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BMC Cancer Nov 2023We aimed to investigate the efficacy and side effects of concurrent chemoradiotherapy, with or without nimotuzumab, for the treatment of locally advanced nasopharyngeal...
Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective study.
PURPOSE
We aimed to investigate the efficacy and side effects of concurrent chemoradiotherapy, with or without nimotuzumab, for the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy.
METHODS
This study retrospectively enrolled 109 patients with NPC from our hospital from July 2019 to May 2021.All patients were treated with docetaxel, cisplatin, and fluorouracil(TPF) neoadjuvant chemotherapy for 2 cycles, and concurrent chemoradiotherapy was performed 2 weeks after chemotherapy. According to whether nimotuzumab was added in concurrent chemoradiotherapy, they were divided into the nimotuzumab group and the control group, with 52 cases in the nimotuzumab group and 57 cases in the control group.The efficacy and adverse reactions of the two groups were retrospectively analyzed.
RESULTS
The objective remission and complete remission rates in the nimotuzumab and control groups were 100% vs 98.2% (p = 1.000), and 92.3% vs 78.9% (p = 0.049), respectively. The 3-year distant metastasis-free survival of the nimotuzumab and control groups was 91.6% and 77.3% (p = 0.047), respectively.The 3-year progression-free survival, locoregional relapse-free survival, and overall survival of the nimotuzumab and control groups were 87.6% vs 75.5% (p = 0.110), 90.5% vs 86.9% (p = 0.566), and 94.5% vs 87.1% (p = 0.295), respectively. In the nimotuzumab group, subgroup analysis showed that patients aged < 60 years (hazard ratio [HR] = 0.350, 95% confidence interval [CI]: 0.131-0.934, p = 0.036) and those with a neutrophil-to-lymphocyte ratio (neutrophil/lymphocyte ratio) ≤ 4 (HR = 0.365, 95% CI: 0.144-0.923, p = 0.033) achieved a better result. Additionally, multivariate analysis demonstrated that neutrophil/lymphocyte ratio was an independent risk factor for disease progression (HR = 7.485, p = 0.012) and distant metastasis (HR = 17.540, p = 0.009).No grade 4 adverse reactions were observed in either group. Grade 3 oral mucosal reactions, as well as pharyngeal and esophageal reactions were slightly higher in the nimotuzumab group than in the control group, but the difference was not statistically significant. No significant differences were observed in the incidence of adverse reactions such as leukopenia, HB reduction, thrombocytopenia between the two groups (P > 0.05).
CONCLUSION
The concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma achieved a higher complete remission rate and significantly improved distant metastasis-free survival compared with concurrent chemoradiotherapy alone. Additionally, an increasing trend was observed in progression-free survival, and the incidence of side effects was similar in both groups.
Topics: Humans; Nasopharyngeal Carcinoma; Retrospective Studies; Neoadjuvant Therapy; Nasopharyngeal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Chemoradiotherapy; Cisplatin; Leukopenia
PubMed: 37996813
DOI: 10.1186/s12885-023-11608-5 -
Endoscopy Dec 2023
Topics: Humans; Traction; Endoscopic Mucosal Resection; Dental Devices, Home Care; Pharyngeal Neoplasms; Stomach Neoplasms; Treatment Outcome
PubMed: 37984391
DOI: 10.1055/a-2197-9514 -
Nature Communications Nov 2023Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at...
Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into "Metabolic genotypes" (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.
Topics: Child; Humans; Animals; Mice; Infant; Child, Preschool; Streptococcus pneumoniae; Pneumococcal Infections; Anti-Bacterial Agents; Malawi; Virulence; Drug Resistance, Bacterial; Pneumococcal Vaccines; Serogroup; Nasopharynx; Carrier State
PubMed: 37978177
DOI: 10.1038/s41467-023-43160-y -
Wellcome Open Research 2023(StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year,...
BACKGROUND
(StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year, predominantly in low- and middle-income countries (LMIC). Superficial StrepA infections of the skin and pharynx can lead to rheumatic heart disease, the largest cause of StrepA-related deaths in LMIC. StrepA can also asymptomatically colonise normal skin and the pharynx (carriage), potentially increasing infection risk. (SDSE) carriage is also common in LMIC and may interact with StrepA. This study aims to investigate StrepA and SDSE carriage and infection epidemiology, transmission dynamics and naturally acquired immunity within households in The Gambia.
METHODS
A longitudinal household observational cohort study will be conducted over one year. 45 households will be recruited from the urban area of Sukuta, The Gambia, resulting in approximately 450 participants. Households will be visited monthly, and available participants will undergo oropharyngeal and normal skin swabbing. Incident cases of pharyngitis and pyoderma will be captured via active case reporting, with swabs taken from disease sites. Swabs will be cultured for the presence of group A, C and G beta-haemolytic streptococci. Isolates will undergo whole genome sequencing. At each visit, clinical, socio-demographic and social mixing data will be collected. Blood serum will be collected at baseline and final visit. Oral fluid and dried blood spot samples will be collected at each visit. Mucosal and serum anti-StrepA antibody responses will be measured.
OUTCOME
This study will report StrepA and SDSE clinical epidemiology, risk factors, transmission dynamics, and serological responses to carriage and infection. Detailed social mixing behaviour will be combined with phylogenetic relatedness to model the extent of transmission occurring withing and between households. The study will provide data to help meet global strategic StrepA research goals.
PubMed: 37954923
DOI: 10.12688/wellcomeopenres.18716.2 -
EBioMedicine Dec 2023Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in...
BACKGROUND
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associated factors.
METHODS
We tested M.pneumoniae carriage by qPCR in children with recurrent infections and their healthy family members in a cross-sectional study. Serum and mucosal total and M.pneumoniae-specific antibody levels were measured by ELISA and nasopharyngeal microbiota composition was characterized by 16S-rRNA sequencing.
FINDINGS
Prevalence of M.pneumoniae carriage was higher in children with recurrent infections (68%) than their family members without infections (47% in siblings and 27% in parents). M.pneumoniae carriage among family members appeared to be associated with transmission within the household, likely originating from the affected child. In logistic regression corrected for age and multiple comparisons, IgA (OR 0.16 [0.06-0.37]) and total IgG deficiency (OR 0.15 [0.02-0.74]) were less prevalent in M.pneumoniae carriers (n = 78) compared to non-carriers (n = 36). In multivariable analysis, the nasopharyngeal microbiota of M.pneumoniae carriers had lower alpha diversity (OR 0.27 [0.09-0.67]) and a higher abundance of Haemophilus influenzae (OR 45.01 [2.74-1608.11]) compared to non-carriers.
INTERPRETATION
M.pneumoniae carriage is highly prevalent in children with recurrent infections and carriers have a less diverse microbiota with an overrepresentation of disease-associated microbiota members compared to non-carriers. Given the high prevalence of M.pneumoniae carriage and the strong association with H. influenzae, we recommend appropriate antibiotic coverage of M.pneumoniae and H. influenzae in case of suspected pneumonia in children with recurrent respiratory tract infections or their family members.
FUNDING
Wilhelmina Children's Hospital Research Fund, 'Christine Bader Stichting Irene KinderZiekenhuis', Sophia Scientific Research Foundation, ESPID Fellowship funded by Seqirus, Hypatia Fellowship funded by Radboudumc and The Netherlands Organisation for Health Research and Development (ZonMW VENI grant to LM Verhagen).
Topics: Child; Humans; Infant; Streptococcus pneumoniae; Mycoplasma pneumoniae; Pneumococcal Infections; Cross-Sectional Studies; Reinfection; Respiratory Tract Infections; Nasopharynx; Pneumonia; Haemophilus influenzae; Carrier State; Microbiota
PubMed: 37950996
DOI: 10.1016/j.ebiom.2023.104868 -
Science Advances Nov 2023The constant exposure of the fish branchial cavity to aquatic pathogens causes local mucosal immune responses to be extremely important for their survival. Here, we used...
The constant exposure of the fish branchial cavity to aquatic pathogens causes local mucosal immune responses to be extremely important for their survival. Here, we used a marker for T lymphocytes/natural killer (NK) cells (ZAP70) and advanced imaging techniques to investigate the lymphoid architecture of the zebrafish branchial cavity. We identified a sub-pharyngeal lymphoid organ, which we tentatively named "Nemausean lymphoid organ" (NELO). NELO is enriched in T/NK cells, plasma/B cells, and antigen-presenting cells embedded in a network of reticulated epithelial cells. The presence of activated T cells and lymphocyte proliferation, but not V(D)J recombination or hematopoiesis, suggests that NELO is a secondary lymphoid organ. In response to infection, NELO displays structural changes including the formation of T/NK cell clusters. NELO and gill lymphoid tissues form a cohesive unit within a large mucosal lymphoid network. Collectively, we reveal an unreported mucosal lymphoid organ reminiscent of mammalian tonsils that evolved in multiple teleost fish families.
Topics: Humans; Animals; Palatine Tonsil; Zebrafish; Lymphoid Tissue; Pharynx; T-Lymphocytes; Mammals
PubMed: 37910624
DOI: 10.1126/sciadv.adj0101 -
Radiotherapy and Oncology : Journal of... Dec 2023Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment...
PURPOSE
Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment paradigms have been refined and continue to evolve in the modern era.
METHODS AND MATERIALS
This study was designed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A literature search of peer-reviewed publications was undertaken to identify works pertaining to the use of radiation for squamous cell carcinoma of unknown primary origin presenting as cervical lymph node metastases. Articles published from January 2002 to January 2023 with full text available on PubMed and restricted to the English language and human subjects were included. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.
RESULTS
While such breakthroughs as intensity-modulated radiotherapy, positron emission tomography, biomarker testing with immune-histochemistry, and minimally invasive surgical techniques such as transoral robotic surgery have fundamentally changed the approach to this disease in recent decades, controversies still exist with respect to the manner in which radiation is delivered. Although the incidence of head and neck unknown primary cancer is relatively low, questions regarding the necessity of comprehensive radiation using the age-old standard method of targeting the bilateral necks and entire pharyngeal axis to encompass all putative sites of mucosal disease persist.
CONCLUSIONS
Prospective evidence is lacking, and the available studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in work-up, treatment, inclusion criteria, and follow-up. Regardless, advances in science and technology have ushered in more precise approaches with a high degree of customization, particularly given the increased proportion of patients presenting with human papillomavirus-related disease.
Topics: Humans; Head and Neck Neoplasms; Human Papillomavirus Viruses; Meta-Analysis as Topic; Neoplasms, Unknown Primary; Papillomavirus Infections; Systematic Reviews as Topic
PubMed: 37844736
DOI: 10.1016/j.radonc.2023.109952 -
Medicine Oct 2023Foreign body (FB) ingestion is a common clinical emergency, although in most cases, the FB can pass safely through the entire gastrointestinal tract without causing any... (Review)
Review
RATIONALE
Foreign body (FB) ingestion is a common clinical emergency, although in most cases, the FB can pass safely through the entire gastrointestinal tract without causing any damage. However, ingestion of large dentures is very rare and alarming, as it can threaten the intestinal mucosa and cause perforation of the gastrointestinal tract, among other complications.
PATIENT CONCERNS
A 64-year-old Chinese male was referred to our hospital for removal of a FB, which was a large denture. Clinical symptoms included chest and upper abdominal pain. He had no cough or dyspnea. Medical history included a recent cerebral infarction, craniocerebral surgery, and being bedridden for a long term.
DIAGNOSES
We initially suspected a single and smooth denture, complicated by pharyngeal and esophageal mucosal injury. Radiographic examination however showed a 70-mm long opaque object located in the middle and upper esophagus, close to the trachea and aorta.
INTERVENTIONS
Multiple dentures and metal hooks were removed via endoscopy using a net, grasping forceps, and rubber jacket.
OUTCOMES
The patient recovered well and experienced no postoperative complications. The patient was discharged 5 days after endoscopic therapy.
LESSONS
Our case showed that endoscopy was effective for the retrieval of an esophageal FB. For sharp FBs, the use of a net and rubber jacket is a good choice. However, we advocate for appropriate surgery in patients in whom endoscopy is not possible after an accurate diagnosis or those with severe complications.
Topics: Male; Humans; Adult; Middle Aged; Rubber; Endoscopy, Gastrointestinal; Esophageal Diseases; Foreign Bodies; Eating; Dentures
PubMed: 37832100
DOI: 10.1097/MD.0000000000035426 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Oct 2023To study the application value of narrow-band imaging in the diagnosis of laryngopharyngeal reflux. A total of 275 patients admitted to the inpatient department or...
To study the application value of narrow-band imaging in the diagnosis of laryngopharyngeal reflux. A total of 275 patients admitted to the inpatient department or laryngoscopy room of the Otolaryngology Head and Neck Surgery Department of the First Affiliated Hospital of Harbin Medical University from September 2022 to April 2023 due to throat discomfort were selected as the research subjects. All of them completed RSI, RFS scoring scales and electronic laryngoscopy(including ordinary white light and NBI). According to the expert consensus of LPRD in 2022, RSI and RFS scoring scale were used as diagnostic criteria to divide them into LPR group and non-LPR group. Chi-square test was used to analyze the differences of positive rates of characteristic manifestations under NBI among different groups. The consistency of NBI and scale diagnostic methods was analyzed by Kappa, and RSI and RFS scoring were used as diagnostic criteria, The diagnostic efficiency of NBI method was analyzed. There were 190 people in the LPR group, 157 of whom showed characteristic performance under the NBI mode, with a positive rate of 82.6%(157/190); there were 85 people in the non-LPR group, with a positive rate of 18.8%(16/85). There was a statistically significant difference in the positive rate between the two groups(χ²=102.47, <0.05). The consistency rate between RSI, RFS and NBI was 82.2%(226/275). Kappa consistency analysis was used, and Kappa=0.605(<0.05), indicating good consistency between the two diagnostic methods. Using RSI and RFS as diagnostic criteria for LPR, the sensitivity of NBI diagnostic method was 82.6%(157/190), specificity 81.2%(69/85), positive predictive value 90.8%(157/173) and negative predictive value 67.6%(69/102). Narrow-band imaging, as a new endoscopic imaging technique, can show small changes in mucosal surface micro vessels and play an important role in the diagnosis of laryngopharyngeal reflux.
Topics: Humans; Laryngopharyngeal Reflux; Narrow Band Imaging; Laryngoscopy; Pharynx; Predictive Value of Tests
PubMed: 37828884
DOI: 10.13201/j.issn.2096-7993.2023.10.008 -
Acta Histochemica Oct 2023Situated in the oral cavity, the rabbit palatine tonsils are part of the mucosal immune system and help to defend the body against foreign pathogens. Expressed as two...
Situated in the oral cavity, the rabbit palatine tonsils are part of the mucosal immune system and help to defend the body against foreign pathogens. Expressed as two oval protrusions in the wall of the oropharynx, the rabbit palatine tonsils are characterized by excretory ducts and trabeculae. We here compare paraffin embedded and cryosections of the healthy rabbit tonsils. This analysis centers on evaluating the differential outcomes resulting from the application of these fixation methodologies in conjunction with immunohistochemical assays targeting collagen I, collagen III, fibronectin, α-smooth muscle actin (α-SMA), and ki67. Subsequent recommendations are provided based on our findings. Furthermore, we demonstrate the advantage of an antigen retrieval step in immunohistochemical labeling of paraffin sections. Basic classical histological stainings as HE, GT and elastin were also performed. Comparison of different stainings and labelings was furthermore performed in serial sections, showing that adjacent to the excretory ducts, the tonsillar tissue was particularly composed of collagen I and fibronectin, while the vessel walls were predominantly α-SMA positive. Moreover, PAR-2 immunohistochemical staining was performed, where a small fraction of the cells found in the tonsillar connective tissue were PAR-2 positive (probably a subpopulation of mast cells), as well as the lumen of some excretory ducts and trabeculae. Collagen III on the other hand was only weakly expressed in the tonsils. Proliferating ki67 positive cells were rare. This endeavor serves to furnish the scientific community with reference imagery pertinent to researchers opting for the rabbit palatine tonsil model. The diversity of staining techniques employed herein establishes a foundational repository of images, primed for comparative analysis against pathological conditions. Furthermore, these images hold the potential to illustrate inter-species variations. For instance, they can be juxtaposed against murine or rodent tonsils, or even offer insights into the human context.
Topics: Humans; Rabbits; Animals; Mice; Palatine Tonsil; Immunohistochemistry; Fibronectins; Ki-67 Antigen; Paraffin; Collagen
PubMed: 37804548
DOI: 10.1016/j.acthis.2023.152098