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During 2003-2009, the National Tuberculosis (TB) Laboratory Network in Argentina gave 830 patients a new diagnosis of multidrug-resistant (MDR) TB and 53 a diagnosis of extensively drug- resistant (XDR) TB. HIV co-infection was involved in nearly one third of these cases. Strain genotyping showed that 7 major clusters gathered 56% of patients within restricted geographic areas. The 3 largest clusters corresponded to epidemic MDR TB strains that have been undergoing transmission for >10 years. The indigenous M strain accounted for 29% and 40% of MDR and XDR TB cases, respectively. Drug-resistant TB trends in Argentina are driven by spread of a few strains in hotspots where the rate of HIV infection is high. To curb transmission, the national TB program is focusing stringent interventions in these areas by strengthening infection control in large hospitals and prisons, expediting drug resistance detection, and streamlining information-sharing systems between HIV and TB programs. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral palsy (CP) is the predominant cause of children disability. It is characterized by motor, sensory, and postural deficits due to a non-progressive injury to the developing central nervous system. In recent years, new rehabilitation techniques targeting the central representations of motor patterns have been introduced: the most used are action observation therapy (AOT), motor imagery (MI), and mirror therapy (MT). Aim of this study is to assess the effectiveness of these cognitive strategies on the recovery of upper limb motor functions in children with CP., Evidence Acquisition: This study was designed as a systematic review and meta-analysis, registered in PROSPERO (CRD42023403794). For the report and methodological definitions of this study, the recommendations of the PRISMA protocol and the Cochrane collaboration, were followed. A total of 3 electronic databases (PubMed, Scopus, and Web of Science) were searched for relevant Randomized Control Trials (RCT) using the combinations of terms "cerebral palsy" AND "action observation" OR "motor imagery" OR "mirror therapy" OR "cognitive therapy." A meta-analysis was carried out to compare cognitive and conventional approaches and combine direct and indirect effects. A random-effects meta-analysis model was used to derive pooled effect estimates., Evidence Synthesis: Out of 328 records, 12 RCTs were analyzed in this systematic review published from 2012 to 2022, and included 375 children, of whom 195 received cognitive therapies, and 180 underwent conventional rehabilitation. AOT was the most investigated (RCTs N.=7), and showed significant results in the recovery of upper limb motor functions, albeit the meta-analysis demonstrated a non-significant difference in Melbourne Unilateral Upper limb Scale (MUUL) (95% CI: -7.34, 12); in Assisting Hand Assessment (AHA) (95% CI: -4.84, 10.74), and in AbilHand-Kids Questionnaire (95% CI: -1.12, 1.45). Five RCTs investigated MT showing significant improvements in grip and dexterity; none used MI as intervention therapy., Conclusions: Cognitive therapies provided with encouraging results in the recovery of upper limb motor functions, although not a clinical effect in bimanual or unimanual performance; they could represent a valid therapeutic solution integrated to conventional rehabilitation in the treatment of upper limb motor impairment in children with CP.

Microsatellite Instability (MSI-H) occurs in approximately 15% of non-metastatic colon cancers, influencing patient outcomes positively compared to microsatellite stable (MSS) cancers. This systematic review focuses on the prognostic significance of KRAS, NRAS, and BRAF mutations within MSI-H colon cancer. Through comprehensive searches in databases like MEDLINE, EMBASE, and others until 1 January 2024, we selected 8 pertinent studies from an initial pool of 1918. These studies, encompassing nine trials and five observational studies involving 13,273 patients, provided insights into disease-free survival (DFS), survival after recurrence, and overall survival. The pooled data suggest that while KRAS and BRAF mutations typically predict poorer outcomes in MSS colorectal cancer, their impact is less pronounced in MSI contexts, with implications varying across different stages of cancer and treatment responses. In particular, adverse effects of these mutations manifest significantly upon recurrence rather than affecting immediate DFS. Our findings confirm the complex interplay between genetic mutations and MSI status, emphasizing the nuanced role of MSI in modifying the prognostic implications of KRAS, NRAS, and BRAF mutations in colon cancer. This review underscores the importance of considering MSI alongside mutational status in the clinical decision-making process, aiming to tailor therapeutic strategies more effectively for colon cancer patients.

Background: It is possible to induce immunomodulation in HER2-positive breast cancer (BC) by modifying the route of administration of trastuzumab., Methods: In this multicenter randomized phase II trial, all enrolled patients (pts) with T2-T4d HER2-positive BC received 3 cycles of neoadjuvant treatment (NAT) with fluorouracil, epirubicin and cyclophosphamide every 3 weeks (q21), followed by docetaxel/pertuzumab plus intravenous trastuzumab (arm A) or, docetaxel/pertuzumab plus subcutaneous (SC) trastuzumab (arm B) q21x4 cycles. After surgical operation, each pt was treated with trastuzumab q21x14 cycles using the same SC or intravenous formulation of NAT. Primary endpoint was the proportion of subjects with high stromal tumor-infiltrating lymphocytes (sTILs) in postneoadjuvant residual disease (RD)., Results: Sixty-three pts (31 (arm A) and 32 (arm B)) were enrolled. Pathological complete response was obtained by 20/31 pts (64.5%; 95% CI 45.4% to 80.1%) in arm A and 19/32 pts (59.4%; 95% CI 40.1% to 76.3%) in arm B. High sTILs were observed in 27% and 46% of postneoadjuvant residual tumors in arms A and B, respectively. CD8+ T cells increased significantly in RDs of both arms (p=0.014 and 0.002 for arm A and B, respectively), whereas a significant decline in the level of CD4+ FoxP3+ regulatory T cells was observed only in arm B (p=0.016). A significant upregulation of PD-1 on sTILs was found in RD of pts enrolled in arm B (p=0.012), while programmed death-ligand 1 (PD-L1) was significantly overexpressed in residual tumors of arm A (p=0.02). A strong negative correlation was reported in arm B between expression of PD-L1 on pretreatment sTILs and CD3 expression on sTILs in RD (τ: -0.73). Grade≥3 AE incidence rates were similar between the two arms., Conclusions: SC trastuzumab induced relevant sTILs enrichment, with favorable variations of immune parameters in HER2-positive BC pts with RD after NAT. Novel immunotherapy strategies should be tested to achieve SC-specific, antitumor immune response., Trial Registration Number: NCT03144947, and EudraCT number: 2016-000435-41., Competing Interests: Competing interests: BP reports research grants from Lilly, Pfizer, Novartis; and personal fees from MSD outside the submitted work. EC reports travel grants from Pfizer and Ipsen outside the submitted work. EB reports research grants from Roche, AstraZeneca; personal fees from MSD, AstraZeneca, BMS, Roche, Novartis, Pfizer, Lilly; and travel grants from Roche and AstraZeneca outside the submitted work. LC reports personal fees from AstraZeneca, Novartis and Lilly outside the submitted work. LG reports personal fees from Daiichi, Seagen; and travel grants from Ipsen, Novartis, Pfizer outside the submitted work. AZ reports personal fees from AstraZeneca, Lilly, Pfizer, Daiichi, MSD, Roche, Seagen, Exact Sciences, Gilead and Istituto Gentili outside the submitted work. FM reports personal fees from Roche, Novartis, AstraZeneca, Daiichi, Seagen, MSD, Lilly, Pfizer, Pierre Fabre; and travel grants from Roche and AstraZeneca outside the submitted work; from May 15th 2023, FM is Roche employee. AM reports research grants from Lilly; personal fees from Seagen, Daiichi, Gilead, Novartis, AstraZeneca; and travel grants from Gilead and Novartis outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Little is known about the real impact of the COVID-19 outbreak on the qualitative and quantitative fall-out on the management of cancer patients. Our objective was to provide evidence of the effects of SARS-COV-2 on the management of cancer patients in the real world., Methods: In a general hospital in a district in Italy with high prevalence of COVID-19 during the first wave, we retrospectively analyzed the data of oncologic activity, namely new cancer diagnosis, types of treatment (intravenous or by mouth), clinical research studies, and drug utilization, and compared the findings with those of 2019, before the pandemic. The data have been summarized in boxplot figures for median and interquartile range., Results: In 2020, a significant reduction in new cancer diagnosis was demonstrated when compared with 2019, with 17.4% fewer cancer diagnoses, 84.5% fewer patients enrolled in clinical trials, a 10.6% reduction in intravenous antitumor treatment, and a 42.7% increase in oral anticancer treatment., Conclusion: Our data indicate a significant reduction in cancer diagnosis, antitumor venous treatment, and patients enrolled in clinical research studies in 2020 compared with 2019, although there was a significant increase in oral treatment. These data suggest that the COVID-19 pandemic had a deep impact on the real-world management of cancer patients in a district of Italy with a high prevalence of COVID-19., (© 2021. The Author(s).)

Background Cancer patients are presumed a frail group at high risk to contract coronavirus disease (COVID-19). The aim of this study was to investigate the prevalence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection in asymptomatic cancer patients attending the outpatient clinic of a general hospital in a region with a high prevalence of SARS-CoV-2 infection (North Italy, first wave). Methods We retrospectively analyzed data of consecutive cancer patients attending the outpatient clinic of the oncology unit, General Hospital of Piacenza. All the patients having underlying cancer, without clinical suspicion of COVID-19, attending the outpatient clinic underwent nasopharyngeal swabs, from April 3, 2020 to June 3, 2020 and were included in this study. Results In a two-month period, 260 consecutive, asymptomatic (for COVID-19) cancer patients were tested for COVID-19. There were 160 women and 100 men; 218 patients were under active anticancer treatment, 32 in the diagnostic/staging phase waiting for treatment, and 10 treated with supportive care only. Ten of the 260 patients (3.85%) showed COVID-19 positivity. All but one (treated with hormone therapy) of the COVID-19 positive patients delayed anticancer treatment. The mean delay of anticancer treatment was 45.86±27.66 days (range 21-87 days), and the mean time for viral clearance was 25.7±22.68 days (range 7-79 days). All the 10 patients with COVID-19 and cancer overcame the infection, and treated patients could restart anticancer treatment. Conclusion Our data indicate a high prevalence of COVID-19 in cancer patients in an area with a high prevalence of SARS-CoV-2 infection. Routine COVID-19 testing of cancer patients when asymptomatic allowed an early detection, isolation, and treatment, avoiding viral spread among other frail patients and among medical/nurse staff., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Cavanna et al.)

Background: Cancer patients are considered a highly fragile group in the current coronavirus disease 2019 (COVID-19) pandemic., Material & Methods: In this study, patients with COVID-19 and cancer, hospitalized in Piacenza, Italy, from 4 April to 4 May 2020 were included. Risk factors for death were analyzed., Results: Fifty-one COVID-19 cancer patients were included, of which the median age was 71.02 years (range: 51-86) and 70.59% were male. Cancer types included gastrointestinal (25.49%), genitourinary (25.49%) and lung (23.53%). Forty-five (88.24%) patients received hydroxychloroquine-based therapy. In addition, 25 of 51 patients died (49%): 12 of 51 (23.53%) owing to cancer and 13 of 51 (25.49%) owing to COVID-19., Conclusion: The risks for death were related to later onset of treatment for COVID-19, severe/critical COVID-19, age, elevated basal CRP and elevated lactate dehydrogenase., Competing Interests: Financial & competing interests disclosure L Cavanna holds a consulting or advisory role for AstraZeneca and Merck, and received travel and accommodation expenses from Celgene, Pfizer and Ipsen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Luigi Cavanna.)

Prior research has revealed that ultrasound (US) guided central venous catheterization (CVC) is associated with a reduction in the complication rate such as pneumothorax and an improved first-pass success placing CVC in the internal jugular vein. The present study investigated if US-guided CVC, in a subset of cancer patients with severe thrombocytopenia, reduced bleeding risk and avoided prophylactic platelet transfusion. The efficacy and safety of US-guided CVC placement in cancer patients with severe thrombocytopenia was retrospectively analyzed over a period of 9 years (Dec 2000-Jan 2009), 1,660 and 207 patients with cancer underwent US-guided CVC placement into internal jugular vein respectively at the Department of Onco-Haematology, Hospital of Piacenza. The first group of patients included patients in active antitumor treatment, while the second group included patients in the palliative phase. A total of 110 (5.89%) of these 1,867 patients exhibited severe thrombocytopenia defined as platelet count ≤20x10 9 /l, and formed the basis of this study. All procedures were evaluated for bleeding complications as defined by the National Institute of Health Common Terminology Criteria for Adverse Events (CTCAE 3.0). In the subgroup of the 110 patients with severe thrombocytopenia a single needle puncture of the vein was employed in 121 of the 122 procedures (99.18%) and no attempt failures were registered. No pneumothorax, no major bleeding and no nerve and arterial puncture were reported, only one self-limiting hematoma (0.90%) at the site of CVC insertion was reported (CTCAE 3.0 grade 1). No platelet transfusions were performed in the 110 patients, pre and post CVC placement. We believe that US-guided CVC insertion procedures into the internal jugular vein makes the difference in safety, also in thrombocytopenic patients avoiding prophylactic or post procedure platelet transfusion., (Copyright: © Cavanna et al.)

Purpose: Metastatic non-small-cell lung cancer (NSCLC), the leading cause of death from cancer worldwide, is a debilitating disease that results in a high burden of symptoms and poor quality of life; the estimated prognosis after the diagnosis has been established was less than 1 year until some years ago. At the present, the new targeted therapies and immunotherapy are changing the course of the disease. However, advanced NSCLC remains an incurable disease, with a poor prognosis for the majority of the affected patients, so that quality of life and relief from symptoms are primary objectives of treatment. Some evidences suggest that early palliative care (EPC) for these patients can improve quality of life and even survival., Design: A systematic review of the studies evaluating the impact on objective and on patient-reported outcomes of the introduction of EPC in opposition to standard care (SC), for advanced lung cancer patients, was performed. Because of the small number of studies conducted in this area, retrospective studies were also considered for the review., Results: Five studies were included because they matched the inclusion criteria previously defined as relevant for the study. The review found that both survival and quality of life were better for patients included in EPC groups., Conclusions: While results of the studies included in this review are not always comparable because different methods and scales have been used, there is enough evidence for clinical oncologists to implement the use of EPC in clinical practice for advanced lung cancer patients.

The burden of travel from a patient's residence to health care providers is an important issue that can influence access to diagnosis and treatment of cancer. Although several studies have shown that the travel burden can result in delays in diagnosis and treatment of many common cancers, its role appears underestimated in the treatment of patients in clinical practice. Therefore, we performed a review of the published data on the role of travel burden influencing four items: delay of diagnosis, adequate treatment of cancer, outcome, and quality of life of cancer patients. Forty-seven studies published up to December 2014 were initially identified. Twenty studies were excluded because they did not regard specifically the four items of our review. Twenty-seven studies formed the basis of our study and involved 716,153 patients. The associations between travel burden and (a) cancer stage at diagnosis (12 studies), (b) appropriate treatment (8 studies), (c) outcome (4 studies), and (d) quality of life (1 study) are reported. In addition, in two studies, the relation between travel burden and compliance with treatment was examined. The results of our review show that increasing travel requirements are associated with more advanced disease at diagnosis, inappropriate treatment, a worse prognosis, and a worse quality of life. These results suggest that clinical oncologists should remember the specific travel burden problem for cancer patients, who often need health care services every week or every month for many years., (©AlphaMed Press.)

Background: Malignant mesothelioma is a rare neoplasm that generally develops in the pleural or peritoneal cavity. Distant metastases are common; it rarely metastatizes to the head and neck region., Case Presentation: A 54-year-old white man, a non-smoker, was treated with chemotherapy, surgery and radiation for a malignant pleural mesothelioma. Seven months after the last treatment, he developed a right submandibular enlargement: clinical examination, ultrasound and computerized tomography scans revealed a salivary gland hypertrophy. Anti-inflammatory and antibiotic treatment was then started, without improvement. An ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) showed atypical mesothelial cells with nuclear enlargement and increased chromatin representation. Immunocytochemistry showed positivity for calretinin and WT-1.A diagnosis of right submandibular salivary gland involvement from mesothelioma was established, allowing an adequate treatment., Conclusion: We report a very rare site of metastasis from malignant pleural mesothelioma. We suggest that US-guided FNAB is a useful, quick, and cheap procedure for a definite diagnosis.

Luminal gastrointestinal (GI) metastases from breast cancer are rare, reports are fragmentary and poor. The purposes of this study are to assess the gastrointestinal involvement from breast cancer in a retrospective study at a single institution and reviewing the related literature. Between January 2007 and December 2011 a total of 980 patients with breast cancer were treated at our institution, patients' records and report database were analysed. Institutional Review Board approval was obtained for this study. A search of the literature using PubMed, CancerLit, Embase, was performed. Selected for the present review were papers published in English before June 2012. Five of 980 patients (0.5%) showed gastrointestinal metastases from breast cancer, 3 patients had gastric involvement, 1 jejunum, and 1 rectum. Reviewing the literature, 206 patients affected by gastrointestinal metastasis from breast cancer were identified: the most frequent site of metastasis was the stomach (60%). The majority of the patients underwent chemotherapy and endocrine therapy, someone surgery and radiotherapy. GI metastases from breast cancer are rare, but possible, and a very late recurrence can also occur. Cyto-histological diagnosis is mandatory, to differentiate GI metastases from breast cancer to other diseases and to allow an adequate treatment.

Background: The proinflammatory cytokine interleukin 17 (IL-17) plays an important role in immune responses but it is also associated with tissue-damaging inflammation. So, we evaluated the ability of Mycobacterium tuberculosis clinical isolates to induce IL-17 in tuberculosis (TB) patients and in healthy human tuberculin reactors (PPD(+)HD)., Methods: IL-17, interferon γ (IFN-γ), and interleukin 23 (IL-23) receptor expression were evaluated ex vivo and cultured peripheral blood mononuclear cells from TB and PPD(+)HD stimulated with irradiated clinical isolates from multidrug resistant (MDR) outbreaks M (Haarlem family) and Ra (Latin American-Mediterranean family), as well as drug-susceptible isolates belonging to the same families and laboratory strain H37Rv for 48 hours in T-cell subsets by flow cytometry., Results: We observed that: (1) MDR strains M and Ra are stronger IL-17 inducers than drug-susceptible Mtb strains of the Haarlem and Latin American-Mediterranean families, (2) MDR-TB patients show the highest IL-17 expression that is independent on the strain, (3) IL-17 expression is dependent on CD4(+) and CD8(+) T cells associates with persistently high antigen load., Conclusions: IL-17--producing T cells could play an immunopathological role in MDR-TB promoting severe tissue damage, which may be associated with the low effectiveness of the second-line drugs employed in the treatment.

Background: Most patients with advanced cancer are frequently malnourished and frequently they develop decreased oral fluid intake and dehidratation. Home parenteral nutrition (HPN) is an increasingly used therapy for patients with advanced cancer. A central venous access device is often an essential component allowing parenteral nutrition and hidratation. However central venous catheter (CVC) insertion represents a risk for pneumothorax or other mechanical complications. This study aimed to determine the reduction of risks related to central venous catheter positionement in the setting of cancer patients with palliative programm., Methods: Consecutive patients with a variety of cancer in advanced phase requiring palliative care who were undergoing placement of central venous catheter for parenteral nutrition or hydratation have been prospectively studied in a program of ultrasound-guided CVC placement. Four types of possible complications were defined:mechanical, thrombotic, infection and malfunctioning. After sterilization, local anesthesia is applied and a 7.5 MHZ puncturing US probe is placed in the supraclavicular site and a 16-gauge needle is advanced under real-time US guidance, into the last portion of internal jugular vein by experienced physicians. The Seldinger tecnique is used to place the catheter that is advanced into the superior vena cava until insertion to right atrium. Two hours after each procedure a chest X-ray and US scanning are carried out to confirm CVC position and rule out a pneumotorax., Results: From 30 October 2000 to 31 October 2008: 209 CVC insertional procedure were applied in 207 patients with cancer in the palliative phase only. There were 101 women and 106 men with a mean age of 67.68 year (range 22-86). A single needle puncture of the vein was performed on 206 of 209 procedures (98.6%), the technique was efficacious at the first attempt in 98.6% of cases, in 2 patients (0.96%) the CVC was positioned at the second attempt. The procedure failed only one case (0.44%). No cases of pneumothorax, of major bleeding or nerve punctured were reported. Symptomatic vein thrombosis developed in one patient (0.44%). Infection episodes were reported in two cases. Mean time for CVC permanence was 92.5±9.1 days (range 8-158)., Conclusion: This study indicates that US-guided CVC insertion is a safe, cheap procedure for cancer patients in advanced phase and with palliative program, allowing parenteral nutrition and hydratation., Competing Interests: The authors declare no conflict of interest.

To analyze the molecular epidemiology of Mycobacterium tuberculosis strains at a hospital in Buenos Aires, Argentina, and mutations related to multidrug-resistant and extensively drug-resistant tuberculosis, we conducted a prospective case-control study. Our findings reinforce the value of incorporating already standardized molecular methods for rapidly detecting resistance.