Influence of intercostal muscles contraction on sonographic evaluation of lung sliding: a physiological study on healthy subjects.

OBJECTIVES: To investigate the following: (a) effects of intercostal muscle contraction on sonographic assessment of lung sliding and (b) inter-rater and intra-observer agreement on sonographic detection of lung sliding and lung pulse. METHODS: We used Valsalva and Muller maneuvers as experimental models in which closed glottis and clipped nose prevent air from entering the lungs, despite sustained intercostal muscles contraction. Twenty-one healthy volunteers underwent bilateral lung ultrasound during tidal breathing, apnea, hyperventilation, and Muller and Valsalva maneuvers. The same expert recorded 420 B-mode clips and 420 M-mode images, independently evaluated for the presence or absence of lung sliding and lung pulse by three raters unaware of the respiratory activity corresponding to each imaging. RESULTS: During Muller and Valsalva maneuvers, lung sliding was certainly recognized in up to 73.0% and up to 68.7% of imaging, respectively, with a slight to fair inter-rater agreement for Muller maneuver and slight to moderate for Valsalva. Lung sliding was unrecognized in up to 42.0% of tidal breathing imaging, and up to 12.5% of hyperventilation imaging, with a slight to fair inter-rater agreement for both. During apnea, interpretation errors for sliding were irrelevant and inter-rater agreement moderate to perfect. Even if intra-observer agreement varied among raters and throughout respiratory patterns, we found it to be higher than inter-rater reliability. CONCLUSIONS: Intercostal muscles contraction produces sonographic artifacts that may simulate lung sliding. Clinical studies are needed to confirm this hypothesis. We found slight to moderate inter-rater agreement and globally moderate to almost perfect intra-observer agreement for lung sliding and lung pulse. TRIAL REGISTRATION: ClinicalTrials.gov registration number. NCT02386696.

Brain abscess caused by Actinomyces turicensis in a non-immunocompromised adult patient: a case report and systematic review of the literature.

BACKGROUND: Actinomyces turicensis is rarely responsible of clinically relevant infections in human. Infection is often misdiagnosed as malignancy, tuberculosis, or nocardiosis, therefore delaying the correct identification and treatment. Here we report a case of a 55-year-old immunocompetent adult with brain abscess caused by A. turicensis. A systematic review of A. turicensis infections was performed. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases MEDLINE, Embase, Web of Science, CINAHL, Clinicaltrials.gov and Canadian Agency for Drugs and Technology in Health (CADTH) were searched for all relevant literature. RESULTS: Search identified 47 eligible records, for a total of 67 patients. A. turicensis infection was most frequently reported in the anogenital area (n = 21), causing acute bacterial skin and skin structure infections (ABSSSI) including Fournier's gangrene (n = 12), pulmonary infections (n = 8), gynecological infections (n = 6), cervicofacial district infections (n = 5), intrabdominal or breast infections (n = 8), urinary tract infections (n = 3), vertebral column infections (n = 2) central nervous system infections (n = 2), endocarditis (n = 1). Infections were mostly presenting as abscesses (n = 36), with or without concomitant bacteremia (n = 7). Fever and local signs of inflammation were present in over 60% of the cases. Treatment usually involved surgical drainage followed by antibiotic therapy (n = 51). Antimicrobial treatments most frequently included amoxicillin (+clavulanate), ampicillin/sulbactam, metronidazole or cephalosporins. Eighty-nine percent of the patients underwent a full recovery. Two fatal cases were reported. CONCLUSIONS: To the best of our knowledge, we hereby present the first case of a brain abscess caused by A. turicensis and P. mirabilis. Brain involvement by A. turicensis is rare and may result from hematogenous spread or by dissemination of a contiguous infection. The infection might be difficult to diagnose and therefore treatment may be delayed. Nevertheless, the pathogen is often readily treatable. Diagnosis of actinomycosis is challenging and requires prompt microbiological identification. Surgical excision and drainage and antibiotic treatment usually allow for full recovery.

Transcranial Doppler and Color-Coded Doppler Use for Brain Death Determination in Adult Patients: A Pictorial Essay.

Transcranial Doppler (TCD) is a repeatable, at-the-bedside, helpful tool for confirming cerebral circulatory arrest (CCA). Despite its variable accuracy, TCD is increasingly used during brain death determination, and it is considered among the optional ancillary tests in several countries. Among its limitations, the need for skilled operators with appropriate knowledge of typical CCA patterns and the lack of adequate acoustic bone windows for intracranial arteries assessment are critical. The purpose of this review is to describe how to evaluate cerebral circulatory arrest in the intensive care unit with TCD and transcranial duplex color-coded doppler (TCCD).

Diagnostic Accuracy of Procalcitonin in Bacterial Infections of the CNS: An Updated Systematic Review, Meta-Analysis, and Meta-Regression.

OBJECTIVES: To evaluate diagnostic accuracy of serum and cerebrospinal fluid (CSF) procalcitonin for diagnosing CNS bacterial infections. DATA SOURCES: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and International Web of Science databases from January 1, 2016, to September 30, 2022. STUDY SELECTION: Randomized controlled trials and observational studies, either prospective or retrospective, focusing on procalcitonin as a biomarker for CNS infections. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool. Data for diagnostic sensitivity and specificity were pooled using the bivariate or hierarchical model, as appropriate. DATA SYNTHESIS: Of 5,347 citations identified, 23 studies were included. Overall, CSF procalcitonin showed slightly higher pooled sensitivity, specificity, and positive likelihood ratio compared with serum procalcitonin. In adults, pooled sensitivity of CSF procalcitonin was 0.89 (95% CI, 0.71-0.96), specificity 0.81 (95% CI, 0.66-0.91); pooled sensitivity of serum procalcitonin was 0.82 (95% CI, 0.58-0.94), specificity 0.77 (95% CI, 0.60-0.89). In children, pooled sensitivity of CSF procalcitonin was 0.96 (95% CI, 0.88-0.99), specificity 0.91 (95% CI, 0.72-0.97); pooled sensitivity of serum procalcitonin was 0.90 (95% CI, 0.75-0.97), specificity 0.83 (95% CI, 0.67-0.92). In post-neurosurgical patients, pooled sensitivity of CSF procalcitonin was 0.82 (95% CI, 0.53-0.95), specificity 0.81 (95% CI, 0.63-0.91); pooled sensitivity of serum procalcitonin was 0.65 (95% CI, 0.33-0.88), specificity 0.61 (95% CI, 0.41-0.78). Logistic regression revealed between-study heterogeneity higher for serum than CSF procalcitonin. For the latter, threshold variability was found as source of heterogeneity. CONCLUSIONS: In children and critical post-neurosurgical patients, CSF procalcitonin gains superior sensitivity and specificity compared with serum procalcitonin. Overall, CSF procalcitonin appears to have a higher pooled positive likelihood ratio compared with serum procalcitonin.

Feasibility and safety of deep sedation with propofol and remifentanil in spontaneous breathing during endoscopic retrograde cholangiopancreatography: an observational prospective study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an interventional procedure that requires deep sedation or general anaesthesia. The purpose of this prospective observational study was to assess the feasibility and safety of deep sedation in ERCP to maintain spontaneous breathing. METHODS: This is a single-centre observational prospective cohort study conducted in a tertiary referral university hospital. All consecutive patients who needed sedation or general anaesthesia for ERCP were included from January 2021 to June 2021. Deep sedation was achieved and maintained by continuous infusion of an association of propofol and remifentanil. The primary endpoint was to assess the prevalence of major anaesthesia-related complications, such as arrhythmias, hypotension, gas exchange dysfunction, and vomiting (safety endpoint). Secondary endpoints were: (a) to assess the prevalence of signs of an insufficient level of sedation, such as movement, cough, and hiccups (feasibility endpoint): (b) time needed to achieve the target level of sedation and for recovery from anaesthesia. In order to do so we collect the following parameters: peripheral oxygen saturation, fraction of inspired oxygen, noninvasive systemic blood pressure, heart rate, number of breaths per minute, neurological functions with the use of the bispectral index to determine depth of anaesthesia, and partially exhaustive CO2 end pressure to continuously assess the ventilatory status. The collected data were analysed by several tests: Shapiro-Wilk, Student's t, Tuckey post-hoc, Wilcoxon rank-sum and Kruskall-Wallis ran. Statistical analysis was performed using Stata/BE 17.0 (StataCorp LLC). RESULTS: 114 patients were enroled. Eight patients were excluded because they did not meet the inclusion criteria. We found that all patients were hemodynamically stable: intraoperative mean systolic blood pressure was 139,23 mmHg, mean arterial pressure was on average 106,66 mmHg, mean heart rate was 74,471 bpm. The mean time to achieve the target level of sedation was 63 s, while the mean time for the awakening after having stopped drug infusion was 92 s. CONCLUSIONS: During ERCP, deep sedation and analgesia using the association of propofol and remifentanil and maintaining spontaneous breathing are safe and feasible, allowing for a safe and quick recovery from anaesthesia.

Adjuvant Transthoracic Negative-Pressure Ventilation in Nonintubated Thoracoscopic Surgery.

BACKGROUND: To minimize the risks of barotrauma during nonintubated thoracoscopic-surgery under spontaneous ventilation, we investigated an adjuvant transthoracic negative-pressure ventilation (NPV) method in patients operated on due to severe emphysema or interstitial lung disease. METHODS: In this retrospective study, NPV was employed for temporary low oxygen saturation and to achieve end-operative lung re-expansion during nonintubated lung volume reduction surgery (LVRS) for severe emphysema (30 patients, LVRS group) and in the nonintubated wedge resection of undetermined interstitial lung disease (30 patients, wedge-group). The results were compared following 1:1 propensity score matching with equivalent control groups undergoing the same procedures under spontaneous ventilation, with adjuvant positive-pressure ventilation (PPV) performed on-demand through the laryngeal mask. The primary outcomes were changes (preoperative-postoperative value) in the arterial oxygen tension/fraction of the inspired oxygen ratio (ΔPO2/FiO2;) and ΔPaCO2, and lung expansion completeness on a 24 h postoperative chest radiograph (CXR-score, 2: full or 1: incomplete). RESULTS: Intergroup comparisons (NPV vs. PPV) showed no differences in demographic and pulmonary function. NPV could be accomplished in all instances with no conversion to general anesthesia with intubation. In the LVRS group, NPV improved ΔPO2/FiO2 (9.3 ± 16 vs. 25.3 ± 30.5, p = 0.027) and ΔPaCO2 (-2.2 ± 3.15 mmHg vs. 0.03 ± 0.18 mmHg, p = 0.008) with no difference in the CXR score, whereas in the wedge group, both ΔPO2/FiO2 (3.1 ± 8.2 vs. 9.9 ± 13.8, p = 0.035) and the CXR score (1.9 ± 0.3 vs. 1.6 ± 0.5, p = 0.04) were better in the NPV subgroup. There was no mortality and no intergroup difference in morbidity. CONCLUSIONS: In this retrospective study, NITS with adjuvant transthoracic NPV resulted in better 24 h oxygenation measures than PPV in both the LVRS and wedge groups, and in better lung expansion according to the CXR score in the wedge group.

Awake Breast Surgery: A Systematic Review.

BACKGROUND/AIM: Awake surgery has become a valid alternative to general anesthesia in many surgery fields. This technique played a very important role during the COVID-19 period. The growing use of this technique has many advantages. We performed a systematic review to study the potentialities of awake breast surgery. MATERIALS AND METHODS: We searched Pubmed, Embase, and Cochrane library database and retrieved a total of 109 records. Forty-nine of them were excluded as unsuitable. Finally, we selected a total of 12 records concerning different types of studies for topic appropriateness. Three reviewers reviewed independently each record. RESULTS: Five articles analyzing the sustainability of awake surgery during the COVID-19 period were selected. In addition, one article analyzing the impact on the immune system and six articles and eight case reports analyzing anesthetic techniques were also selected. The studies analyzing awake breast surgery during the COVID-19 period showed advantages in terms of sustainability and length of hospitalization. The study analyzing the immune response after awake breast surgery showed lesser lymphocyte response than the general anesthesia group. The studies analyzing anesthetic techniques in awake breast surgery showed that the nerve blocks allow good level of safety and postoperative pain control. CONCLUSION: The awake breast surgery and fast track implementation shortened hospital stays and reduced costs, without influencing the surgical results. Furthermore, awake breast surgery reduced surgical stress compared to general anesthesia. Among the various anesthetic techniques, nerve blocks are the most advantageous in terms of safety and efficacy compared to epidural anesthesia.

Surgical Treatments for Ductal Carcinoma In Situ (DCIS) in Elderly Patients.

BACKGROUND/AIM: Despite an aging population, there is no consensus regarding ductal carcinoma in situ (DCIS) treatment for elderly women. Breast surgery can be well tolerated even in elderly patients. The aim of this study is to evaluate the surgical management of DCIS in elderly patients. PATIENTS AND METHODS: We retrospectively analyzed patients with DCIS from 2016 to 2022 at our Breast Unit and divided our population according to age. RESULTS: Out of 231 patients with DCIS, 45 (19.5%) were elderly. The Charlson comorbidity index and American Society of Anesthesiology (ASA) score was significantly higher in the elderly (p<0.001 for both). Among the elderly, 10 (22.2%) patients received upstaging diagnoses, versus 18 (9.7%) in the control (p=0.048). Twelve (26.7%) of the elderly patients underwent sentinel lymph node biopsy, versus 93 (50%) in the control group (p=0.005). No difference was reported between groups in terms of breast conserving surgeries performed. A higher incidence of surgeries performed using local anesthesia was reported in the elderly group (p=0.041). Thirty-day surgical complications, according to Clavien-Dindo, did not show significant differences. CONCLUSION: Despite higher comorbidity and ASA score, breast surgery is safe and feasible in elderly patients. Due to the higher risk of upstaging to invasive ductal carcinoma, surgery should be performed but sentinel lymph node biopsy should be omitted, owing to the low risk of lymph node metastasis and lower use of adjuvant treatments.

The impact of COVID-19 on elective and urgent digestive endoscopic procedures: a report on a year of pandemic in a gastroenterology centre in Italy.

Introduction: The COVID-19 pandemic (COVID-19) affected digestive endoscopic activity worldwide. Resumption and maintenance of elective endoscopic activity are crucial to containing the impact of COVID-19 on mortality and prognosis of gastrointestinal disorders, primarily cancers. Aim: To assess the impact of COVID-19 during and after the lockdown period on endoscopic activity. Material and methods: The endoscopic activity undertaken during the COVID-19-related lockdown (March 2020-May 2020) and in the post-lockdown period (June 2020-March 2021) was compared with that in the corresponding periods of the year before COVID-19 in a gastroenterology centre in Italy. Results: During the lockdown period, there was a reduction in esophagogastroduodenoscopy (EGD), colonoscopy (CSPY), endoscopic ultrasound (EUS), and endoscopic-retrograde cholangiopancreatography (ERCP) of 75.8%, 74.8%, 60%, and 42%, respectively, compared with the corresponding period of the year before COVID-19. During the post-lockdown period to date, EGD, CSPY, EUS, and ERCP increased as compared to the lockdown period (30.6%, 50.6%, 33.6%, and 65.4%, respectively), but only ERCP showed a full recovery when compared with the corresponding period of the year before COVID-19. Conclusions: Endoscopic activity decreased significantly during the COVID-19 lockdown, and only ERCP had a full recovery in the post-lockdown period. The pandemic-related limitations and the backlog of endoscopic procedures represent important reasons for the increased risk or delayed diagnosis of GI cancers.

Ultrasound-guided pulsed radiofrequency of the saphenous nerve for knee osteoarthritis pain: a pilot randomized trial.

Aim: Knee osteoarthritis is a degenerative disease complicated by pain and functional limitation. Newer pain-relieving interventions include pulsed radiofrequency (PRF), but studies on its efficacy have limitations including lack of control group and retrospective design that prevent sound conclusions. Materials & methods: We conducted a blind prospective randomized sham-controlled crossover pilot trial according to the CONSORT guidelines, to evaluate the efficacy of ultrasound-guided saphenous nerve PRF in gonarthritis pain. Results: Sixteen patients completed the study. Pain and function significantly improved after real PRF (numerical rating scale mean difference = 3.31), which was superior to sham PRF over time for pain (3 months) and function (6 months). Conclusion: PRF of the saphenous nerve is an alternative to relieve pain in gonarthritis. Our results provide data to support a sample size calculation for future trials. Clinical trial registration: NCT04454710.

Lay abstract Aim: Knee osteoarthritis is a degenerative disease associated with severe pain and functional limitation. While treatment options exist to manage knee arthritis symptoms, few have achieved very good results. Newer pain-relieving treatments include pulsed radiofrequency (PRF), where electrical pulses are delivered to the painful nerves to change the way electrical signals are transmitted and reduce pain, but studies on its efficacy have limitations that prevent sound conclusions. Materials & methods: We conducted a study specifically designed to reveal efficacy of PRF over a sham (fake) treatment in patients affected by severe knee arthritis by targeting one single nerve involved in transmitting pain signals from the knee. Results: Pain and function significantly improved after real PRF, which was superior to sham PRF over time for pain (3 months) and function (6 months). Conclusion: PRF of the saphenous nerve is an alternative to relieve pain in knee arthritis.

Erector Spinae Plane Block Versus Serratus Plane Block in Breast Conserving Surgery: Α Randomized Controlled Trial.

BACKGROUND/AIM: Erector spinae plane block (ESP Block) was introduced in 2016 as a surgical post-operative analgesia procedure. The present prospective, randomized trial aimed to compare ESP Block with serratus plane block (SPB) plus pectoral nerve blocks (PECS I) during breast conserving surgery (BCS). PATIENTS AND METHODS: Between February 2019 and March 2021, 104 patients undergoing BCS were randomized to receive either ESP block (ESP group n=54) or SPB+PECS I (SPB group=49). Assessment of postoperative pain was recorded by the dynamic and static visual analog scale (VAS) and was compared between groups. RESULTS: Between-group two-way ANOVA did not reach a statistically significant difference in static and dynamic VAS (p=0.879; p=0.917, respectively). Despite ESP group requiring for higher value of patient-controlled analgesia (PCA) bolus, no statistically significant difference was found in PCA activation pattern between groups (p=0.109). ESP block was a faster technique when compared to SPB+PECS I (p=0.007) and no complications or opioid side-effects were recorded in all groups examined. CONCLUSION: ESP Block could represent a safe, faster alternative with a single injection to SPB+PECS I in BCS.

Quasilobar minimalist lung volume reduction surgery.

OBJECTIVES: Our goal was to assess the results and the costs of the quasilobar minimalist (QLM) thoracoscopic lung volume reduction (LVR) surgical method developed to minimize the trauma from the operation and the anaesthesia and to maximize the effect of the lobar volume reduction. METHODS: Forty patients with severe emphysema underwent QLM-LVR that entailed adoption of sole intercostal block analgesia and lobar plication through a single thoracoscopic incision. Results were compared after propensity matching with 2 control groups undergoing non-awake resectional LVR with double-lumen tracheal intubation or awake non-resectional LVR by plication with thoracic epidural anaesthesia. As a result, we had 3 matched groups of 30 patients each. RESULTS: Baseline forced expiratory volume in 1 s, residual volume, the 6-min walking test and the modified Medical Research Council dyspnoea index were 0.77 ± 0.18, 4.97 ± 0.6, 328 ± 65 and 3.3 ± 0.7, respectively, with no intergroup difference after propensity score matching. The visual pain score was better (P < 0.007), the hospital stay was shorter (P < 0.04) and overall costs were lower (P < 0.04) in the QLM-LVR group than in the control groups. The morbidity rate was lower with QLM-LVR than with non-awake resectional-LVR (P = 0.006). Significant improvements (P < 0.001) occurred in all study groups during the follow-up period. At 24 months, improvements in residual volume and dyspnoea index were significantly better with QLM-LVR (P < 0.04). CONCLUSIONS: QLM-LVR proved safe and showed better perioperative outcomes and lower procedure-related costs than the control groups. Similar clinical benefit occurred at 12 months, but absolute improvements in residual volume and dyspnoea index were better in the QLM-LVR group at 24 months.

Lymphocytes, Interleukin 6 and D-dimer Cannot Predict Clinical Outcome in Coronavirus Cancer Patients: LyNC1.20 Study.

BACKGROUND/AIM: Knowledge of Coronavirus 19 (COVID19) pathogenetic mechanisms is necessary to provide new treatment strategies. This study aims to assess how oncological disease impacts on the clinical course of COVID-19 patients. PATIENTS AND METHODS: From 1st March to 30th April 2020, 96 COVID-19 patients were classified according to clinical outcome as severe (n=67) and moderate (n=29). Demographic data, medical history, admission lymphocytes, procalcitonin (PCT), c-reactive-protein (CRP), D-dimer, and Interleukin-6 (IL-6) were collected. RESULTS: A statistically significant association was found between hypertension (p=0.007) and three or more comorbidities with severe outcomes (p=0.034). No statistical differences were found between the severe and moderate groups with regards to the rate of patients with past oncological history. However, no patient allocated in the moderate group had received oncological treatment within 12 months. Higher values of CRP, IL-6, D-Dimer and lower values of lymphocytes were reported in the severe group (p=0.0007, p=0.00386, p=0.041, and p=0.007, respectively). Using binary logistic regression, higher values of CRP (OR=8.861; p=0.012) and PCT were associated with a higher risk of severe outcome (OR=21.075; p=0.008). Within the oncological population, D-Dimer and IL-6 did not confirm their prognostic significance as in the general population (p>0.05). CONCLUSION: Specific prognostic factors for oncological patients should be designed for COVID-19 clinical practice.

Happy hypoxemia, or blunted ventilation?

Happy hypoxemia is an unspecified definition that is used in COVID-19 patients to define hypoxemia without dyspnoea. Dyspnoea is a very complex symptom, and although hypoxemia can cause breathlessness, dyspnoea is not related to hypoxemia, but is more closely related to inspiratory drive and mechanical alterations. The lack of dyspnoea in the early stages of the disease is likely related to the absence of increased inspiratory drive due to compensatory mechanisms of hypoxemia, while in the advanced stages there is no evidence of a lack of dyspnoea in COVID-19 patients.

Role of Breast-Conserving Surgery on the National Health System Economy From and to SARS-COVID-19 Era.

Day surgery breast-conserving surgery (DS-BCS) is a surgical approach applied in many specialized breast surgery departments. This study demonstrates the benefits of this approach from the perspectives of patients and of the Hospital/National Health System compared to ordinary breast-conserving surgery (ORD-BCS) under general anesthetic. A comparison of costs and diagnosis-related group (DRG) reimbursement demonstrated improved cost-effectiveness in DS-BCS compared to ORD-BCS.

Awake breast cancer surgery: strategy in the beginning of COVID-19 emergency.

INTRODUCTION: COVID-19 is a declared worldwide pandemic. In our country, due to shortage of hospitals and beds in intensive care unit, oncological and breast cancer (BC) resources are temporarily shifted to COVID-19 patients. In addition, risk of cross-infections should be considered in these frail patients. To accomplish more surgical procedures and to reduce the length of hospital stay (LOS), fast track awake BC surgery should be implemented. The aim of the study is to estimate the effects of surgical shift in our facility during the early COVID-19 outbreak. MATERIALS AND METHODS: From 30th January 2020 to 30th of March 2020, 86 consecutive patients were retrospectively enrolled and divided into pre-COVID-19-BC and COVID-19-BC. Clinical parameters and anamnestic data were collected and analyzed. Surgical procedures, relative complications and type of anaesthesia were reported. The effect on surgical time (ST), operative room time (ORT) and length of stay (LOS) were described and examined. RESULTS: No statistical difference was found in complications rate, clinical data and surgical procedures (p > 0.05). Awake breast conservative surgery (BCS) was the most frequent procedure in COVID-19-BC (p = 0.006). A statistically significant decrease in ORT and LOS was reported in COVID-19-BC (p = 0.040 and p = 0.0015 respectively), while comparable time resulted for ST (p = 0.976). Mean ORT and LOS reduction were 20.79 min and 0.57 hospital bed days. CONCLUSION: In the "COVID-19 era", fast track awake breast surgery provides a reduction of ORT, LOS and potentially surgical treatment for a wider number of oncological patients.

Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study.

PURPOSE: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. METHODS: Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use. RESULTS: Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients' cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy. CONCLUSION: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care.

COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry into the Host Cells.

The recent global COVID-19 public health emergency is caused by SARS-CoV-2 infections and can manifest extremely variable clinical symptoms. Host human genetic variability could influence susceptibility and response to infection. It is known that ACE2 acts as a receptor for this pathogen, but the viral entry into the target cell also depends on other proteins. The aim of this study was to investigate the variability of genes coding for these proteins involved in the SARS-CoV-2 entry into the cells. We analyzed 131 COVID-19 patients by exome sequencing and examined the genetic variants of TMPRSS2, PCSK3, DPP4, and BSG genes. In total we identified seventeen variants. In PCSK3 gene, we observed a missense variant (c.893G>A) statistically more frequent compared to the EUR GnomAD reference population and a missense mutation (c.1906A>G) not found in the GnomAD database. In TMPRSS2 gene, we observed a significant difference in the frequency of c.331G>A, c.23G>T, and c.589G>A variant alleles in COVID-19 patients, compared to the corresponding allelic frequency in GnomAD. Genetic variants in these genes could influence the entry of the SARS-CoV-2. These data also support the hypothesis that host genetic variability may contribute to the variability in infection susceptibility and severity.

Is transcranial direct current stimulation (tDCS) effective for chronic low back pain? A systematic review and meta-analysis.

Transcranial direct current stimulation (tDCS) has been used to reduce pain in range of chronic pain states. The aim of this review is to evaluate the effectiveness of tDCS on pain reduction and related disability in patients with non-specific chronic low back pain (CLBP). A computer-based systematic literature search was performed in five databases according to PRISMA guidelines. Randomized controlled trials (RCTs) that assessed the effects of tDCS on pain and related disability in patients with non-specific CLBP were included. Modified Jadad scale and Cochrane's risk of bias assessment were used to determine the studies' quality and risk of bias. Meta-analyses were performed by calculating the standardized mean difference (SMD) at 95% confidence interval (CI). Nine RCTs (411 participants) were included in the systematic review according to inclusion criteria, while only five studies could be included in the meta-analysis. The primary motor cortex (M1) was the main stimulated target. The meta-analysis showed non-significant effect of multiple sessions of tDCS over M1 on pain reduction and disability post-treatment respectively, (SMD = 0.378; 95% CI = - 0.264-1.020; P = 0.249), (SMD = 0.143; 95% CI = - 0.214-0.499; P = 0.434). No significant adverse events were reported. The current results do not support the clinical use of tDCS for the reduction of pain and related disability in non-specific CLBP. However, the limited number of available evidence limits our conclusions on the effectiveness of these approaches.