Gastrointestinal symptoms and digestive comorbidities in an Italian cohort of patients with COVID-19.

OBJECTIVE: The Coronavirus Disease 2019 (COVID-19) pandemic mainly involves respiratory symptoms, though gastrointestinal (GI) symptoms are increasingly being recognized. In this context, the presence of comorbidities appears to be associated with adverse outcomes. However, the role of digestive manifestations is not yet well defined. The primary aim of this study was to assess the prevalence of GI symptoms and digestive comorbidities in a cohort of patients with COVID-19 compared to controls. The secondary aim was to determine the association of GI-symptoms and digestive comorbidities with clinical outcomes. PATIENTS AND METHODS: Inpatients with COVID-19 and controls with similar symptoms and/or radiological findings were enrolled. Symptoms at admission and throughout hospitalization were collected as they were comorbidities. The measured clinical outcomes were mortality, intensive care unit admission and cumulative endpoint. RESULTS: A total of 105 patients were included: 34 with COVID-19 and 71 controls. At admission, the prevalence of GI symptoms among COVID-19 patients was 8.8%. During hospitalization, the frequency of GI symptoms was higher in patients with COVID-19 than in controls (p=0.004). Among patients with COVID-19, the mortality and a cumulative endpoint rates of those with GI symptoms were both lower than for those without GI symptoms (p=0.016 and p=0.000, respectively). Finally, we found digestive comorbidities to be associated with a milder course of COVID-19 (p=0.039 for cumulative endpoint). CONCLUSIONS: Our results highlighted the non-negligible frequency of GI symptoms in patients with COVID-19, partly attributable to the therapies implemented. In addition, the presence of GI symptoms and digestive comorbidities is associated with better outcomes. Most likely, digestive comorbidities do not hinder the host's immune response against SARS-COV-2, and the occurrence of GI symptoms might be linked to a faster reduction of the viral load via the faecal route.

SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV.

BACKGROUND: Neuropsychiatric symptoms (NPs) have been reported with dolutegravir use. We hypothesized that increasing dolutegravir trough concentrations (Ctrough) and/or polymorphism in the SLC22A2 gene, encoding the organic cation transporter-2 (OCT2), which is involved in monoamine clearance in the CNS and is inhibited by dolutegravir, might be associated with NPs. METHODS: A cross-sectional cohort of HIV-positive patients treated with a dolutegravir-containing regimen underwent determination of allelic discrimination for SLC22A2 808 C → A polymorphism and dolutegravir Ctrough. The Symptom Checklist-90-R [investigating 10 psychiatric dimensions and reporting a general severity index (GSI)], a self-reported questionnaire and the Mini-International Neuropsychiatric Interview were offered to investigate current NPs. The effects of dolutegravir Ctrough and the SLC22A2 gene variant on NPs were explored by multivariable logistic regression. RESULTS: A cohort of 203 patients was analysed: 71.4% were male, with median age 51 years and 11 years of ART exposure. Median time on dolutegravir was 18 months. Dolutegravir was associated with different antiretroviral combinations (mainly lamivudine, 38.9%, and abacavir/lamivudine, 35.5%). SLC22A2 CA genotype was independently associated with an abnormal GSI [adjusted OR (aOR) 2.43; P = 0.072], anxiety (aOR 2.61; P = 0.044), hostility (aOR 3.76; P = 0.012) and with moderate to severe headache (aOR 5.55; P = 0.037), and dolutegravir Ctrough was associated with hostility (fourth versus first quartile aOR 6.70; P = 0.007) and psychoticism (fourth versus first quartile aOR 19.01; P = 0.008). Other NPs were not associated with SLC22A2 polymorphism or dolutegravir Ctrough. CONCLUSIONS: A variant of the OCT2-encoding gene, in addition to or in synergy with higher dolutegravir Ctrough, is associated with a set of NPs observed during dolutegravir therapy.

Modelling tumour volume variations in head and neck cancer: contribution of magnetic resonance imaging for patients undergoing induction chemotherapy.

Primary tumour volume evaluation has predictive value for estimating survival outcomes. Using volumetric data acquired by MRI in patients undergoing induction chemotherapy (IC) these outcomes were estimated before the radiotherapy course in head and neck cancer (HNC) patients. MRI performed before and after IC in 36 locally advanced HNC patients were analysed to measure primary tumour volume. The two volumes were correlated using the linear-log ratio (LLR) between the volume in the first MRI and the volume in the second. Cox's proportional hazards models (CPHM) were defined for loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS). Strict evaluation of the influence of volume delineation uncertainties on prediction of final outcomes has been defined. LLR showed good predictive value for all survival outcomes in CPHM. Predictive models for LRC and DFS at 24 months showed optimal discrimination and prediction capability. Evaluation of primary tumour volume variations in HNC after IC provides an example of modelling that can be easily used even for other adaptive treatment approaches. A complete assessment of uncertainties in covariates required for running models is a prerequisite to create reliable clinically models.

Preoperative embolization of meningiomas with polyvinyl alcohol particles: The benefits are not outweighed by risks.

PURPOSE: The purpose of this study was to define the feasibility, the efficacy and the safety of preoperative embolization (POE) of meningiomas using polyvinyl alcohol (PVA) particles. MATERIALS AND METHODS: Between January 2006 and June 2014, 191 consecutive patients were referred to our institution for the treatment of meningiomas; of these 57 patients were excluded from the study. A total of 64 patients (22 men and 42 women) with a mean age of 58.4±10.8 [SD] years (range: 14-82years) who underwent POE with PVA particles, achieving extensive (>90%) devascularization were ultimately included and compared to 70 patients who had surgery without POE. Surgical time and intraoperative blood loss were compared between the two groups. The duration of procedures and complications related to POE were analyzed. RESULTS: No differences were found between the two groups with respect to intraoperative blood loss. A significant reduction in surgical time was observed for the group who had POE (207.4±79.5 [SD] min vs. 226.9±117.6 [SD] min; P=0.028). In a subgroup analysis, the size and location of meningiomas did not influence these results. The duration of procedures was 41.4±10.5 [SD] min. Minor complications related to POE occurred in 3 out of 64 patients (4.7%). CONCLUSION: POE of meningiomas using PVA particles is effective in reducing surgical time, when extensive tumor devascularization is achieved. However, radiation exposure, the duration of procedures and complications related to POE with PVA particles do not justify this technique in most patients.

Pharmacokinetics of etravirine in HIV-infected patients concomitantly treated with rifampin for tuberculosis.

Etravirine is metabolized by three cytochrome P450 enzymes that are in turn induced by rifampin. Consequently, co-administration of etravirine and rifampin is not recommended. To date, however, no clinical studies exploring the drug-drug interaction of this combination have been conducted. Here we report two cases of off-label etravirine use concurrently with antitubercular treatment, dictated by the unavailability of other treatments. Plasma drug concentrations were monitored by regular measurements. Our results appear to confirm the increased metabolism of etravirine through the induction of cytochrome P450 enzymes, but the adequacy of drug levels in all of the measurements and subsequent virological suppression suggest that this drug interaction may not be clinically relevant.

Aetiological factors related to a positive direct antiglobulin test result in human immunodeficiency virus-infected patients.

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the clinical importance and causes of a positive result in the direct antiglobulin test (DAT) in human immunodeficiency virus-infected (HIV(+)) patients. We therefore studied haematological parameters in outpatient samples, and also analysed the impact of highly active anti-retroviral therapy (HAART) on the DAT results. STUDY DESIGN AND METHODS: Haematological parameters, clinical stages, chemo-antibiotic treatments and HAART treatment were studied to determine any relationships with DAT results in 115 consecutive HIV(+) patients. RESULTS: Significantly lower haemoglobin (Hb) levels were detected in patients with HIV who had a positive DAT result. Hepatitis C virus (HCV) co-infection (odds ratio 2.529) and trimethoprim-suphamethoxazfole (TMP-SMX) prophylaxis (odds ratio 3.751) had a significant association with DAT positivity. Patients receiving HAART were less likely to have a positive DAT [odds ratio (OR) 0.383; P = 0.035]. Among the patients treated with TMP-SMX, those with a positive DAT had lower Hb levels (11.9 g/dl) than those with a negative DAT (14.2 g/dl; P = 0.04). HCV antibody positivity and TMP-SMX prophylaxis showed a cumulative effect on positive DATs (OR 4.533). The surface exploratory analysis indicated the distribution of the positive DATs in relationship with the CD4(+) count and Hb levels. CONCLUSIONS: Significantly lower Hb levels were detected in DAT-positive HIV(+) patients. HCV co-infection and TMP-SMX prophylaxis appear to confer an increased risk of DAT positivity. The presence of red blood cell autoantibodies may be associated with anaemia in HIV disease in the absence of overt haemolysis.

Mother to child human immunodeficiency virus (HIV) transmission: what HIV-infected women think. Our experience in Rome, Italy.

OBJECTIVES: To investigate the knowledge of the risk of HIV vertical transmission as well as the feeling about the new therapy in reducing that rate. METHODS: We included 152 HIV-infected women. A self reported questionnaire was administered from September to December 2000. RESULTS: About the risk rate of transmitting HIV to their baby, 21 (13.8%) women indicated 100%; 67 (44.1%) 50-80%; 35 (23%) 10-50% and only 22 women (14.5%) answered the correct value of less than 5%. Regarding the effect of highly active antiretroviral therapy, 82 women (53.9%) considered therapy effective in reducing vertical HIV transmission, while 63 women (41.4%) considered therapy powerless in preventing mother to child HIV transmission. Any statistically significant difference in sociodemographic, clinical, viroimmunological characteristics and antiretroviral therapy emerged between the groups. CONCLUSIONS: Our data highlight the importance of providing appropriate counselling about perinatal HIV transmission to all childbearing age HIV infected women.

Mutations in dihydropteroate synthase gene of Pneumocystis carinii in HIV patients with Pneumocystis carinii pneumonia.

The purpose of this study was to determine whether dihydropteroate synthase gene (DHPS) mutations were associated with the failure of sulpha/sulphone drugs used as prophylaxis agents in HIV infected patients. Results suggested that DHPS mutations were significantly associated with failure of anti-Pneumocystis carinii sulphone prophylaxis (P=0.031). An increasing number of mutant P. carinii strains have been isolated from patients no longer having prophylaxis. There was no statistically significant difference in severity or outcome of the pneumonia caused by wild-type or mutant DHPS. Moreover, two of the three patients with mutant P. carinii pneumonia (PCP) were successfully treated with sulpha drugs. We think that P. carinii drug-resistance could be an emerging problem for immunocompromised patients including those with HIV infection.

Bacteroides peritonitis associated with colon cancer in a continuous ambulatory peritoneal dialysis patient.

Peritonitis is not an uncommon complication of continuous ambulatory peritoneal dialysis (CAPD). We report a case of Bacteroides fragilis-induced bacterial peritonitis, probably due to clinically occult malignancy, in a 76-year-old woman on CAPD.

Descending aorta substitution with expandable ends prosthesis. Case report.

A case of esophageal cancer infiltrating the left bronchus pars membranacea and the aneurysmal aortic wall was resected en bloc with the bronchial and aortic wall. Descending aorta was substituted by means of a Dacron prosthesis fitted with expandable devices at both ends, allowing a very significant reduction of the clamping time and simplification of this part of the procedure.

Pneumocystis carinii infection in young non-immunosuppressed rabbits. Kinetics of infection and of the primary specific immune response.

The aim of this study was to determine the kinetics, the dissemination of the infection and the immunological response to Pneumocystis carinii primary infection in a non-immunosuppressed rabbit model. For this purpose, we developed a nested PCR that amplified a portion of the mitochondrial large-subunit rRNA gene of rabbit-derived P. carinii. The PCR detected P. carinii DNA in lung and bronchoalveolar lavage fluids from 14- to 45-day-old rabbits but not in their serum. No P. carinii DNA was detected in extrapulmonary organs from 28-day-old rabbits with P. carinii pneumonia. ELISA and immunoblotting analysis showed that 5-day-old pups had elevated specific IgG. The IgG concentration sharply decreased, reaching a trough on day 21, and from then onwards progressively increased as the infection cleared. Conversely, the specific IgM concentration increased during the infection and peaked on day 28. IgG mainly recognized a 50-kDa subunit of P. carinii organisms; IgM recognized first a 45-kDa subunit on day 21, whereas from day 28 onwards it also recognized the 50-kDa subunit. A P. carinii-specific splenocyte proliferative response was observed on day 45. These findings suggest that P. carinii primary infection is a time-limited and a lung-limited event and contribute new information on the relationship between the kinetics of primary P. carinii infection and the immunological response in a model that mimics the primary infections in humans.