Therapeutic Response to PRRNT in a Rare Case of Metastatic Renal Neuroendocrine Carcinoma.

Neuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in view of the heterogeneity in differentiation and behavior. Primary renal origin NETs are rare and only a few cases have been reported in the literature. There is limited knowledge on their presentation and response to various lines of treatment. We report a case of a patient with a metastatic renal NET from a rare histological subtype of large cell neuroendocrine carcinoma, known to cause aggressive disease with poor prognosis. A multimodality treatment approach was followed. In spite of surgical management and second-line chemotherapy, the disease progressed. The patient subsequently received peptide receptor radionuclide therapy (PRRNT) using lutetium-177 DOTATATE, following which the patient demonstrated a remarkable clinical and radiological response and is stable to date. In a rare tumor with poor prognosis, the relevance of theranostics and the efficacy of targeted therapies like PRRNT are noteworthy.

Curative Resection for Metastatic Solid Pseudopapillary Neoplasm of Pancreas-a Case Series.

Solid pseudopapillary neoplasm (SPN) is an unusual tumor of the pancreas. Unlike ductal adenocarcinoma, SPN is commoner in young women and is indolent with better prognosis. Fifteen percent of patients, however, develop metastases, often synchronous and involving the liver or peritoneum. Owing to the paucity of cases, management of the metastatic disease is not clearly defined. Retrospective review of case notes of patients treated between 2006 and 2019. There were 53 patients with SPN of which 4 had hepatic metastases-3 synchronous and 1 metachronous. Two patients underwent simultaneous distal pancreatectomy and splenectomy with liver resection (right posterior sectionectomy and metastasectomy). One required right hepatectomy with metastasectomy for metachronous liver metastases. The other underwent a staged operation-remnant tumor excision with metastasectomy followed by right hepatectomy after portal vein embolization. All four patients are recurrence free on median follow-up of 38.5 months. In view of the excellent prognosis, we recommend radical resection of both the primary lesion and metastases for SPN.

Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data.

INTRODUCTION: Fibrosis is a typical pathological characteristic in IgG4-RD patients and often irreversible. There exists a lack of suitable markers for detection of earlier onset of fibrosis in various organs in IgG4-RD patients. Hence, this study aims at analysing ambispectively the myofibroblasts and the pro-fibrotic cytokines, IFN gamma and IL-33 involved in IgG4-RD associated fibrosis in South Asian patients. METHOD: Archived biopsy samples of definite/probable/possible cases of IgG4-RD, classified according to diagnostic criteria, taken from patients who attended the OPD and IPD of our tertiary care centre during January 2015-January 2020 were chosen for this study. The paraffin sections were examined qualitatively for fibrosis and the excessive collagen deposition by Hematoxylin & Eosin and Masson's Trichrome staining. Also, the presence of alpha-Smooth muscle actin (α-SMA) expressing myofibroblasts and the involvement of pro-fibrotic cytokines (IFN-gamma, IL-33) were assessed by Immunohistochemistry and scored semi-quantitatively (+mild, ++moderate, +++ severe). Serum IL-33 levels were analysed by indirect Elisa (R & D Systems). RESULTS: Myofibroblasts were present in 10/12 biopsy samples, in moderate levels in 4 (33%) and very high levels (+++) in 3 (25%) of the patients. IFN-gamma was expressed at low levels in 6 (50%) and absent in 6 (50%). All patients showed IL-33 expression with very high levels in tissue (6, 50%), as well as in serum samples. CONCLUSION: The findings of this study reinforce the role of myofibroblasts and profibrotic cytokines like IL-33 in fibrosis of Ig4-RD patients, pointing to their potential as earlier predictive markers of onset and extent of fibrosis.

Surgical management of sternal tumours-a decade of experience from a tertiary care centre in India.

Tumours of the sternum can be either primary or secondary with malignancy being the most common etiology. Wide local excision of these tumours results in a midline defect which pose a unique challenge for reconstruction. As limited data on the management of these tumours exists in the literature, we hereby report 14 consecutive patients who were treated at our institute between January 2009 to December 2020. Most of them were malignant with majority of them, 11 (78%) patients, with manubrial involvement requiring partial sternectomy. Overall, the average defect size was 75 cm2. Reconstruction of the chest wall defect was done using a semi-rigid fixation: mesh and suture stabilization in 3 (21%) or suture stabilization in 7 (50%) and without mesh or suture stabilization in 3 (21%) patients. Rigid fixation with polymethyl methacrylate (PMMA) was done for one patient (7%). Pectoralis major advancement flap was most commonly used for soft tissue reconstruction with flap necrosis noted in one patient (7%). There was no peri-operative mortality and one patient required prolonged post-operative ventilation. On a median follow-up of 37.5 months, one patient (7%) had a recurrence. Sternal defects after surgical resection reconstructed with semi-rigid fixation and suture stabilization render acceptable post-operative outcomes.

Impact on patient attitudes towards lung cancer screening and smoking cessation with radiology consultation: Pilot survey project.

PURPOSE: We developed a novel patient-radiologist consultation for patients scheduled for lung cancer screening (LCS). We hypothesized that this intervention would improve patient attitudes towards LCS adherence and smoking cessation. METHODS: This quality improvement project enrolled 38 LCS patients (a majority were African American) and included 20 current and 18 former smokers. The intervention, a 5-10 min consultation with a radiologist who provided preliminary interpretation of pertinent imaging findings in conjunction with smoking cessation counseling, took place in the radiology reading room immediately after the low dose computed tomography (LDCT) patient scan. Pre- and post-intervention surveys assessed patient attitudes towards LCS and smoking cessation. RESULTS: All recruited patients consented to participate in this project. Regarding viewing their LCS imaging, 86.8% (33/38) expressed general interest initially, with 100.0% (38/38) being more interested afterwards. On LCS logistics, 71.1% (27/38) reported prior knowledge at baseline, while 89.5% (34/38) reported being more informed following the intervention. Among current smokers, 90.0% (18/20) were already motivated towards quitting smoking at baseline, with 100.0% (20/20) exiting the intervention being more interested in doing so. Regarding smoking cessation resources, 95.0% (19/20) were interested in accessing such resources at baseline, and 90.0% (18/20, 2 were same/neutral) were more interested afterwards. CONCLUSIONS: Patients' attitudes towards LCS and self-reported interest in quitting smoking were directionally higher after the consultation than at baseline. Incorporating LCS consultations with radiologists as part of patient-centered care provides a resource to educate patients on their own LCS imaging findings while promoting LCS adherence and smoking cessation.

Evidence of syndemic effects influencing older transgender persons' likelihood of contemplating suicide: results from a large national study.

OBJECTIVES: Very little research has examined suicidal ideation or the factors associated with contemplating suicide among older transgender adults. This paper examines whether or not there is evidence of syndemic effects influencing suicidal ideation among transgender persons aged 50 or older. METHODS: Data from the 2015 U.S. National Transgender Survey were used to examine five domains of potentially-syndemic effects (workplace issues, interactions with professionals, using public services, personal safety, and socioeconomic disadvantages) in a sample of 3,724 transgender Americans aged 50 or older. A dichotomous measure of suicidal ideation during the past year was the main outcome measure. RESULTS: The odds of contemplating suicide increased anywhere from 96% to 121% among people experiencing any of the problems under study, and anywhere from 258% to 1,552% (depending upon the syndemic effect domain in question) when they were faced by all of the experiences included in any particular domain. When all items were combined, exposure to any of the domains' problems elevated the risk of contemplating suicide by 276% and exposure to all of the problems examined increased the risk by 861%. The syndemic effects measure remained significant in multivariate analysis controlling for the influence of other potentially-relevant factors. CONCLUSIONS: Considerable evidence for the presence of syndemic effects was found, demonstrating that the more different types of adverse conditions that older transgender person's face, the more likely they are to experience to contemplate suicide. There is evidence that these effects diminish with advancing age.

The Relationship of Anti-Transgender Discrimination, Harassment, and Violence to Binge Drinking among Transgender Adults.

Purpose: Using a minority stress paradigm, this paper examines the relationship between anti-transgender discrimination, harassment, and violence among transgender adults. Methods: Data from the 2015 U.S. National Transgender Survey were used to examine twenty types of anti-transgender experiences/problems (e.g., harassment at work, problems with police officials, verbal and physical assaults) in a sample of 27,715 transgender Americans aged 18 or older. Binge drinking during the previous month was the dependent variable, and eight control measures were examined in the multivariate analysis. Results: Experiencing any of the twenty types of anti-transgender discrimination, harassment, or violence increased the odds of binge drinking by 48%. Experiencing many such problems increased the odds of binge drinking by 104%. Multivariate analysis showed that anti-transgender discrimination, harassment, and violence remains a predictor of binge drinking even when other key measures are taken into account. Younger people, racial minority group members, and persons who were not married or "involved" were at particularly great risk. Conclusions: Consistent with the minority stress paradigm, the more different types of anti-transgender experiences people had, the more likely they were to engage in binge drinking. Targeted intervention needs to help transgender persons to avoid anti-transgender discrimination, harassment, and violence to the greatest extent possible, and to develop resiliency skills whenever they are victimized. This is particularly true for transgender persons who are younger, minority, and not "involved" in a relationship.

Causal Analysis of Physiological Sleep Data Using Granger Causality and Score-Based Structure Learning.

Understanding how the human body works during sleep and how this varies in the population is a task with significant implications for medicine. Polysomnographic studies, or sleep studies, are a common diagnostic method that produces a significant quantity of time-series sensor data. This study seeks to learn the causal structure from data from polysomnographic studies carried out on 600 adult volunteers in the United States. Two methods are used to learn the causal structure of these data: the well-established Granger causality and "DYNOTEARS", a modern approach that uses continuous optimisation to learn dynamic Bayesian networks (DBNs). The results from the two methods are then compared. Both methods produce graphs that have a number of similarities, including the mutual causation between electrooculogram (EOG) and electroencephelogram (EEG) signals and between sleeping position and SpO2 (blood oxygen level). However, DYNOTEARS, unlike Granger causality, frequently finds a causal link to sleeping position from the other variables. Following the creation of these causal graphs, the relationship between the discovered causal structure and the characteristics of the participants is explored. It is found that there is an association between the waist size of a participant and whether a causal link is found between the electrocardiogram (ECG) measurement and the EOG and EEG measurements. It is concluded that a person's body shape appears to impact the relationship between their heart and brain during sleep and that Granger causality and DYNOTEARS can produce differing results on real-world data.

The "triple whammy": Serious psychological distress, suicidal ideation, and substance misuse among transgender persons.

PURPOSE: This paper examines the conjoint effects of serious psychological distress, suicidal ideation, and substance abuse among transgender adults. The principal aims are to determine the prevalence of this "triple whammy," identify the factors underlying the co-occurrence of all three problems, and to determine if there is evidence of syndemic effects underlying the "triple whammy." METHODS: Data from the 2015 U.S. National Transgender Survey were used to examine the "triple whammy" relationship in a sample of 27,715 transgender Americans aged 18 or older. Odds ratios and multivariate logistic regression were performed to examine the data. RESULTS: 13.3 % of the study participants reported experiencing serious psychological distress, suicidal ideation, and substance abuse. The most potent predictors of the "triple whammy" were younger age, a greater number of anti-transgender experiences, and not reaching various transition milestones. Strong evidence emerged to indicate the presence of syndemic effects in operation. CONCLUSIONS: Experiencing the combination of adverse mental health and substance abuse was not uncommon in this population of transgender adults. Being young, experiencing a larger variety of types of anti-transgender discrimination, harassment, and violence, and not reaching specific transition milestones all had a significant impact on the odds that people would experience the "triple whammy." This was particularly true when these measures were examined in conjunction with one another, because of strong syndemic effects.

Focused panel sequencing points to genetic predisposition in non-cirrhotic intrahepatic portal hypertension patients in India.

OBJECTIVE: Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. METHODS: In this case-control study, we analyzed genes associated with microangiopathy-VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme - a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolism and with familial NCIPH. RESULT: Eighty-four Indian patients with liver biopsy-proven NCIPH (cases) and 103 healthy controls (matched for residential region of India) were included in the study. Targeted next-generation sequencing (NGS) panel, comprising 11 genes of interest, was done on 54 cases. Genotyping of selected variants was performed in 84 cases and 103 healthy controls. We identified variants in MBL2, CD46 and VWF genes either associated or predisposing to NCIPH. We also identified a single case with a novel compound heterozygous mutation in MBL2 gene, possibly contributing to development of NCIPH. CONCLUSION: In this first of a kind comprehensive gene panel study, multiple variants of significance have been noted, especially in ADAMTS13-VWF and complement pathways in NCIPH patients in India. Functional significance of these variants needs to be further studied.

Family-Reflections.com: Creating a parent-to-parent web-based tool regarding pediatric home ventilation.

BACKGROUND: The decision to initiate pediatric mechanical ventilation via tracheostomy ("home ventilation") is complex and parents often desire information from other parents who have faced this decision. However, parent-to-parent communication is challenging as it is difficult to connect new families to experienced families in ways that optimize informed, balanced decision-making. OBJECTIVE: Create a parent-to-parent web-based tool to support decision-making about pediatric home ventilation. PATIENT INVOLVEMENT: The tool was created based on interviews and feedback from parents. METHODS: We interviewed parents who previously chose for, or against, home ventilation for their child. Interview themes and family comments guided website development. Viewer feedback was solicited via an embedded survey in the tool. RESULTS: We created 6 composite character families to communicate 6 themes about home ventilation: 1) Considering treatment options, 2) Talking with medical team, 3) Impact on life at home, 4) Impact on relationships, 5) Experience for the child, and 6) If the child's life is short. Nine families who reviewed the draft tool felt it would have helped with their decision about home ventilation. Specifically, it supported families in thinking through what was "most important about their child's breathing problems" (7 of 9 parents) and feeling "more at peace with the decision" (8 of 9 parents). Between 6/1/20-12/31/22, nearly 5500 viewers have accessed the tool and 56 viewers completed the survey (including 13 families and 39 clinicians). Feedback from experienced families and clinicians reported the tool taught them something new. DISCUSSION: This novel parent-to-parent tool shows promise for expanding access to balanced, family-centered information about pediatric home ventilation. PRACTICAL VALUE: The diverse stories and decisions let parents access multiple family perspectives. The tool's focus is on family-centric information that parents reported was usually missing from clinician counseling. FUNDING: This work was supported by the National Palliative Care Research Center.

Rib malignancies masquerading as benign mediastinal tumours.

Mediastinal tumours are commonly encountered in general thoracic surgery practice. Benign tumours like thymoma and teratoma often need direct surgical resection if resectable. Pre-operative biopsy is not recommended. We report 2 cases which were radiologically diagnosed as thymoma and teratoma turned out to be Ewing sarcoma and chondrosarcoma respectively after surgical excision. This has challenged the notion whether biopsy is really not needed. More elaborate studies are needed to find out tumour characteristics which would warrant a biopsy even if they are resectable. In our cases, pre-operative biopsy would have changed the line of management in both patients. This has led to a change in institutional protocol that now, we do biopsy for any mediastinal tumour more than 8 cm and abutting the chest wall.

Global genomic analysis of microbial biotransformation of arsenic highlights the importance of arsenic methylation in environmental and human microbiomes.

Arsenic is a ubiquitous toxic element, the global cycle of which is highly affected by microbial redox reactions and assimilation into organoarsenic compounds through sequential methylation reactions. While microbial biotransformation of arsenic has been studied for decades, the past years have seen the discovery of multiple new genes related to arsenic metabolism. Still, most studies focus on a small set of key genes or a small set of cultured microorganisms. Here, we leveraged the recently greatly expanded availability of microbial genomes of diverse organisms from lineages lacking cultivated representatives, including those reconstructed from metagenomes, to investigate genetic repertoires of taxonomic and environmental controls on arsenic metabolic capacities. Based on the collection of arsenic-related genes, we identified thirteen distinct metabolic guilds, four of which combine the aio and ars operons. We found that the best studied phyla have very different combinations of capacities than less well-studied phyla, including phyla lacking isolated representatives. We identified a distinct arsenic gene signature in the microbiomes of humans exposed or likely exposed to drinking water contaminated by arsenic and that arsenic methylation is important in soil and in human microbiomes. Thus, the microbiomes of humans exposed to arsenic have the potential to exacerbate arsenic toxicity. Finally, we show that machine learning can predict bacterial arsenic metabolism capacities based on their taxonomy and the environment from which they were sampled.

Review of contaminant levels and effects in shorebirds: Knowledge gaps and conservation priorities.

Environmental pollution has emerged as a major threat to bird populations. Many shorebird populations are declining, although contamination has been documented in some shorebirds, evidence of negative impacts is sparse and this important topic remains understudied. To guide future research and develop effective conservation strategies, we carried out a comprehensive review of environmental pollutants and their consequences on shorebirds. In total, we found 93 relevant articles which examined pollutant contamination in ~37% (79 of 215) of all shorebird species, mostly from the Charadriidae and Scolopacidae families. Studies were geographically biased: the majority were conducted in American flyways, while only 1 was found from Australasia and few were conducted in Asian flyways. The main geographic gap for research includes East Africa, South Asia and Siberian Arctic. The most well-documented pollutants included mercury (Hg, 37 studies), cadmium (33), and lead (Pb, 28); less well studied pollutants were barium (1), calcium (1), strontium (1), dicofols (1), and other newly emerging contaminants, such as plastic debris/microplastics (4) and antibiotics resistance (2). Several pollutants have caused considerable concerns in shorebirds, including embryotoxicity caused by PCBs at non-optimum temperature (laboratory experiments); reduced reproduction performance linked to maternal Hg and paternal Pb (field evidence); and reduced refueling and flight performance related to oil contamination (both field and laboratory evidence). Our results confirm that an in-depth understanding of the local, regional and global factors that influence population trends of shorebirds in light of increasing pollution threats is essential for accurate and effective management and conservation strategies.

Gold-Mediated Multiple Cysteine Arylation for the Construction of Highly Constrained Bicycle Peptides.

Bicycles are constrained bicyclic peptides formed through reaction of three cysteine residues within a linear sequence with a trivalent, symmetrical small molecule scaffold. Bicycles with high binding affinities to therapeutically important targets can be discovered using screening technologies such as phage display. Increasing the chemical diversity of Bicycles should improve the probability of finding hits to new targets and can be achieved by expanding the toolbox of Bicycle forming chemistries. Gold(III) S-arylation has recently been described as a method for the efficient bioconjugation of cysteine residues under conditions compatible with phage display. Herein, we explore the scope and generality of this methodology for Bicycle construction through the synthesis and evaluation of four novel tris-Gold complexes. These new scaffolds were systematically reacted with a variety of peptide sequences, varying in amino acid loop lengths. All four scaffolds proved to be capable and selective reactive partners for each peptide sequence and afforded the desired Bicycle products in 13-48% isolated yield. This work exemplifies Gold-mediated arylation as a general approach for construction of novel, highly constrained Bicycles.

Pulmonary sclerosing pneumocytoma-a case series.

Pulmonary sclerosing pneumocytoma (PSP) is a rare and interesting pulmonary tumour that presents a diagnostic challenge to the surgeon due to its bland symptomatology, indolent course, non-specific radiological features and ambiguous histopathological findings, which could lead to errors in management and prognostication. Herein, we present a series of 4 patients with PSP who were managed in our institution over a period of 8 years and briefly discuss relevant literature.

Pulmonary mucormycosis-a case series.

Pulmonary mucormycosis (PM) is a rare disease. Literature about the surgical management of PM in India is sparse. Recently, there has been a surge in the number of cases of mucormycosis in association with the coronavirus disease 2019 (COVID-19) pandemic, igniting the interest in PM. Hence, we endeavoured to analyse our surgical experience in treating PM prior to the pandemic, in a tertiary care centre, to provide insight into this disease. Data of 10 adult patients with isolated PM, who underwent surgery between the years 2009 and 2020, and maintained in our departmental database, were retrieved and analysed.