Prevalence and risk factors of post-COVID-19 condition in adults and children at 6 and 12 months after hospital discharge: a prospective, cohort study in Moscow (StopCOVID).

BACKGROUND: Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, amongst previously hospitalised adults and children and assessed risk factors. METHODS: Prospective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge. RESULTS: One thousand thirteen of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95% CI 47-53) in adults and 20% (95% CI 16-24) in children at 6 months, with decline to 34% (95% CI 31-37) and 11% (95% CI 8-14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47). CONCLUSIONS: Although prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

Stop COVID Cohort: An Observational Study of 3480 Patients Admitted to the Sechenov University Hospital Network in Moscow City for Suspected Coronavirus Disease 2019 (COVID-19) Infection.

BACKGROUND: The epidemiology, clinical course, and outcomes of patients with coronavirus disease 2019 (COVID-19) in the Russian population are unknown. Information on the differences between laboratory-confirmed and clinically diagnosed COVID-19 in real-life settings is lacking. METHODS: We extracted data from the medical records of adult patients who were consecutively admitted for suspected COVID-19 infection in Moscow between 8 April and 28 May 2020. RESULTS: Of the 4261 patients hospitalized for suspected COVID-19, outcomes were available for 3480 patients (median age, 56 years; interquartile range, 45-66). The most common comorbidities were hypertension, obesity, chronic cardiovascular disease, and diabetes. Half of the patients (n = 1728) had a positive reverse transcriptase-polymerase chain reaction (RT-PCR), while 1748 had a negative RT-PCR but had clinical symptoms and characteristic computed tomography signs suggestive of COVID-19. No significant differences in frequency of symptoms, laboratory test results, and risk factors for in-hospital mortality were found between those exclusively clinically diagnosed or with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR. In a multivariable logistic regression model the following were associated with in-hospital mortality: older age (per 1-year increase; odds ratio, 1.05; 95% confidence interval, 1.03-1.06), male sex (1.71; 1.24-2.37), chronic kidney disease (2.99; 1.89-4.64), diabetes (2.1; 1.46-2.99), chronic cardiovascular disease (1.78; 1.24-2.57), and dementia (2.73; 1.34-5.47). CONCLUSIONS: Age, male sex, and chronic comorbidities were risk factors for in-hospital mortality. The combination of clinical features was sufficient to diagnose COVID-19 infection, indicating that laboratory testing is not critical in real-life clinical practice.

Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19.

BACKGROUND: The long-term sequalae of COVID-19 remain poorly characterized. We assessed persistent symptoms in previously hospitalized patients with COVID-19 and assessed potential risk factors. METHODS: Data were collected from patients discharged from 4 hospitals in Moscow, Russia between 8 April and 10 July 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire. RESULTS: 2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56 years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32). CONCLUSIONS: Almost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8 months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms.

Patient-reported outcomes for typical single cheek harvesting vs atypical lingual, labial or bilateral cheeks harvesting: a single-center analysis of more than 800 patients.

PURPOSE: The optimal harvesting site for oral grafting in patients with urethral strictures remain controversial, with no study investigating morbidity on large scale. We aimed to compare typical single cheek harvesting vs atypical lingual, labial or bilateral cheeks harvesting in terms of complications and patient-reported outcomes. METHODS: Within 827 patients treated at our referral center with oral graft urethroplasty, we compared typical vs atypical harvesting techniques. A self-administered, semiquantitative, non-validated questionnaire assessed early (10 days) and late (4 months) postoperative complications and patient-reported outcomes. A semiquantitative score was calculated according to patient responses, and it was used to assess early (6 questions) and late (13 questions) patient dissatisfaction status. Patients were defined early and/or late dissatisfied when they scored ≥ 7 and ≥ 10 at the early or late questionnaires, respectively. RESULTS: Between 1998 and 2019, our patients predominantly received typical single cheek harvesting (89% vs 11%), with + 1.5% increase rate per year (p < 0.001). Early and late dissatisfied patients were, respectively, 170 (23%) vs 39 (44%) and 59 (8%) vs 16 (18%) in the typical vs atypical groups. Atypical harvesting was associated with higher rates of early (Odds ratio [OR]: 2.34; 95% Confidence interval [CI] 1.44-3.75; p = 0.001) and late (OR: 2.37; 95%CI 1.22-4.42; p = 0.008) postoperative dissatisfaction. CONCLUSIONS: Typical single cheek harvesting was the preferred surgical option at our center and it was associated with negligible early and late rates of complications and patient's dissatisfaction. Conversely, atypical lingual, labial or bilateral cheeks harvesting was associated with higher complications and frequent patient dissatisfaction.

Assessing in-hospital morbidity after urethroplasty using the European Association of Urology Quality Criteria for standardized reporting.

PURPOSE: To conduct a rigorous assessment of in-hospital morbidity after urethroplasty according with the European Association of Urology (EAU) guidelines for complication reporting. METHODS: We retrospectively (2015-2019) identified 469 consecutive patients receiving urethroplasty (e.g. bulbar urethroplasty with grafts, penile urethroplasty with/without grafts/flaps, Johanson, de novo or revision perineostomy, end-to-end anastomosis, meatoplasty and/or meatotomy) at our tertiary care institution. Complications were graded with Clavien-Dindo score and Comprehensive Complication Index (CCI). Complications were classified in: bleeding no gastrointestinal, cardiac, gastrointestinal, genitourinary, infectious, neurological, oral, wound, miscellaneous, and pulmonary. Logistic regression tested for predictors of in-hospital complications and prolonged hospitalization (> 75th percentile). Kaplan-Meier and Cox regression investigated the effect of complications on failure after urethroplasty. RESULTS: Overall, 161 (34.3%) patients experienced at least one complication. Of those, 47 (10%) experienced two or more complications and 59 (12.6%) experienced at least one Clavien-Dindo ≥ II complication. Only two patients had Clavien-Dindo III complications. Infectious was the most frequent complication, and de novo or revision perineostomy was associated with the highest rate of complications. The occurrence of any complications, as well as complication with Clavien-Dindo ≥ II were associated with prolonged hospitalizations, but not with higher rates of post-urethroplasty failure. CONCLUSIONS: Complications after urethroplasty were common events, but rarely with severe sequelae. Infectious were the most common complications and perineostomy was the type of urethroplasty with the highest rate of complications. The application of the EAU recommendations allowed the identifications of a higher number of complications after urethroplasty if compared with previous reports based on unsupervised chart review.

Human ucMSCs seeded in a decellularized kidney scaffold attenuate renal fibrosis by reducing epithelial-mesenchymal transition via the TGF-ß/Smad signaling pathway.

BACKGROUND: Renal fibrosis occurs largely through epithelial-mesenchymal transition (EMT). This study explored the beneficial effects of a human umbilical cord mesenchymal stem cell-loaded decellularized kidney scaffold (ucMSC-DKS) on renal fibrosis in a rodent model of post-transplantation renal failure, and the underlying mechanism. METHODS: Rat-derived DKSs were examined after preparation, and then recellularized with human ucMSCs to prepare cell-loaded patches. A rat model of renal failure was established after subtotal nephrectomy (STN). The cell patches were transplanted to remnant kidneys. Changes in renal function, histology, EMT, and proteins related to the transforming growth factor-ß (TGF-ß)/Smad signaling pathway in the remnant kidneys were examined 8 weeks after surgery, compared with non-cell patch controls. RESULTS: The DKSs were acellular and porous, with rich cytokine and major extracellular matrix components. The ucMSCs were distributed uniformly in the DKSs. Renal function was improved, renal fibrosis and EMT were reduced, and the TGF-ß/Smad signaling pathway was inhibited compared with controls at 8 weeks after ucMSC-DKS patch transplantation. CONCLUSIONS: The ucMSC-DKS restores renal function and reduces fibrosis by reducing EMT via the TGF-ß/Smad signaling pathway in rats that have undergone STN. It provides an alternative for renal fibrosis treatment.

Surgical treatment of bulbar urethral strictures: tips and tricks.

The surgical treatment of bulbar urethral strictures is still one of the most challenging reconstructive surgery problems. Bulbar urethral strictures are usually categorized as traumatic and non-traumatic strictures depending on the aetiology. The traumatic strictures are caused by trauma and they determine disruption of the urethra with obliteration of the urethral lumen, ending with fibrotic gaps between the urethral ends. Differently, the non-traumatic urethral strictures are mainly caused by catheterization, instrumentation, and infection, or they can also be idiopathic. They are usually asso-ciated with spongiofibrosis of the segment of the urethra that has been involved. Worldwide, two different surgical approaches are currently adopted for bulbar urethral repair: transecting techniques with end-to-end anastomosis and non-transecting techniques followed by grafting. Traumatic obliterated strictures require transection of the urethra allowing complete removal of the fibrotic tissue that involves the urethral ends. Conversely, non-traumatic, non-obliterated urethral strictures require augmentation of the urethral plate using oral mucosa grafts. Nowadays, it is still difficult to choose the correct surgical management for non-obliterated bulbar stricture repair. Indeed, different surgical techniques have been proposed (pedicled flap vs free graft, dorsal vs ventral placement of the graft, non-transecting technique using or non-using free graft, etc.) but none emerged as the best solution since all techniques have showed similar success and complication rates. Consequently, the final choice is still based on surgeon's preferences and patient's characteristics. Within the current manuscript, we like to present some of our tips and tricks that we developed along our prolonged surgical experience on the treatment of bulbar urethral strictures. These might be of interest for surgeons that approach this complex surgery. Moreover, our suggestions want to be useful regardless the type of chosen technique being adaptable for different scenario.

Penile urethroplasty using Orandi's dorsal skin flap: a new technique.

OBJECTIVES: To describe, step by step, a new one-stage dorsal skin flap urethroplasty for penile stricture repair. MATERIALS AND METHODS: The surgery was accomplished through a midline incision on the ventral penile surface, the urethra was fully dissected from the corpora cavernosa and longitudinally opened along its dorsal surface. A penile skin island, based on the dartos fascia flap, was dissected and moved over the corpora cavernosa, and the urethra was moved and sutured over the penile skin flap. RESULTS: Out of the 12 cases, 10 were classified successful and there were two failures. The operating time was 60 min. There was no postoperative fistula or urethral diverticulum. CONCLUSION: Our modified Orandi's technique was easy and feasible, and avoided fistula and diverticulum formation after repair.

Collagen fibrillar structures in vocal fold scarring and repair using stem cell therapy: a detailed histological, immunohistochemical and atomic force microscopy study.

Regenerative medicine opens new opportunities in the repair of cicatricial lesions of the vocal folds. Here, we present a thorough morphological study, with the focus on the collagen structures in the mucosa of the vocal folds, dedicated to the effects of stem cells on the vocal folds repair after cicatricial lesions. We used a conventional experimental model of a mature scar of the rabbit vocal folds, which was surgically excised with a simultaneous implantation of autologous bone marrow-derived mesenchymal stem cells (MSC) into the defect. The restoration of the vocal folds was studied 3 months postimplantation of stem cells and 6 months after the first surgery. The collagen structure assessment included histology, immunohistochemistry and atomic force microscopy (AFM) studies. According to the data of optical microscopy and AFM, as well as to immunohistochemical analysis, MSC implantation into the vocal fold defect leads not only to the general reduction of scarring, normal ratio of collagens type I and type III, but also to a more complete restoration of architecture and ultrastructure of collagen fibres in the mucosa, as compared to the control. The collagen structures in the scar tissue in the vocal folds with implanted MSC are more similar to those in the normal mucosa of the vocal folds than to those of the untreated scars. AFM has proven to be an instrumental technique in the assessment of the ultrastructure restoration in such studies. LAY DESCRIPTION: Regenerative medicine opens new opportunities in the repair of the vocal fold scars. Because collagen is a main component in the vocal fold mucosa responsible for the scar formation and repair, we focus on the collagen structures in the mucosa of the vocal folds, using a thorough morphological study based on histology and atomic force microscopy (AFM). Atomic force microscopy is a scanning microscopic technique which allows revealing the internal structure of a tissue with a resolution up to nanometres. We used a conventional experimental model of a mature scar of the rabbit vocal folds, surgically excised and treated with a mesenchymal stem cells transplant. Our morphological study, primarily AFM, explicitly shows that the collagen structures in the scarred vocal folds almost completely restore after the stem cell treatment. Thus, the modern microscopic methods, and especially AFM are instrumental tools for monitoring the repair of the vocal folds scars.

Treatments of 1242 bulbar urethral strictures: multivariable statistical analysis of results.

PURPOSE: We investigated the success rate of different surgical techniques for bulbar stricture repair. METHODS: Retrospective study of patients with bulbar urethral strictures treated using different techniques. The primary outcome of the study was to evaluate the overall results of treatment (success vs. failure); the secondary outcome was to evaluate the outcome according to any surgical technique. Cysto-urethrography was performed 1 month following surgery. Patients underwent clinical evaluation, uroflowmetry and residual urine measurement every 6 months for 2 years after surgery and later once on year. When patient showed obstructive symptoms, Qmax < 12 ml/s, the urethrography was repeated. Patients who underwent further treatment for recurrent stricture were classified as failures. A bivariable and multivariable statistical analysis was performed. RESULTS: Overall, 1242 patients were included in the study with mean age 40 years (range 12-84). Median stricture length was 4 cm (range 1-8). The median follow-up was 103 months (range 12-362). Over 1242 patients, 916 (73.8%) were success and 326 (26.2%) failures. Fourteen different surgical techniques showed a success rate ranging from 87.5 to 14.3%. The multivariable analysis showed that stricture length was an independent predictor factors for failure: p < 0.0001 CI 1146-1509. End-end anastomosis and oral mucosa graft urethroplasty are independent predictor factor of success after internal urethrotomy failure. CONCLUSIONS: Our results showed that treatment of bulbar urethral stricture is satisfactory on 73.8% of patients, but with a wide range of success rate (from 14.3 to 87.5%) using different techniques. Oral mucosa is greatly superior to the skin as substitute material.

From Aggregates to Porous Three-Dimensional Scaffolds through a Mechanochemical Approach to Design Photosensitive Chitosan Derivatives.

The crustacean processing industry produces large quantities of waste by-products (up to 70%). Such wastes could be used as raw materials for producing chitosan, a polysaccharide with a unique set of biochemical properties. However, the preparation methods and the long-term stability of chitosan-based products limit their application in biomedicine. In this study, different scale structures, such as aggregates, photo-crosslinked films, and 3D scaffolds based on mechanochemically-modified chitosan derivatives, were successfully formed. Dynamic light scattering revealed that aggregation of chitosan derivatives becomes more pronounced with an increase in the number of hydrophobic substituents. Although the results of the mechanical testing revealed that the plasticity of photo-crosslinked films was 5⁻8% higher than that for the initial chitosan films, their tensile strength remained unchanged. Different types of polymer scaffolds, such as flexible and porous ones, were developed by laser stereolithography. In vivo studies of the formed structures showed no dystrophic and necrobiotic changes, which proves their biocompatibility. Moreover, the wavelet analysis was used to show that the areas of chitosan film degradation were periodic. Comparing the results of the wavelet analysis and X-ray diffraction data, we have concluded that degradation occurs within less ordered amorphous regions in the polymer bulk.

3D reconstruction of CT scans aid in preoperative planning for sarcomatoid renal cancer: A case report and mini-review.

Contrast-enhanced multi-slice computed tomography (MSCT) is commonly used in the diagnosis of complex malignant tumours. This technology provides comprehensive and accurate information about tumour size and shape in relation to solid tumours and the affected adjacent organs and tissues. This case report demonstrates the benefit of using MSCT 3D imaging for preoperative planning in a patient with late-stage (T4) sarcomatoid renal cell carcinoma, a rare renal malignant tumour. The surgical margin on the liver was negative, and no metastases to veins, lungs or other organs were detected by abdominal and chest contrast-enhanced CT. Although sarcomatoid histology is considered to be a poor prognostic factor, the patient is alive and well 17 months after surgery. The MSCT imaging modality enables 3D rendering of an area of interest, which assists surgical decision-making in cases of advanced renal tumours. In this case, as a result of MSCT 3D reconstruction, the patient received justified surgical treatment without compromising oncological principles.

EVs vs. EVs: MSCs and Tregs as a source of invisible possibilities.

Extracellular vesicles (EVs) are produced by various cells and exist in most biological fluids. They play an important role in cell-cell signaling, immune response, and tumor metastasis, and also have theranostic potential. They deliver many functional biomolecules, including DNA, microRNAs (miRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA), lipids, and proteins, thus affecting different physiological processes in target cells. Decreased immunogenicity compared to liposomes or viral vectors and the ability to cross through physiological barriers such as the blood-brain barrier make them an attractive and innovative option as diagnostic biomarkers and therapeutic carriers. Here, we highlighted two types of cells that can produce functional EVs, namely, mesenchymal stem/stromal cells (MSCs) and regulatory T cells (Tregs), discussing MSC/Treg-derived EV-based therapies for some specific diseases including acute respiratory distress syndrome (ARDS), autoimmune diseases, and cancer.

Liquid Biopsy in Diagnosis and Prognosis of Non-Metastatic Prostate Cancer.

Currently, sensitive and specific methods for the detection and prognosis of early stage PCa are lacking. To establish the diagnosis and further identify an appropriate treatment strategy, prostate specific antigen (PSA) blood test followed by tissue biopsy have to be performed. The combination of tests is justified by the lack of a highly sensitive, specific, and safe single test. Tissue biopsy is specific but invasive and may have severe side effects, and therefore is inappropriate for screening of the disease. At the same time, the PSA blood test, which is conventionally used for PCa screening, has low specificity and may be elevated in the case of noncancerous prostate tumors and inflammatory conditions, including benign prostatic hyperplasia and prostatitis. Thus, diverse techniques of liquid biopsy have been investigated to supplement or replace the existing tests of prostate cancer early diagnosis and prognostics. Here, we provide a review on the advances in diagnosis and prognostics of non-metastatic prostate cancer by means of various biomarkers extracted via liquid biopsy, including circulating tumor cells, exosomal miRNAs, and circulating DNAs.

Isolation of Circulating Tumor Cells from Seminal Fluid of Patients with Prostate Cancer Using Inertial Microfluidics.

Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min-1, respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF samples of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF sample in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.

A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021.

Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID. Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery. Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study. Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms. Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane. Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.

Frontiers in urethra regeneration: current state and future perspective.

Despite the positive achievements attained, the treatment of male urethral strictures and hypospadiases still remains a challenge, particularly in cases of severe urethral defects. Complications and the need for additional interventions in such cases are common. Also, shortage of autologous tissue for graft harvesting and significant morbidity in the location of harvesting present problems and often lead to staged treatment. Tissue engineering provides a promising alternative to the current sources of grafts for urethroplasty. Since the first experiments in urethral substitution with tissue engineered grafts, this topic in regenerative medicine has grown remarkably, as many different types of tissue-engineered grafts and approaches in graft design have been suggested and testedin vivo. However, there have been only a few clinical trials of tissue-engineered grafts in urethral substitution, involving hardly more than a hundred patients overall. This indicates that the topic is still in its inception, and the search for the best graft design is continuing. The current review focuses on the state of the art in urethral regeneration with tissue engineering technology. It gives a comprehensive overview of the components of the tissue-engineered graft and an overview of the steps in graft development. Different cell sources, types of scaffolds, assembling approaches, options for vascularization enhancement and preclinical models are considered.