+ count. Selection of the combination regimen must take into account the patient's prior history of antiretroviral use, the side effects of these agents and drug-drug interactions that occur among these agents and with other drugs as well. Because of the potential for viral resistance, nonnucleoside reverse transcriptase inhibitors and protease inhibitors should only be used in combination therapy. Antiretroviral agents are rapidly being developed and approved, so physicians must make increasingly complex treatment decisions about medications with which they may be unfamiliar.

ACTG 343: (why) we can't relax our grip on viral suppression.

AIDS: An AIDS Clinical Trials Group study examined whether less intensive maintenance antiretroviral regimens could be effective after the initial use of highly active induction therapy. Results from 309 patients, who were evaluated in the maintenance phase, demonstrated that 6 months of therapy with AZT/3TC/IDV, followed by less intensive treatment, is not an effective strategy. Results suggest that once viral suppression has been achieved, intensity of therapy should not be lessened.^ieng

Infection due to fluconazole-resistant Candida in patients with AIDS: prevalence and microbiology.

A cross-sectional study was conducted to assess the prevalence and microbiology of oral infection due to fluconazole-resistant Candida in patients with AIDS. Oral swab specimens for fungal cultures were obtained from 100 consecutive outpatients with CD4 lymphocyte counts of < 200/mm3. At least one fungal organism demonstrating in vitro resistance to fluconazole (minimum inhibitory concentration, > or = 8 micrograms/mL) was isolated from 26 (41%) of 64 patients for whom cultures were positive. When fluconazole-resistant C. albicans was isolated, in vitro resistance correlated with clinical thrush. None of 10 patients from whom only non-albicans species of Candida were isolated had active thrush. The patients from whom fluconazole-resistant Candida albicans was isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated episodes of thrush (median, 4.5), and a greater median duration of prior fluconazole treatment (231 days) than did patients from whom fluconazole-susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004]; median number of treated episodes of thrush, 2.0 [P = .001]; and median duration of prior fluconazole treatment, 10 days [P = .01]; respectively). In a multivariate analysis, the number of episodes and duration of fluconazole therapy were independent predictors of resistance.

Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients.

In a case-control study to identify risk factors for fluconazole-resistant oroesophageal candidiasis in human immunodeficiency virus-infected patients, 25 patients with clinical and in vitro fluconazole-resistant candidiasis were paired with controls who had treatment-responsive candidiasis and who had been observed for similar time periods. After their first episode of candidiasis, patients who later developed fluconazole resistance had more treated episodes than did matched controls (cases, 3.1; controls, 1.8; P = .004), lower median CD4 cell counts (11/mm3 vs. 71/mm/3; P = .004), and greater median durations of all antifungal therapy (419 vs. 118 days; P < .001) and of systemic azole therapy (272 vs. 14 days; P < .001). When paired with a second set of controls matched by CD4 cell count as well as first diagnosis of candidiasis, cases continued to show greater median exposure to azoles (272 vs. 88 days; P = .005). These data indicate that advanced immunosuppression and exposure to oral azoles are risk factors for the development of fluconazole resistance.