The impact of bowel dysfunction on health-related quality of life after rectal cancer surgery: a systematic review.

BACKGROUND: Symptoms of bowel dysfunction after sphincter-preserving rectal cancer surgery have an important impact on health-related quality of life (HRQOL), but that relationship is complex. A better understanding of this relationship allows for better informed shared decision-making about surgery. Our objective was to perform a systematic review to determine which HRQOL domains are most affected by postoperative bowel dysfunction. METHODS: A systematic review of the CINAHL, Cochrane Library, Embase, Medline, PsycInfo, PubMed, Web of Science, and Scopus databases was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included studies that evaluated bowel function after sphincter-preserving rectal cancer surgery and assessed HRQOL using a validated instrument. The quality of HRQOL analysis was assessed using an 11-item checklist. The main outcome was the impact bowel dysfunction had on global and domain specific quality-of-life indices. The impact was evaluated for clinical relevance using the Minimum Clinical Important Difference (MCID) for each specific HRQOL instrument. RESULTS: Out of 952 unique citations, 103 studies were full-text reviews. Eighteen studies met the inclusion criteria (4 prospective cohorts and 9 cross-sectional studies). Of the 15 studies with long-term follow-up, the time to assessment after surgery ranged from 1.2 to 14.6 years. The low anterior resection syndrome score and European Organization for Research and Treatment core quality-of-life questionnaire (EORTC QLQ-C30) were the most commonly used instruments. Medium and large magnitudes in MCID were seen for global health, social functioning, emotional functioning, fatigue, diarrhea, and financial difficulties. Among included studies, the most consistently reported functional domains affected by bowel function were social functioning and emotional functioning. CONCLUSIONS: Following sphincter-preserving rectal cancer surgery, poor bowel function mainly affects the social and emotional functional domains of HRQOL, which in turn impact global scores. This finding can help inform patients about expected changes in HRQOL after rectal cancer surgery and facilitate individualized treatment decisions.

Trajectory of change of low anterior resection syndrome over time after restorative proctectomy for rectal adenocarcinoma.

BACKGROUND: Restorative proctectomy for rectal cancer is associated with a high incidence of low anterior resection syndrome (LARS), but few studies report longitudinal results for bowel function. The aim of our study was to examine the trajectory of change of LARS over the first 18 months after restorative proctectomy for rectal cancer. METHODS: A prospective database measuring functional outcomes in rectal cancer patients from a single university-affiliated specialist colorectal referral center from 10/2018 to 03/2020 was queried. Patients were included in this study if they underwent restorative proctectomy for rectal cancer and had at least three assessments in the first 18 months after primary surgery or after closure of proximal diversion. Bowel function was assessed using the LARS score, administered at every surveillance follow-up after restoration of bowel continuity. Latent-class growth curve (trajectory) analysis was used to identify different trajectories of LARS changes over the first 18 months and group patients into these trajectory groups. These groups were then compared to identify predictors for each trajectory. RESULTS: A total of 95 patients were included (63 males, mean age. 61.3 ± 12.5 years). Trajectory analysis identified three distinct trajectory groups. Group 1 had stable minimal LARS over time (26%). Group 2 had early LARS scores consistent with the minor LARS category and improved with time (28%). Group 3 had persistently high LARS scores (45%). Neoadjuvant therapy, intersphincteric resection, and proximal diversion were more common in group 3. CONCLUSIONS: We identified three main trajectories of change of LARS in the 18 months after restorative proctectomy. These data may be used to better inform patients of their expected postoperative bowel function.

Two nasal swabs may not be enough to exclude SARS-CoV-2 infection in symptomatic patients.

Abstracts: The spread of COVID-19 (COronaVIrus Disease 2019), due to SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) has taken on dramatic pandemic proportions, affecting over 100 countries in a matter of weeks. Italy has had 237,828 confirmed cases according to the Istituto Superiore di Sanità as of May 13, and 34,448 deaths (1).

Caffeine prevents prostaglandin E1-induced disturbances in respiratory control in neonatal rats: implications for infants with critical congenital heart disease.

Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-ß (PDGF-ß) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.

Hospital discharge criteria following colorectal surgery: a systematic review.

AIM: The aim of this study was to identify and synthesize the hospital discharge criteria that have been used in the colorectal surgery literature. METHODS: A systematic literature search was conducted using eight bibliographic databases. Searches were limited to English language journal articles published between January 1996 and October 2009. Primary research applying hospital discharge criteria following colorectal surgery was included. Study selection was made independently by two reviewers. Discharge criteria were extracted from each included study. RESULTS: The 156 studies identified by the search strategy described 70 different sets of criteria to indicate readiness for discharge. The majority of studies applied a combination of three or four criteria; those most frequently cited were tolerance of oral intake (80%), return of bowel function (70%), adequate pain control (44%) and adequate mobility (35%). End-points employed to determine the achievement of criteria were generally poorly defined. CONCLUSION: A variety of hospital discharge criteria were applied in the colorectal surgery literature. Development of standardized criteria will allow more accurate comparison of results between studies assessing hospital length of stay or other discharge-related outcome measures.

Physiologic basis for intermittent hypoxic episodes in preterm infants.

Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are commonly underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia [IH] progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks six to eight. Over this period of unstable respiratory control, increased oxygen-sensitive peripheral chemoreceptor activity has been associated with a higher incidence of apnea of prematurity. In contrast, infants with bronchopulmonary dysplasia [chronic neonatal lung disease] exhibit decreased peripheral chemosensitivity, although the effect on respiratory stability in this population is unclear. Such episodic hypoxia/reoxygenation in early life has the potential to sustain a proinflammatory cascade with resultant multisystem, including respiratory, morbidity. Therapeutic approaches for intermittent hypoxic episodes comprise careful titration of baseline or supplemental inspired oxygen as well as xanthine therapy to prevent apnea of prematurity. Characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management.

Locoregionally advanced nasopharyngeal carcinoma: induction chemotherapy with cisplatin and 5-fluorouracil followed by radiotherapy and concurrent cisplatin: a phase II study.

BACKGROUND: Chemoradiotherapy is the current standard of care for locoregionally advanced nasopharyngeal carcinoma. The purpose of this study was to assess the feasibility and efficacy of induction chemotherapy (CHT) followed by concomitant chemoradiotherapy in this patient population. PATIENTS AND METHODS: In this single-arm, phase II study, patients with locoregionally advanced nasopharyngeal carcinoma were treated with 3 cycles of induction CHT with cisplatin (100 mg/m(2) on day 1) and 5-fluorouracil (1,000 mg/m(2) continuous infusion on days 1-4) followed by 3 cycles of cisplatin (100 mg/m(2) on days 1, 22 and 43) and concurrent radiotherapy up to 70 Gy. The primary endpoint was objective response. RESULTS: Thirty-four patients were enrolled, and all completed both induction treatment and subsequent chemoradiotherapy. Objective response rates were 79.4% (95% CI 62.1-91.3) and 85.3% (95% CI 68.9-95.0) after induction CHT and chemoradiation, respectively. Treatment was well tolerated and toxicity was manageable. At a median follow-up of 29 months, 3-year overall survival and progression-free survival rates are 80.0% (95% CI 0.64-0.95) and 54.0% (95% CI 0.36-0.73), respectively. CONCLUSIONS: Induction CHT with cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy is a feasible and active regimen for patients with stage IIB-IVB nasopharyngeal carcinoma. This regimen resulted in excellent locoregional disease control and overall survival.

The effect of inhaled nitric oxide on pulmonary function in preterm infants.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) in preterm infants is associated with impaired alveolar growth, inflammation and airway hyperreactivity. In animal models of BPD, inhaled nitric oxide (NO) improves alveolar growth and inhibits airway smooth muscle proliferation. This study was designed to assess the effect of inhaled NO on resistance and compliance in ventilated preterm infants with evolving BPD. STUDY DESIGN: Expiratory resistance and compliance of the respiratory system were measured in 71 ventilated preterm infants, < or = 32 weeks gestation, randomized to NO (n=34) versus placebo (n=37) for > or = 24 days at 7 to 21 days of life. RESULT: At baseline expiratory resistance (231+/-71 versus 215+/-76 cm H(2)O l(-1) s(-1)) and compliance (0.49+/-0.14 versus 0.53+/-0.13 ml cm H(2)O(-1) kg(-1)) were comparable between placebo and NO groups, respectively. There was no effect of NO on expiratory resistance or compliance at 1 h, 1 week or 2 weeks of study gas administration. CONCLUSION: NO had no short- or medium-term effect on expiratory resistance or compliance in ventilated preterm infants.

Detection of hepatitis C virus-RNA in saliva from chronically HCV-infected patients.

The possibility of the non-parenteral Hepatitis C Virus (HCV) transmission is supported by the demonstration that the actual virus is present in several body fluids, including saliva. From a review of the literature many investigators have found the presence of HCV-RNA in saliva, however, widely contrasting results emerge, with detection rates ranging from 0-100%. To further examine HCV salivary shedding, saliva samples were collected from 46 chronically HCV-infected patients and tested for HCV-RNA and occult blood. Quantification and genotyping of serum HCV-RNA were also carried out for each patient. HCV-RNA was detected in 39.13% of the saliva samples. The viral salivary shedding was significantly related to viraemia levels, serum viral genotype and the presence of salivary occult blood. Our findings indicate that the HCV salivary shedding occurs in about one third of HCV infected patients, but seem to suggest that it is unlikely when the serum viral genotype is 3a. Moreover, blood leakage into the oral cavity is possibly the main source of the salivary HCV-RNA. Although the occurrence of the viral salivary shedding does not necessarily mean that HCV transmission occurs by saliva, our results suggest the need for further investigations into the biological factors possibly involved in HCV mucosal transmission related to both the source and the exposed subjects.

Normal G2 chromosomal radiosensitivity and cell survival in the cancer family syndrome.

Recent reports have suggested that elevated chromosomal aberration yields following X-irradiation of skin fibroblasts in the G2 phase of the cell cycle are characteristic of affected members of cancer-prone families. These studies propose that this phenomenon is a consequence of impaired DNA repair and might be a useful predictor of genetic susceptibility to cancer. We have tested G2 chromosomal X-ray sensitivity in skin fibroblasts and peripheral blood lymphocytes from members of a kindred with the cancer family syndrome, a disorder in which susceptibility to colon cancer and other epithelial cancers is inherited in an autosomal dominant pattern. Further, using a cell survival assay, we tested cancer family syndrome skin fibroblasts for sensitivity to four classes of mutagens, including X-rays. In the assays used, skin fibroblasts and lymphocytes from both affected and unaffected family members exhibited responses indistinguishable from normal controls. Karyotypic analysis of lymphocytes and fibroblasts revealed no consistent constitutional cytogenetic abnormality. Thus, affected patients with the cancer family syndrome do not have increased sensitivity to irradiation and chemical mutagens and lack a germ-line chromosomal defect.

Cardiorespiratory events in preterm infants: etiology and monitoring technologies.

Every year, an estimated 15 million infants are born prematurely (<37 weeks gestation) with premature birth rates ranging from 5 to 18% across 184 countries. Although there are a multitude of reasons for this high rate of preterm birth, once birth occurs, a major challenge of infant care includes the stabilization of respiration and oxygenation. Clinical care of this vulnerable infant population continues to improve, yet there are major areas that have yet to be resolved including the identification of optimal respiratory support modalities and oxygen saturation targets, and reduction of associated short- and long-term morbidities. As intermittent hypoxemia is a consequence of immature respiratory control and resultant apnea superimposed upon an immature lung, improvements in clinical care must include a thorough knowledge of premature lung development and pathophysiology that is unique to premature birth. In Part 1 of a two-part review, we summarize early lung development and diagnostic methods for cardiorespiratory monitoring.

Cardiorespiratory events in preterm infants: interventions and consequences.

Stabilization of respiration and oxygenation continues to be one of the main challenges in clinical care of the neonate. Despite aggressive respiratory support including mechanical ventilation, continuous positive airway pressure, oxygen and caffeine therapy to reduce apnea and accompanying intermittent hypoxemia, the incidence of intermittent hypoxemia events continues to increase during the first few months of life. Even with improvements in clinical care, standards for oxygen saturation targeting and modes of respiratory support have yet to be identified in this vulnerable infant cohort. In addition, we are only beginning to explore the association between the incidence and pattern of cardiorespiratory events during early postnatal life and both short- and long-term morbidity including retinopathy of prematurity, growth, sleep-disordered breathing and neurodevelopmental impairment. Part 1 of this review included a summary of lung development and diagnostic methods of cardiorespiratory monitoring. In Part 2 we focus on clinical interventions and the short- and long-term consequences of cardiorespiratory events in preterm infants.

Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignancies.

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m(2) over 1 hour and a 5-FU 450 mg/m(2) IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m(2)/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest. RESULTS: The MTD of gemcitabine was established at 900 mg/m(2) given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m(2). One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months. CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.

Protein A immunoadsorption in the treatment of malignant disease.

Circulating immune complexes (CIC) are known to be present in cancer patients and are responsible for much of the cancer-associated immunosuppression. Removal or modulation of these "blocking factors" can reverse the immunosuppression. Protein A from Staphylococcus aureus has the unusual property of binding to CIC with high avidity. Use of protein A as an immunoadsorbent in extracorporeal immunotherapy affinity columns has resulted in antitumor and antiviral responses in animals. Our group developed a multicenter trial to assess toxicity and antitumor response with this biologic response modifier alone. Overall, 24% (21 of 87 patients) had objective tumor regressions including both partial responses (PR) and less than PR. No complete responses (CR) were observed. Responses were observed in acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (six of 17 PR; two of 17 less than PR; overall, 47%), breast adenocarcinoma (five of 22 PR; three of 22 less than PR; overall response, 36%), colon adenocarcinoma, (one PR, one less than PR; overall response, 11%), and non-oat cell lung carcinoma (two of seven less than PR). The procedure was well tolerated and could be performed on an outpatient basis. No adverse reaction was observed in 735 of 1,113 treatments (66%). The most common adverse effect was an "influenza-like" syndrome consisting of fever and chills. Pain was present in 12% of the patients. There were no study-related deaths. Serum IgG and CIC levels did not statistically change due to therapy in responding or nonresponding patients. Complement levels remained within the normal range. Liver and renal tests remained stable throughout the study. In summary, protein A immunoadsorption of plasma is well tolerated in the outpatient clinic, has demonstrated antitumor activity in resistant solid tumors, and functions as a biologic response modifier.

Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small-cell lung cancer treated with combination chemotherapy.

To determine the frequency and prognostic importance of pretreatment clinical characteristics in patients currently undergoing treatment for stage III non-small-cell lung cancer (NSCLC), data were collected on 378 patients receiving high-dose (120 mg/m2) cisplatin plus vinca alkaloid combination chemotherapy regimens since 1978. Variables analyzed included age, sex, weight loss, performance status, histologic subtype, presence of extrathoracic metastases, number of metastatic organ sites, presence of liver, bone, or brain involvement, prior radiation or surgery, and serum lactate dehydrogenase (LDH). The effect of a major response to chemotherapy on survival was also investigated. Using multivariable analyses, the following were found to be associated with outcome: initial performance status, with patients having a performance status of 80% to 100% having an increased major objective response rate and survival; bone metastases, which were adversely predictive of response rate and survival; elevated serum LDH and male sex, both of which were associated with shortened survival and remission duration; and the presence of two or more extrathoracic metastatic organ sites, which was associated with shorter survival. When major objective response with chemotherapy was included in a conditional multivariable analysis, it was strongly associated with longer median survival. Information from this analysis may be useful when comparing the response data of completed studies in similar patients, in designing future trials, and in the selection of cisplatin plus vinca alkaloid therapy for individual patients with advanced NSCLC.

Correlation between seroreactivity to HIV-1 V3 loop peptides and male-to-female heterosexual transmission.

OBJECTIVE: To evaluate the correlation between seroreactivity to peptides corresponding to the V3 loop of the major envelope glycoprotein from different HIV-1 strains and the risk of heterosexual HIV-1 transmission. METHODS: Sera from 39 infected individuals (16 transmitters and 23 non-transmitters) were tested for reactivity against synthetic peptides representing sequences of the V3 loop apex from HIV-1 strains MN, SC, WMJ2, RF and IIIB. RESULTS: A skewed distribution in seroreactivity to RF and IIIB peptides was observed between the two groups: reactivity was more prevalent in sera from non-transmitting than from transmitting individuals. Reactivity to the MN, SC and WMJ2 peptides was very frequent and there were no differences between the two groups. CONCLUSION: These data suggest that antibodies reactive with a larger set of V3 apex peptides (i.e., cross-reactive antibodies) could play a role in the prevention of heterosexual transmission.

Biological correlates of HIV-1 heterosexual transmission.

OBJECTIVES: To study the role of HIV-1 biological phenotype, viral load and neutralizing antibodies in male-to-female heterosexual transmission of HIV-1. METHODS: Seven transmitting and seven non-transmitting HIV-1-seropositive heterosexual male index cases were included in the present study. All couples had engaged in unprotected sex for a period of over 1 year. Transmission was defined by the seroconversion of the female sexual partner. Virus isolates were tested in MT-2 cells for replication and syncytia induction. HIV-1 RNA plasma load was measured by the branched DNA technique. Serum neutralizing activity to primary HIV-1 isolates was tested by using peripheral blood mononuclear cells (PBMC) as target cells. RESULTS: Non-transmitting index cases had a lower HIV-1 RNA concentration in plasma than transmitting index cases. Non-transmitting index cases also tended to have serum neutralizing activity with broad specificity and to have viruses with low replicative capacity, as characterized by 50% infectious dose titres in PBMC and by the lack of MT-2 tropism. CONCLUSIONS: The results indicate that plasma viral-RNA load is a marker for transmission. Moreover, an interplay between the host immune response and viral replication may modulate the level of viral load and thereby influence HIV-1 transmission.

Measurement of viral sequences in cerebrospinal fluid of AIDS patients with cerebral white-matter lesions using polymerase chain reaction.

OBJECTIVES: To optimize the use of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for the evaluation of central nervous system (CNS) white-matter lesions that along with clinical findings and magnetic resonance imaging (MRI) can allow a definite diagnosis to be made; also to evaluate treatment with zidovudine plus foscarnet. DESIGN AND METHODS: Fifteen AIDS patients with uncertain CNS white-matter lesions were identified. HIV-1 RNA, cytomegalovirus (CMV) and JC virus (JCV) DNA were measured in a total of 29 CSF samples. The results were correlated with clinical and MRI findings and treatment with zidovudine plus foscarnet was evaluated. RESULTS: Four and five out of 15 patients with CMV DNA > or = 1 : 625 and JCV DNA > or = 10(3) copies/microl detected in the CSF were diagnosed with CMV and progressive multifocal leukoencephalopathy (PML), respectively. Six patients who were CMV/JCV-negative with the highest levels of HIV RNA (median, 6.87 log10 copies/ml) in CSF were considered as having HIV-1 encephalitis. Neurological symptoms were non-supportive for diagnosis as was MRI in 11 out of 15 patients. Nine patients completed a 21-day course of zidovudine plus foscarnet. HIV RNA decreased irrespective of neurological diagnosis. All three HIV-1 encephalitis patients and two out of three patients with CMV leukoencephalopathy improved. In these two latter patients, relief of clinical symptoms coincided with decreased CMV DNA. JCV DNA remained unchanged and all three PML patients deteriorated. CONCLUSIONS: Measurement of CSF viral sequences supports the diagnosis of CNS white-matter lesions in AIDS patients. While effective therapy for PML remains elusive, treatment including zidovudine plus foscarnet may be a promising option for HIV-1 and CMV-related manifestations.

Neurological disorders during HIV-1 infection correlate with viral load in cerebrospinal fluid but not with virus phenotype.

OBJECTIVES: To verify the compartmentalization of HIV-1 within the central nervous system (CNS) and to define whether viral phenotype of HIV-1 isolates from cerebrospinal fluid (CSF) samples and CSF viral load correlate with the presence and type of neurological disorders. METHODS: A total of 33 HIV-1-infected patients with and without neurological disorders were included in the study. HIV-1 isolation from paired CSF and peripheral blood mononuclear cell (PBMC) samples was attempted by a standard cocultivation technique; the biological phenotype of HIV-1 isolates was assessed by the MT-2 cell assay. CSF and plasma HIV-RNA levels were measured by a quantitative reverse transcripase-polymerase chain reaction. RESULTS: The rate of HIV-1 isolation from CSF and PBMC was 66% (22 isolates) and 85% (28 isolates), respectively. Seventeen out of 22 (77%) CSF HIV-1 isolates were characterized as non-syncytium-inducing, and 15 out of 28 (68%) isolates from PBMC were typed as syncytium-inducing (SI). The presence of SI isolates in CSF was limited to patients with HIV-1-, cytomegalovirus- or JC virus-related disorders and was often associated with high levels of HIV-1 RNA in the CSF. DISCUSSION: Our results demonstrate a correlation between high levels of HIV RNA in CSF and the presence of neurological disorders thus indicating a possible role for HIV-1 RNA in the CSF as a biological marker of neurological disease. The finding of viruses with a different phenotype in paired CSF and PBMC indicates that HIV-1 may evolve differently in the brain and in the blood. This suggests compartmentalization of HIV-1 within the CNS.