Neutrophil-to-Lymphocyte Ratio as a Marker for Cardiac Autonomic Neuropathy in Egyptian Patients With Type 2 Diabetes: A Cross-Sectional Study.

OBJECTIVE: Cardiac autonomic neuropathy (CAN) is one of the most serious complications of diabetes. This study aimed to analyze the correlation between neutrophil-to-lymphocyte ratio (NLR) and CAN in patients with type 2 diabetes (T2D) using 24-hour Holter ECG and to assess the relationship between NLR and severity of diabetic peripheral neuropathy (DPN). SUBJECTS & METHODS:  This cross-sectional study included 90 T2D patients with DPN confirmed by nerve conduction study (NCS). A 24-hour Holter ECG was done to detect the decrease in heart rate variability (HRV). Laboratory parameters, including fasting blood glucose, creatinine, cholesterol, triglyceride, and glycosylated hemoglobin (HbA1c) levels, as well as CBC, neutrophils, lymphocytes, NLR, and platelet-to-lymphocyte ratio (PLR), were calculated accordingly. An albumin-to-creatinine ratio (ACR) test was done and the estimated glomerular filtration rate (eGFR) was calculated. Chronic kidney disease was diagnosed by the presence of albuminuria (≥30 mg/g creatinine) and/or eGFR less than 60. RESULTS: Based on the 24-hour Holter ECG, 25 patients out of 90 (27.7%) had CAN. On comparing both the CAN and non-CAN groups, the CAN group had higher HbA1C (p = 0.005), higher NLR (p = 0.014), and higher neutrophils (p = 0.10). Also, PLR was higher in the CAN group than in the non-CAN group, but this was not statistically significant (p = 0.180). Receiver operator characteristic curve analysis revealed that NLR with a cutoff of 1.7 succeeded in detecting patients with CAN. CONCLUSION: NLR can be used as an inexpensive and accessible marker to detect patients with diabetes at risk for developing CAN.

Single-Atom Catalysts through Pressure-Controlled Metal Diffusion.

Single-atom catalysts (SACs) open up new possibilities for advanced technologies. However, a major complication in preparing high-density single-atom sites is the aggregation of single atoms into clusters. This complication stems from the delicate balance between the diffusion and stabilization of metal atoms during pyrolysis. Here, we present pressure-controlled metal diffusion as a new concept for fabricating ultra-high-density SACs. Reducing the pressure inhibits aggregation substantially, resulting in almost three times higher single-atom loadings than those obtained at ambient pressure. Molecular dynamics and computational fluid dynamics simulations reveal the role of a metal hopping mechanism, maximizing the metal atom distribution through an increased probability of metal-ligand binding. The investigation of the active site density by electrocatalytic oxygen reduction validates the robustness of our approach. The first realization of Ullmann-type carbon-oxygen couplings catalyzed on single Cu sites demonstrates further options for efficient heterogeneous catalysis.

Unusual Cause of Acute Stroke in a Young Woman with Patent Foramen Ovale - Duplicated Inferior Vena Cava and May-Thurner Syndrome.

The etiology of acute ischemic stroke (AIS) may often remain uncertain despite diligent work-up, especially in young people. Although patent foramen ovale (PFO) is a frequent association during such work-up, the actual source of thromboembolism, like deep vein thrombosis (DVT), may not be found. Such associative pathology makes it challenging to prescribe anticoagulation for secondary stroke prevention. We describe a young woman with a known history of PFO who presented with AIS and underwent endovascular reperfusion therapy. Post-thrombectomy, she developed hypoxic respiratory failure due to pulmonary embolism. Initiation of therapeutic anticoagulation was complicated by a retroperitoneal bleed necessitating imaging studies for etiological work-up. Computed tomographic angiography and venogram showed no active contrast extravasation but demonstrated duplication of the inferior vena cava with DVT in the right iliofemoral vein (RIFV). The proximity of the right common iliac artery compressing RIFV against the pelvic inlet is described as May-Thurner syndrome (MTS). Afterward, the patient was successfully treated with anticoagulation and PFO closure. MTS is a rare and underdiagnosed cause of iliofemoral DVT. In patients with known PFO, MTS is a possible cause that needs consideration. Hence, appropriate diagnostic tests are necessary to initiate appropriate management and to prevent AIS recurrence.

Diabetes surpasses obesity as a risk factor for low serum testosterone level.

BACKGROUND: Male obesity is one of the most associated factors with substandard testosterone levels. However, there is growing evidence linking low testosterone levels to insulin resistance and diabetic complications. We aimed to study the impact of diabetes mellitus on testosterone levels and to assess the correlation of various clinical and biochemical factors with hypogonadism. SUBJECTS AND METHODS: This case-control study was conducted on 160 adult males categorized into four equal groups (40 each); Group A: lean men with T2DM, Group B: obese with T2DM, Group C: lean with normal glycemic profile, Group D: obese with normal glycemic profile. Serum total testosterone (TT), SHBG and HbA1c have been measured. Free testosterone (cFT) and HOMA-IR were calculated. RESULTS: A significant negative correlation of serum TT and cFTwith BMI (r -0.16, p 0.04/ r -0.26, p < 0.001, respectively) and with waist circumference (WC) (r -0.23, p 0.003 and r -0.3, p < 0.001, respectively). A significant decrease in TT and cFT in the diabetes group versus the non-diabetes one (p < 0.001 for both). TT level was significantly lower in the diabetic lean group than in the non-diabetic lean (p < 0.001), and even significantly lower than in the non-diabetic obese (p < 0.001). TT level in the diabetic obese group was lower than in the non-diabetic obese (p < 0.001). The same for cFT level, lower in the diabetic lean group than in non-diabetic lean (p < 0.001) and lower in the diabetic obese than in the non-diabetic obese (p < 0.001). Concomitant significant reduction in SHBG in the diabetes group (p < 0.001). Linear regression analysis revealed that TT significantly correlated with HOMA-IR. HOMA-IR with WC, age and the duration of diabetes correlated significantly with cFT. In our model, HOMA-IR and HbA1c accounted for approximately 51.3% of TT variability (adjusted R-squared 0.513). CONCLUSIONS: The impact of T2DM on serum testosterone levels was more significant than that of obesity. Our study showed a decrease in SHBG together with cFT among the diabetes group. Hypogonadism is significantly correlated to insulin resistance and poor glycemic control, which implies another perspective on the impact of suboptimal glycemic control on the development of hypogonadism.

Thermally Stable P-Chiral Supramolecular Phosphines, their Self-Assembly and Implication in Rh-Catalyzed Asymmetric Hydrogenation.

P-chiral supramolecular phosphine ligands are crucial for asymmetric transformations, but their synthesis is tedious. We report a one-step synthesis of thermally stable P-chiral supramolecular phosphines and their performance in the asymmetric hydrogenation of functionalized alkenes. A rational designing and synthesis of (R, R)-QuinoxP* ligated palladium complex (Pd-2) in excellent yield is reported. This Pd-2 catalyzed a direct P-C coupling of 2,3-dihydro-1-H-phosphindole (A1)/1,2,3,4-tetrahydrophosphindoline (A2) with 1-(3-iodophenyl)urea/2-iodo (B1)/6-hydroxy pyridine (B2) and, produced corresponding ligands L1-L3. The P-C coupling between A1 and B2 produced 6-(2,3-dihydro-1H-phosphindol-1-yl)pyridine-2(1H)-one (L2) with an excellent enantiomeric excess of up to 99%. L2 was found to be remarkably stable even at 150 °C and did not oxidize/hydrolyze for at least 24 hours in open air. Such thermal stability and an impediment to oxidation are unprecedented. L2 self-assembled and produced L2-C1 (Pt), L2-C2(Pd), and L2-C3(Rh) assemblies. The utility of the self-assembled P-chiral ligand was demonstrated in the Rh-catalyzed asymmetric hydrogenation (AH) of functionalized olefins. The L2-C3 catalyzed AH of functionalized alkenes and delivered chiral products with excellent enantioselectivity of >99%. A small library of 16 substrates was subjected to AH using L2-C3 to produce chiral compounds with excellent conversion and ee.

Elective Irradiation of Retropharyngeal Lymph Nodes as an Indication for Adjuvant Radiation Therapy After Transoral Surgery for Tonsil Cancer.

Treatment of squamous cell carcinoma of the tonsil involves primary radiation therapy (RT) or surgical resection. Historically, if RT was the primary or adjuvant treatment modality, most of the bilateral retropharyngeal lymph nodes (RPLNs) were treated electively with a therapeutic dose for subclinical disease, regardless of whether radiographically pathologic lymph nodes were seen on initial diagnostic imaging. De-escalation strategies include the incorporation of transoral surgery with the goal to either eliminate or reduce the dose of adjuvant RT or chemotherapy. Transoral surgery does not include elective removal of the RPLNs, and no guideline or outcome paper recommends adjuvant RT specifically to electively treat RPLNs. In this Topic Discussion, we discuss pertinent literature and suggest management decisions. The management decisions discussed in this Topic Discussion pertain to only tonsillar primaries and not those of the soft palate or base of the tongue.

Characterization of Acinetobacter baumannii-calcoaceticus complex isolates and microbiological outcome for patients treated with sulbactam-durlobactam in a phase 3 trial (ATTACK).

Acinetobacter baumannii-calcoaceticus complex (ABC) causes severe, difficult-to-treat infections that are frequently antibiotic resistant. Sulbactam-durlobactam (SUL-DUR) is a targeted ß-lactam/ß-lactamase inhibitor combination antibiotic designed to treat ABC infections, including those caused by multidrug-resistant strains. In a global, pathogen-specific, randomized, controlled phase 3 trial (ATTACK), the efficacy and safety of SUL-DUR were compared to colistin, both dosed with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC. Results from ATTACK showed that SUL-DUR met the criteria for non-inferiority to colistin for the primary efficacy endpoint of 28-day all-cause mortality with improved clinical and microbiological outcomes compared to colistin. This report describes the characterization of the baseline ABC isolates from patients enrolled in ATTACK, including an analysis of the correlation of microbiological outcomes with SUL-DUR MIC values and the molecular drivers of SUL-DUR resistance.

Clinical Outcomes for Patients With Monomicrobial vs Polymicrobial Acinetobacter baumannii-calcoaceticus Complex Infections Treated With Sulbactam-Durlobactam or Colistin: A Subset Analysis From a Phase 3 Clinical Trial.

Background: In a previous study, the efficacy and safety of sulbactam-durlobactam vs colistin for the treatment of patients with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRABC) infections were evaluated in a randomized controlled phase 3 trial. Both arms were dosed on a background of imipenem-cilastatin to treat coinfecting gram-negative pathogens. Thirty-six percent of infections in the primary efficacy population were polymicrobial. Methods: A subset analysis was performed to compare clinical and microbiological outcomes at test of cure (7 ± 2 days after the last dose) for patients with monomicrobial and polymicrobial CRABC infections. Minimal inhibitory concentrations of antibiotics against baseline isolates were determined by broth microdilution according to Clinical and Laboratory Standards Institute methodology. Results: Clinical cure, 28-day all-cause mortality, and microbiological outcomes were similar for patients in the sulbactam-durlobactam treatment arm with monomicrobial or polymicrobial A baumannii-calcoaceticus infections. Patients in the colistin arm with monomicrobial CRABC infections had higher mortality rates with worse clinical and microbiological outcomes as compared with those with polymicrobial infections. For patients who received sulbactam-durlobactam, imipenem susceptibility of coinfecting gram-negative pathogens trended with clinical benefit for patients with polymicrobial A baumannii-calcoaceticus infections. When tested in vitro, durlobactam restored imipenem susceptibility to the majority of coinfecting gram-negative pathogens from the sulbactam-durlobactam arm. This phenotype appeared to be related to the clinical outcome in 13 of 15 evaluable cases. Conclusions: These results suggest that the use of sulbactam-durlobactam plus a carbapenem could be an effective approach to treat polymicrobial infections that include CRABC, but additional clinical data are needed to demonstrate efficacy.

Knowledge-based quality assurance of a comprehensive set of organ at risk contours for head and neck radiotherapy.

Introduction: Manual review of organ at risk (OAR) contours is crucial for creating safe radiotherapy plans but can be time-consuming and error prone. Statistical and deep learning models show the potential to automatically detect improper contours by identifying outliers using large sets of acceptable data (knowledge-based outlier detection) and may be able to assist human reviewers during review of OAR contours. Methods: This study developed an automated knowledge-based outlier detection method and assessed its ability to detect erroneous contours for all common head and neck (HN) OAR types used clinically at our institution. We utilized 490 accurate CT-based HN structure sets from unique patients, each with forty-two HN OAR contours when anatomically present. The structure sets were distributed as 80% for training, 10% for validation, and 10% for testing. In addition, 190 and 37 simulated contours containing errors were added to the validation and test sets, respectively. Single-contour features, including location, shape, orientation, volume, and CT number, were used to train three single-contour feature models (z-score, Mahalanobis distance [MD], and autoencoder [AE]). Additionally, a novel contour-to-contour relationship (CCR) model was trained using the minimum distance and volumetric overlap between pairs of OAR contours to quantify overlap and separation. Inferences from single-contour feature models were combined with the CCR model inferences and inferences evaluating the number of disconnected parts in a single contour and then compared. Results: In the test dataset, before combination with the CCR model, the area under the curve values were 0.922/0.939/0.939 for the z-score, MD, and AE models respectively for all contours. After combination with CCR model inferences, the z-score, MD, and AE had sensitivities of 0.838/0.892/0.865, specificities of 0.922/0.907/0.887, and balanced accuracies (BA) of 0.880/0.900/0.876 respectively. In the validation dataset, with similar overall performance and no signs of overfitting, model performance for individual OAR types was assessed. The combined AE model demonstrated minimum, median, and maximum BAs of 0.729, 0.908, and 0.980 across OAR types. Discussion: Our novel knowledge-based method combines models utilizing single-contour and CCR features to effectively detect erroneous OAR contours across a comprehensive set of 42 clinically used OAR types for HN radiotherapy.

Implementation of the REFLECT Communication Curriculum for Clinical Oncology Graduate Medical Education.

Background: Communication and interpersonal skills are essential medical components of oncology patient care. Patients and families rely on physicians for treatment, expertise, guidance, hope, meaning, and compassion throughout a life-threatening illness. A provider's inability to empathize with patients is linked to physician-related fatigue and burnout. Because oncology training programs focus on teaching evidence-based medicine and clinical acumen, little time may be dedicated to professional development and acquisition of interactive skills. Traditional communication courses typically include two components: formal, knowledge-based learning skills, which are gained from didactic lectures, and role-playing, which usually occurs in small groups. We report the implementation of a novel longitudinal communication curriculum for trainees in Oncology. Materials and Methods: At a single-center institution, an innovative communication curriculum titled "REFLECT" (Respect, Empathy, Facilitate Effective Communication, Listen, Elicit Information, Compassion, and Teach Others) was implemented for radiation oncology residents and medical oncology fellows to improve and refine physician/patient interactions. All oncology specialty residents and fellows were eligible to participate in this communication curriculum. The curriculum emphasized a reflective process to guide trainees through challenging scenarios. Results: Since October 2018, this comprehensive course consisted of quarterly (four hour) workshops comprising assigned reading, knowledge assessments, didactic lectures, expert guest lecturers, standardized patient simulations, role-playing, patient/expert panels, coaching, reflective writing, and debriefing/feedback sessions. The curriculum provided longitudinal communication training integrated with the learners' daily physician/patient encounters rather than occasional isolated experiences. Fifteen workshops have been completed. Each focused on navigating challenging situations with patients, loved ones, or colleagues. Conclusions: Future directions of the curriculum will entail improving the communication skills of oncology trainees and gathering communication improvement data to assess the program's success formally.

Consensus Statement of the IAP - Neurodevelopmental Chapter On Neurodevelopmental Disorders Habilitation Process: Strategic Plan for Prevention, Early Detection and Early Intervention.

JUSTIFICATION: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders. PROCESS: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines. The guidelines were then discussed by the whole group through online meetings, and the contentious issues were discussed until a general consensus was arrived at. Following this, the final guidelines were drafted by the writing group and approved by all contributors. OBJECTIVES: These guidelines aim to provide practical clinical guidelines for pediatricians on the prevention, early diagnosis and management of neurodevelopmental disorders (NDDs) in the Indian settings. It also defines the roles of developmental pediatricians and development nurse counselor. STATEMENT: There is a need for nationwide studies with representative sampling on epidemiology of babies with early NDD in the first 1000 days in India. Specific learning disability (SLD) has been documented as the most common NDD after 6 years in India, and special efforts should be made to establish the epidemiology of infants and toddlers at risk for SLD, where ever measures are available. Preconception counseling as part of focusing on first 1000 days; Promoting efforts to organize systematic training programs in Newborn Resuscitation Program (NRP); Lactation management; Developmental follow-up and Early stimulation for SNCU/ NICU graduates; Risk stratification of NICU graduates, Newborn Screening; Counseling parents; Screening for developmental delay by trained professionals using simple validated Indian screening tools at 4, 8, 12, 18 and 24 months; Holistic assessment of 10 NDDs at child developmental clinics (CDCs) / district early intervention centre (DEICs) by multidisciplinary team members; Confirmation of diagnosis by developmental pediatrician/developmental neurologist/child psychiatrist using clinical/diagnostic tools; Providing parent guided low intensity multimodal therapies before 3 years age as a center-based or home-based or community-based rehabilitation; Developmental pediatrician to seek guidance of pediatric neurologist, geneticist, child psychiatrist, physiatrist, and other specialists, when necessary; and Need to promote ongoing academic programs in clinical child development for capacity building of community based therapies, are the chief recommendations.

Mean Oral Cavity Organ-at-Risk Dose Predicts Opioid Use and Hospitalization during Radiotherapy for Patients with Head and Neck Tumors.

BACKGROUND: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient's quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ-at-risk (OAR) avoidance structure, provider- and patient-reported outcomes (PROs), opioid use, and hospitalization. METHODS: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. RESULTS: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p = 0.0082) and hospitalization (p = 0.0356) during and within 30 days of completing RT. CONCLUSIONS: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.

Impact of diabetic peripheral neuropathy on gait abnormalities in patients with type 2 diabetes mellitus.

Background: Many patients with type 2 diabetes (T2DM) suffer from diabetic peripheral neuropathy (DPN) and impaired muscle coordination. These changes may lead to walking instability, and gait abnormalities resulting in increased fall risk and lower limb amputations. The aim of this study was to assess the impact of DPN and patient footwear on the gait in patients with diabetes, in addition to Comparing the peak plantar pressure (PPP) in patients with and without DPN and assessing its association with gait abnormalities. Methodology: This is an observational case-control study. Forty Subjects with T2DM were divided into two age and sex-matched groups, 20 subjects each. Group A: subjects with DPN. Group B: subjects without DPN. All study participants were subjected to a thorough history taking, clinical examinations focusing on detailed foot examination, PPP assessment, and functional gait evaluation. Results: The results obtained in this study showed a median gait assessment score of 21 (17.0-22.5) for group A and 26 (23.5-26.0) for group B which was statistically significant (p < 0.001). There was no statistically significant difference between both groups (p > 0.05) regarding the assessment of footwear appropriateness. Comparing the PPP measurement among both studied groups, the prevalence of an elevated PPP was 80% in group A compared to 65% in group B, which was statistically non-significant, p = 0.288. Conclusions: Gait abnormalities are common among patients with T2DM even in the absence of DPN. However, the presence of DPN was the strongest independent risk factor for gait abnormalities among the studied factors.

Tuning the Inter-Nanoplatelet Distance and Coupling Strength by Thermally Induced Ligand Decomposition.

CdSe nanoplatelets (NPLs) are promising 2D semiconductors for optoelectronic applications, in which efficient charge transport properties are desirable. It is reported that thermal annealing constitutes an effective strategy to control the optical absorption and electrical properties of CdSe NPLs by tuning the inter-NPL distance. Combining optical absorption, transmission electron microscopy, and thermogravimetric analysis, it is revealed that the thermal decomposition of ligands (e.g., cadmium myristate) governs the inter-NPL distance and thus the inter-NPL electronic coupling strength. Employing ultrafast terahertz spectroscopy, it is shown that this enhanced electronic coupling increases both the free carrier generation efficiency and the short-range mobility in NPL solids. The results show a straightforward method of controlling the interfacial electronic coupling strength for developing functional optoelectronic devices through thermal treatments.

Modelling small block aperture in an in-house developed GPU-accelerated Monte Carlo-based dose engine for pencil beam scanning proton therapy.

Purpose. To enhance an in-house graphic-processing-unit accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS).Methods and materials. A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3 cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4 cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45 mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 c.c. with range of 0.4-43.3 c.c.). Finally, 3 typical patients were selected for robust optimization with aperture blocks using VPMC.Results. In the water phantoms, 3D gamma passing rate (2%/2 mm/10%) between VPMC and MCsquare was 99.71 ± 0.23%. In the patient geometries, 3D gamma passing rates (3%/2 mm/10%) between VPMC/MCsquare and RayStation MC were 97.79 ± 2.21%/97.78 ± 1.97%, respectively. Meanwhile, the calculation time was drastically decreased from 112.45 ± 114.08 s (MCsquare) to 8.20 ± 6.42 s (VPMC) with the same statistical uncertainties of ~0.5%. The robustly optimized plans met all the dose-volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 s and the subsequent on-the-fly 'trial-and-error' optimization procedure took only 71.4 s on average for the selected three patients.Conclusion. VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.

Low contralateral failure rate with unilateral proton beam radiotherapy for oropharyngeal squamous cell carcinoma: A multi-institutional prospective study from the proton collaborative group.

INTRODUCTION: Unilateral radiation therapy is appropriate for select patients with oropharyngeal squamous cell carcinoma (OPSCC). The use of proton beam therapy (PBT) in the unilateral setting decreases the dose to the contralateral neck and organs at risk. This study aims to evaluate contralateral recurrences in patients who received ipsilateral PBT. METHODS: We evaluated the Proton Collaborative Group database for patients treated with PBT for head and neck squamous cell carcinoma between the years 2015-2020 at 12 institutions. Dosimetric analysis was performed in five cases. RESULTS: Our analysis included 41 patients that received ipsilateral PBT with a mean follow-up of 14.7 months. 37% patients (n = 15) were treated for recurrent disease, and 63% (n = 26) were treated for de novo disease. Oropharyngeal sites included tonsillar fossa (n = 30) and base of tongue (n = 11). The median dose and BED delivered were 69.96 CGE and 84 Gy, respectively. Eight (20%) patients experienced at least one grade 3 dysphagia (n = 4) or esophagitis (n = 4) toxicity. No grade ≥ 4 toxicities were reported. There was one (2.4%) failure in the contralateral neck. The 1-year locoregional control was 88.9% and the freedom from distant metastasis was 95.5% (n = 2). The dosimetric analysis demonstrated similar ipsilateral level II cervical nodal region doses, whereas contralateral doses were higher with photon plans, mean: 15.5 Gy and 0.7CGE, D5%: 25.1 Gy and 6.6CGE. CONCLUSIONS: Our series is the first to report outcomes for patients with OPSCC receiving unilateral PBT. The contralateral neck failure rate was excellent and comparable to failure rates with photon irradiation.

Ante-mortem and Post-mortem Diagnosis Modalities and Phylogenetic Analysis of Rabies Virus in Domestic and Wild Animals of Gujarat, India.

In the present study, total of 32 ante-mortem (AM) samples (saliva = 18 and corneal smears = 14) from six animal species (cattle = 5; camel = 1; goat = 1; horse = 1; buffalo = 4; dog = 6) and 28 post-mortem (PM) samples of domestic (cattle = 6; camel = 1; goat = 1; buffalo = 5; dog = 7) and wild animals (lion = 4, mongoose = 2; bear = 1; leopard = 1) were examined for rabies diagnosis in Gujarat, India. Direct fluorescent antibody test (dFAT) and reverse transcriptase polymerase chain reaction (RT-PCR) were applied on AM samples, whereas along with dFAT and RT-PCR, histopathological examination, immunohistochemistry (IHC) and real time PCR (qPCR) were used for PM diagnosis. Nucleotide sequencing of full nucleoprotein (N) and glycoprotein (G) genes were carried out upon representative amplicons. In AM examination, 7/18 saliva and 5/14 corneal impressions samples were found positive in dFAT and 8/18 saliva samples were found positive in RT-PCR. In PM examination, 14/28 samples showed positive results in dFAT and IHC with unusual large fluorescent foci in two samples. In histopathology, 11/28 samples showed appreciable lesion and Negri bodies were visible in 6 samples, only. Out of 23 brain samples examined. 12 samples were found positive in N gene RT-PCR and qPCR, and 10 samples in G gene RT-PCR. Phylogenetic analysis of N gene revealed that test isolates (except sample ID: lion-1; lion, Gir) form a close group with sequence ID, KM099393.1 (Mongoose, Hyderabad) and KF660246.1 (Water Buffalo, Hyderabad) which was far from some south Indian and Sri Lankan isolates but similar to Indian isolates from rest of India and neighboring countries. In G gene analysis, the test isolates form a close group with sequence ID, KP019943.1. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01126-0.

Presentation and outcomes of KRASG12C mutant non-small cell lung cancer patients with stage IV disease at diagnosis (de novo) versus at recurrence.

Close monitoring after diagnosis of patients with stage I-III non-small cell lung cancer (NSCLC) may result in fitter patients with lower disease burden at the time of metastatic recurrence or progression compared to patients diagnosed initially as stage IV (de novo). We compared the presentation, treatments, and outcomes of patients with KRASG12C-mutated NSCLC with de novo versus recurrent stage IV disease. Of 109 patients, 94% had a smoking history. When compared to patients with KRASG12C-mutated NSCLC who developed stage IV disease at recurrence (n = 38), de novo stage IV patients (n = 71) had worse ECOG performance status (p = 0.007), greater numbers of extra-thoracic metastatic sites (p = 0.001), and were less likely to receive 2nd/3rd line systemic therapy (p = 0.05, p = 0.002) or targeted therapy (p = 0.001). De novo metastatic patients had shorter overall survival than metastatic patients at recurrence (9.1 versus 24.2 months; adjusted-hazard-ratio=1.94 (95% CI: 1.14-3.28; p = 0.01)). There is a critical need for well-tolerated targeted therapies in the first-line setting for metastatic patients with de novo, high-burden, stage IV KRASG12C-mutated NSCLCs.

In Vivo Emergence of Pandrug-Resistant Acinetobacter baumannii Strain: Comprehensive Resistance Characterization and Compassionate Use of Sulbactam-Durlobactam.

The treatment of patients with infection secondary to carbapenem-resistant Acinetobacter baumannii with emerging cefiderocol resistance remains challenging and unclear. We present a case of in vivo emergence of pandrug-resistant A baumannii that was successfully treated with the compassionate use of investigational sulbactam-durlobactam-based antibiotic regimen. We also performed a longitudinal genomic analysis of the bacterial isolates and showed the development of resistance and genetic mutations over time.