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.

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.

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.

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.

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.

Diagnosis of Pneumocystis carinii pneumonia: specificity and sensitivity of polymerase chain reaction in comparison with immunofluorescence in bronchoalveolar lavage specimens.

DNA amplification by the polymerase chain reaction (PCR) is a promising method for the detection of Pneumocystis carinii in immunosuppressed patients. The sensitivity and specificity of the PCR technique has been assessed in comparison with the immunofluorescence method (IF) on bronchoalveolar lavage fluid (BALF). Results correlated in 43 (78.8%) of 52 cases studied. P. carinii PCR gave positive results with BALF from all 32 patients found to have P. carinii pneumonia (PCP); IF gave positive results with 26 of them. PCR was more sensitive and as specific as IF. However, at the present time, we do not believe that it is clinically useful for detection of P. carinii in BALF samples. P. carinii DNA amplification by PCR should be reserved for testing IF-negative BALF samples from patients judged clinically to have PCP.

Imbalance between Pneumocystis carinii cysts and trophozoites in bronchoalveolar lavage fluid from patients with pneumocystosis receiving prophylaxis.

Detection and quantification of different Pneumocystis carinii (PC) life cycle forms were performed by polymerase chain reaction (PCR) and by morphological stains on bronchoalveolar lavage fluids (BALF) from HIV-infected patients with P. carinii pneumonia (PCP). The number of PC trophozoites was higher in patients with PCP who were receiving prophylaxis than in those not receiving prophylaxis. Also the cyst: trophozoite ratio was lower in the first group. No difference was observed between patients receiving different prophylactic medications. The imbalance between PC forms in BALF from patients with PCP receiving anti-PC prophylaxis may hamper the sensitivity of cyst stains. Multiple stains or PCR examination should be performed on BALF from patients with clinically suspected PCP who are receiving prophylaxis.

Prosthesis for aortic arch substitution.

BACKGROUND: The risk of neurologic complications in aortic arch prosthetic substitution is directly related to the duration of the circulatory arrest. The purpose of this article is to report the experiments on animals of a device for simplifying and quickening the vascular anastomosis in aortic arch substitution. METHODS: The device consists of expandable loops of stainless steel wire, sewn to the proximal end of a Dacron prosthesis. An actuating removable guide allows the stainless steel wire loops to be expanded and tightened, in such a way that the prosthesis diameter is varied, while maintaining a regular cylindric shape. The prosthesis end is then transformed into a rigid cylindrical ring, approximately half the maximal diameter in length, with a variable and controllable diameter. A composite graft was prepared, fitted with the expandable device at the distal end of the main prosthesis as well as at each end of the branches for the supraaortic trunks. Cardiopulmonary bypass was established by cannulation of the right atrium and left iliac artery. The prosthesis was positioned very easily and quickly during a brief hypothermic circulatory arrest; ascending aorta anastomosis was carried out by the standard technique after central nervous system reperfusion was resumed. Acute experiments were carried out in 5 swine. RESULTS: Four of 5 animals survived the procedure without detectable neurologic sequelae. At sacrifice the prosthesis was found to be properly sited without lumen distortion or thrombosis. CONCLUSIONS: The main advantages of this device and modality of arch substitution in a clinical setting would include drastic reduction of the circulatory arrest time, easy and reliable hemostasis of the anastomosis line, and accurate and firm approximation of the dissection layers in case of dissecting aneurysms.

Potential impact of Pneumocystis genetic diversity on the molecular detection of the parasite in human host.

Our aim was to evaluate if genetic diversity of Pneumocystis carinii could influence the detection by molecular techniques in bronchoalveolar lavage (BAL) fluids and in non-invasive specimens (induced sputum, oropharyngeal washing and serum/blood). P. carinii is morphologically similar in different hosts although several strains have been identified by biomolecular techniques. Variations of mt-LSU and ITSs sequences could determine a lack of hybridization of some clinical samples and could have diagnostic consequences with loss in sensitivity and specificity of available molecular tests, but at the moment no data support a significant impact of genetic diversity in these sequences on molecular detection of P. carinii for clinical purposes.

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.

Vancomycin treatment of cerebrospinal fluid shunt infections. Report of two cases.

The successful use of vancomycin is reported in two children with shunt infections due to Staphylococcus epidermidis which failed to respond to shunt removal. The previously reported experience with this drug is reviewed. The use of vancomycin should be considered in cases of shunt infections due to susceptible microorganisms and refractory to other therapeutic measures.

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.

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.

Genetic variability in different Pneumocystis isolates from man and rats.

To gain further insight into the genetic variability between different isolates of Pneumocystis carinii of rat and human origin, we sequenced three DNA regions from the mitochondrial rRNA gene, the 5S rRNA gene and the dihydrofolate reductase gene (DHFR) of microorganisms isolated from three different immunosuppressed rat sources and from one HIV + patient with P. carinii pneumonia. Some point mutations and deletions were found among rat isolates in two regions (mitochondrial rRNA gene and 5S rRNA gene). Nucleotide sequence variations in these conserved regions support the hypothesis of the existence of several Pneumocystis strains infecting the same host species.

[A device for synthesis of the costal plane after posterolateral thoracotomy using transosseous incisions to prevent compression of intercostal nerves]. / Uno strumento per la sintesi del piano costale dopo toracotomia postero-laterale con punti trans-ossei per prevenire la compressione dei nervi intercostali.

The purpose of this paper is to illustrate the use of a device to quickly perform little holes in the costal lateral arch for synthesis of the standard posterolateral thoracotomy. The working principle of the instrument is similar to that of a hollow punch device. Preliminary laboratory experience allowed to identify the best diameter of the costal holes (2 mm), without fracture. Absorbable suture were passed through the holes and tied to approximate the facing ribs. The modality of costal plane synthesis, very easy and quick with this device, makes possible to prevent intercostal nerve compression and accidental intercostal vessel lacerations. The so frequent, severe and often long lasting painful sequelae of thoracotomy, on the other hand so rare in other surgical wound (i.e. laparotomy, sternotomy, etc.) justify in our opinion the routine use of this costal plane synthesis technique.

[The clinical and immunological efficacy of a combination of immunoglobulins and an oral polyvalent antibacterial vaccine in recurrent respiratory infections]. / Efficacia clinica ed immunologica dell'associazione di immunoglobuline e vaccino antibatterico polivalente orale nelle infezioni ricorrenti respiratorie.

Ninety patients with a history of recurrent upper and lower respiratory infections were randomized into three groups of 30 patients each. Group 1 was treated with i.m. immunoglobulins and oral polyvalent bacterial vaccine, group 2 with vaccine only, while group 3 was not submitted to prophylactic treatment. During and after prophylaxis, all three groups were evaluated for frequency of recurrent respiratory infections and the most relevant immunological parameters. In groups 1 and 2, a significant reduction of minor and major upper and lower respiratory infections was observed compared to the control group. Patients treated with Ig+vaccine or vaccine alone showed an increase of IgG2 subclasses and CD4 lymphocytes and positive changes of delayed skin tests. These findings confirm the results of previous preliminary studies which had shown the polyvalent bacterial vaccine to be useful for the reduction of recurrent infections of the respiratory tract, especially during the winter. Further studies will have to be carried out in order to identify the precise mechanism by which antigen stimulation with the oral vaccine improves the immunological response of the respiratory tract.