Clinical implications of serum anti-PLA2R levels and glomerular PLA2R deposits in primary membranous nephropathy.

Introduction. The clinical implications of serum anti-PLA2R with glomerular PLA2R deposits in primary membranous nephropathy (PMN) is scarcely reported. Hence the study was designed to demonstrate the prevalence of serum anti-PLA2R levels and PLA2R staining in glomeruli in PMN and the clinical implications of the two parameters. Objectives. Investigate the prevalence of anti PLA2R positivity in PMN. Ascertain correlation between serum anti-PLA2R levels and glomerular staining for PLA2R with clinical and lab parameters in PMN. Patients and Methods. Fifty PMN patients during the period from October 2017 to December 2018 were included. Labs were done and eGFR was calculated as per MDRD 6. Anti-PLA2R titres were done in all patients. Titres more than 20 RU/ml were considered positive. Glomerular staining for PLA2R was graded on fresh frozen tissue by immunofluorescence technique. Results. Anti-PLA2R antibody positivity and glomerular PLA2R deposition was observed in 42% (21/50) and 86% (43/50) patients respectively. 79.3% (23/29) had positive glomerular PLA2R deposition with negative serum anti PLA2R. Positive correlation were observed between serum PLA2R antibody and serum creatinine (p = 0.0001) and urine protein-creatinine ratio levels with tissue PLA2R staining grades (p = 0.04). Negative association was found between serum albumin (p = 0.026) and tissue PLA2R staining grades. Conclusion. Serum anti-PLA2R wasn't a sensitive marker of primary membranous nephropathy in our study group emphasising the need to consider a compendium of serological markers for diagnosis of primary membranous nephropathy and to rely more on glomerular deposition of PLA2R as a better clinical indicator for PMN.

First Measurement of η Meson Production in Neutrino Interactions on Argon with MicroBooNE.

We present a measurement of η production from neutrino interactions on argon with the MicroBooNE detector. The modeling of resonant neutrino interactions on argon is a critical aspect of the neutrino oscillation physics program being carried out by the DUNE and Short Baseline Neutrino programs. η production in neutrino interactions provides a powerful new probe of resonant interactions, complementary to pion channels, and is particularly suited to the study of higher-order resonances beyond the Δ(1232). We measure a flux-integrated cross section for neutrino-induced η production on argon of 3.22±0.84(stat)±0.86(syst) 10^{-41} cm^{2}/nucleon. By demonstrating the successful reconstruction of the two photons resulting from η production, this analysis enables a novel calibration technique for electromagnetic showers in GeV accelerator neutrino experiments.

Postoperative parathyroid hormone (PTH) is equivalent to perioperative PTH drop in predicting postsurgical hypoparathyroidism.

INTRODUCTION: Postoperative surgical hypoparathyroidism (PoSH) following thyroid surgery is an established complication. Several predictive factors have been identified including perioperative parathyroid hormone (PTH) levels. The aim of the study is to compare the drop in perioperative PTH to postoperative day 1 PTH in predicting hypocalcaemia and hypoparathyroidism. METHODS: Records of consecutive patients who had either total or completion thyroidectomy with or without central neck dissection in a 3-year period in a single thyroid surgery unit were accessed to retrieve data on demographics, pathology, surgery, perioperative biochemistry and management. RESULTS: Of 295 included patients, there were 227 (76.9%) females. Forty-five (15.3%) had completion thyroidectomy, and the rest had total thyroidectomy. Seventy-eight (26.4%) had concomitant central neck dissection. Sixty-four (21.7%) had hypocalcaemia on the day after surgery. Hypoparathyroidism persisted in 10.5% of patients at 6 months. Both day 1 PTH and a drop in PTH predicted day 1 hypocalcaemia (p < 0.001) and 6-month hypoparathyroidism (p < 0.001). The area under the receiver operating characteristic (ROC) curves for day 1 PTH and drop in PTH for the prediction of day 1 hypocalcaemia (0.729 vs 0.726, respectively) and for 6-month hypoparathyroidism (0.964 vs 0.958, respectively) were similar, albeit slightly better for day 1 PTH. CONCLUSIONS: Day 1 PTH is equivalent to (if not better than) drop in PTH in predicting short- and long-term PoSH. Preoperative PTH measurements may not be needed in the detection and/or management of PoSH after thyroid surgery.

A randomized controlled trial on the effectiveness of laparoscopic-guided transversus abdominis plane block in patients undergoing laparoscopic IPOM plus.

INTRODUCTION: Ventral hernia repairs, particularly laparoscopic ventral hernia repair (LVHR), have become common procedures among general surgeons worldwide. Despite the benefits of LVHR, acute postoperative pain remains a significant concern. Transversus abdominis plane (TAP) blocks have been employed to alleviate postoperative pain in various laparoscopic procedures. This study aimed to assess the effectiveness of laparoscopic-guided TAP block in laparoscopic IPOM plus and its impact on postoperative pain and analgesic requirements. MATERIALS AND METHODS: A randomized controlled trial was conducted at a tertiary care center in India involving 72 patients undergoing laparoscopic IPOM plus. Patients were randomized into two groups: Group I received laparoscopic-guided TAP block, while Group II received standard general anesthesia without TAP block. Pain scores were assessed at 6, 12, and 24 h postoperatively using the numerical rating scale. Postoperative analgesic requirements were also recorded. RESULTS: Group I demonstrated significantly lower pain scores at 6 and 24 h postoperatively compared to Group II. The need for additional analgesics was significantly lower in Group I (13.8%) compared to Group II (72.2%). There were no significant differences in age, BMI, duration of surgery, or other demographic characteristics between the two groups. CONCLUSION: The findings of this randomized controlled trial demonstrate the effectiveness of laparoscopic-guided TAP blocks in reducing postoperative pain and analgesic requirements after laparoscopic IPOM plus.

Surgery for phaeochromocytomas and paragangliomas: Current practice in the United Kingdom.

INTRODUCTION: There is wide variability in the perioperative management of phaeochromocytoma and paraganglioma (PPGL) in different centres. This study aimed to summarise the management of PPGLs as reported in the United Kingdom Registry for Endocrine and Thyroid Surgery (UKRETS) database and to determine current perioperative management of PPGLs by surveying UK clinicians. METHODS: Data recorded on UKRETS from 2005 to 2021 were subjected to descriptive analyses. British Association of Endocrine and Thyroid Surgeons members were invited to participate in an open survey relating to the perioperative management of patients with PPGLs. RESULTS: A total of 2,007 operations for PPGL from 49 participating centres were included. The median annual workload in each centre was four cases. Operations were performed predominantly laparoscopically (69%). The median length of stay (4 days) was the same in groups of surgeons stratified by volume. The survey had 29 respondents from 22 centres across the UK, and a formal protocol for perioperative management exists in 48% of the centres. Phenoxybenzamine (72%) was preferred for alpha-blockade. The practice of admitting patients for optimisation from 1 to 7 days before the day of surgery was common (62%). Central venous pressure and blood glucose monitoring were mentioned as routine intraoperative adjuncts by 72% of the responders. CONCLUSIONS: There is significant variation in the workload and perioperative management of PPGLs in the UK. This is potentially detrimental to patient outcomes and a consensus document might be beneficial to harmonise practice across the UK.

Search for Heavy Neutral Leptons in Electron-Positron and Neutral-Pion Final States with the MicroBooNE Detector.

We present the first search for heavy neutral leptons (HNLs) decaying into νe^{+}e^{-} or νπ^{0} final states in a liquid-argon time projection chamber using data collected with the MicroBooNE detector. The data were recorded synchronously with the NuMI neutrino beam from Fermilab's main injector corresponding to a total exposure of 7.01×10^{20} protons on target. We set upper limits at the 90% confidence level on the mixing parameter |U_{µ4}|^{2} in the mass ranges 10≤m_{HNL}≤150 MeV for the νe^{+}e^{-} channel and 150≤m_{HNL}≤245 MeV for the νπ^{0} channel, assuming |U_{e4}|^{2}=|U_{τ4}|^{2}=0. These limits represent the most stringent constraints in the mass range 35

Dosimetric and radiobiological comparison of IMRT, VMAT, and helical tomotherapy planning techniques in hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases.

To compare treatment planning and dosimetric outcomes for hippocampal sparing whole brain radiotherapy (WBRT) with the simultaneous integrated boost (SIB) in brain metastasis (BM) patients using tumour control probability (TCP) and normal tissue complication probability (NTCP) formalism between IMRT, VMAT, and HT techniques. In this retrospective study, the treatment data of 20 BM patients who typically received whole brain radiation with SIB treatment were used. Prescription doses of 30 Gy and 36 Gy was delivered in 10 fractions for WBRT and SIB, respectively. Niemierko and LKB models were applied for calculating TCP and NTCP. All the plans were evaluated for the RTOG 0933 protocol criteria and found acceptable. Additionally, the homogeneity of the PTV boost is 0.07 ± 0.01, 0.1 ± 0.04, and 0.08 ± 0.02 for IMRT, VMAT, and HT, respectively (P < 0.05). The percentage of TCP for the PTV boost was 99.99 ± 0.003, 99.98 ± 0.004, and 99.99 ± 0.002 of IMRT, VMAT, and HT, respectively, (P < 0.005). The NTCP value of the lenses was higher with the VMAT plan as compared to IMRT and HT Plans. The hippocampal NTCP values are equal in all three planning proficiencies. The techniques like IMRT, VMAT, and HT can reduce the dose received by hippocampus to the dosimetric threshold during the delivery of WBRT with hippocampal sparing and can simultaneously boost multiple metastases. Overall, the high-quality dose distribution, TCP, and NTCP comparison between all three planning techniques show that the HT technique has better results when compared to the VMAT and IMRT techniques.

First Double-Differential Measurement of Kinematic Imbalance in Neutrino Interactions with the MicroBooNE Detector.

We report the first measurement of flux-integrated double-differential quasielasticlike neutrino-argon cross sections, which have been made using the Booster Neutrino Beam and the MicroBooNE detector at Fermi National Accelerator Laboratory. The data are presented as a function of kinematic imbalance variables which are sensitive to nuclear ground-state distributions and hadronic reinteraction processes. We find that the measured cross sections in different phase-space regions are sensitive to different nuclear effects. Therefore, they enable the impact of specific nuclear effects on the neutrino-nucleus interaction to be isolated more completely than was possible using previous single-differential cross section measurements. Our results provide precision data to help test and improve neutrino-nucleus interaction models. They further support ongoing neutrino-oscillation studies by establishing phase-space regions where precise reaction modeling has already been achieved.

First Measurement of Quasielastic Λ Baryon Production in Muon Antineutrino Interactions in the MicroBooNE Detector.

We present the first measurement of the cross section of Cabibbo-suppressed Λ baryon production, using data collected with the MicroBooNE detector when exposed to the neutrinos from the main injector beam at the Fermi National Accelerator Laboratory. The data analyzed correspond to 2.2×10^{20} protons on target running in neutrino mode, and 4.9×10^{20} protons on target running in anti-neutrino mode. An automated selection is combined with hand scanning, with the former identifying five candidate Λ production events when the signal was unblinded, consistent with the GENIE prediction of 5.3±1.1 events. Several scanners were employed, selecting between three and five events, compared with a prediction from a blinded Monte Carlo simulation study of 3.7±1.0 events. Restricting the phase space to only include Λ baryons that decay above MicroBooNE's detection thresholds, we obtain a flux averaged cross section of 2.0_{-1.7}^{+2.2}×10^{-40} cm^{2}/Ar, where statistical and systematic uncertainties are combined.

Differentiating Multisystem Inflammatory Syndrome in Children (MIS-C) and Its Mimics - A Single-Center Experience From a Tropical Setting.

OBJECTIVE: Identifying clinical and laboratory indicators that differentiate multisystem inflam-matory syndrome in children (MIS-C) apart from other febrile diseases in a tropical hospital setting. METHODS: Review of hospital records done in a tertiary care exclusive children's hospital for children admitted from April, 2020 till June, 2021. Laboratory values, severe acute respiratory syndrome coronavirus (SARS-CoV-2) serological status, and clinical signs and symptoms of patients with MIS-C, and those with similar presentations were analyzed. RESULTS: 114 children fulfilled the inclusion criteria (age group of 1 mo-18 y) for whom a diagnosis of MIS-C was considered in the emergency room based on the clinical features. Among them, 64 children had the final diagnosis of MIS-C, and the remaining 50 children had confirmatory evidence of infections mimicking MIS-C such as enteric fever, scrub typhus, dengue and appendicitis. CONCLUSION: Older age group, presence of muco-cutaneous symptoms, very high C-reactive protein, neutrophilic leukocytosis, abdominal pain and absence of hepatosplenomegaly favor a diagnosis of MIS-C.

Distribution of inadvertently excised parathyroid glands during thyroid surgery and the link with post-surgical hypoparathyroidism.

OBJECTIVES: To evaluate the incidence of inadvertent parathyroidectomy, identify risk factors, determine the location of inadvertently excised glands, review pathology reporting in inadvertent parathyroidectomy, and explore relationships between inadvertent parathyroidectomy and post-surgical hypoparathyroidism or hypocalcaemia. METHODS: A retrospective cohort study of 899 thyroidectomies between 2015 and 2020 was performed. Histopathology slides of patients who had an inadvertent parathyroidectomy and a random sample of patients without a reported inadvertent parathyroidectomy were reviewed. RESULTS: Inadvertent parathyroidectomy occurred in 18.5 per cent of thyroidectomy patients. Central neck dissection was an independent risk factor (inadvertent parathyroidectomy = 49.4 per cent with central neck dissection, 12.0 per cent without central neck dissection, p < 0.001). Most excised parathyroid glands were extracapsular (53.3 per cent), followed by subcapsular (29.1 per cent) and intrathyroidal (10.9 per cent). Parathyroid tissue was found in 10.2 per cent of specimens where no inadvertent parathyroidectomy was reported. Inadvertent parathyroidectomy was associated with a higher incidence of six-month post-surgical hypoparathyroidism or hypocalcaemia (19.8 per cent who had an inadvertent parathyroidectomy, 7.7 per cent without inadvertent parathyroidectomy). CONCLUSION: Inadvertent parathyroidectomy increases the risk of post-surgical hypoparathyroidism or hypocalcaemia. The proportion of extracapsular glands contributing to inadvertent parathyroidectomy highlights the need for preventative measures.

First Constraints on Light Sterile Neutrino Oscillations from Combined Appearance and Disappearance Searches with the MicroBooNE Detector.

We present a search for eV-scale sterile neutrino oscillations in the MicroBooNE liquid argon detector, simultaneously considering all possible appearance and disappearance effects within the 3+1 active-to-sterile neutrino oscillation framework. We analyze the neutrino candidate events for the recent measurements of charged-current ν_{e} and ν_{µ} interactions in the MicroBooNE detector, using data corresponding to an exposure of 6.37×10^{20} protons on target from the Fermilab booster neutrino beam. We observe no evidence of light sterile neutrino oscillations and derive exclusion contours at the 95% confidence level in the plane of the mass-squared splitting Δm_{41}^{2} and the sterile neutrino mixing angles θ_{µe} and θ_{ee}, excluding part of the parameter space allowed by experimental anomalies. Cancellation of ν_{e} appearance and ν_{e} disappearance effects due to the full 3+1 treatment of the analysis leads to a degeneracy when determining the oscillation parameters, which is discussed in this Letter and will be addressed by future analyses.

Pertussis in India: Past, Present, and Future.

While vaccines have markedly reduced the incidence of pertussis, a resurgence has occurred in many countries. Until recently, pertussis has not been recognized as an important public health challenge in India due to its successful infant immunization program. However, India still accounts for a large proportion of the world's cases, and increasing reports of pertussis in other countries and in neonates have regenerated interest in pertussis among Indian authorities. The Global Pertussis Initiative (GPI) Annual Meeting was held virtually in October 2020, in part, to gain a better understanding of the epidemiology and disease burden of pertussis and to explore opportunities to improve its prevention in India. There was a consensus that pertussis cases are being underestimated in India due to multiple factors, such as a reliance on passive surveillance and diagnostic challenges. India offers both whole-cell pertussis and acellular pertussis vaccines, but vaccine coverage is inconsistent across regions due to differences in vaccine availability, access to health care, and regional administrative challenges. This report summarizes the outcomes and considers the key clinical implications of this meeting. The GPI agreed that active surveillance of pertussis in India would be optimal and recommended several studies, including serosurveillance among women of reproductive age to assess the prevalence of recent pertussis infection and to enable policy changes that will enhance the rational use of acellular and whole-cell vaccines. It also recommended engagement with nongovernmental organizations in order to encourage pregnancy immunization in the public sector. To achieve effective control of pertussis in the future, the GPI recognizes there are opportunities to characterize the burden of pertussis in India appropriately and increase vaccination coverage in multiple age groups.

Evaluation of hypoparathyroidism following laryngectomy.

BACKGROUND: Hypoparathyroidism is a recognised complication following laryngectomy; it is associated with significant short-and long-term morbidity. This study aimed to further characterise this condition, identify risk factors and describe preventative and management strategies in a large cohort. MATERIALS AND METHODS: This was a retrospective study at a tertiary referral centre for head and neck cancers. All consecutive patients who had total laryngectomy over an eight-year period were included. RESULTS: A total of 140 patients were included. Rates of transient and long-term hypoparathyroidism were 14.3% and 10.1%, respectively. The following factors were significantly associated with transient post-surgical hypocalcaemia or hypoparathyroidism: total thyroidectomy (relative risk, RR, 4.33; 95% confidence interval, CI, 1.86-10.10), oesophagectomy (RR 6.05; 95% CI 2.92-12.53) and female sex (RR 3.23; 95% CI 1.45-7.19). In addition, total thyroidectomy (RR 5.89; 95% CI 1.94-17.86), central neck dissection (RR 3.97; 95% CI 1.42-11.10), oesophagectomy (RR 9.38; 95% CI 4.13-21.3), pharyngectomy (RR 7.14; 95% CI 2.08-24.39) and female sex (RR 5.52; 95% CI 1.95-15.63) were risk factors for long-term hypoparathyroidism. There was variability in the use of preventative measures, monitoring and management of hypocalcaemia and hypoparathyroidism following total laryngectomy. CONCLUSIONS: Transient hypocalcaemia and long-term hypoparathyroidism occur in a significant proportion of patients after laryngectomy. A standard protocol is required to improve care.

A Dosimetric and Radiobiological Comparison of Intensity Modulated Radiotherapy, Volumetric Modulated Arc Therapy and Helical Tomotherapy Planning Techniques in Synchronous Bilateral Breast Cancer.

OBJECTIVE: The present investigation intends to identify the optimal radiotherapy treatment plan for synchronous bilateral breast cancer (SBBC) using dosimetric and radiobiological indexes for three techniques, namely, helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT). METHODS: Twenty SBBC treated female patients treatment planning data (average age of 52.5 years) were used as the sample for the present study. Three different plans were created using 50 Gy in a 25 fraction dose regime. Poisson, Niemierko, and LKB models were applied for calculating normal tissue complication probability (NTCP) and tumour control probability (TCP). RESULT: The target average dose comparison between IMRT with HT and VMAT with HT was highly substantial (P=0.001). The percentage of TCP for IMRT, VMAT, and HT in the Poisson model were 93.70±0.28, 94.68±0.30, and 94.34±0.57, respectively (p<0.05). The dose maximum was lower for the whole lung in the HT plan, with an average dose of 49.31Gy±3.9 (p<0.009). The NTCP values of both Niemierko and LKB models were lower for the heart, lungs, and liver for the IMRT plan. CONCLUSION: The sparing of organs at risk was higher in the HT plan dosimetrically, and the TCP was higher in the three techniques. The comparison between the three techniques shows that the IMRT and HT techniques could be considered for treating SBBC.

Search for an Excess of Electron Neutrino Interactions in MicroBooNE Using Multiple Final-State Topologies.

We present a measurement of ν_{e} interactions from the Fermilab Booster Neutrino Beam using the MicroBooNE liquid argon time projection chamber to address the nature of the excess of low energy interactions observed by the MiniBooNE Collaboration. Three independent ν_{e} searches are performed across multiple single electron final states, including an exclusive search for two-body scattering events with a single proton, a semi-inclusive search for pionless events, and a fully inclusive search for events containing all hadronic final states. With differing signal topologies, statistics, backgrounds, reconstruction algorithms, and analysis approaches, the results are found to be either consistent with or modestly lower than the nominal ν_{e} rate expectations from the Booster Neutrino Beam and no excess of ν_{e} events is observed.

Is conservative management of the indeterminate thyroid nodule [Thy3f or Bethesda category IV] safe?

PURPOSE: The histological diagnosis after diagnostic thyroidectomy for indeterminate thyroid nodules is often non-malignant and some cancers detected are considered 'indolent'. The safety and effectiveness of conservative management in these patients are unclear. The aim of this study was to determine the safety of conservative management of indeterminate thyroid nodules and to explore association between clinical features and pathology in patients undergoing surgery. METHODS: This is a retrospective cohort study of patients presenting to a single centre over a 4-year period (2013-2016) with thyroid nodules that were considered indeterminate (thy3f in the UK RCPath classification) on cytology. Demographic data, ultrasound features, follow-up details (in those undergoing conservative management) and histology details (in those undergoing surgery) were collected. RESULTS: Of 164 patients that had Thy3f cytology, 34 were initially managed conservatively; however, 4 of these eventually had surgery (due to patient preference). No patient on conservative management had significant disease progression on ultrasound at a median (interquartile range) of 27 (16-40) months. Of the 134 patients that underwent surgery, 26 had thyroid malignancy. The BTA 'U' classification, gender and age (> 55) were not associated with malignancy in these nodules, but larger nodules (> 40 mm) were more likely to be malignant (p = 0.042). CONCLUSIONS: Conservative management of indeterminate (Thy3f or Bethesda stage IV) thyroid nodules is safe in the short term and may be indicated in selected cases after appropriate discussion of risks and benefits of surgery.

First Measurement of Energy-Dependent Inclusive Muon Neutrino Charged-Current Cross Sections on Argon with the MicroBooNE Detector.

We report a measurement of the energy-dependent total charged-current cross section σ(E_{ν}) for inclusive muon neutrinos scattering on argon, as well as measurements of flux-averaged differential cross sections as a function of muon energy and hadronic energy transfer (ν). Data corresponding to 5.3×10^{19} protons on target of exposure were collected using the MicroBooNE liquid argon time projection chamber located in the Fermilab booster neutrino beam with a mean neutrino energy of approximately 0.8 GeV. The mapping between the true neutrino energy E_{ν} and reconstructed neutrino energy E_{ν}^{rec} and between the energy transfer ν and reconstructed hadronic energy E_{had}^{rec} are validated by comparing the data and Monte Carlo (MC) predictions. In particular, the modeling of the missing hadronic energy and its associated uncertainties are verified by a new method that compares the E_{had}^{rec} distributions between data and a MC prediction after constraining the reconstructed muon kinematic distributions, energy, and polar angle to those of data. The success of this validation gives confidence that the missing energy in the MicroBooNE detector is well modeled and underpins first-time measurements of both the total cross section σ(E_{ν}) and the differential cross section dσ/dν on argon.