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Background: Superficial cutaneous fungal infections are common dermatologic conditions. A significant proportion do not present with typical clinical findings. However, the 10 potassium hydroxide (KOH) smear, a simple bedside test, is often underused when diagnosing cutaneous fungal infections. Aims: We aimed to evaluate whether KOH smear results altered dermatologists' diagnosis and management, and the factors that influenced its ability to detect cutaneous fungal infections. Methods: A total of 373 patients with suspected cutaneous fungal infection were identified retrospectively from the dermatology database of inpatient referrals in a Singapore tertiary hospital between 1 January 2017 and 30 June 2020. The dermatologists' eventual diagnoses, based on their assessment until 2 months post-discharge to allow consideration of KOH smear results and response to treatment, were taken as a gold standard. Statistical analyses evaluated for changes between initial and eventual diagnoses and management relative to the KOH smear. Use of topical steroids, topical and/or systemic antifungals before skin sampling, and whether sampling was done by dermatologically-trained personnel, were assessed for association with KOH smear positivity in eventually diagnosed cases. Results: The percentage of uncertain diagnoses was reduced, and the use of topical antifungal as the sole treatment significantly changed after the KOH smear result was available. The adjusted odds ratio of a positive KOH smear in eventually diagnosed cases was 0.19 when systemic antifungals were used before skin sampling, and 3.03 if sampling was performed by a dermatologically-trained person. Limitations: Limitations of our study include dependence on retrospective medical records which may result in misclassification bias and the limited generalisability of our results to patients managed by non-dermatologists. Conclusions: KOH smear is a useful adjunct in diagnosing and managing cutaneous fungal infections. Clinicians should consider the presence of confounders affecting KOH smears when making an overall clinical diagnosis. Focused training of personnel on skin sample collection may improve the detection rate of KOH smear. Keywords: Candidiasis, dermatomycoses, Malassezia, potassium hydroxide, tinea, Author(s): Xuan Qi Koh (corresponding author) [1]; Huirong Han [1]; Liang Shen [2]; Nisha S. Chandran [1,3] Introduction Cutaneous fungal infections are one of the most common dermatological conditions referred [...]

Introduction: Deep mycoses acquired by penetrating trauma to the skin can have varied and sometimes atypical morphological presentations resulting in diagnostic dilemmas and delay in treatment onset. Histopathology can be a useful tool in not only diagnosing but also differentiating various deep mycoses. Aims and Objectives: To observe various morphological presentations and histopathological features of deep fungal infections. Materials and Methods: A retrospective multi-centric study was conducted from 2010 to 2020 at 16 centres. The cases with diagnoses of various deep mycoses were included in the study. The patients presenting with cutaneous manifestations were included in the study. Their demographic details, history, presenting signs and symptoms, morphological presentations, histopathological features and treatment details were collected from the case sheets. Results: A total of 124 cases were found from the case records. The most common type was chromoblastomycosis (42) followed by mycetoma (28) and rhinosporidiosis (17). The mean age was 43.76 ± 5.44 years. The average duration of symptoms before presentation was between 2 months to 10 years (average 2.5 ± 1.33 years). Male to female ratio was 1:0.7. Prior history of trauma was recorded in 36 of cases. Chromoblastomycosis cases presented with verrucous to atrophic plaques with black dots on the surface and histopathology findings included pesudoepitheliomatous hyperplasia, epithelioid cell granulomas, copper penny bodies within granulomas and abscesses. Rhinosporidiosis cases had polypoid grape-like lesions in the nose and eyes most commonly with histopathology findings of abundant thick-walled sporangia in dermis packed with thousands of spores. Eumycetoma patients had pigmented, indurated swelling with multiple sinuses discharging black granules and histopathology showed dermal abscesses and foreign body granulomatous reaction with PAS-positive hyphae. Histoplasmosis patients presented with few to multiple nodulo-pustular lesions on skin and palatal ulcers while small basophilic bodies packed in the cytoplasm of histiocytes were noted in histopathology. Phaeohyphomycosis cases presented as deep-seated cystic lesions and biopsy revealed deepithelialized cysts in the dermis or hypodermis with lumen showing necro inflammatory debris and fungal hyphae. Sporotrichosis cases had erythematous, tender nodules and papules either as single lesions or as multiple lesions arranged in a linear fashion and histopathology showed pseudoepitheliomatous hyperplasia of epidermis, loose to well-defined epithelioid cell granulomas and microabscesses. Spores were found in two cases. Cryptococcosis patient had multiple umbilicated lesions resembling giant molluscum contagiosum loose epithelioid cell granulomas and medium-sized spores lying in both intra and extracellularly on histopathology. Penicilliosis patients had nodulo-pustular lesions and histopathology showed an admixture of histiocytes, epithelioid cells, plasma cells, lymphocytes and polymorphs in the dermis with the presence of yeast-like spores in the cytoplasm of histiocytes and epithelioid cells. Entomophthoromycosis cases presented with asymptomatic subcutaneous firm swelling with loss of skin pinchability. Conclusion: Though clinical findings of deep fungal infections are characteristic similar morphology and atypical presentations can be sometimes confusing. Histopathology is useful for confirming the diagnosis. Keywords: Clinical presentation, deep mycoses, histopathology, morphologies, Author(s): Subhra Dhar (corresponding author) [1]; Swetalina Pradhan [2]; Abhijit Saha [3]; Gautam Mazumder [4]; Sudip K. Ghosh [5]; Manas Biswas [6]; Abhishek De [7]; Pradip Srivastava [8]; Amrita Madnani [...]

Abstract Introduction: The aim of this study was to analyse the effect of perioperative dexmedetomidine (DEX) application on stress response, post-operative pain and prognosis in patients undergoing gynaecologic laparoscopy. Patients and Methods: One hundred and sixty-eight patients admitted for gynaecologic laparoscopic surgery from May 2020 to November 2022 were included in the study. The patients were randomly divided into pre-operative DEX group (n = 56), intraoperative DEX group (n = 56) and post-operative DEX group (n = 56) according to the application of DEX in the perioperative period. The visual analogue scale (VAS), time awake, extubation time, pneumoperitoneum time, post-anaesthesia care unit (PACU) stay time and Richmond agitation-sedation scale score (RASS) were recorded. Results: Patients in both the pre-operative and intraoperative DEX groups had substantially shorter wakeup and extubation times than those in the post-operative DEX group. Patients in the pre-operative DEX group had considerably shorter wakeup and extubation times than those in the intraoperative DEX group, and their pneumoperitoneum time was significantly shorter than that of the post-operative DEX group (P < 0.001). The RASS scores of the pre-operative DEX group and intraoperative DEX group were significantly lower than those of the post-operative DEX group at 1 h, 6 h and 12 h after surgery. Meanwhile, at all time periods, the RASS scores of patients in the pre-operative DEX group were considerably lower than those in the intraoperative DEX group (P < 0.01). The VAS scores of patients in the pre-operative DEX group and intraoperative DEX group were evidently lower than those in the post-operative DEX group at 0.5 h, 2 h and 12 h postoperatively, and the VAS scores of patients in the pre-operative DEX group were markedly lower than those in the intraoperative DEX group (P 2-12 h and >12-24 h postoperatively (P < 0.001). The incidence of nausea and vomiting in the intraoperative DEX group was significantly lower than that in the post-operative DEX group from 0 to 2 h after surgery (P < 0.05). The incidence of adverse reactions was not significantly different amongst the three groups of patients (P > 0.05). Conclusion: Pre-operative and intraoperative application of DEX can help reduce post-operative pain and stress responses, help patients recover quickly after surgery and improve patient prognosis, especially the pre-operative application of DEX. Keywords: Dexmedetomidine, gynaecologic laparoscopic surgery, pain, prognosis, stress response, Author(s): Xing Wu [1]; Yuhang Xing [2]; Lili Pan (corresponding author) [1]; Mao Chai (corresponding author) [1] INTRODUCTION With the rapid development of minimally invasive techniques, laparoscopic surgery has become [...]

Objectives: In this study, we evaluated the risk factors for urinary retention after freehand transrectal ultrasound (TRUS) guided transperineal prostate biopsy (TPB). Patients and Methods: Data from 102 cases of freehand TPB at a single institution were retrospectively collected and analyzed. All patients underwent magnetic resonance imaging (MRI)-TRUS cognitive fusion TPB using a transperineal needle guide, with systematic biopsies from 10 prostate sectors and additional MRI-guided targeted biopsies. Exclusions comprised patients with coagulation abnormalities, prior prostate surgeries including biopsy, active urinary tract infection, or a lack of pre-biopsy multiparametric MRI. Results: 14/102 (13.72) had urinary retention and required urethral catheterization for voiding difficulty or discomfort along with a bladder volume of ≥500 ml. Patients with retention exhibited significantly larger prostate volumes (median 75 cc vs. 40 cc; P < 0.05). Receiver operating curve analysis revealed a prostate volume threshold of 57.5 cc and a core number cutoff of 23 for predicting post-TPB urinary retention, with sensitivities of 78.57 and 85.71, specificities of 75 and 82.95, positive predictive values of 33.33 and 44.44, and negative predictive values of 95.75 and 97.33, respectively, whereas the number of biopsy cores correlated positively with the development of urinary retention (median 25 vs. 22; P < 0.05). Urinary retention was independent of the patient's age, comorbidities, presenting prostate-specific antigen levels, prebiopsy severity of lower urinary tract symptoms, and use of alpha-blockers. Conclusion: Patients with larger prostates and higher number of biopsy cores are at a higher risk of postfreehand TPB urinary retention and should receive appropriate counselling. Targeted biopsies alone, rather than a full template, may help mitigate urinary retention in these high-risk groups., Author(s): Shashank Agrawal [1]; Vivek Dadasaheb Patil [2]; Vishnu Prasad [1]; Arun Ramadas Menon [2]; Ginil Kumar Pooleri (corresponding author) [2] INTRODUCTION The utilization of transperineal prostate biopsy (TPB) for [...]

Introduction: Intradetrusor onabotulinumtoxinA (Botox) injections, to treat idiopathic overactive bladder (OAB), can be performed in the office setting under local analgesia alone or in the operating room (OR) under local and/or sedation. The objective of this study was to compare the symptomatic improvement in patients with OAB who underwent treatment with intradetrusor onabotulinumtoxinA injections in an in-office versus the OR setting. Methods: We performed a multicenter retrospective cohort study of women with the diagnosis of refractory non-neurogenic OAB who elected to undergo treatment with intradetrusor onabotulinumtoxinA injections between January 2015 and December 2020. The electronic medical records were queried for all the demographic and peri-procedural data, including the report of subjective improvement post procedure. Patients were categorized as either 'in-office' versus 'OR' based on the setting in which they underwent their procedure. Results: Five hundred and thirty-nine patients met the inclusion criteria: 297 (55) in the in-office group and 242 (45) in the OR group. A total of 30 (5.6) patients reported retention after their procedure and it was more common in the in-office group (8.1) versus the OR group (2.5), (P = 0.003). The rate of urinary tract infection within 6 months of the procedure was higher in the OR group (26.0 vs. 16.8, P = 0.009). The overall subjective improvement rate was 77 (95 confidence interval: 73-80). Patients in the OR group had a higher reported improvement as compared to the in-office group (81.4 vs. 73.3, P = 0.03). Conclusions: In this cohort study of patients with OAB undergoing intradetrusor onabotulinumtoxinA injections, post procedural subjective improvement was high regardless of the setting in which the procedure was performed., Author(s): James H. Ross (corresponding author) [1]; Megan Abrams [2]; Sandip P. Vasavada [3]; Jeffrey M. Mangel [2]; Cecile A. Ferrando [1] INTRODUCTION Overactive bladder (OAB) is a common and [...]

Introduction: Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). Methods: We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003-2022). Surgical and clinicopathological features and oncological outcomes are presented. Results: The mean age was 28.27 years (15-48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54 and 21.21 in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06) required adjunctive procedures. Thirteen patients (17.8) had ≥ class 3 Clavien-Dindo complications and postoperative mortality occurred in 5 (6.8) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7, 45.2, and 15.1, respectively. Seven patients underwent metastasectomy. An 85 size reduction in the size of RPLN predicted necrosis. There was 71.4 concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range - 13.25-47.84). The 2-year recurrence-free survival (RFS) rate was 93 (95 confidence interval [CI]-83-97) and the overall survival (OS) rate was 90 (95 CI-80-95). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Conclusion: Although most of the cohort belonged to stage III, an RFS and OS rate of >90 at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers., Author(s): Rakesh Kumar [1,2]; Madhuri Evangeline Sadanala [2]; Santosh Nagasubramanian [2]; Anjana Joel [3]; Arun Joseph Philip George [2]; S Mahasampath Gowri [4]; Partho Mukherjee [2]; Ashish Singh [3]; Rajiv [...]

Background: To evaluate the relation between serum-25-hydroxy Vitamin-D levels (S25OHVDL) and concurrent chemoradiation therapy (CTRT) toxicities in patients of head and neck squamous cell cancer (HNSCC). Methods: After an institutional ethics committee approval, consecutive HNSCC patients who received radical/adjuvant CTRT were prospectively evaluated. Patients were assessed for CTRT toxicities using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE-v5.0) and the response was evaluated according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST-1.1). S25OHVDL was assessed at the time of the first follow-up. Patients were divided into group A (Optimal) and group B (suboptimal) according to S25OHVDL. The treatment toxicities were correlated with S25OHVDL. Results: Twenty-eight patients were evaluated for the study. S25OHVDL was optimal in eight (28.57%) and suboptimal in 20 patients (71.42%). Mucositis and radiation dermatitis were significantly more in subgroup B (P-value 0.0011 and 0.0505, respectively). Relatively lower but nonsignificant hemoglobin and peripheral white blood cell counts were observed in subgroup B. Conclusion: Suboptimal S25OHVDL was associated with significantly more skin and mucosal toxicities in HNSCC patients treated with CTRT. Keywords: 25-hydroxy vitamin-D, head and neck squamous cell cancer, radiation toxicities, Author(s): Arya Bhanu [1]; Chaitali M. Waghmare (corresponding author) [1]; Vandana S. Jain [1]; Hemant J. Pawar [2] Introduction Head and neck squamous cell cancers (HNSCC) account for a major [...]

Several waves of COVID-19 have occurred in Germany (1). After low incidence rates in summer 2021, case numbers started to increase in late August because of the Delta variant (2). [...]

Background: Previous electroencephalography (EEG) studies have indicated altered brain oscillatory [alpha]-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized [alpha]-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual [alpha]-peak-frequency-guided rTMS ([alpha]TMS) on treatment-refractory schizophrenia. Methods: We recruited medication-refractory male patients with schizophrenia or schizoaffective disorder in this double-blind, sham-controlled study. We randomized patients to a 3-week course of either active [alpha]TMS or sham stimulation applied to the left dorsolateral prefrontal cortex (DLPFC). We assessed participants with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) at baseline and after treatment. We conducted a follow-up assessment with the PANSS 3 months after intervention. Results: We included 44 patients. After treatment, we observed a significantly lower PANSS total score (p = 0.029), PANSS general psychopathology score (p = 0.027) and PANSS 5-factor model cognitive-disorganized factor score (p = 0.011) in the [alpha]TMS group than the sham group. In addition, the CGI-Improvement score was significantly higher among those who received [alpha]TMS compared with sham stimulation (p = 0.048). Limitations: The limited number of study participants included only male patients. Depression was not formally evaluated. Conclusion: Navigated [alpha]TMS to the left DLPFC reduced total, general psychopathological, and cognitive-disorganized symptoms of schizophrenia. These results provide evidence for the therapeutic efficacy of individual [alpha]-peak-frequency-guided rTMS in treatment-refractory schizophrenia. Clinical trial registration: NCT01941251; ClinicalTrials.gov, Introduction Around 30% of patients with schizophrenia are mostly unresponsive to antipsychotic medication. (1) Treatment resistance usually refers to persistent positive symptoms, although negative and cognitive symptoms may be the [...]

Genital tucking (tucking) is the practice of hiding or minimizing the appearance of one's genitals and gonads. We aimed to better understand the prevalence of tucking and its potential effect on behavior and health. An online questionnaire was distributed to adults with a diagnosis of gender dysphoria or gender incongruence (n = 98). The risk of side effects increased with the length of tucking sessions (P = 0.046) with many patients avoiding medical care despite experiencing side effects. Health care providers should empathetically discuss tucking and its potential risks and benefits with transgender and gender diverse patients. Further research is needed to better quantify the potential risks involved with tucking and to assist in developing educational resources. Key words: gender affirming health care; genital tucking; gender incongruence; gender dysphoria; transgender; gender diverse individuals, INTRODUCTION Transgender and gender diverse individuals often experience significant harassment, abuse, and discrimination which can impact their self-beliefs and lead to negative health outcomes. (1,2) As a result, they require [...]

PURPOSE Lung cancer screening (LCS) has less benefit and greater potential for iatrogenic harm among people with multiple comorbidities and limited life expectancy. Yet, such individuals are more likely to undergo screening than healthier LCS-eligible people. We sought to understand how patients with marginal LCS benefit conceptualize their health and make decisions regarding LCS. METHODS We interviewed 40 people with multimorbidity and limited life expectancy, as determined by high Care Assessment Need scores, which predict 1-year risk of hospitalization or death. Patients were recruited from 6 Veterans Health Administration facilities after discussing LCS with their clinician. We conducted a thematic analysis using constant comparison to explore factors that influence LCS decision making. RESULTS Patients commonly held positive beliefs about screening and perceived LCS to be noninvasive. When posed with hypothetical scenarios of limited benefit, patients emphasized the nonlongevity benefits of LCS (eg, peace of mind, planning for the future) and generally did not consider their health status or life expectancy when making decisions regarding LCS. Most patients were unaware of possible additional evaluations or treatment of screen-detected findings, but when probed further, many expressed concerns about the potential need for multiple evaluations, referrals, or invasive procedures. CONCLUSIONS Patients in this study with multimorbidity and limited life expectancy were unaware of their greater risk of potential harm when accepting LCS. Given patient trust in clinician recommendations, it is important that clinicians engage patients with marginal LCS benefit in shared decision making, ensuring that their values of desiring more information about their health are weighed against potential harms from further evaluations. Key words: lung cancer; lung cancer screening; qualitative methods: key informant/depth interviewing; cancer: screening; chronic care: comorbidity/multimorbidity; primary care issues: patient-centered care, INTRODUCTION Achieving mortality reduction with lung cancer screening (LCS) (1,2) while minimizing iatrogenic harm requires optimizing patient selection: screening people likely to benefit from early detection and not screening those [...]

Background Efficient and scalable solutions are needed to identify patients who qualify for germline cancer genetic testing. We evaluated the clinical validity of a brief, patient-administered hereditary cancer risk assessment digital tool programmed to assess if patients meet criteria for germline genetic testing, based on personal and family history, and in line with national guidelines. Methods We applied the tool to cases seen in a nationwide telehealth genetic counseling practice. Validity of the tool was evaluated by comparing the tool's assessment to that of the genetic counselor who saw the patient. Patients' histories were extracted from genetic counselor-collected pedigrees and input into the tool by the research team to model how a patient would complete the tool. We also validated the tool's assessment of which specific aspects of the personal and family history met criteria for genetic testing. Descriptive statistics were used. Results Of the 152 cases (80% female, mean age 52.3), 56% had a personal history of cancer and 66% met genetic testing criteria. The tool and genetic counselor agreed in 96% of cases. Most disagreements (4/6; 67%) occurred because the genetic counselor's assessment relied on details the tool was not programmed to collect since patients typically don't have access to the relevant information (pathology details, risk models). We also found complete agreement between the tool and research team on which specific aspects of the patient's history met criteria for genetic testing. Conclusion We observed a high level of agreement with genetic counselor assessments, affirming the tool's clinical validity in identifying individuals for hereditary cancer predisposition testing and its potential for increasing access to hereditary cancer risk assessment. Keywords: Hereditary cancer, Genetic testing, Cancer risk assessment, Author(s): Callan D. Russell[sup.1,2], Ashley V. Daley[sup.1], Durand R. Van Arnem[sup.1], Andi V. Hila[sup.1], Kiley J. Johnson[sup.1], Jill N. Davies[sup.1], Hanah S. Cytron[sup.1], Kaylene J. Ready[sup.3], Cary M. Armstrong[sup.1], Mark [...]

Neurological disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD) have no disease-modifying treatments, resulting in a global dementia crisis that affects more than 50 million people. Amyloid-beta (A[beta]), tau, and alpha-synuclein ([alpha]-Syn) are three crucial proteins that are involved in the pathogenesis of these age-related neurodegenerative diseases. Only a few approved AD medications have been used in the clinic up to this point, and their results are only partial symptomatic alleviation for AD patients and cannot stop the progression of AD. Immunotherapies have attracted considerable interest as they target certain protein strains and conformations as well as promote clearance. Immunotherapies also have the potential to be neuroprotective: as they limit synaptic damage and spread of neuroinflammation by neutralizing extracellular protein aggregates. Lately, disease-modifying therapies (DMTs) that can alter the pathophysiology that underlies AD with anti-A[beta] monoclonal antibodies (MAbs) (e.g., aducanumab, lecanemab, gantenerumab, donanemab, solanezumab, crenezumab, tilavonemab). Similarly, in Parkinson's disease (PD), DMTs utilizing anti-[alpha]Syn (MAbs) (e.g., prasinezumab, cinpanemab,) are progressively being developed and evaluated in clinical trials. These therapies are based on the hypothesis that both AD and PD may involve systemic impairments in cell-dependent clearance mechanisms of amyloid-beta (A[beta]) and alpha-synuclein ([alpha]Syn), respectively, meaning the body's overall inability to effectively remove A[beta] and [alpha]Syn due to malfunctioning cellular mechanisms. In this review we will provide possible evidence behind the use of immunotherapy with MAbs in AD and PD and highlight the recent clinical development landscape of anti-A[beta] (MAbs) and anti-[alpha]Syn (MAbs) from these clinical trials in order to better investigate the therapeutic possibilities and adverse effects of these anti-A[beta] and anti-[alpha]Syn MAbs on AD and PD. Keywords: Immune checkpoint, Age-related neurodegenerative disorders, Alzheimer's disease, Parkinson's disease, Monoclonal antibodies, Author(s): Noha N. Lasheen[sup.1,2], Salma Allam[sup.3], Abdullrahman Elgarawany[sup.3], Darin W. Aswa[sup.3], Rana Mansour[sup.3] and Ziad Farouk[sup.3] Introduction Aging is a progressive degenerative process that can be physiological and pathological [1-3] [...]

Background 3D cell culture models have recently garnered increasing attention for replicating organ microarchitecture and eliciting in vivo-like responses, holding significant promise across various biological disciplines. Broadly, 3D cell culture encompasses organoids as well as single- and multicellular spheroids. While the latter have found successful applications in tumor research, there is a notable scarcity of standardized intestinal models for infection biology that mimic the microarchitecture of the intestine. Hence, this study aimed to develop structured multicellular intestinal spheroids (SMIS) specifically tailored for studying molecular basis of infection by intestinal pathogens. Results We have successfully engineered human SMIS comprising four relevant cell types, featuring a fibroblast core enveloped by an outer monolayer of enterocytes and goblet cells along with monocytic cells. These SMIS effectively emulate the in vivo architecture of the intestinal mucosal surface and manifest differentiated morphological characteristics, including the presence of microvilli, within a mere two days of culture. Through analysis of various differentiation factors, we have illustrated that these spheroids attain heightened levels of differentiation compared to 2D monolayers. Moreover, SMIS serve as an optimized intestinal infection model, surpassing the capabilities of traditional 2D cultures, and exhibit a regulatory pattern of immunological markers similar to in vivo infections after Campylobacter jejuni infection. Notably, our protocol extends beyond human spheroids, demonstrating adaptability to other species such as mice and pigs. Conclusion Based on the rapid attainment of enhanced differentiation states, coupled with the emergence of functional brush border features, increased cellular complexity, and replication of the intestinal mucosal microarchitecture, which allows for exposure studies via the medium, we are confident that our innovative SMIS model surpasses conventional cell culture methods as a superior model. Moreover, it offers advantages over stem cell-derived organoids due to scalability and standardization capabilities of the protocol. By showcasing differentiated morphological attributes, our model provides an optimal platform for diverse applications. Furthermore, the investigated differences of several immunological factors compared to monotypic monolayers after Campylobacter jejuni infection underline the refinement of our spheroid model, which closely mimics important features of in vivo infections. Keywords: Multilayered spheroid, 3D cell culture, Intestinal mucosa, Infection model, Author(s): Angelina Kraski[sup.1], PaweÅ MigdaÅ[sup.2], Robert Klopfleisch[sup.3], Clara Räckel[sup.1], Jutta Sharbati[sup.4], Markus M. Heimesaat[sup.5], Thomas Alter[sup.6], Carlos Hanisch[sup.7], Greta Gölz[sup.6], Ralf Einspanier[sup.1] and Soroush Sharbati[sup.1] Background For many years, cell [...]

Nocardia is a ubiquitous, filamentous, gram-positive bacillus present in soil and decaying plants (2), affecting immunocompromised patients by way of inhalation, with a risk of secondary dissemination. Invasive Nocardia infections [...]

Case investigation and contact tracing (CICT) were among the primary nonpharmaceutical interventions for COVID-19 before vaccines became widely available. Previous studies estimated that CICT played an important role in mitigating [...]

Natural infections and experimental studies have indicated that diverse species of mammals can be infected with SARS-CoV-2 (1). The angiotensin-converting enzyme 2 receptor of white-tailed deer is closely homologous to [...]

* Context.--End-stage kidney disease (ESKD) is defined as renal impairment requiring renal replacement therapy to sustain life. With a 1-year mortality of ~20% to 30%, many die of complications related to this disease. Objective.--To determine the percentage of autopsy cases of decedents with ESKD in which the contribution of ESKD to death is accurately reflected in the final report. Design.--Autopsy case records were retrospectively reviewed at 4 institutions (Yale New Haven Hospital, University of Chicago Medical Center, University of Illinois at Chicago Hospital, University of Iowa Hospital). Clinical, macroscopic, and microscopic autopsy findings were reviewed, with attention to renal disease findings. Results.--One hundred sixty decedents with documented ESKD and premortem dialysis who underwent autopsy assessment were identified. ESKD was implicated as a cause of death (CoD) or significant contributing factor in 44 cases (28%), but not in the remaining 116 cases (72%). Cardiovascular disease was the most common CoD in ESKD. There was significant interpathologist variation in the inclusion of ESKD as a CoD across institutions. These rates ranged from 85% correlation (23 of 27 cases), to 13% (4 of 31 and 8 of 62 cases at 2 institutions), and 22.5% (9 of 40 cases) across the 4 participating institutions. Conclusions.--The recognition at autopsy of ESKD as a CoD or contributing CoD at autopsy in patients undergoing dialysis remains low (28%). The detrimental impact of ESKD is not reflected in hospital autopsy reports, which carries implications for collection of vital statistics and allocation of research funding for kidney diseases. doi: 10.5858/arpa.2022-0338-OA, End-stage kidney disease (ESKD) is the most severe form of renal impairment, which requires renal replacement therapy (RRT) to sustain life. (1) RRT is defined as replacement of nonendocrine renal [...]

Peripheral intravenous catheters (PVCs) and central venous catheters (CVCs) are frequently used in hospitalized patients. Estimates from global device sales illustrated that [approximately equal to] 1.2 billion PVCs are used [...]

Author(s): Josef Finsterer [1] Sir, We read with interest Al Shammari et al.'s article on a retrospective, single-center study on the clinical, demographic characteristics, and prognostic impact of myasthenia gravis [...]

Background: Psychosocial interventions have emerged as an important component of a comprehensive therapeutic approach in early-onset schizophrenia, typically representing a more severe form of the disorder. Despite the feasibility and efficacy of Theory of Mind (ToM) psychotherapy for schizophrenia, relatively little is known regarding the neural mechanism underlying its effect on early-on-set schizophrenia. Methods: We performed a randomized, active controlled trial in patients with early-onset schizophrenia, who were randomly allocated into either an intervention (ToM psychotherapy) or an active control (health education) group. Diffusion tensor imaging data were collected to construct brain structural networks, with both global and regional topological properties measured using graph theory. Results: We enrolled 28 patients with early-onset schizophrenia in our study. After 5 weeks of treatment, both the intervention and active control groups showed significant improvement in psychotic symptoms, yet the improvement was greater in the intervention group. Importantly, in contrast with no brain structural network change after treatment in the active control group, the intervention group showed increased nodal centrality of the left insula that was associated with psychotic symptom improvement. Limitations: We did not collect important information concerning the participants' cognitive abilities, particularly ToM performance. Conclusion: These findings suggest a potential neural mechanism by which ToM psychotherapy exerts a beneficial effect on early-onset schizophrenia via strengthening the coordination capacity of the insula in brain structural networks, which may provide a clinically translatable biomarker for monitoring or predicting responses to ToM psychotherapy. Clinical trial registration: NCT05577338; ClinicalTrials.gov, Introduction Schizophrenia is a chronic mental disorder expressed as a complex behavioural syndrome with a heterogeneous combination of psychotic symptoms (e.g., delusions, hallucinations and disorganization) and cognitive dysfunctions, which may [...]

Since SARS-CoV-2 was first reported in late 2019, infection has been observed primarily in humans; however, animals of various species have also been infected, partially because their angiotensin-converting enzyme 2 [...]

Campylobacter is a genus of microaerophilic, fastidious, gram-negative, occasionally partially anaerobic, non-spore forming, motile bacteria with a characteristic spiral or corkscrew-like appearance (1). Such morphology enables the bacteria to colonize [...]

* Context.--The COVID-19 pandemic has triggered a worldwide crisis that created unprecedented challenges for the health care system, including diagnostic laboratories that faced an ever-increasing demand for SARS-CoV-2 testing. Objective.--To share our experiences mobilizing a large-scale volunteer operation within a diagnostic laboratory in response to the COVID-19 crisis. In particular, during the early stages of the pandemic, research scientists at Vanderbilt University Medical Center were called upon to address challenges put forth by the rapid increase in testing demands. Volunteer scientists became a valuable resource to the clinical laboratory team after stay-at-home orders were in place and rapid diagnostic capabilities for COVID-19 were not yet widespread, thus necessitating significant manual laboratory analysis to support patient care. However, these volunteer efforts were not without challenges, including considerations around the licensure of clinical laboratory workers. Requirements can differ significantly between states and, in our case, were alleviated by an emergency gubernatorial decree. Data Sources.--We summarize these experiences here as an operational roadmap for other institutions that wish to leverage biomedical research staff in response to future emergencies. We include recruitment and organizational schemes, as well as results of a survey that details participant experiences and identifies strategies for optimization. Lastly, we present considerations around long-term hosting of clinical laboratory volunteers, beyond just the initial stages of an emergency. Conclusions.--Through strategic implementation, scientists can provide diagnostic laboratories with invaluable support in times of need, while maintaining high clinical quality and regulatory compliance. doi: 10.5858/arpa.2022-0155-SA, The SARS-CoV-2 virus was initially identified in December 2019 in Wuhan, China, and is the causative agent of the COVID-19 pandemic that has resulted in more than 6 million deaths [...]

Purpose Music intervention is commonly used as a non-pharmacologic therapeutic modality to alleviate anxiety in perioperative patients. This study aimed to assess the sedative and anxiolytic effects of music on elderly patients receiving transurethral resection of prostate (TURP) under spinal anesthesia. Methods This was a prospective randomized controlled trial on patients who aged over 60 and received TURP under spinal anesthesia. Participants were randomized to the music group or the control group (no music). The primary outcome was perioperative BIS values, and the secondary outcomes were patient's perioperative anxiety levels, heart rate (HR), blood pressure, and patient satisfaction score. Results A total of 82 patients were analyzed. The perioperative BIS values in the music group were significantly lower than those of the control group at almost all time points (P < 0.001), as well as showed a significant reduction compared with baseline (P < 0.001), whereas the control group did not. In comparison with the control group, systolic blood pressure (SBP) significantly decreased in the music group at the beginning (mean difference, - 8.0 mmHg; 95% CI - 15.70 to 0.35; P = 0.041) and the 60th minute (mean difference, - 7.9 mmHg; 95% CI - 15.30 to 0.51; P = 0.037) of TURP. Furthermore, compared with baseline within the music group, diastolic blood pressure (DBP) and HR significant reduced at whole time points (P < 0.05), yet the control group not. Conclusion Music intervention effectively provided slight sedation for elderly patients when undergoing TURP under spinal anesthesia without sedatives., Author(s): Yi-Wen Zhang [sup.1], Zhan-Ying Guan [sup.2], Ling-Ling Wang [sup.1], Chang-Ming Wang [sup.1], Jing Zhang [sup.1] Author Affiliations: (1) https://ror.org/02s8x1148, grid.470181.b, Department of Anesthesiology, People's Hospital of China Medical University [...]

Context.--Disease courses in COVID-19 patients vary widely. Prediction of disease severity on initial diagnosis would aid appropriate therapy, but few studies include data from initial diagnosis. Objective.--To develop predictive models of COVID-19 severity based on demographic, clinical, and laboratory data collected at initial patient contact after diagnosis of COVID-19. Design.--We studied demographic data and clinical laboratory biomarkers at time of diagnosis, using backward logistic regression modeling to determine severe and mild outcomes. We used deidentified data from 14147 patients who were diagnosed with COVID-19 by polymerase chain reaction SARS-CoV-2 testing at Montefiore Health System, from March 2020 to September 2021. We generated models predicting severe disease (death or more than 90 hospital days) versus mild disease (alive and fewer than 2 hospital days), starting with 58 variables, by backward stepwise logistic regression. Results.--Of the 14147 patients, including Whites, Blacks, and Hispanics, 2546 (18%) patients had severe outcomes and 3395 (24%) had mild outcomes. The final number of patients per model varied from 445 to 755 because not all patients had all available variables. Four models (inclusive, receiver operating characteristic, specific, and sensitive) were identified as proficient in predicting patient outcomes. The parameters that remained in all models were age, albumin, diastolic blood pressure, ferritin, lactic dehydrogenase, socioeconomic status, procalcitonin, B-type natriuretic peptide, and platelet count. Conclusions.--These findings suggest that the biomarkers found within the specific and sensitive models would be most useful to health care providers on their initial severity evaluation of COVID-19. doi: 10.5858/arpa.2023-0039-SA, The COVID-19 pandemic has fundamentally altered the way health data are collected, analyzed, and released to healthcare professionals and the general public. From the earliest availability of COVID-19 data, it [...]

Objective To conduct a systematic review of verbal autopsy studies in low- and middle-income countries to estimate the fraction of deaths due to cardiovascular disease. Method We searched MEDLINE[R], Embase[R] and Scopus databases for verbal autopsy studies in low- and middle-income countries that reported deaths from cardiovascular disease. Two reviewers screened the studies, extracted data and assessed study quality. We calculated cause-specific mortality fractions for cardiovascular disease for each study, both overall and according to age, sex, geographical location and type of cardiovascular disease. Findings We identified 42 studies for inclusion in the review. Overall, the cardiovascular disease cause-specific mortality fractions for people aged 15 years and above was 22.9%. This fraction was generally higher for males (24.7%) than females (20.9%), but the pattern varied across World Health Organization regions. The highest cardiovascular disease mortality fraction was reported in the Western Pacific Region (26.3%), followed by the South-East Asia Region (24.1%) and the African Region (12.7%). The cardiovascular disease mortality fraction was higher in urban than rural populations in all regions, except the South-East Asia Region. The mortality fraction for ischaemic heart disease (12.3%) was higher than that for stroke (8.7%). Overall, 69.4% of cardiovascular disease deaths were reported in people aged 65 years and above. Conclusion The burden of cardiovascular disease deaths outside health-care settings in low- and middle-income countries is substantial. Increasing coverage of verbal autopsies in these countries could help fill gaps in cardiovascular disease mortality data and improve monitoring of national, regional and global health goals. Objectif Mener une revue systematique des etudes d'autopsie verbale dans les pays a revenu faible et intermediaire afin d'estimer la part des deces causes par des maladies cardiovasculaires. Methodes Nous avons explore les bases de donnees MEDLINE[R], Embase[R] et Scopus a la recherche d'etudes d'autopsie verbale signalant des deces lies a une maladie cardiovasculaire dans les pays a revenu faible et intermediaire. Deux reviseurs ont passe ces etudes au crible, en ont extrait des informations et ont evalue leur qualite. Pour chaque etude, nous avons calcule la part de mortalite par cause pour les maladies cardiovasculaires, tant de maniere globale qu'en fonction de l'age, du sexe, de la situation geographique et du type de maladie cardiovasculaire. Resultats Nous avons identifie 42 etudes a inclure dans la revue. Dans l'ensemble, la part de mortalite par cause pour les maladies cardiovasculaires s'elevait a 22,9% pour les personnes agees de 15 ans et plus. Cette part etait generalement plus importante chez les hommes (24,7%) que chez les femmes (20,9%), mais le schema variait selon les regions de l'Organisation mondiale de la Sante. C'est dans la Region du Pacifique occidental que le plus haut taux de mortalite cardiovasculaire a ete observe (26,3%), puis dans la Region d'Asie du Sud-Est (24,1%) et dans la Region africaine (12,7%). La part de mortalite due aux maladies cardiovasculaires etait plus grande au sein des populations urbaines plutot que rurales dans toutes les regions, a l'exception de la Region d'Asie du Sud-Est. La part de mortalite liee aux cardiopathies ischemiques (12,3%) etait superieure a celle des AVC (8,7%). Au total, 69,4% des deces cardiovasculaires ont ete constates chez des personnes agees de 65 ans ou plus. Conclusion Limpact des deces causes par une maladie cardiovasculaire en dehors des structures de sante dans les pays a revenu faible et intermediaire est considerable. Etendre la couverture des autopsies verbales dans ces pays pourrait contribuer a combler les lacunes dans les donnees sur la mortalite cardiovasculaire et a ameliorer le suivi des objectifs nationaux, regionaux et mondiaux en matiere de sante. Objetivo Llevar a cabo una revision sistematica de los estudios sobre autopsias verbales de paises con ingresos medios y bajos para estimar la proporcion de fallecimientos causados por enfermedades cardiovasculares. Metodos Buscamos en bases de datos como MEDLINE[R], Embase[R] y Scopus para acceder a estudios sobre autopsias verbales de paises con ingresos medios y bajos que hubieran registrado fallecimientos causados por enfermedades cardiovasculares. Dos revisores analizaron los estudios, extrajeron datos y evaluaron la calidad de dichos estudios. Calculamos las fracciones de mortalidad por enfermedad cardiovascular como causa especifica en cada uno de los estudios, de manera general y segun la edad, el sexo, la u bicacion geografica y el tipo de enfermedad cardiovascular. Resultados Seleccionamos 42 estudios para incluirlos en la revision. En general, las fracciones de mortalidad por enfermedad cardiovascular como causa especifica en personas con una edad de 15 anos o superior fueron del 22,9%. Por lo general, esta fraccion fue mas elevada en el caso de los hombres (24,7%) que en el de las mujeres (20,9%), pero el patron vario entre las diferentes regiones de la Organizacion Mundial de la Salud. La fraccion mas alta de mortalidad por enfermedad cardiovascular se registro en la Region del Pacifico Occidental (26,3%), seguida de la Region de Asia Sudoriental (24,1%) y la Region de Africa (12,7%). La fraccion de mortalidad por enfermedad cardiovascular fue mas elevada en las poblaciones urbanas que en las rurales en todas las regiones, excepto en la Region de Asia Sudoriental. La fraccion de mortalidad por cardiopatia isquemica (12,3%) fue superior a la de ictus (8,7%). En general, el 69,4% de los fallecimientos por enfermedad cardiovascular se registro en personas de 65 anos o mas. Conclusion La carga de fallecimientos por enfermedad cardiovascular fuera de los centros de atencion sanitaria en los paises con ingresos medios y bajos es considerable. El aumento de la cobertura de las autopsias verbales en estos paises podria ayudar a subsanar la falta de datos sobre mortalidad por enfermedad cardiovascular, y mejorar el control de los objetivos de salud a nivel nacional, regional y mundial. [phrase omitted], Introduction Cardiovascular disease is the largest cause of death due to noncommunicable disease globally. Data from the Global Burden of Disease (GBD) indicate that cardiovascular disease caused 18.5 million deaths [...]

In 2010, cholera, caused by the bacterium Vibrio cholerae, was introduced into Haiti, resulting in >800,000 cases and >10,000 deaths (1,2). Case incidence peaked in 2012, then decreased, and the [...]

Hepatitis E virus (HEV) is a nonenveloped, single-stranded, positive-sense RNA virus within the family Hepeviridae, subfamily Orthohepevirinae, which is divided into 4 genera: Paslahepevirus, Rocahepevirus, Chirohepevirus, and Avihepevirus (1). Human [...]

Influenza A viruses (IAVs) have pandemic potential and remain a threat to human and animal health, mainly owing to their intrinsic ability to continually diversify and infect a broad range [...]

Background: Primary nonparasitic splenic cysts (NPSC) are typically diagnosed incidentally. The management of large ([greater than or equal to] 5 cm) asymptomatic cysts remains controversial; there is a lack of evidence guiding management. The purpose of this study was to describe the outcomes of nonoperative management of large NPSC. Methods: Patients diagnosed with NPSC between January 2004 and December 2019 were identified at our academic institution. Adult patients with an NPSC of at least 5 cm who had at least 1 additional hospital visit were included. Data are presented as medians with interquartile ranges (IQR). Results: We identified 512 medical records that included the term splenic cyst during the study period. Sixty-eight of the patients had no reported cyst size, 410 had cysts smaller than 5 cm, 1 patient underwent an elective splenectomy at another institution and 12 patients were excluded for other reasons; 21 patients with cysts of at least 5 cm were included in the study. Eight symptomatic patients underwent surgery at our institution. Of these, 2 presented acutely: 1 with hemoperitoneum who required admission for transfusions and later underwent elective laparoscopic splenectomy and 1 with increasingly severe abdominal pain who underwent laparoscopic cyst unroofing. The remaining 6 symptomatic patients had elective surgery for pain (4 cyst unroofing, 1 total splenectomy, 1 partial splenectomy). Thirteen patients were asymptomatic (10 female, median age 49.2 [IQR 38.1 to 64.6] yr). Two of these patients chose to undergo elective surgery. The remaining 11 asymptomatic patients, with a median initial cyst size of 8.0 (IQR 5.3 to 10.8) cm, were followed for a median of 31.0 (IQR 23.5 to 71.0) months. There was no change in median cyst size (0 [IQR -1 to 0] cm), and none of these patients underwent intervention for their NPSC. Conclusion: Asymptomatic patients managed nonoperatively for large NPSC did not become symptomatic or require intervention during the study period. This supports watchful waiting with serial radiologic and clinical monitoring for asymptomatic large NPSC. Contexte : Les kystes spléniques non parasitaires primaires (KSNPP) sont généralement découverts fortuitement. La prise en charge des kystes volumineux ([greater than or equal to] 5 cm) asymptomatiques ne fait pas l'unanimité; les données probantes manquent pour orienter le traitement. Cette étude avait pour but de décrire les résultats d'une prise en charge non chirurgicale des KSNPP. Méthodes : Nous avons identifié les patients ayant reçu un diagnostic de KSNPP entre janvier 2004 et décembre 2019 dans notre établissement universitaire. Nous avons inclus les patients adultes porteurs d'un KSNPP d'au moins 5 cm qui avaient consulté au moins 1 autre fois à l'hôpital. Les données sont présentées sous forme de médianes et d'écarts interquartiles (ÉI). Résultats : Nous avons recensé 512 dossiers médicaux incluant le terme kyste splénique durant la période de l'étude. Chez 68 patients, la taille du kyste n'était pas indiquée; 410 avaient un kyste de moins de 5 cm; 1 patient a subi une splénectomie non urgente dans un autre établissement et 12 ont été exclus pour d'autres raisons; 21 patients porteurs d'un kyste d'au moins 5 cm ont été retenus pour l'étude. Huit patients symptomatiques ont subi une chirurgie dans notre établissement. Parmi eux, 2 étaient des cas urgents : 1 cas d'hémopéritoine pour lequel le patient a dû être hospitalisé pour des transfusions et a ensuite subi une splénectomie laparoscopique non urgente, et 1 cas d'intense douleur abdominale croissante pour lequel le patient a subi une fenestration laparoscopique. Les 6 autres patients symptomatiques ont subi une chirurgie non urgente pour la douleur (4 fenestrations, 1 splénectomie totale, 1 splénectomie partielle). Treize patients étaient asymptomatiques (10 femmes, âge médian 49,2 [écart interquartile (ÉI) de 38,1 à 64,6] ans). Deux d'entre eux ont opté pour la chirurgie non urgente. Les 11 patients asymptomatiques restants, dont la taille médiane des kystes initiaux était de 8,0 (EI de 5,3 à 10,8) cm, ont été suivis pendant une durée médiane de 31,0 (ÉI de 23,5 à 71,0) mois. On n'a noté aucun changement de la taille médiane des kystes (0 [ÉI de -1 à 0] cm) et aucun de ces patients n'a subi d'intervention pour son KSNPP. Conclusion : Les patients asymptomatiques traités non chirurgicalement pour un KSNPP volumineux ne sont pas devenus symptomatiques et n'ont pas été obligés d'être opérés pendant la période de l'étude. Cela milite en faveur de l'attente vigilante, avec suivi radiologique et clinique, pour les cas de KSNPP volumineux asymptomatiques., Hydatid cysts are the most common subtype of splenic cysts worldwide. (1) However, in North America, splenic cysts are relatively rare, given the low prevalence of echinococcal disease. In fact, [...]

Purpose and objectives Phantom limb pain (PLP) is a major cause of physical limitation and disability accounting for about 85% of amputated patients. Mirror therapy is used as a therapeutic modality for patients with phantom limb pain. Primary objective was to study the incidence of PLP at 6 months following below-knee amputation between the mirror therapy group and control group. Methods Patients posted for below-knee amputation surgery were randomized into two groups. Patients allocated to group M received mirror therapy in post-operative period. Two sessions of therapy were given per day for 7 days and each session lasted for 20 min. Patients who developed pain from the missing portion of the amputated limb were considered to have PLP. All patients were followed up for six months and the time of occurrence of PLP and intensity of the pain were recorded among other demographic factors. Results A total of 120 patients completed the study after recruitment. The demographic parameters were comparable between the two groups. Overall incidence of phantom limb pain was significantly higher in the control group (Group C) when compared to the mirror therapy (Group M) group [Group M = 7 (11.7%) vs Group C = 17 (28.3%); p = 0.022]. Intensity of PLP measured on the Numerical Rating Scale (NRS) was significantly lower at 3 months in Group M compared to Group C among patients who developed PLP [NRS - median (Inter quartile range): Group M 5 (4,5) vs Group C 6 (5,6); p 0.001]. Conclusion Mirror therapy reduced the incidence of phantom limb pain when administered pre-emptively in patients undergoing amputation surgeries. The severity of the pain was also found to be lower at 3 months in patients who received pre-emptive mirror therapy. Trial Registration This prospective study was registered in the clinical trial registry of India. Trial Registration number: CTRI/2020/07/026488., Author(s): Samatharman Purushothaman [sup.1], Pankaj Kundra [sup.1], Muthapillai Senthilnathan [sup.1], Sarath Chandra Sistla [sup.2], Shathish Kumar [sup.3] Author Affiliations: (1) grid.414953.e, 0000000417678301, Department of Anaesthesiology and Critical Care, Second Floor, [...]

Byline: Zhou. Yong, Li. Ang, Zha. Wen-Zhang, Wu. Xu-Dong, Fan. Ren-Gen Background: Incidental gall bladder cancer (IGBC) is often discovered unexpectedly in patients after cholecystectomy. Currently, magnetic resonance imaging (MRI) [...]

In the relentless battle against the COVID-19 pandemic, the deployment of mRNA vaccines has stood out as a beacon of hope. The successes of Pfizer-BioNTech NT162b2 and Moderna mRNA-1273 vaccines have been remarkable, marking a revolutionary advancement in the field of vaccinology. Despite their rapid development and impressive efficacy, challenges have emerged, particularly concerning the waning immune response over time and the evolving landscape of SARS-CoV-2 variants. The study published in this issue of JCI by Fazli et al. introduces an approach to potentially enhancing the immune responses generated by COVID-19 mRNA vaccines. The study meticulously examines the outcomes of nearly 1,000 participants who received one or two booster doses with the Pfizer-BioNTech NT162b2 vaccine either ipsilaterally or contralaterally in relation to the initial vaccine dose. Intriguingly, those who received the booster contralaterally exhibited a heightened antibody response that was particularly noteworthy in the later time points after boost., mRNA COVID-19 vaccination successes and limitations The advent of mRNA technology in vaccine development has been transformative, allowing scientists to respond rapidly to the urgent global need for effective COVID-19 [...]

BACKGROUND. Sanaria PfSPZ Vaccine, composed of attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), protects against malaria. We conducted this clinical trial to assess the safety and efficacy of PfSPZ Vaccine in HIV-positive ([HIV.sup.+]) individuals, since the HIV-infection status of participants in mass vaccination programs may be unknown. METHODS. This randomized, double-blind, placebo-controlled trial enrolled 18- to 45-year-old HIV-negative (HIV) and well-controlled [HIV.sup.+] Tanzanians (HIV viral load 500 cells/[micro]L). Participants received 5 doses of PfSPZ Vaccine or normal saline (NS) over 28 days, followed by controlled human malaria infection (CHMI) 3 weeks later. RESULTS. There were no solicited adverse events in the 9 [HIV.sup.-] and 12 [HIV.sup.+] participants. After CHMI, 6 of 6 NS controls, 1 of 5 [HIV.sup.-] vaccinees, and 4 of 4 [HIV.sup.+] vaccinees were Pf positive by quantitative PCR (qPCR). After immunization, anti-Pf circumsporozoite protein (anti-PfCSP) (isotype and IgG subclass) and anti-PfSPZ antibodies, anti-PfSPZ [CD4.sup.+] T cell responses, and V[delta][2.sup.+] [sigma][delta] [CD3.sup.+] T cells were nonsignificantly higher in [HIV.sup.-] than in [HIV.sup.+] vaccinees. Sera from [HIV.sup.-] vaccinees had significantly higher inhibition of PfSPZ invasion of hepatocytes in vitro and antibody-dependent complement deposition (ADCD) and Fc[gamma]3B binding by anti-PfCSP and ADCD by anti-cell-traversal protein for ookinetes and SPZ (anti-PfCelTOS) antibodies. CONCLUSIONS. PfSPZ Vaccine was safe and well tolerated in [HIV.sup.+] vaccinees, but not protective. Vaccine efficacy was 80% in HIV- vaccinees (P = 0.012), whose sera had significantly higher inhibition of PfSPZ invasion of hepatocytes and enrichment of multifunctional PfCSP antibodies. A more potent PfSPZ vaccine or regimen is needed to protect those living with HIV against Pf infection in Africa. TRIAL REGISTRATION. ClinicalTrials.gov NCT03420053. FUNDING. Equatorial Guinea Malaria Vaccine Initiative (EGMVI), made up of the Government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon Equatorial Guinea Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG; Swiss government, through ESKAS scholarship grant no. 2016.0056; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; NIH grant 1U01AI155354- 01., Introduction Our long-term goal is the development of a malaria vaccine against Plasmodium falciparum (Pf) malaria that can be used in endemic areas for mass vaccination programs (MVPs) to immunize [...]

Attention is beginning to focus on the need for vaccines to tackle antimicrobial resistant pathogens. Gary Humphreys reports. Until fairly recently, debates about how to tackle the looming threat of [...]

Purpose Central venous catheter (CVC)-related thrombosis (CRT) is a known complication in critically ill patients. However, its clinical significance remains unclear. The objective of the study was to evaluate the occurrence and evolution of CRT from CVC insertion to removal. Methods A prospective multicenter study was conducted in 28 intensive care units (ICUs). Duplex ultrasound was performed daily from CVC insertion until at least 3 days after CVC removal or before patient discharge from the ICU to detect CRT and to follow its progression. CRT diameter and length were measured and diameter > 7 mm was considered extensive. Results The study included 1262 patients. The incidence of CRT was 16.9% (95% confidence interval 14.8-18.9%). CRT was most commonly found in the internal jugular vein. The median time from CVC insertion to CRT onset was 4 (2-7) days, and 12% of CRTs occurred on the first day and 82% within 7 days of CVC insertion. CRT diameters > 5 mm and > 7 mm were found in 48% and 30% of thromboses. Over a 7-day follow-up, CRT diameter remained stable when the CVC was in place, whereas it gradually decreased after CVC removal. The ICU length of stay was longer in patients with CRT than in those without CRT, and the mortality was not different. Conclusion CRT is a frequent complication. It can occur as soon as the CVC is placed and mostly during the first week following catheterization. Half of the thromboses are small but one-third are extensive. They are often non-progressive and may be resolved after CVC removal., Author(s): Chunshuang Wu [sup.1] [sup.2] [sup.3], Mao Zhang [sup.1] [sup.2] [sup.3], Wenjie Gu [sup.1] [sup.2] [sup.3], Caimu Wang [sup.4], Xudong Zheng [sup.5], Junfeng Zhang [sup.6], Xingwen Zhang [sup.7], Shijin Lv [...]

Engagement of microribonucleic acids (miRNA) in the regulation of cutaneous cellular health and diseases is a rapidly advancing niche in dermatology basic research. miRNAs have been identified to play a key role in the pathogenesis of various cutaneous inflammatory, autoimmune and neoplastic conditions, among others. In addition, their purported role as therapeutic targets and biomarkers in diseased conditions harbours exciting news for the approaching years in clinical research. The current review outlines the possible translational role of miRNA in skin health and diseases (encompassing pathogenesis, diagnosis, biomarkers and therapy) from bench to bedside. Keywords: Biomarkers, inflammatory skin disease, microRNAs, novel therapy, pathogenesis, Author(s): Abheek Sil [1]; Disha Chakraborty (corresponding author) [2] Introduction Microribonucleic acids (miRNA) represent a family of noncoding RNAs, which consists of 19-25 nucleotides and regulates the expression of approximately [...]

Background: Dermatophytosis is a major public health concern in India, especially in recent years, with an alarmingly rising trend, particularly in relation to recurrent and chronic infection. The number of studies examining the relationship between an individual's glycemic status and the development of dermatophytosis, and a comparison of the evolving species trend between diabetic and non-diabetic patients infected with dermatophytes, is limited. Aims and Objectives: To study and compare the clinical and mycological aspects of dermatophytosis among diabetic and non-diabetic patients and to compare the culture isolates in both groups. Materials and Methods: The study included 378 patients of clinically suspected dermatophytosis, divided into two groups of 189 known diabetics and non-diabetics each. We subsequently analysed and compared the demographics, clinical data, potassium hydroxide (KOH) mount, calcofluor white (CW) staining and fungal culture results of all patients in both groups. Results: Among the 378 patients, diabetic patients had a significantly greater extent of involvement and higher rates of recurrence when compared to non-diabetics. The overall positivity rate was higher in CW staining (77.8) as compared to KOH (57.7) in both non-diabetics and diabetics. Trichophyton mentagrophytes was the most common isolate (47.6) in both diabetic (55.0) and non-diabetic (61.4) patients, followed by Trichophyton rubrum (31.8 and 29.6, respectively). The positivity percentages of fungal culture, KOH and CW staining increased to 100, 77.9 and 95.7, respectively, when scrapings were taken from ≥2 sites. Conclusion: The pattern of dermatophytosis is comparatively more chronic and severe in diabetics compared to non-diabetics. T. mentagrophytes was the most common culture isolate in both groups. CW staining can potentially be used as the initial method of choice for the diagnosis of dermatophytosis as it has significantly outperformed the conventional KOH mount. Scrapings can regularly be taken from ≥2 sites to avoid false negative results. Keywords: Calcofluor white, dermatophytosis, diabetics, fungal culture, KOH, Author(s): Abarna Rajagopal [1]; Rangappa Vinutha [1]; Padubidri Kombettu Ashwini [1]; Veeranna Shastry (corresponding author) [1]; Chitharagi B. Vidyavathi [2] Introduction The word ‘dermatophytosis' (tinea) is used to describe a [...]

Heat exposure is a leading environmental risk factor, responsible for an estimated 300,000-500,000 deaths annually. (1,2) Despite a rapid increase in our understanding of heat-related mortality and morbidity over the [...]

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous pulmonary disease affecting 16 million Americans. Individuals with COPD are susceptible to environmental disturbances including heat and cold waves that can exacerbate disease symptoms. Objective: Our objective was to estimate heat and cold wave-associated mortality risks within a population diagnosed with a chronic respiratory disease. Methods: We collected individual level data with geocoded residential addresses from the Veterans Health Administration on 377,545 deceased patients with COPD (2016 to 2021). A time stratified case-crossover study was designed to estimate the incidence rate ratios (IRR) of heat and cold wave mortality risks using conditional logistic regression models examining lagged effects up to 7 d. Attributable risks (AR) were calculated for the lag day with the strongest association for heat and cold waves, respectively. Effect modification by age, gender, race, and ethnicity was also explored. Results: Heat waves had the strongest effect on all-cause mortality at lag day 0 [IRR: 1.04; 95% confidence interval (CI): 1.02, 1.06] with attenuated effects by lag day 1. The AR at lag day 0 was 651 (95% CI: 326, 975) per 100,000 veterans. The effect of cold waves steadily increased from lag day 2 and plateaued at lag day 4 (IRR: 1.04; 95% CI: 1.02, 1.07) with declining but still elevated effects over the remaining 7-d lag period. The AR at lag day 4 was 687 (95% CI: 344, 1,200) per 100,000 veterans. Differences in risk were also detected upon stratification by gender and race. Discussion: Our study demonstrated harmful associations between heat and cold waves among a high-risk population of veterans with COPD using individual level health data. Future research should emphasize using individual level data to better estimate the associations between extreme weather events and health outcomes for high-risk populations with chronic medical conditions. https://doi.org/10.1289/EHP13176, Introduction Anthropogenic climate change is causing harmful planetary effects with increased frequency, intensity, duration, and geographic extent of extreme weather events, including heat waves, droughts, wildfires, and floods. (1,2) Furthermore, [...]

BACKGROUND. Disease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus. METHODS. Two randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2[DELTA]30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3[DELTA]30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2[DELTA]30 or rDEN3[DELTA]30 strain. RESULTS. TV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype. CONCLUSIONS. TV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model. TRIAL REGISTRATION. ClinicalTrials.gov NCT02317900 and NCT02873260. FUNDING. Intramural Research Program, NIH (contract HHSN272200900010C)., Introduction Dengue viruses are estimated to cause 100-400 million symptomatic illnesses each year, with a significant and expanding burden of severe disease and mortality in both endemic populations and travelers [...]