Radiotherapy Results in Locally Advanced Sinonasal Cancer: Turkish Society for Radiation Oncology, Head and Neck Study Group 01-005.

OBJECTIVES: This study aims to examine the treatment outcomes and related factors in locally advanced sinonasal cancer across Turkiye. METHODS: Twelve centers participants of the Turkish Society for Radiation Oncology Head and Neck Study Group attended the study. One hundred and ninety-four patients treated with intensity-modulated radiation therapy between 2001 and 2021 were analyzed retrospectively. The survival analysis was performed using the Kaplan-Meier method. Acute and late toxicity were recorded per Common Toxicity Criteria for Adverse Events V4.0. RESULTS: The median age was 58 years and 70% were male. The majority of tumors were located in maxillary sinus (59%). Most of the patients (%83) had T3 and T4A disease. Fifty-three percent of patients were in stage 4A. Radiotherapy was administered to 80% of the patients in the adjuvant settings. Median 66 Gy dose was administered in median 31 fractions. Chemotherapy was administered concomitantly with radiotherapy in 45% of the patients mostly with weekly cisplatin. No grade ≥4 acute and late toxicity was observed. The median follow-up was 43 months. The 5-year and 10-year overall survival (OS); locoregional recurrence-free survival (LRFS); distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 61% and 47%; 69% and 61%; 72%, and 69%, and 56% and 49%, respectively. In the multivariate analysis, several factors demonstrated significant influence on OS, such as performance status, surgery, and lymph node involvement. Moreover, surgery was the key prognostic factor for LRFS. For DMFS, lymph node involvement and surgical margin were found to be influential factors. In addition, performance status and lymph node involvement were identified as significantly affecting PFS. CONCLUSIONS: In our study, the authors obtained promising results with IMRT. Performance status, lymph node involvement, and surgery emerged as the primary factors significantly influencing OS.

Nosocomial infections by diverse carbapenemase-producing Aeromonas hydrophila associated with combination of plumbing issues and heat waves.

BACKGROUND: Aquatic opportunistic pathogen Aeromonas hydrophila, known to persist in low-nutrient chlorinated waters, can cause life-threatening infections. Two intensive care units experienced a cluster of Aeromonas infections following outdoor temperature spikes coinciding with recurrent plumbing issues, with fatalities due to severe underlying comorbidities co-occurring with extensively-drug resistant (XDR) Aeromonas. METHODS: We investigated this cluster using whole genome sequencing to assess genetic relatedness of isolates and identify antimicrobial resistance determinants. Three A. hydrophila were isolated from patients staying in or adjacent to rooms with plumbing issues during or immediately after periods of elevated outdoor temperatures. Sinks and faucets were swabbed for culture. RESULTS: All A. hydrophila clinical isolates exhibited carbapenem resistance but were not genetically related. Diverse resistance determinants corresponding to extensively-drug resistant were found, including co-occurring KPC-3 and VIM-2, OXA-232, and chromosomal CphA-like carbapenemase genes, contributing to major treatment challenges. All 3 patients were treated with multiple antibiotic regimens to overcome various carbapenemase classes and expired due to underlying comorbidities. Environmental culture yielded no Aeromonas. CONCLUSIONS: While the investigation revealed no singular source of contamination, it supports a possible link between plumbing issues, elevated outdoor temperatures and incidence of nosocomial Aeromonas infections. The diversity of carbapenemase genes detected in these wastewater-derived Aeromonas warrants heightened infection prevention precautions during periods of plumbing problems especially with heat waves.

Domestically Acquired NDM-1-Producing Pseudomonas aeruginosa, Southern California, USA, 2023.

We describe a case of New Delhi metallo-ß-lactamase 1-producing carbapenem-resistant Pseudomonas aeruginosa (CRPA) in a transplant patient with multiple hospitalizations in California, USA. Whole-genome sequencing revealed the isolate was genetically distinctive, despite ≈95% similarity to other global strains. The patient's lack of international travel suggests this CRPA was acquired domestically.

Triple vs. single uterine tourniquet to reduce hemorrhage at myomectomy: a randomized trial.

PURPOSE: This study aimed to compare the effect of triple uterine tourniquet and single tourniquet on intraoperative blood loss during open myomectomy. METHODS: Women were randomized to undergo open myomectomy with a triple (n = 30) or single uterine tourniquet (n = 30). All symptomatic women aged 18-48 who had three or more myomas or at least one myoma greater than 8 cm if there were less than three myomas were eligible for the study. The primary outcome variable was the volume of intraoperative blood loss. The sample size was set to detect a 240 ml difference in blood loss with 80% power at α = 0.05, with an effect size of 0.8. The rate of transfusions, change in hemoglobin, volume of drains, operation time, tourniquet time, and perioperative complications were secondary outcomes. RESULTS: We found no significant difference in intraoperative blood loss between triple and single uterine tourniquets (527 [102-2931]) ml vs. 508 [172-2764] ml, p = 0.238). Between the single and triple tourniquet groups, the median weight of myoma (379 [136-3850] vs. 330 [140-1636] g, p = 0.451) and median number (1 [1-18] vs. 2 (1-13), p = 0.214), total operation time (84 ± 31 min vs. 79 ± 27 min, p = 0.503), ischemia time (35 ± 21 min vs. 30 ± 14 min., p = 0.238), drain volume at 48th hour (196 ± 89)ml vs. 243 ± 148 ml, p = 0.144) and decrease in hemoglobin (2.3 ± 1.8 g/dl vs. 2.8 ± 1.4 g/dl, p = 0.437) were similar. Eight (27%) patients in the triple tourniquet group and 12 (40%) patients in the single tourniquet group were transfused (p = 0.273). One patient underwent hysterectomy 6-8 h after myomectomy in a single tourniquet group. CONCLUSION: There was no clinically significant difference in intraoperative blood loss between triple and single uterine tourniquets during open myomectomy. CLINICAL TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov ID: NCT02392585, 03/13/2015.

Risk factors for infection in patients with a failed kidney allograft on immunosuppressive medications.

Patients with a failing kidney allograft are often continued on immunosuppression (IS) to preserve residual kidney function and prevent allosensitization. It has been previously accepted that maintaining patients on immunosuppressive therapy results in an increased risk of infection, hospitalization, and mortality. However, as the management of IS in patients with a failed kidney allograft continues to evolve, it is important to review the data regarding associations between infection and specific immunosuppression regimens. We present a review of the literature of failed kidney allograft management and infection risk, and discuss practices for infection prevention. Fifteen studies, published from 1995 to 2022, which investigated the experience of patients with failed allograft and infection, were identified. Infection was most commonly documented as a general event, but when specified, included infections caused by Candida, Mycobacterium tuberculosis, and Aspergillus. In addition, the definition of reduced "IS" varied from decreased doses of a triple drug regimen to monotherapy, whereas others did not specify which medications patients were receiving. Despite attempts at lowering net immunosuppression, patients with failed allografts remain at risk of acquiring opportunistic and non-opportunistic infections. Although opportunistic infections secondary to IS are expected, somewhat surprisingly, it appears that the greatest risk of infection may be related to complications of dialysis. Therefore, mitigating strategies, such as planning for an arteriovenous (AV) fistula over a hemodialysis catheter placement, may reduce infection risk. Additional studies are needed to provide more information regarding the types and timing of infection in the setting of a failed kidney allograft. In addition, more data are needed regarding specific medications, doses, and timing of taper of IS to guide future patient management and inform strategies for infection surveillance and prophylaxis.

Transient SARS-CoV-2 RNA-Dependent RNA Polymerase Mutations after Remdesivir Treatment for Chronic COVID-19 in Two Transplant Recipients: Case Report and Intra-Host Viral Genomic Investigation.

Remdesivir is the first FDA-approved drug for treating severe SARS-CoV-2 infection and targets RNA-dependent RNA polymerase (RdRp) that is required for viral replication. To monitor for the development of mutations that may result in remdesivir resistance during prolonged treatment, we sequenced SARS-CoV-2 specimens collected at different treatment time points in two transplant patients with severe COVID-19. In the first patient, an allogeneic hematopoietic stem cell transplant recipient, a transient RdRp catalytic subunit mutation (nsp12:A449V) was observed that has not previously been associated with remdesivir resistance. As no in vitro study had been conducted to elucidate the phenotypic effect of nsp12:A449V, its clinical significance is unclear. In the second patient, two other transient RdRp mutations were detected: one in the catalytic subunit (nsp12:V166A) and the other in an accessory subunit important for processivity (nsp7:D67N). This is the first case report for a potential link between the nsp12:V166A mutation and remdesivir resistance in vivo, which had only been previously described by in vitro studies. The nsp7:D67N mutation has not previously been associated with remdesivir resistance, and whether it has a phenotypic effect is unknown. Our study revealed SARS-CoV-2 genetic dynamics during remdesivir treatment in transplant recipients that involved mutations in the RdRp complex (nsp7 and nsp12), which may be the result of selective pressure. These results suggest that close monitoring for potential resistance during the course of remdesivir treatment in highly vulnerable patient populations may be beneficial. Development and utilization of diagnostic RdRp genotyping tests may be a future direction for improving the management of chronic COVID-19.

Targeting the epithelial-mesenchymal transition (EMT) pathway with combination of Wnt inhibitor and chalcone complexes in lung cancer cells.

Non-small cell lung cancer (NSCLC) is the most common type of the lung cancer. Despite development in treatment options in NSCLC, the overall survival ratios is still poor due to epithelial and mesenchymal transition (EMT) feature and associated metastasis event. Thereby there is a need to develop strategy to increase antitumor response against the NSCLC cells by targeting EMT pathway with combination drugs. Niclosamide and chalcone complexes are both affect cancer cell signaling pathways and therefore inhibit the EMT pathway. In this study, it was aimed to increase antitumor response and suppress EMT pathway in NSCLC cells by combining niclosamide and chalcone complexes. SRB cell viability assay was performed to investigate the anticancer activity of drugs. The drugs were tested on both NSCLC cells (A549 and H1299) and normal lung bronchial cells (BEAS-2B). Then the two drugs were combined and their effects on cancer cells were evaluated. Fluorescence imaging and enzyme-linked immunosorbent assay were performed on treated cells to observe the cell death manner. Wound healing assay, real-time quantitative polymerase chain reaction, and western blot analysis were performed to measure EMT pathway activity. Our results showed that niclosamide and chalcone complexes combination kill cancer cells more than normal lung bronchial cells. Compared to single drug administration, the combination of both drugs killed NSCLC cells more effectively by increasing apoptotic activity. In addition, the combination of niclosamide and chalcone complexes decreased multidrug resistance and EMT activity by lowering their gene expressions and protein levels. These results showed that niclosamide and chalcone complexes combination could be a new drug combination for the treatment of NSCLC.

The effects of metyrosine on ischemia-reperfusion-induced oxidative ovarian injury in rats: Biochemical and histopathological assessment.

The aim of this study is to investigate the effect of metyrosine on ischemia-reperfusion (I/R) induced ovarian injury in rats in terms of biochemistry and histopathology. Rats were divided into: ovarian I/R (OIR), ovarian I/R+50 mg/kg metyrosine (OIRM) and sham (SG) operations. OIRM group received 50 mg/kg metyrosine one hour before the application of the anesthetic agent, OIR and SG group rats received equal amount of distilled water to be used as a solvent orally through cannula. Following the application of the anesthetic agent, ovaries of OIRM and OIR group rats were subjected to ischemia and reperfusion, each of which took two hours. This biochemical experiment findings revealed high levels of malondialdehyde (MDA) and cyclo-oxygenase-2 (COX-2) and low levels of total glutathione (tGSH), superoxide dismutase (SOD) and cyclo-oxygenase-1 (COX-1) in the ovarian tissue of OIR group, with significant histopathological injury. In metyrosine group, MDA and COX-2 levels were lower than the OIR group whereas tGSH, SOD and COX-1 levels were higher, with slighter histopathological injury. Our experimental findings indicate that metyrosine inhibits oxidative and pro-inflammatory damage associated with ovarian I/R in rats. These findings suggest that metyrosine could be useful in the treatment of ovarian injury associated with I/R.

COVID-19 vaccinations in pregnancy: Save mother and baby from COVID-19 pandemic.

OBJECTIVE: The current study investigated the immune response of maternal coronavirus disease 2019 (COVID-19) vaccination and vertical transmission of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) and nucleocapsid (N) proteins. STUDY DESIGN: This retrospective study included pregnant women in Bahrain Defense Force Hospital from March 2021 to September 2021 who were vaccinated with Sinopharm or Pfizer/BioNTech. Testing of anti-N and -S levels from paired samples of maternal and umbilical cord blood was performed at the time of delivery. The immune response to vaccination, association with maternal and fetal factors, and vertical transmission of antibodies were studied. RESULTS: The current study included 79 pregnant women. The median gestational age for those vaccinated with Sinopharm was 28 weeks and those vaccinated with Pfizer was 31 weeks, with 100% of the vaccinated population generating antibodies and showing vertical transmission. The anti-N and -S titers and interval frequencies varied in both vaccinations. The anti-N and -S and transfer ratio statistically correlated with maternal age, gestational age at delivery, latency period, and birth weight of the neonates differently in both vaccines. In addition, the peak level of antibodies and transfer ratios varied. CONCLUSION: Although variations are exhibited in both types of vaccination, the vaccinated pregnant population generated a significant level of anti-N and -S and showed vertical transmission.

Evaluating utility and feasibility of mismatch repair testing of colorectal cancer patients in a low-middle-income country.

Molecular pathology services for colorectal cancer (CRC) in Sudan represent a significant unmet clinical need. In a retrospective cohort study involving 50 patients diagnosed with CRC at three major medical settings in Sudan, we aimed to outline the introduction of a molecular genetic service for CRC in Sudan, and to explore the CRC molecular features and their relationship to patient survival and clinicopathological characteristics. Mismatch repair (MMR) and BRAF (V600E) mutation status were determined by immunohistochemistry. A mismatch repair deficient (dMMR) subtype was demonstrated in 16% of cases, and a presumptive Lynch Syndrome (LS) diagnosis was made in up to 14% of patients. dMMR CRC in Sudan is characterized by younger age at diagnosis and a higher incidence of right-sided tumours. We report a high mortality in Sudanese CRC patients, which correlates with advanced disease stage, and MMR status. Routine MMR immunohistochemistry (with sequential BRAF mutation analysis) is a feasible CRC prognostic and predictive molecular biomarker, as well as a screening tool for LS in low-middle-income countries (LMICs).

Impact of solid organ transplant status on outcomes of hospitalized patients with COVID-19 infection.

BACKGROUND: The COVID-19 pandemic has caused significant morbidity and mortality in solid organ transplant (SOT) recipients. However, it remains unclear whether the risk factor for SOT patients is the immunosuppression inherent to transplantation versus patient comorbidities. METHODS: We reviewed outcomes in a cohort of SOT (n = 129) and non-SOT (NSOT) patients (n = 708) admitted to the University of California, Los Angeles for COVID-19 infection. Data analyses utilized multivariate logistic regression to evaluate the impact of patient demographics, comorbidities, and transplant status on outcomes. SOT patients were analyzed by kidney SOT (KSOT) versus nonkidney SOT (NKSOT) groups. RESULTS: SOT and NSOT patients with COVID-19 infection differed in terms of patient age, ethnicity, and comorbidities. NKSOT patients were the most likely to experience death, with a mortality rate of 16.2% compared with 1.8% for KSOT and 8.3% for NSOT patients (p = .013). Multivariable analysis of hospitalized patients revealed that patient age (odds ratio [OR] 2.79, p = .001) and neurologic condition (OR 2.66, p < .001) were significantly associated with mortality. Analysis of ICU patients revealed a 2.98-fold increased odds of death in NKSOT compared with NSOT patients (p = .013). CONCLUSIONS: This study demonstrates the importance of transplant status in predicting adverse clinical outcomes in patients hospitalized or admitted to the ICU with COVID-19, especially for NKSOT patients. Transplant status and comorbidities, including age, could be used to risk stratify patients with COVID-19. This data suggests that immunosuppression contributes to COVID-19 disease severity and mortality and may have implications for managing immunosuppression, especially for critically ill patients admitted to the ICU.

Mycoplasma hominis infections in solid organ transplant recipients: Clinical characteristics, treatment outcomes, and comparison of phenotypic and genotypic susceptibility profiles.

BACKGROUND: Mycoplasma hominis can cause significant infections after solid organ transplantation (SOT). Treatment should be guided by susceptibility testing, but conventional lab methods are laborious with prolonged turnaround time (TAT). This case series compares the phenotypic and genotypic susceptibility profiles of M. hominis isolates identified from SOT patients. METHODS: This is a single-center retrospective study evaluating SOT recipients with confirmed M. hominis infections. Patients' demographic, clinical, microbiological, and radiographic data were collected. Culture of M. hominis isolates was performed according to current Clinical and Laboratory Standards Institute guidelines. Phenotypic susceptibility testing was performed by University of Alabama Diagnostic Mycoplasma Laboratory. Whole genome sequencing (WGS) was performed followed by bioinformatic analysis of known genetic determinants of resistance. RESULTS: Seven SOT recipients with M. hominis infections were identified. Two out of seven (28.5%) patients had resistance detected by phenotypic susceptibility testing (Case 5 to levofloxacin and Case 7 to tetracycline). Genomic analyses confirmed the presence of mutations in the parC and parE topoisomerase genes at positions conferring to fluoroquinolone resistance in the isolate from Case 5, while the tetracycline-resistant isolate from Case 7 harbored the tetM gene. The median TAT from the date of specimen collection was 24 days for phenotypic susceptibility testing and 14 days for genotypic susceptibility testing. All seven patients received antimicrobials directed toward M. hominis and recovered with complete resolution of infection. CONCLUSIONS: WGS may offer a novel and more rapid methodology for M. hominis susceptibility testing to help optimize antimicrobial usage, but more data are needed.

Utilization of whole genome sequencing for resolution of discrepant Mycobacterium tuberculosis drug susceptibility results: A case report.

A 44-year-old woman undergoing therapy for acute promyelocytic leukemia (APL) developed disseminated tuberculosis. Mycobacterium tuberculosis (TB) was isolated from the blood and sputum. Initial drug susceptibility testing (DST) of the blood isolate revealed resistance to isoniazid and ethambutol but the sputum isolate showed no resistance. Due to drug resistance concerns, the patient was treated with multiple second and third-line drugs, and suffered from drug side effects. To further investigate the DST discrepancies, whole genome sequencing (WGS) was performed on both isolates. No known resistance mutations to first line or second line drugs were identified in either isolate, which was confirmed by additional susceptibility testing performed by a different reference laboratory and the California Department of Public Health (CDPH) laboratory. Treatment was reduced to a simpler and less toxic regimen due to these investigations. WGS is shown to be a valuable tool for resolving discordant phenotypic DST results of TB isolates and has the potential to provide accurate and timely results guiding appropriate therapy in the clinical setting.

Performance of roof-mounted misting fans to regulate heat stress in dairy cows.

Heat stress can negatively affect cow's physiology, behavior, and milk production. This study evaluates the effectiveness of roof mounting misting fans to improve heat and humidity index which reduces heat stress in a cowshed. Local climatic conditions were monitored and cooling system ability to control heat stress were assessed. Measurements were conducted at different cooling zones and levels comparing with shaded and open zones. The temperature and humidity index measurements outside the cowshed THIout showed that animals exposed to high degrees of heat stress during most of the day. The average value of THIout was 87.49, whereas the average value of adjusted outside temperature and humidity index THIadj was greater than THIout by 10% when solar radiation was considered. The maximum difference of hourly averages for temperature and humidity indices THIadj and THI occurred at noon when the intensity of solar radiation was highest. The average value for temperature and humidity index under misting fans THIfan was 82.27 whereas inside the cowshed under shade THIshade was 85.20. This conclude that the misting fans was able to reduce heat stress in a limited degree. Further improvement in terms of the cowshed design aspects and an increase of cooling efficiency is needed.

Endogenous Endophthalmitis Caused by ST66-K2 Hypervirulent Klebsiella pneumoniae, United States.

We describe a case of endogenous endophthalmitis caused by sequence type 66-K2 hypervirulent Klebsiella pneumoniae in a diabetic patient with no travel history outside the United States. Genomic analysis showed the pathogen has remained highly conserved, retaining >98% genetic similarity to the original strain described in Indonesia in 1935.

COVID-19 versus SARS: A comparative review.

The two genetically similar severe acute respiratory syndrome coronaviruses, SARS-CoV-1 and SARS-CoV-2, have each been responsible for global epidemics of vastly different scales. Although both viruses arose from similar origins, they quickly diverged due to differences in their transmission dynamics and spectrum of clinical presentations. The potential involvement of multiple organs systems, including the respiratory, cardiac, gastrointestinal and neurological, during infection necessitates a comprehensive understanding of the clinical pathogenesis of each virus. The management of COVID-19, initially modelled after SARS and other respiratory illnesses, has continued to evolve as we accumulate more knowledge and experience during the pandemic, as well as develop new therapeutics and vaccines. The impact of these two coronaviruses has been profound for our health care and public health systems, and we hope that the lessons learned will not only bring the current pandemic under control, but also prevent and reduce the impact of future pandemics.

Spectrum of Coronavirus Disease 2019 Outcomes in Kidney Transplant Recipients: A Single-Center Experience.

PURPOSE: We reviewed the clinical experience of kidney transplant recipients diagnosed with severe acute respiratory syndrome coronavirus 2 infection in order to understand the impact of the current coronavirus disease 2019 (COVID-19) pandemic infection on transplant recipients. Given that early reports from heavily affected areas demonstrated a very high mortality rate amongst kidney transplant recipients, ranging between 30% and 40%, we sought to evaluate outcomes at a center with a high burden of cases but not experiencing acute crisis due to COVID-19. PROCEDURES: In this single center retrospective observational study, medical records of all kidney transplant recipients at the UCLA Medical Center were reviewed for a diagnosis of COVID-19 by polymerase chain reaction, followed by chart review to determine kidney transplant characteristics and clinical course. MAIN FINDINGS: A total of 41 kidney transplant recipients were identified with COVID-19 positive polymerase chain reaction. Recipients had been transplanted for a median of 47 months before diagnosis. The large proportion of infected individuals were minorities (Hispanic 65.9%, black 14.6%), on prednisone, tacrolimus, and mycophenolate mofetil (95.1%, 87.8%, and 87.8%, respectively), and had excellent allograft function (median 1.25 mg/dL). The most common presenting symptoms were fever, dyspnea, or cough. Most patients were hospitalized (63.4%); mortality was 9.8% and occurred only in patients in the intensive care unit. The most common treatment was reduction or removal of antimetabolite (77.8%). Approximately 26.9% presented with AKI. CONCLUSIONS: COVID-19 infection in kidney transplant recipients results in a higher rate of hospitalization and mortality than in the general population. In an area with a high number of infections, the mortality rate was lower compared with earlier reports from areas experiencing early surge and strain on the medical system. Minorities were disproportionately affected. Future studies are needed to determine optimal approach to treatment and management of immunosuppression in kidney transplant recipients with COVID-19 infection.

A Collaborative Tale of Diagnosing and Treating Chronic Pulmonary Aspergillosis, from the Perspectives of Clinical Microbiologists, Surgical Pathologists, and Infectious Disease Clinicians.

Chronic pulmonary aspergillosis (CPA) refers to a spectrum of Aspergillus-mediated disease that is associated with high morbidity and mortality, with its true prevalence vastly underestimated. The diagnosis of CPA includes characteristic radiographical findings in conjunction with persistent and systemic symptoms present for at least three months, and evidence of Aspergillus infection. Traditionally, Aspergillus infection has been confirmed through histopathology and microbiological studies, including fungal culture and serology, but these methodologies have limitations that are discussed in this review. The treatment of CPA requires an individualized approach and consideration of both medical and surgical options. Most Aspergillus species are considered susceptible to mold-active triazoles, echinocandins, and amphotericin B; however, antifungal resistance is emerging and well documented, demonstrating the need for novel therapies and antifungal susceptibility testing that correlates with clinical response. Here, we describe the clinical presentation, diagnosis, and treatment of CPA, with an emphasis on the strengths and pitfalls of diagnostic and treatment approaches, as well as future directions, including whole genome sequencing and metagenomic sequencing. The advancement of molecular technology enables rapid and precise species level identification, and the determination of molecular mechanisms of resistance, bridging the clinical infectious disease, anatomical pathology, microbiology, and molecular biology disciplines.