Protein family annotation for the Unified Human Gastrointestinal Proteome by DPCfam clustering.

Technological advances in massively parallel sequencing have led to an exponential growth in the number of known protein sequences. Much of this growth originates from metagenomic projects producing new sequences from environmental and clinical samples. The Unified Human Gastrointestinal Proteome (UHGP) catalogue is one of the most relevant metagenomic datasets with applications ranging from medicine to biology. However, the low levels of sequence annotation may impair its usability. This work aims to produce a family classification of UHGP sequences to facilitate downstream structural and functional annotation. This is achieved through the release of the DPCfam-UHGP50 dataset containing 10,778 putative protein families generated using DPCfam clustering, an unsupervised pipeline grouping sequences into single or multi-domain architectures. DPCfam-UHGP50 considerably improves family coverage at protein and residue levels compared to the manually curated repository Pfam. In the hope that DPCfam-UHGP50 will foster future discoveries in the field of metagenomics of the human gut, we release a FAIR-compliant database of our results that is easily accessible via a searchable web server and Zenodo repository.

Survival and complications after carotid resection for head and neck squamous cell carcinoma: A systematic review and pooled analysis.

OBJECTIVE: The aim of this study is to analyze oncologic outcomes and complications rate after common or internal carotid artery (CCA/ICA) resection for head and neck squamous cell carcinoma (HNSCC). METHODS: This study was conducted in conformity with the PRISMA statement. A systematic review and pooled analysis was performed for overall survival (OS), disease specific survival (DSS) (primary outcomes), and perioperative death rate (secondary outcome). RESULTS: A total of 276 patients (males: 76.7%, n = 191/249) with a median age of 59 years (n = 239/276; 95% CI 55.0-61.7) who underwent CCA/ICA resection for HNSCC were included. The median follow-up time was 11 months (n = 276). Estimated pooled OS rates (95% CI) at 1 and 2 years were 52.7% (46.9-59.2) and 29.8% (24.3-36.5), respectively. The median OS (95% CI) was 14 months (12-17). Estimated pooled DSS rates (95% CI) at 1 and 2 years were 58.6% (52.7-65.2) and 34.6% (28.5-41.9), respectively. The median DSS (95% CI) was 16 months (14-19). The perioperative death rate was 6.9% (n = 19/276). CONCLUSIONS: CCA/ICA resection should be considered as a treatment option for accurately selected patients. Multicentric prospective studies are recommended to develop a predictive score guiding the decision-making process.

Sleep quality burden in chronic rhinosinusitis with nasal polyps and its modulation by dupilumab.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with a substantial burden on patients' quality of life and impaired sleep quality. The most common CRSwNP endotype is characterized by type 2 inflammation, with enhanced production of interleukin (IL)-4, IL-5, and IL-13. Dupilumab is a monoclonal antibody against IL-4 receptor-α, which inhibits both IL-4 and IL-13 signaling, and was recently approved for treatment of CRSwNP. OBJECTIVE: We investigated the effect of dupilumab on the sleep quality of patients with CRSwNP in a real-life setting. METHODS: Patients were evaluated at baseline and after 1 and 3 months of dupilumab treatment by means of the Epworth sleepiness scale (ESS), insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), and sinonasal outcome test 22 (SNOT-22) sleep domain. RESULTS: A total of 29 consecutive patients were enrolled, and their baseline sleep quality assessment were as follows: ESS of 7.9 (± 4.5); ISI of 13.1 (± 6.2); PSQI of 9.2 (± 3.7); and SNOT-22 sleep domain of 12.1 (± 4.2). Excessive daily sleepiness, insomnia, and globally impaired sleep quality were present in 24.1%, 79.3%, and 93.1% respectively. Treatment with dupilumab was associated with significant improvement in ESS, ISI, PSQI, and SNOT-22 sleep domain with concomitant reduction of the proportion of patients with insomnia and globally impaired sleep quality. CONCLUSION: CRSwNP was associated with a significant impact on global sleep quality, in particular, insomnia, and treatment with dupilumab induced a rapid improvement (after 1 single month of treatment) in all the sleep quality parameters, suggesting that sleep disturbances should be more carefully evaluated as an additional outcome in these patients.

Postoperative Morbidity of Different Tonsillectomy Techniques: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To compare different tonsillectomy techniques in terms of postoperative bleeding incidence and postoperative pain. METHODS: An arm-based network analysis was conducted using a Bayesian hierarchical model. The primary and secondary outcomes were postoperative bleeding incidence and mean postoperative pain score. RESULTS: A total of 6464 patients were included for five different interventions (cold dissection tonsillectomy; extracapsular coblation tonsillectomy; intracapsular coblation tonsillectomy [ICT]; bipolar diathermy tonsillectomy [BDT]; monopolar diathermy tonsillectomy). ICT showed the lowest absolute risk (4.44%) of postoperative bleeding incidence (73.31% chance of ranking first) and the lowest mean postoperative pain score (1.74 ± 0.68) with a 94.0% chance of ranking first, whereas BDT showed both the highest absolute risk of bleeding incidence (10.75%) and the highest mean postoperative pain score (5.67 ± 1.43). CONCLUSIONS: ICT seems to offer better postoperative outcomes, in terms of reduced risk of bleeding and reduced pain. Further prospective studies are advised to confirm these findings. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1696-1704, 2024.

Preoperative systemic inflammatory markers as prognostic factors in differentiated thyroid cancer: a systematic review and meta-analysis.

BACKGROUND: Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid tumors. However, the role of inflammation markers in differentiated thyroid carcinoma (DTC) is still uncertain. OBJECTIVE: This meta-analysis aimed to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with DTC. METHODS: Studies investigating the association between survival and preoperative circulating inflammatory markers in DTC patients were included. The primary outcome was disease-free survival (DFS). Cumulative logarithms of the hazard ratio (log-HRs) with 95% CI were calculated through the inverse variance method using a random-effects model. RESULTS: A total of 7599 patients with a mean age of 48.89 (95% CI 44.16-53.63) were included. The estimated pooled log-HRs for DFS were 0.07 for NLR (95% CI -0.12-0.26; p = 0.43), -0.58 for LMR (95% CI -1.21-0.05; p = 0.06), and 0.01 (95% CI 0-0.01; p = 0.21) for PLR. CONCLUSIONS: Our meta-analysis showed no association between NLR, PLR, LMR and DFS in DTC; however, more prospective data are needed to better define the association between inflammatory status and prognosis of DTC.

Barriers to Human Papillomavirus Vaccination Initiation and Completion among Adults Aged 18-26 Years in a Large Healthcare System.

Human papillomavirus (HPV) is a common sexually transmitted infection, with over 40% prevalence in the US. Oropharyngeal cancers (OPCs) driven by high-risk HPV are increasing (up to 90%), with HPV vaccination being the only prevention available. The aim of this study was to investigate HPV vaccination among patients aged between 18 and 26 years old with at least one encounter at a large healthcare system and identify sociodemographic factors associated with vaccine initiation and completion. A cross-sectional retrospective study was conducted between 2018 and 2021, including 265,554 patients identified from the Clinical Data Warehouse. HPV vaccination status by age, sex, race/ethnicity, insurance type, primary care (PCP) visits in the past year, alcohol, tobacco, illicit drug use, and age at vaccination was examined. Overall, 33.6% of females and 25.4% of males have completed the HPV vaccine. Black Americans were 35% more likely to initiate the vaccine than White Americans but were less likely to complete the entire course. Overall, HPV vaccination prevalence was far below the Health People 2030 goal of 80%, especially in young males. This low rate is troubling, since many patients had a PCP visit and remained unvaccinated, which serves as a missed opportunity for vaccination.

Functional outcomes of soft palate reconstruction after oncologic surgery: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to analyze functional outcomes of soft palate reconstruction after oncologic surgery. METHODS: This study was conducted in conformity with the PRISMA statement. A single arm meta-analysis was performed for feeding tube dependence (FTD) (primary outcome), velopharyngeal insufficiency (VPI) and hypernasality (HN) (secondary outcomes) incidences. RESULTS: A total of 510 patients (males: 77.75%, n = 353/454) with a median age of 58 years (n = 480/510; 95% CI 57.0-61.0) who underwent soft palate surgical resection with primary reconstruction were included. Overall, the cumulative FTD rate was 1.55% (n = 28/510; 95% CI 0.24-3.96%), the VPI rate was 22.18% (n = 119/379; 95% CI 12.99-33.02%), and the HN rate was 33.01% (n = 88/234; 95% CI 19.03-46.61%). CONCLUSIONS: Soft palate reconstruction results in a low incidence of FTD, and most patients resume a full oral diet. Both obturators, primary closure, local and free flaps seem good reconstructive options. Nevertheless, more specific postoperative functional deficiencies like VPI and HN owns higher incidences, potentially affecting the quality of the swallowing and speaking function and the patient's quality of life.

Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. METHODS: PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects. RESULTS: Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7-88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7-89.4), 53.9% (38.5-75.3), and 39.1% (25.2-60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0-95.3), 67.8% (50.9-90.3), and 58.9% (42.7-81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9-104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7-80.6), 53.2% (42.2-66.9), and 40.4% (29.6-55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5-99.1), 77.0% (64.4-92.0), and 67.1% (51.6-87.3). CONCLUSIONS: TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1425-1433, 2023.

Functional outcomes and complications of total glossectomy with laryngeal preservation and flap reconstruction: A systematic review and meta-analysis.

OBJECTIVE: To analyze the functional outcomes and complications of total glossectomy with laryngeal preservation and reconstruction with free or pedicled flaps. METHODS: A search was conducted using Pubmed/MEDLINE, Cochrane Library, Scopus, and Google Scholar databases. A single arm meta-analysis was performed for feeding tube dependence (FTD), tracheostomy dependence (TD), and speech intelligibility (SI) rates. Peri-operative sequels and complications were evaluated as secondary outcomes. RESULTS: A total number of 642 patients (median age: 54.2 years; 95% CI 52.1-58) were included. Functional assessment was performed after a median of 12 months (n = 623/642; 95% CI 10.6-12). Overall, the cumulative FTD rate was 22.9% (n = 188/627; 95% CI 10.2-38.7), the TD rate was 7.3% (n = 95/549; 95% CI 1.9-15.8), and the SI was 91.1% (n = 314/409; 95% CI 80.7%-97.8). The cumulative complication rate was 33.1% (n = 592/642). Eighteen patients (n = 18/592; 3.0%) experienced a major fistula, while aspiration pneumonia occurred in 17 cases (n = 17/592; 2.8%). CONCLUSIONS: Total glossectomy with laryngeal preservation and pedicled/free flaps reconstruction may guarantee good functional results and an acceptable quality of life. Further prospective studies are advised to define clinical guidelines about proper patients' and flaps' selection.

Use, Abuse, and Misuse of Nasal Medications: Real-Life Survey on Community Pharmacist's Perceptions.

BACKGROUND: Medication overuse is an increasing global problem, especially for those rhinology diseases whose management requires over-the-counter drugs. This observational community pharmacy-based study aimed to investigate the actual use of the best-selling topical nasal medications and to characterize the clinical issues underlying their query through the pharmacist's perception. METHODS: In the pilot phase, a preliminary survey was developed by a team of researchers and tested on a small sample of practitioners to assess usability and intelligibility. Eventual amendments were made according to the feedback obtained, and the final version was submitted to practitioners working in 376 pharmacies evenly distributed over the Italian territory. RESULTS: Two groups of customers (18-30 years old and 60-75 years old) were the ones who most frequently purchased topical decongestants. The dosage applied for sympathomimetic amines was higher than recommended in up to 44.4% and the duration of use longer than 5 days in up to 31.9% of the cases. Patients' queries of alpha agonists and topical corticosteroids resulted in significantly higher numbers than practitioners' prescriptions. Allergic rhinitis was the most common disease affecting patients seeking sympathomimetic amines. CONCLUSIONS: The prolonged use of sympathomimetic amines in patients suffering from rhinology diseases is a significant problem that requires greater attention in terms of social education and surveillance.

Different surgical approaches in retropharyngeal lymph nodes dissection in head and neck cancer: A systematic review.

OBJECTIVE: To perform a systematic review of studies analyzing different surgical approaches in the treatment of retropharyngeal lymph node (RPLN) metastases. METHODS: The study was performed according to the PRISMA guidelines. RESULTS: Twenty-one studies were included in the review, for a total of 481 patients (median age: 55.8 years; male: n = 279/393, 70.1%). The success rate by type of approach was 100% (n = 233/233), 93.5% (n = 29/31), 95.7% (n = 67/70), 100% (n = 14/14), 100% (n = 82/82), and 100% (n = 51/51) in the transcervical, endoscopic-assisted transcervical, TORS, transoral, maxillary swing and transmandibular cohorts, respectively. The complication rate by type of approach was 11.2% (n = 26/233), 48.4% (n = 15/31), 48.6% (n = 34/70), 14.3% (n = 2/14), 6.1% (n = 5/82) in the transcervical, endoscopic-assisted transcervical, TORS, transoral and maxillary swing cohorts, respectively. Oncological outcomes were reported by 17 studies (n = 404/481; 84%). Overall, after a median follow-up of 28 months (n = 339/481; IQR 23-40.5), no evidence of disease (NED) was found in 238 patients (58.9%), recurrence at the RPLNs in 14 (3.5%), local recurrence in 22 (5.4%), regional recurrence in 23 (5.7%), locoregional recurrence in 16 (4%), distant metastases in 42 (10.4%), death from disease in 36 (8.9%), death from other cause in 23 (5.7%), and death from unspecified cause in 26 (6.4%). CONCLUSIONS: Further prospective randomized controlled trials are needed to provide direct comparison between different approaches for RPLNs dissection.

Nasal cytology as a reliable non-invasive procedure to phenotype patients with type 2 chronic rhinosinusitis with nasal polyps.

Background: The identification of type-2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) acquires a crucial role in the endotypization needed for selecting patients for biological drugs targeting type-2 inflammation: to date, the parameters used include systemic and histological biomarkers. The aim of this study was to investigate whether nasal cytology could identify type-2 inflammation in patients with CRSwNP. Methodology: Thirty-three consecutive patients with CRSwNP underwent nasal cytology sampling at the level of the lower nasal turbinate, and of the polypoid tissue, and surgical polyp tissue sample was collected. The cellularity of the 3 collected samples were compared. Results: Mean nasal polyp tissue, nasal polyps cytology and inferior turbinate cytology eosinophils counts were 43.7 ± 39.6 cells/HPF, 32.8 ± 44.7 cells/HPF and 27.6 ± 58.0 cells/HPF respectively with inferior turbinate cytology eosinophils significantly lower than nasal polyp tissue count (p = 0.007). Both mean nasal polyps cytology eosinophils and mean inferior turbinate cytology eosinophils were significantly higher in patients with type-2 CRSwNP (52.5 ± 67.0 cells/HPF vs 12.2 ± 17.3 cells/HPF, p = 0.012, and 32.0 ± 62.1 cells/HPF vs 2.9 ± 2.9 cells/HPF, p = 0.020 respectively). Conclusions: Nasal cytology is suitable tool for assessing local biomarkers of type-2 inflammation in CRSwNP.

Three-dimensional exoscope-assisted single-stage tracheal resection.

The three-dimensional (3D) 4K exoscope is a surgical tool recently introduced in numerous fields of otolaryngology, such as microvascular surgery, otology, and laryngology. However, other surgical fields may also benefit from this technology. In this case, a single-stage tracheal resection was planned with the aid of the 3D 4K exoscope, in a 75-year-old female with post-tracheostomy tracheal stenosis. High-quality magnification of the surgical field was obtained, with facilitated skeletonization of the laryngotracheal axis. The exoscope provided greater involvement in surgery and allowed more interactions among all operating room personnel and learners, as they could access the same field of view of the first surgeon, as well as perceiving depth of the surgical field with 3D technology. The exoscope represents a valid application in open surgery performed for laryngotracheal stenosis, with advantages of enhancing training and education, allowing precise surgical dissection, and reducing risks of iatrogenic damage to surrounding structures.

DPCfam: Unsupervised protein family classification by Density Peak Clustering of large sequence datasets.

Proteins that are known only at a sequence level outnumber those with an experimental characterization by orders of magnitude. Classifying protein regions (domains) into homologous families can generate testable functional hypotheses for yet unannotated sequences. Existing domain family resources typically use at least some degree of manual curation: they grow slowly over time and leave a large fraction of the protein sequence space unclassified. We here describe automatic clustering by Density Peak Clustering of UniRef50 v. 2017_07, a protein sequence database including approximately 23M sequences. We performed a radical re-implementation of a pipeline we previously developed in order to allow handling millions of sequences and data volumes of the order of 3 TeraBytes. The modified pipeline, which we call DPCfam, finds ∼ 45,000 protein clusters in UniRef50. Our automatic classification is in close correspondence to the ones of the Pfam and ECOD resources: in particular, about 81% of medium-large Pfam families and 72% of ECOD families can be mapped to clusters generated by DPCfam. In addition, our protocol finds more than 14,000 clusters constituted of protein regions with no Pfam annotation, which are therefore candidates for representing novel protein families. These results are made available to the scientific community through a dedicated repository.

Reply to Adrian, G. Comment on "Russo et al. Does Tumor Volume Have a Prognostic Role in Oropharyngeal Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis. Cancers 2022, 14, 2465".

The authors raised some interesting points [...].

Surgical prevention of pharyngocutaneous fistula in salvage total laryngectomy: a systematic review and network meta-analysis.

PURPOSE: To compare the efficacy of different reconstructive techniques in preventing pharyngocutaneous fistula (PCF) after salvage total laryngectomy (STL). METHODS: An arm-based network analysis was conducted using a Bayesian hierarchical model according to the PRISMA-NMA guidelines. RESULTS: A total of 1694 patients with a median age of 64 years (n = 1569, 95% CI: 62-66 years) were included. If compared to primary pharyngeal closure alone, only a pedicled flap onlay (PFO) showed a statistically significant reduction in PCF rate (OR: 0.35, CI: 0.20-0.61). PFO seemed to perform better than other treatments according to the rank probabilities test (39.9% chance of ranking first). CONCLUSIONS: A pedicled flap placed with an overlay technique might be preferred over a patch reconstruction to prevent PCF after STL.

Long-standing gustatory and olfactory dysfunction in COVID-19 patients: a prospective study.

PURPOSE: Our study aimed to describe recovery of gustatory dysfunction (GD) and olfactory dysfunction (OD) in COVID-19 patients, and to analyze variables associated with early or late recovery. METHODS: Telephone surveys were administered during an 18-month follow-up after COVID-19 diagnosis. One hundred and thirty-two included patients rated olfactory and gustatory function at each follow-up. RESULTS: One hundred and twenty-nine patients reported GD, of whom 91 (70.5%) reported severe GD, and 99 patients reported OD, of whom 84 (84.9%) reported severe OD. Seventy-two/129 (55.8%) and 52/99 (52.5%) patients reported an improvement in GD and in OD during the first 7 days from the onset, respectively. At 3-month follow-up, 110/120 patients (85.3%) recovered from GD, while 80/99 patients (80.8%) recovered from OD. At 18-month follow-up, a total of 120/129 patients (93.0%) recovered from GD and 86/99 patients (86.9%) recovered from OD; while 10 patients (7.0%) still reported GD and 13 patients (13.1%) still reported OD. Severe GD/OD at presentation were associated with late complete recovery of taste/smell (p = 0.019 and p = 0.034, respectively). Improvement over the first 7 days from onset was significantly associated with faster recovery (p < 0.001). CONCLUSIONS: More than 80% of patients reported complete recovery of olfactory/gustatory function in the first 3 months after symptom onset. At 18-month follow-up, patients reporting complete recovery of gustatory and olfactory function were 93% and 87%, respectively. Severity of chemosensory dysfunction at the onset was negatively correlated to recovery, and improvement of taste and/or smell function within the first 7 days from symptom onset was significantly associated with early resolution.