Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program

Background. The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. Methods. Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. Results. Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. Conclusion. Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases (AU)

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Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program.

BACKGROUND: The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. METHODS: Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. RESULTS: Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. CONCLUSION: Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.

Clinical effectiveness of transversus abdominis plane (TAP) block in abdominal surgery: a systematic review and meta-analysis.

AIM: Reduced opioid use in the immediate postoperative period is associated with decreased complications. This study aimed to determine the effect of transversus abdominis plane (TAP) block on morphine requirements 24 h after abdominal surgery. Secondary outcomes included the effect of TAP block on morphine use 48 h after surgery, incidence of postoperative nausea and vomiting (PONV) and impact on reported pain scores (visual analogue scale). METHOD: A systematic review of the literature was conducted for randomised controlled trials (RCTs) evaluating the effects of TAP block in adults undergoing abdominal surgery. For continuous data, weighted mean differences (WMD) were formulated; for dichotomous data, odds ratios (OR) were calculated. Results were produced with a random effects model with 95% confidence intervals (CI). RESULTS: Nine studies, including published and unpublished data, containing a total of 413 patients were included. Of these 205 received a TAP block and 208 a placebo. Cumulative morphine utilization was statistically significantly reduced at 24 h. [WMD=23.71mg (38.66-8.76); P=0.002] and 48h [WMD=38.08mg (18.97-57.19); P<0.0001] in patients who received a TAP block and the incidence of PONV was significantly reduced [OR=0.41(0.22-0.74); P=0.003]. There was a nonsignificant reduction in the visual analogue scales of postoperative pain [WMD=0.73cm (1.84-0.38), P=0.2]. There were no reported adverse events following TAP block. CONCLUSION: Transversus abdominis plane block is safe, reduces postoperative morphine requirements, nausea and vomiting and possibly the severity of pain after abdominal surgery. It should be considered as part of a multimodal approach to anaesthesia and enhanced recovery in patients undergoing abdominal surgery.

Plasma ropivacaine concentrations after ultrasound-guided transversus abdominis plane block.

BACKGROUND: The transversus abdominis plane block is a novel technique involving injection of local anaesthetic between the internal oblique and the transversus abdominis muscles of the abdominal wall. It is possible that injection of a large dose of local anaesthetic into a relatively vascular plane may result in toxic concentrations. One previously published study examined plasma lidocaine concentrations after transversus abdominus plane block and showed potentially toxic plasma concentrations. Although ropivacaine is most commonly used for this technique, plasma concentrations of ropivacaine after this block have not been reported previously. METHODS: Adult female patients undergoing elective open gynaecological surgery received bilateral ultrasound-guided transverse abdominal plane blocks before surgical incision (3 mg kg(-1) of ropivacaine diluted to 40 ml). Venous blood was collected each 15 min for the first hour, each 30 min for the second hour, and then at 3, 4, 12, and 24 h post-block. RESULTS: Twenty-eight patients were recruited. The mean (sd) peak total ropivacaine concentration occurred 30 min post-injection and was 2.54 (sd 0.75) µg ml(-1). The highest measured concentration was 4.00 µg ml(-1), also 30 min post-injection. Mean total concentrations remained above 2.20 µg ml(-1) for up to 90 min post-injection. The mean unbound peak venous concentration was 0.14 (0.05) µg ml(-1), and the peak was 0.25 µg ml(-1). CONCLUSIONS: Transversus abdominus plane block using 3 mg kg(-1) of ropivacaine produces venous plasma concentrations that are potentially neurotoxic, although broadly consistent with plasma levels found after injection at other comparable sites.

[Patient with rhinorrea, destruction of nasal cartilage and hypochronic lesions of the skin]. / Paciente con rinorrea, destrucción del cartílago nasal y lesiones hipocrómicas en la piel.

The leprosy is a chronic illness caused by M. leprae, which affects mucosa mainly at the level of the nasal region. The important destruction of the bone produces the facies leonina. We present the case of a patient with nasal leprosy, describing the clinical characteristics and the diagnostic and therapeutic methods that were carried out on her.

'Airway Alerts'. How UK anaesthetists organise, document and communicate difficult airway management.

A questionnaire on organisation, documentation and communication of airway problems during anaesthesia was sent to 271 anaesthetic college tutors in the UK. Their responses were compared with three published recommendations. There was a 72% response rate (195/271). The recommendations of the American Society of Anaesthesiologists Task Force on the Management of the Difficult Airway were met by 71% of respondents; 2% met those suggested by the Canadian Airway Focus Group and 2% met those suggested in a standard UK textbook on difficulties in tracheal intubation. Guidelines for management of the difficult airway were available in 142 departments (73%), but only 41 (21%) had guidelines for communication and dissemination of information. We present an 'Airway Alert' scheme which has since been adopted by the Difficult Airway Society.

Twin resemblances in creativity and in esthetic and emotional expression.

Three sources of observation relevant to the measurement of individual differences in emotional and esthetic expressiveness were employed to study their heritability by application to a sample of some 60 pairs of young adult like-sexed twins, approximately evenly divided between male and female and MZ and DZ pairs. The sources of observation were objective test performances, trait ascription using a standard list of adjectives, and videotaped enactments of mood and esthetic performances. Perceptual and esthetic abilities do appear to have substantial heritability, although esthetic preferences do not. Heritability is also indicated for such adjectives as artistic, inventive, original, and independent. Ratings of the videotape performances yielded somewhat ambiguous results, due to the presence of a marked halo effect; the most likely interpretation congruent with earlier results is that greater MZ twin resemblances in social extroversion generated greater resemblances in the videotape situation on such other trait-rating variables as creativity, naturalness, and dominance.