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Chronic cavitary pulmonary aspergillosis (CCPA) is a slow destructive type of chronic pulmonary aspergillosis, characterised by multiple pulmonary cavities that develop and expand over several months or years. Pleural involvement in the form of pneumothorax has been rarely reported in CCPA. We report such an unusual case of an immunocompromised male, with a history of chronic cough and fever, presenting with acute onset of shortness of breath. Chest imaging showed bilateral multiple cavitating nodules, ground glass opacities and dense right middle lobe consolidations and right-sided pneumothorax. Bronchoalveolar lavage (BAL) showed septate hyaline hyphae on KOH (potassium hydroxide) staining and fungal culture grew Aspergillus fumigatus. BAL and serum galactomanan were positive and serum IgG for A. fumigatus was 58 MgA/L (0–40MgA/L) confirming the cause of spontaneous secondary pneumothorax in our patient as CCPA.

Problem Definition: Problem Definition: We develop a framework to plan capacity for ambulatory surgery centers (ASCs) typically consisting of three stages. The problem is to determine the capacity in each stage that efficiently covers possible daily patient demand and to coordinate the three stages of patient visits. The objective is to minimize the total cost incurred in satisfying the daily patient demand, where the total cost is defined as the sum of overtime cost and amortized construction cost for the three stages. Academic/Practical Relevance: Timely capacity adjustment is important for ASC practitioners, but related research is limited. We explicitly consider three sequential stages that are typical in ASCs: the pre-operative at holding room (HR), intra-operative at operating room (OR), and post-operative at post-anesthesia care unit (PACU). Such ASCs can be modeled as a hybrid flow shop (HFS) in the scheduling literature. The interdependence of activities and uncertainties in patient-mix as well as their durations pose a significant challenge to manage the capacity of each activity and achieving a smooth patient flow. Methodology: In contrast to the traditional top-down approach to capacity planning, our approach contributes by proposing a bottom-up strategy based on optimization methods combined with analytics that are informed by operational-level archival patient data. Specifically, we use analytics tools to classify patients into groups, which reduces the complexity of the capacity planning problem and improves the model's practicality. Later, we develop several mathematical formulations and heuristics based on scheduling theory to derive the most cost-efficient capacity solution. Results: Given the trade-off between overtime cost and amortized capacity construction cost, this study relaxes the fixed capacity assumption of traditional HFS problems. Because of the computational complexity of the exact HFS model, we develop a heuristic that is straightforward and easy to implement to find cost-efficient capacities for the three stages. Our computational study examines how uncertain business parameters, e.g., patient-mix, service durations, overnight-stay probabilities, affect the capacity planning decision. Managerial implications: This study highlights the benefit of considering multiple stages together in capacity planning, rather than focusing solely on the operating rooms exclusively. We expect our approach to guide the more than 5,000 ASCs in the U.S., performing 23 million surgeries annually, to make appropriate investments that will improve ASC operations via capacity adjustment and patient scheduling.

Spontaneous rupture of a metastatic liver tumour is rarely documented in the literature when compared to hepatocellular carcinoma and other liver lesions, especially from a lung primary. We report a case of ruptured liver metastasis from an adenocarcinoma of the lung mimicking ruptured liver abscess, challenging the clinical diagnosis. A 42-year-female patient presented to a tertiary care institute in 2020 with complaints of abdominal pain, breathlessness and fever. On examination, the patient was tachypnoeic with a right hypochondriac mass. A contrast-enhanced computed tomography of abdomen and thorax revealed an ill-defined heterogeneously enhancing lesion in the liver with a communicating subcapsular collection and hypo-enhancing lesions in the left lobe and heterogeneously enhancing lesion in the left lung. Adenocarcinoma of the lung with hepatic metastasis was confirmed with a core needle biopsy. The patient was managed conservatively with intravenous antibiotics, intercostal drainage tube and gefitinib. However, despite best efforts, the patient succumbed to the disease. Keywords: Metastasis; Spontaneous Rupture; Hepatocellular Carcinoma; Thyroid Transcription Factor; Liver Abscess; Case Report; India.

Morning glory disc (MGD) is known to develop secondary maculopathy and vision loss. We followed a 7-year-old girl with MGD in right eye from 2010 to 2021. Her best-corrected Snellen visual acuity (BCVA) was 20/20 in both eyes till 2017. She presented with reduced vision in right eye with BCVA of 20/80 in 2018. Optical Coherence Tomography (OCT) revealed maculopathy related to MGD in right eye and arcuate Vitelliform neurosensory detachment (V-NSD) temporal to fovea. She underwent 25G vitrectomy with internal limiting membrane peeling. Resolution of retinoschisis and V-NSD was analysed by OCT and fundus autofluorescence (FAF) postoperatively. Arcuate V-NSD was hyperfluorescent on FAF and concentric to optic disc. It resolved slowly with BCVA improving to 20/20 at 18 and 30 months postoperatively. We report excellent outcome following early vitrectomy for MGD-related maculopathy and recommend serial follow-up and considering early vitrectomy whenever traction and BCVA worsens. We also describe arcuate V-NSD with MGD.

Subglottic concretion is a rare and perilous condition usually presenting with existing or impending airway obstruction. Due to long-standing nature of the condition, slow progression of symptoms and rarity of occurrence, the condition is either missed or misdiagnosed. Its resemblance in presentation and symptoms to that of foreign body (FB) bronchus can lead to a diagnostic misadventure. Detailed history, chronology of symptoms and radiological imaging in conjunction with fiberoptic evaluation are keys for establishing correct diagnosis. Treatment outcomes in such cases depend on appropriate management approach with backup plan in tandem. We describe a child with β thalassemia major with subglottic concretion, which was erroneously diagnosed and managed as a case of subglottic FB due to its classical history and presentation. The aim is to highlight the circumstances leading to this diagnostic misadventure with emphasis on airway management, problems faced and lessons learnt during the same.

Extracorporeal membrane oxygenation (ECMO) provides lifesaving circulatory support and gas exchange, although hematologic complications are frequent. The relationship between ECMO and severe thrombocytopenia (platelet count

BACKGROUND: Patients with breast cancer frequently report cognitive impairment both during and after completion of therapy. Evidence suggests that cancer-related cognitive impairments are related to widespread neural network dysfunction. The default mode network (DMN) is a large conserved network that plays a critical role in integrating the functions of various neural systems. Disruption of the network may play a key role in the development of cognitive impairment. METHODS: We compared neuroimaging and neurocognitive data from 43 newly diagnosed primary breast cancer patients (mean age = 48, standard deviation [SD] = 8.9 years) and 50 frequency-matched healthy female controls (mean age = 50, SD = 10 years) before treatment and 1 year after treatment completion. Functional and effective connectivity measures of the DMN were obtained using graph theory and Bayesian network analysis methods, respectively. RESULTS: Compared with healthy females, the breast cancer group displayed higher global efficiency and path length post-treatment (p

Aim This study aimed to assess the impact of treatment sequencing on long-term survival, in distal gastric cancers (GCs) (stage IB/II/III). Methods This retrospective study included patients with distal GC undergoing D2 resection. Outcomes were compared between group 1 (surgery with adjuvant chemotherapy) and group 2 (perioperative chemotherapy with surgery). 1:1 matching for baseline characteristics (age, cT, and cN stage) was performed for outcome comparison. Results At a median follow-up of 47.5 months in the included 342 patients, the 5-year overall survival (OS) was 61.1% and disease-free survival (DFS) was 50.5%. OS was comparable in the unmatched (group 1, n = 118; group 2, n = 224) (HR 0.905, 95%CI 0.64–1.33, P = 0.615) and matched groups (group 1, n = 97; group 2, n = 97) (HR 0.77, 95% CI 0.48–1.26, P = 0.3). Conclusion D2 resection followed by adjuvant chemotherapy provides similar long-term outcomes as compared to perioperative chemotherapy approach for stage IB/II/III distal GCs.

© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/ by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com, Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage frontotemporal dementia, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic frontotemporal dementia using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study. Two-hundred and seventy-five presymptomatic and 127 symptomatic carriers of mutations in GRN, C9orf72 or MAPT, as well as 247 non-carriers, were selected from the GENFI cohort based on availability of one or more of the aforementioned biomarkers. Nine presymptomatic carriers developed symptoms within 18 months of sample collection ('converters'). Sequences of biomarker abnormalities were modelled for the entire group using discriminative event-based modelling (DEBM) and for each genetic subgroup using co-initialized DEBM. These models estimate probabilistic biomarker abnormalities in a data-driven way and do not rely on previous diagnostic information or biomarker cut-off points. Using cross-validation, subjects were subsequently assigned a disease stage based on their position along the disease progression timeline. CSF NPTX2 was the first biomarker to become abnormal, followed by blood and CSF neurofilament light chain, blood phosphorylated neurofilament heavy chain, blood glial fibrillary acidic protein and finally CSF C3b and C1q. Biomarker orderings did not differ significantly between genetic subgroups, but more uncertainty was noted in the C9orf72 and MAPT groups than for GRN. Estimated disease stages could distinguish symptomatic from presymptomatic carriers and non-carriers with areas under the curve of 0.84 (95% confidence interval 0.80-0.89) and 0.90 (0.86-0.94) respectively. The areas under the curve to distinguish converters from non-converting presymptomatic carriers was 0.85 (0.75-0.95). Our data-driven model of genetic frontotemporal dementia revealed that NPTX2 and neurofilament light chain are the earliest to change among the selected biomarkers. Further research should investigate their utility as candidate selection tools for pharmaceutical trials. The model's ability to accurately estimate individual disease stages could improve patient stratification and track the efficacy of therapeutic interventions., This study was supported in the Netherlands by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813,733050103 and 733050513), the Bluefield Project to Cure Frontotemporal Dementia, the Dioraphte foundation (grant number 1402 1300), the European Joint Programme—Neurodegenerative Disease Research and the Netherlands Organisation for Health Research and Development (PreFrontALS: 733051042, RiMod-FTD: 733051024); V.V. and S.K. have received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 666992 (EuroPOND). E.B. was supported by the Hartstichting (PPP Allowance, 2018B011); in Belgium by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie; in the UK by the MRC UK GENFI grant (MR/M023664/1); J.D.R. is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH); I.J.S. is supported by the Alzheimer’s Association; J.B.R. is supported by the Wellcome Trust (103838); in Spain by the Fundació Marató de TV3 (20143810 to R.S.V.); in Germany by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198) and by grant 779357 ‘Solve-RD’ from the Horizon 2020 Research and Innovation Programme (to MS); in Sweden by grants from the Swedish FTD Initiative funded by the Schörling Foundation, grants from JPND PreFrontALS Swedish Research Council (VR) 529–2014-7504, Swedish Research Council (VR) 2015–02926, Swedish Research Council (VR) 2018–02754, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Swedish Demensfonden, Stohnes foundation, Gamla Tjänarinnor, Karolinska Institutet Doctoral Funding and StratNeuro. H.Z. is a Wallenberg Scholar.

Background A single center experience with sporadic pancreatic insulinoma was analyzed to develop an algorithm for modern surgical management. Methods Thirty-four patients undergoing surgery from 2001 to 2019 were reviewed. Results The majority underwent enucleation (10 laparoscopic, 15 open). Laparoscopy was performed in 22 patients with conversion to open in 11, mostly related to the proximity of the tumor to the pancreatic duct (n = 4). Tumors on the anterior and posterior surface of the pancreas in all anatomic locations were completed with laparoscopic enucleation. Overall, the clinically-relevant postoperative pancreatic fistula (CR-POPF) rate was 21%, with no difference between laparoscopic versus open enucleation (10% vs 20%, p = 0.50) or enucleation versus resection (16% vs 33%, p = 0.27). Laparoscopic enucleation had shorter median hospital length of stay (LOS) compared with open (4 vs 7 days, p = 0.02). Conclusions Laparoscopic enucleation does not increase the CR-POPF risk and provides an advantage with a shorter hospital LOS in select patients. Tumor location and relationship to the pancreatic duct guide surgical decision-making. These findings highlight tumor-specific criteria that would benefit from a minimally invasive approach.

Mixed epithelial mesenchymal (MEM) hepatoblastoma with teratoid features is rare histological variant of hepatoblastoma and described in case reports. Growing teratoma syndrome (GTS) is a rare and often unrecognised phenomenon generally associated with less than 5% of germ cell tumour. It is defined by enlarging tumour mass which is generally mature teratoma with normal or significantly decreasing tumour markers during chemotherapy. The treatment outcomes in GTS are dependent on early recognition and complete surgical excision. We describe a rare case of MEM hepatoblastoma with teratoid features with GTS in an infant who had a delay in definitive management due to late diagnosis of GTS.

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8(th) edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

The Anatomy and Radiology Contouring (ARC) Bootcamp was a face-to-face (F2F) intervention providing integrated education for radiation oncology (RO) residents and medical physicists. To increase access, we launched an online offering in 2019. We evaluated the effect of the online course on participants' knowledge acquisition, contouring skills, and self-confidence by comparing it with the F2F course.Using modules, the online course offers content similar to that of the F2F comparator. Participants from the 2019 F2F and the 2019-2020 online course completed pre- and postevaluations assessing anatomy and radiology knowledge, contouring skills, self-confidence, and course satisfaction.There were 180 individuals enrolled (F2F: n = 40; online: n = 140); 57 participants (F2F: n = 30; online: n = 27) completed both evaluations. The online course had a wider geographic participation (19 countries) than F2F (4 countries). F2F had primarily RO resident participation (80%), compared with online (41%). Both cohorts demonstrated similar improvements in self-confidence pertaining to anatomy and radiology knowledge, contouring skills, and interpreting radiology images (all P.001). Both the online (mean ± SD improvement: 6.6 ± 6.7 on a 40-point scale; P.001) and F2F (3.7 ± 5.7; P = .002) groups showed anatomy and radiology knowledge improvement. Only the F2F group demonstrated improvement with the contouring assessment (F2F: 0.10 ± 0.17 on a 1-point Dice scale; P = .004; online: 0.07 ± 0.16; P = .076). Both cohorts perceived the course as a positive experience (F2F: 4.8 ± 0.4 on a 5-point scale; online: 4.5 ± 0.6), stated it would improve their professional practice (F2F: 4.6 ± 0.5; online: 4.2 ± 0.8), and said they would recommend it to others (F2F: 4.8 ± 0.4; online: 4.4 ± 0.6).The online ARC Bootcamp demonstrated improved self-confidence, knowledge scores, and high satisfaction levels among participants. The offering had lower completion rates but was more accessible to geographic regions, provided a flexible learning experience, and allowed for ongoing education during the COVID-19 pandemic.

Objective: To highlight safety and efficacy of sine wave technique (SWT) in superficializing deep arterio venous fistula (AVF) and managing infiltrations and other complications. Methods: It is a single centre observational study done from Jul 2017 to July 2020. All successive cases of deep AVFs, aneurysm / pseudoaneurysms of AVFs and AVF requiring open venoplasty were managed with SWT. Data was collected prospectively and analyzed. SWT is based on random pattern skin flaps. Using ultrasound, a line is marked on either side of centre line (AVF) at a distance of approximately 1.5 - 2 cm. A sine wave is drawn starting from either of the lines to the other with multiple crests and troughs. The base of flap should be double the height of the flap, that is, about 3-4 cm. Skin is incised and flaps are raised at level of AVF. Excess fat is removed. A sliver of unhealthy skin can be sacrificed if required. Flaps are sutured back to restore sine wave continuity. Results: SWT was used in a total of eleven patients. Median age was 58 years (range 10 - 67 years). Eight were females and three males. One was radio-cephalic and rest were brachio-cephalic AVFs. Eight AVFs were deep with median depth of 10.25mm (range 8-13mm), median body mass index of 25.5 kg/m2 (range 23.9- 26.5kg/m2), median vein diameter of 7 mm (range 6-8 mm), and median flow rate of 1137.5ml/min (range 650- 1380 ml/min). Out of eight, four AVFs presented with infiltration. In other three, SWT was used for exposing AVF to treat underlying pathology (one case each of aneurysm, pseudoaneurysm & stenosis). Ten cases were done under local or regional anaesthesia and one under general anaesthesia. There was no peri-operative mortality or loss of AVF. Transient limb oedema developed in one case. Median time to cannulate was 20 days (range 13 - 28 days). Median follow up was 13 months (range 6 - 31months). Cumulative patency at 18 months was 90% (95% CI 47.3% - 98.53%) and 45 % (95% CI 9.9% - 87.1%) at 24months and at the end of the study. Conclusion: SWT is safe and effective in superficialization of deep / difficult to cannulate AVF as well a good approach to treat complications like infiltration. Post procedure cannulation time is reasonably short.

PURPOSE OF REVIEW Extramammary Paget's Disease (EMPD) is an uncommon intra-epithelial malignancy, affecting primarily apocrine gland-bearing skin. EMPD is often considered an orphan diagnosis given its rarity. This review provides a contemporary overview of EMPD management. RECENT FINDINGS The mainstay of EMPD treatment centers around a high index of suspicion to allow for an early and accurate diagnosis, wide local or Mohs micrographic surgical excision with care paid toward the margin status, and thoughtful consideration for lymphadenectomy in patients with clinically positive regional disease. There is currently no consensus regarding adjuvant therapies or systemic therapies although with ongoing improvements in tumor biology and genomics, including molecular pathways and alterations specific to EMPD, targeted or combinatorial therapies may be on the horizon. SUMMARY Clinicians caring for patients with EMPD should seek consultation from or if feasible, consider referral to high-volume, experienced centers with patients counseled and provided with frequent and close follow-up for disease recurrence or progression. Collaboration with groups such as the Global Society for Rare Genitourinary Tumors, and especially patient groups will be vital to designing trials and collaborative databases.

The 2019 WHO classification recognizes two morphologic variants of cholangiocarcinoma: 1) small duct type, and, 2) large duct type; the former is associated with IDH1/2 mutations and FGFR2 fusions. Therapies targeting these genetic alterations have recently been approved by the FDA. The liver is a favored site of metastasis in the body, and it is thus imperative to distinguish metastatic adenocarcinoma from cholangiocarcinoma. The traditional diagnostic approach employs immunohistochemical stains to exclude a metastatic carcinoma. Cholangiocarcinoma has been considered a diagnosis of exclusion and extensive clinical and imaging work-up has been necessary before this diagnosis can be made. The presence of cholangiolar pattern and positive albumin on in situ hybridization favor a diagnosis of cholangiocarcinoma. This review aims to update the reader on the new morphologic classification, and diagnostic and molecular advances in cholangiocarcinoma.

Medication nonadherence among bipolar disorder (BD) is often linked with comorbid substance use disorders. This study aims to investigate cannabis use disorder (CUD) association with medication noncompliance in hospitalized BD patients.Using data on 266,303 BD hospitalizations between 2010 and 2014 from the US Nationwide Inpatient Sample database, we obtained medication noncompliance rates stratified by demographics and CUD. Logistic regression was used to evaluate factors associated with medication noncompliance.Overall mean age, the prevalence of CUD, and medication nonadherence were 41.58 (± 0.11) years, 15.0% and 16.1%, respectively. There were 56.6% females in the overall population. There was a significant difference in the characteristics of those in the medication nonadherence vs adherence groups, including age, sex, race, comorbid substance use, income, insurance type, hospital region, and hospital teaching status (p 0.001). After adjusting for other variables using multivariate analysis, there remained a statistically significant association of medication nonadherence in BD hospitalization and CUD (OR 1.42, 95% CI 1.36-1.48).Confounding multiple substance use could not be accounted for, and the retrospective nature of the database which includes only inpatients is prone to possible selection and reporting bias.CUD statistically predicts increased rates of medication nonadherence among patients with BD. Given the possible association of CUD with medication nonadherence among BD patients, collaborative work between general adult psychiatry and addiction services is imperative in improving the management outcome of patients with BD and comorbid CUD.

Objectives To elucidate the national burden of emergency department (ED) visits for radiation cystitis (RC), a known complication of radiation therapy to the pelvic area, among patients with a prostate cancer history, and identify those who are at increased risk of requiring invasive measures. Methods This study queried the Nationwide Emergency Department Sample for all ED visits from January 2006 to December 2015 with a primary diagnosis of radiation cystitis and secondary diagnosis of prostate cancer. ED visits were characterized by demographic factors, socioeconomic factors, and hospital characteristics. Weighted frequencies were used to create national estimates for all data analysis. Results A weighted total of 17,382 ED visits occurred for RC among patients with a prostate cancer history, of which 9,655 (55.5%) were treated with an invasive procedure. Notable factors associated with undergoing an invasive procedure included having a prior prostatectomy (odds ratio [OR], 5.48; 95% confidence interval [CI], 2.62-11.46), urinary retention (OR, 1.35; 95% CI, 1.12-1.64), hematuria (OR, 1.20; 95% CI, 1.01-1.42), and undergoing a blood transfusion (OR 2.12; 95% CI, 1.72-2.62). ED visits that were associated with invasive procedures had a higher median total charge ($34,707.53 vs $15,632.53) and an increased median length of stay (5 days vs 3 days) compared to visits without an invasive procedure. Conclusions Among ED visits for RC in prostate cancer, approximately one half required an invasive procedure for treatment. While radiation remains an effective modality for patients with prostate cancer, providers should be mindful of RC as a potential complication.

High-risk relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) is associated with poor outcomes after conventional salvage therapy and autologous hematopoietic cell transplantation (AHCT). Post-AHCT consolidation with brentuximab vedotin (BV) improves progression-free survival (PFS), but with increasing use of BV early in the treatment course, the utility of consolidation is unclear. CD25 is often expressed on Reed-Sternberg cells and in the tumor microenvironment in HL, and we hypothesized that the addition of 90Y-antiCD25 (aTac) to carmustine, etoposide, cytarabine, melphalan (BEAM) AHCT would be safe and result in a transplantation platform that is agnostic to prior HL-directed therapy. Twenty-five patients with high-risk R/R HL were enrolled in this phase 1 dose-escalation trial of aTac-BEAM. Following an imaging dose of 111In-antiCD25, 2 patients had altered biodistribution, and a third developed an unrelated catheter-associated bacteremia; therefore, 22 patients ultimately received therapeutic 90Y-aTac-BEAM AHCT. No dose-limiting toxicities were observed, and 0.6 mCi/kg was deemed the recommended phase 2 dose, the dose at which the heart wall would not receive >2500 cGy. Toxicities and time to engraftment were similar to those observed with standard AHCT, though 95% of patients developed stomatitis (all grade 1-2 per Bearman toxicity scale). Seven relapses (32%) were observed, most commonly in patients with ≥3 risk factors. The estimated 5-year PFS and overall survival probabilities among 22 evaluable patients were 68% and 95%, respectively, and non-relapse mortality was 0%. aTac-BEAM AHCT was tolerable in patients with high-risk R/R HL, and we are further evaluating the efficacy of this approach in a phase 2 trial. This trial was registered at www.clinicaltrials.gov as #NCT01476839.

Background The presence of psychiatric disorders in patients with cancer is associated with increased morbidity and poorer outcomes. We sought to determine the impact of a new bladder cancer diagnosis on the incidence of depression and anxiety. Methods We used a database of billing claims (MarketScan®) to identify patients newly diagnosed with bladder cancer between 2009 and 2018. Patients with preexisting psychiatric disorders or use of anxiolytics/antidepressants were excluded. We matched cases to patients without a bladder cancer or psychiatric diagnosis. Our primary outcome was a new diagnosis of depression, anxiety, or use of anxiolytics/antidepressants. Other exposures of interest included gender and treatment received. We used multivariable regression to estimate odds ratios for these exposures. Results We identified 65,846 cases with a new diagnosis of bladder cancer (31,367 privately insured; 34,479 Medicare‐eligible). Compared to controls, bladder cancer patients were more likely to develop new‐onset depression/anxiety at 6 months (privately insured: 6.9% vs. 3.4%, p, Using a large, nationally representative sample, we found that a new diagnosis of bladder cancer was associated with increased burden of mental health diagnoses and medication utilization compared with matched controls. Female patients and those receiving more radical treatments for bladder cancer had higher rates of major depressive disorder, generalized anxiety disorder, and psychiatric medication utilization.

Urinary tract infection (UTI) is a microbial contamination of the bladder and related organs. Study subjects were those who had no structural anomaly and no co-occurring diseases, such as diabetes, or were either immunocompromised or pregnant. Simple UTI is also defined as cystitis or inferior UTI. This study was a prospective, single center study conducted at a tertiary level clinic and its associated bacteriology laboratory. Patients whose urine tests were collected by the microbiology test center over a 6-month period were enrolled in the study. Culture and vulnerability results were obtained directly from the microbiology test center. Of the 1306 samples obtained, 888 (68%) were from females and 418 (32%) from males. This study identified the predominant UTI-causing microbes and the associated antimicrobial vulnerabilities. In males, Escherichia coli (36.8%) was the predominant microbe followed by Klebsiella pneumoniae 19.8%, Proteus spp. 17.4%, Staphylococcus aureus 10.0%, Pseudomonas aeruginosa 5.5%, Citrobacter spp. 5.0%, Staphylococcus saprophyticus 0.7%, Enterococcus faecalis 1.4%, and Acinetobacter spp. 0.7%. In females, E. coli (49.4%) was predominant, whereas Acinetobacter spp. (0.3%) was the least dominant. The considerable susceptibility of E. coli to meropenem (73.6%) and imipenem (73.5%) was similar to that reported in different investigations across India. In this study, the susceptibility of E. coli to piperacillin + tazobactam and ciprofloxacin was 42.7% and 14.3%, respectively. Stewardship of urinalysis and urine culture, especially among clinicians might be a successful upstream strategy for reducing inappropriate antimicrobial use for UTI. Thus, it is critical to routinely screen for resistance or susceptibility in samples of uropathogens, so the protocols for proper antibiotic treatment can be enhanced to incorporate antimicrobials with less resistance, supporting physicians in the appropriate treatment of UTIs resulting in insignificant remedial disappointments.

Purpose: In the current molecular-targeted cancer treatment era, many new agents are being developed so that optimizing therapy with a combination of radiation and drugs is complex. The use of emerging laboratory technologies to further biological understanding of drug-radiation mechanisms of action will enhance the efficiency of the progression from preclinical studies to clinical trials. In 2017, the National Cancer Institute (NCI) solicited proposals through PAR 16-111 to conduct preclinical research combining targeted anticancer agents in the Cancer Therapy Evaluation Program's portfolio with chemoradiation. Methods and Materials The Preclinical Chemo-Radiotherapy Testing Consortium (PCRTC) was formed with 4 U01 programs supported to generate validated high-quality preclinical data on the effects of molecular therapeutics when added to standard-of-care therapies with a concentration on cancers of the pancreas, lung, head and neck, gastrointestinal tract, and brain. Results The PCRTC provides a rational basis for prioritizing NCI-supported investigational new drugs or agents most likely to have clinical activity with chemoradiotherapy and accelerate the pace at which combined modality treatments with greater efficacy are identified and incorporated into standard treatment practices. Conclusions Herein, we introduce and summarize the course of the PCRTC to date and report 3 preliminary observations from the consortium's work to date.

Bioelectronic medicine is a relatively new area that focuses on developing methods for treating diseases that do not need medications. Bioelectronic medicine treatments are now possible thanks to a small embedded system that produces and delivers frequent digital doses to nerve bundles, resulting in a disease-fighting effect that can last hours or days and is based on mechanisms similar to drug therapies. Although this may sound like science fiction, electronic brain and nerve stimulators are now presence applicable to treat so many of ailments, including epilepsy, Parkinson's disease, and bladder control. Progress in treating such disorders has opened up possibilities for boosting memory, improving eyesight, strengthening a shaky gait, and even improving a golfer's swing. Those self-improvement dreams may be a long way off, but bioelectronic medicine is gaining traction as a new way to treat difficult diseases. What distinguishes bioelectronic medicine is its biological effect on the body, which goes beyond symptom management to treat the underlying condition by using the body's own mechanisms. With promising early results in many trials and further trials ongoing, bioelectronic therapies are likely to be accepted for clinical use within the next few years. To make this advancement possible, forward-thinking scientists, engineers, doctors, and innovators with specialised talents combined old and new discoveries in ways no one had before.

Background: Patients with psychiatric disorders are at an increased risk of developing cardiovascular disease, reducing life expectancy. Autonomic dysfunction has been linked to this increased risk; many studies have found reductions in heart rate variability (HRV). Only a few studies have systematically explored the relationship between obsessive–compulsive disorder (OCD) and autonomic function, and they have found contradicting results. The present study is intended to explore comprehensive autonomic functions in OCD patients and compare them with healthy controls. Methods: A total of 18 OCD patients meeting Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5) criteria were enrolled to undergo comprehensive autonomic function testing, and the results were compared with 25 age- and sex-matched healthy controls. Results: Time-domain parameters of HRV such as standard deviation of the RR intervals, coefficient of variance of RR intervals, standard deviation of differences between adjacent RR intervals, root square of the mean of the sum of the squares of differences between adjacent RR intervals, and percentage of number of RR interval differences ≥ 50 ms were significantly lower in OCD patients, indicating lesser parasympathetic tone. Frequency-domain parameters such as total power and very low frequency were significantly lower in OCD patients, indicating a significant decrease in autonomic tone. Nonlinear parameters such as dispersion of points perpendicular to the line of identity and dispersion of points along the line of identity were significantly lower in OCD patients, indicating altered vagal and sympathetic tone. In autonomic reactivity tests, the fall in systolic blood pressure during the lying to standing test and change in diastolic blood pressure during the cold pressor test were significantly altered in OCD patients, indicating abnormal sympathetic reactivity. There was no significant correlation between autonomic parameters and the severity of OCD. Conclusion: OCD is characterized by a decreased parasympathetic tone and abnormal sympathetic reactivity compared to normal controls.

BACKGROUND: The primary objective was to ascertain the predictors of 90-day all-cause morbidity, mortality and poor functional outcome scores following primary total knee arthroplasty (TKA). MATERIAL AND METHOD: The study population comprised 3645 patients who underwent elective primary unilateral TKA at our institution. Demographic variables, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) grade and the Deyo–Charlson comorbidity scores were ascertained. The Functional outcomes, perioperative complications, mortality and readmission rates were monitored prospectively for 90 days and analysed. Patients were assessed twice: at baseline and at 90 days postoperatively. Odds ratio and the corresponding 95% confidence intervals were calculated to quantify the risk. A p 70 years; Deyo–Charlson co-morbidity score ≥ 4, ASA grade-III, Diabetes Mellitus, BMI > 35, Cardiac Issues and Male gender were significant predictors of early morbidity and mortality. Female, Deyo–Charlson comorbidity score ≥ 4, ASA grade-III, BMI > 35, Age > 75 years and poor preoperative scores were significantly associated with poor functional outcome. CONCLUSION: The present study explicates the relative importance of predictors on morbidity, mortality and functional outcome. Efforts to minimize morbidity and mortality should concentrate more on elderly male patients, and those with high Deyo–Charlson comorbidity score, BMI and ASA grade.

Introduction: Atopic dermatitis is a common dermatologic condition that affects millions of people worldwide, and a standardized approach to treatment was published by the American Academy of Dermatology (AAD) in 2013–14. Since 2014, new FDA-approved treatment options such as dupilumab and crisaborole have changed the landscape of AD management, and future therapies such as JAK inhibitors and anti-interleukin 13 and 31 antibodies appear effective, emphasizing the need for a comprehensive review to give clinicians an updated toolbox to aid in pharmacologic management. Areas Covered: In this review, the authors explore the updated efficacy and safety data on established therapeutic options for AD including topical corticosteroids, topical calcineurin inhibitors, cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil. In addition, the authors also explore trial data and studies on dupilumab, crisaborole, omalizumab, tofacitinib, ruxolinitib, abrocitinib, baricitinib, upadacitinib, delgocitinib, nemoliuzumab, and tralokinumab. Expert opinion: The AAD guidelines must be updated in the future to include several new treatment modalities that have revolutionized the pharmacologic management of patients with AD, including dupilumab and crisaborole. The future of AD treatment is also extremely bright, as JAK inhibitors and Il-13/31 antibodies have shown convincing results in the improvement of AD patients’ lives in various trials and studies that have been examined in this paper.

Background Local recurrence of microinvasive sarcoma or benign aggressive pathologies can be limb- and life-threatening. Although frozen pathology is reliable, tumor microinvasion can be subtle or missed, having an impact on surgical margins and postoperative radiation planning. The authors' service has begun to temporize the tumor bed after primary tumor excision with a wound vacuum-assisted closure (VAC) pending formal margin analysis, with coverage performed in the setting of final negative margins. Methods This retrospective analysis included all patients managed at a tertiary referral cancer center with VAC temporization after soft tissue sarcoma or benign aggressive tumor excision from 1 January 2000 to 1 January 2019 and at least 2 years of oncologic follow-up evaluation. The primary outcome was local recurrence. The secondary outcomes were distant recurrence, unplanned return to the operating room for wound/infectious indications, thromboembolic events, and tumor-related deaths. Results For 62 patients, VAC temporization was performed. The mean age of the patients was 62.2 ± 22.3 years (median 66.5 years; 95% confidence interval [CI] 61.7-72.5 years), and the mean age-adjusted Charlson Comorbidity Index was 5.3 ± 1.9. The most common tumor histology was myxofibrosarcoma (51.6%, 32/62). The mean volume was 124.8 ± 324.1 cm3, and 35.5% (22/62) of the cases were subfascial. Local recurrences occurred for 8.1% (5/62) of the patients. Three of these five patients had planned positive margins, and 17.7% (11/62) of the patients had an unplanned return to the operating room. No demographic or tumor factors were associated with unplanned surgery. Conclusions The findings showed that VAC-temporized management of microinvasive sarcoma and benign aggressive pathologies yields favorable local recurrence and unplanned operating room rates suggestive of oncologic and technical safety. These findings will need validation in a future randomized controlled trial.

Gastric cancer is one of the leading causes of death from malignancy. Despite the enormous advancement in medical oncology over the past decade, surgical resection of early tumors remains the most effective treatment. Accurate interpretation of radiologic imaging studies is crucial for staging local disease spread, predicting possible lymphatic involvement, and identifying metastatic disease, thereby guiding management plans. This article reviews imaging patterns of the normal stomach along with appearances of gastric cancer, its local spread patterns and distant metastasis, and also describes key features pertaining to preoperative staging.

Objectives Post-operative radiation therapy (PORT) in locally advanced non-small cell lung cancer (LA-NSCLC) has historically been associated with toxicity. Conformal techniques like intensity modulated radiation therapy (IMRT) have the potential to reduce acute and long-term toxicity from radiation therapy. Among patients receiving PORT for LA-NSCLC, we identified factors associated with receipt of IMRT and evaluated the association between IMRT and toxicity. Methods We queried the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between January 1, 2006 to December 31, 2014 to identify patients diagnosed with Stage II or III NSCLC and who received upfront surgery and subsequent PORT. Baseline differences between patients receiving 3-dimentional conformal radiation therapy (3D-CRT) and IMRT were assessed using the chi-squared test for proportions and the t-test for means. Multivariable logistic regression was used to identify predictors of receipt of IMRT and pulmonary, esophageal, and cardiac toxicity. Propensity-score matching was employed to reduce the effect of known confounders. Results A total of 620 patients met the inclusion criteria, among whom 441 (71.2%) received 3D-CRT and 179 (28.8%) received IMRT. The mean age of the cohort was 73.9 years and 54.7% were male. The proportion of patients receiving IMRT increased from 6.2% in 2006 to 41.4% in 2014 (P Conclusion In a cohort of elderly patients, the use of IMRT in the setting of PORT for LA-NSCLC was not associated with a difference in toxicity compared to 3D-CRT. This finding suggests that outcomes from PORT may be independent of radiotherapy treatment technique.

Background Animal data demonstrate that intracardiac patches of decellularized porcine small intestine submucosa (CorMatrix; CorMatrix Cardiovascular, Atlanta, GA) become repopulated with native cells, suggesting the possibility of a substrate for regenerative tissue in humans. Although human studies have not demonstrated this regenerative property with intracardiac patches, it is possible that other environments may better promote native cell repopulation. We report a prospective series of explanted CorMatrix extracardiac patches placed in infants with congenital heart disease. Methods CorMatrix Tyke patches were used in pulmonary artery patch closure during the Norwood procedure. The patch material was explanted as part of the hemi-Fontan procedure. Specimens were analyzed with the use of hematoxylin and eosin, Movat pentachrome, and trichrome stains. Results Of the 11 implantations, 9 specimens were explanted. One patient did not survive to hemi-Fontan procedure. One patient’s patch was removed, but not analyzed. Acellular material, chronic inflammation, fibrosis, and foreign body giant cell reaction was seen in all explanted patches. No explanted CorMatrix Tyke material demonstrated evidence of ingrowth of native endothelial tissue at a median of 4.9 months in vivo. Conclusions CorMatrix Tyke patch material, placed as a pulmonary artery patch in an extracardiac position, remained pliable and mostly free of calcification. However, these patches did not show evidence of native endothelial tissue at a median of 4.9 months in vivo.

For decades, spinal drains for cerebrospinal fluid (CSF) pressure monitoring and drainage have been used as adjuncts to protect against spinal cord injury resulting from thoracic aortic aneurysm repair. There are many different approaches to placement and management of CSF drains, with no true consensus on best practice. Furthermore, the incidence of complications resulting from spinal drains largely has been stagnant. This review describes the history and rationale behind placement of CSF drains, explore various considerations, techniques, and equipment, and discuss potential considerations for developing more comprehensive protocols.

Purpose The treatment of aneurysms with characteristics such as complex morphology, fusiform, blister-like, wide neck, or large size has been revolutionized with the introduction of flow diverters. Though flow diverters have several advantages over coiling, they also have certain important disadvantages such as the lack of immediate protection against rupture, the risk of ischemic stroke, the need for antiplatelet therapy, and long latency for complete effect. The Derivo Embolization Device (DED) is a second-generation self-expanding device that is claimed to be less thrombogenic than conventional devices. We retrospectively evaluated the periprocedural safety and risks associated with the Derivo Embolization Device across 5 centers in India. Materials and methods This is a multicentric, retrospective, observational study of DED, conducted at 5 high volume endovascular therapy centers in India from May 2018 to June 2020. Periprocedural demographic, clinical, and angiographic data were collected from a retrospective review of patient charts. Results A total of 96 patients, including 56 (58.3%) females, aged between 16-80 years (60±12.7 years) harboring 106 aneurysms were studied. Seven (7.3%) were noted to harbor multiple aneurysms: 6 had 3 aneurysms each, while 1 patient had 5 aneurysms. The following aneurysm characteristics were noted: average size, 9.8±8.2 mm; average neck size, 6.9±8.5 mm; wide-necked (>4mm), 63 (59.4%); giant (>25mm), 8 (7.5%); and anterior circulation location, 98 (92.5%). Eighteen (17%) of these were ruptured. Additional balloon angioplasty was performed in 5 (5.2%) patients. Intraprocedural problems were encountered in 3 (3.1%), of which only 1 had clinical implications, the device fish-mouthing with stent thrombosis resulting in a malignant middle cerebral artery territory infarction. The modified Rankin scale at 3 months was worse in 1 patient. Conclusion DED is a newer generation flow diverter stent with a low periprocedural complication rate.

Background Obesity increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes (T2D) after myocardial infarction (MI). Brown adipose tissue (BAT) is important to combat obesity and T2D, and increasing BAT mass by transplantation improves glucose metabolism and cardiac function. The objective of this study was to determine if BAT had a protective effect on glucose tolerance and cardiac function in high-fat diet (HFD) fed mice subjected to a mild MI. Methods Male C57BL/6 mice were fed a HFD for eight weeks and then divided into Sham (Sham-operated) and +BAT (mice receiving 0.1 g BAT into their visceral cavity). Sixteen weeks post-transplantation, mice were further subdivided into ±MI (Sham; Sham-MI; +BAT; +BAT-MI) and maintained on a HFD. Cardiac (echocardiography) and metabolic function (glucose and insulin tolerance tests, body composition and exercise tolerance) were assessed throughout 22 weeks post-MI. Quantitative PCR (qPCR) was performed to determine the expression of genes related to metabolic function of perigonadal adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), liver, heart, tibialis anterior skeletal muscle (TA); and BAT. Results +BAT prevented the increase in left ventricle mass (LVM) and exercise intolerance in response to MI. Similar to what is observed in humans, Sham-MI mice developed IGT post-MI, but this was negated in +BAT-MI mice. IGT was independent of changes in body composition. Genes involved in inflammation, insulin resistance, and metabolism were significantly altered in pgWAT, scWAT, and liver in Sham-MI mice compared to all other groups. Conclusions BAT transplantation prevents IGT, the increase in LVM, and exercise intolerance following MI. MI alters the expression of several metabolic-related genes in WAT and liver in Sham-MI mice, suggesting that these tissues may contribute to the impaired metabolic response. Increasing BAT may be an important intervention to prevent the development of IGT or T2D and cardiac remodeling in obese patients post-MI.

BACKGROUND Dentists are liable to loss of hearing during dental treatment due to noise exposure. A study was carried out to determine whether or not dental professionals from the Department of Periodontics, Conservative Dentistry and Endodontics and Prosthodontics ought to cause hearing decrement with the aid of using continual excessive frequency sounds created by dental equipments. METHODS This study involved 38 dentists from the specialities of Periodontics, Conservative Dentistry and Endodontics, and Prosthodontics who were subjected to noise during operating for 6 hours per day and 38 medical professionals who were matched served as a control group. Three audiometric examinations included an otoscopic exam; tympanometry and pure tone audiometry were performed by the participants. RESULTS According to the data, 15.8 % of dentists and 2.6 % of the control group suffered from loss of hearing. In the pure tone audiometry test, there was no substantial difference between the two groups; however, the qualitative analysis showed that the dentists' group had a greater percentage of hearing loss than their control counterparts. In the pure tone audiometry test, there was a statistically significant difference between the specialists from periodontics, conservative dentistry and endodontics, and prosthodontics (P = 0.005). CONCLUSIONS Noise from dental clinics has been shown to cause hearing problems, with the left ear being affected when compared to that of the right; again, these problems aren't serious. Dentists were common among noise-induced hearing impairment and periodontic specialists than conservative dentistry and endodontics, and prosthodontic specialists than the control group. KEY WORDS Dental Professionals, Long Term Exposure, Noise-Induced Hearing Loss, Pure Tone Audiometry.

Background GNAS encodes the Gαs (stimulatory G-protein alpha subunit) protein, which mediates G protein-coupled receptor (GPCR) signaling. GNAS mutations cause developmental delay, short stature, and skeletal abnormalities in a syndrome called Albright's hereditary osteodystrophy. Because of imprinting, mutations on the maternal allele also cause obesity and hormone resistance (pseudohypoparathyroidism). Methods We performed exome sequencing and targeted resequencing in 2548 children who presented with severe obesity, and we unexpectedly identified 22 GNAS mutation carriers. We investigated whether the effect of GNAS mutations on melanocortin 4 receptor (MC4R) signaling explains the obesity and whether the variable clinical spectrum in patients might be explained by the results of molecular assays. Results Almost all GNAS mutations impaired MC4R signaling. A total of 6 of 11 patients who were 12 to 18 years of age had reduced growth. In these patients, mutations disrupted growth hormone-releasing hormone receptor signaling, but growth was unaffected in carriers of mutations that did not affect this signaling pathway (mean standard-deviation score for height, -0.90 vs. 0.75, respectively; P = 0.02). Only 1 of 10 patients who reached final height before or during the study had short stature. GNAS mutations that impaired thyrotropin receptor signaling were associated with developmental delay and with higher thyrotropin levels (mean [±SD], 8.4±4.7 mIU per liter) than those in 340 severely obese children who did not have GNAS mutations (3.9±2.6 mIU per liter; P = 0.004). Conclusions Because pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for GNAS deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. GNAS mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.).

Food insecurity and gun violence are timely and relevant public health issues impacting many regions within the USA with a potential association. Terminology surrounding food access and food security can be confusing, which is important to understand when examining the relationship between these issues and gun violence. Food insecurity is an individual level risk factor that appears to correlate with an increased rate of exposure and future involvement in violence. Food deserts represent geographic regions with limited access to food but do not necessarily represent regions with high prevalence of food insecurity. Although both food insecurity and food deserts in urban regions have been linked with increased incidence of gun violence, a high prevalence of food insecurity was found to be more predictive. A high prevalence of food insecurity in urban regions likely serves as a marker for socioeconomic disadvantage and intentional disinvestment. These regions are predictably associated with a higher incidence of interpersonal gun violence. Food deserts in rural areas have not, to date, been shown to correlate with interpersonal gun violence. Urban food insecurity and gun violence are both likely the byproduct of structural violence. Despite the significant overlap and similar contributors, the application of the public health framework in addressing these two issues has historically been quite different.

ObjectiveMucormycosis is a rapidly progressive and fulminant fungal infection mainly affecting the nose and paranasal sinuses and often requiring aggressive surgical debridement, which commonly includes inferior maxillectomy. Conventional inferior maxillectomy involves removal of the bony hard palate and its mucoperiosteum. This can lead to formation of an oroantral fistula and thereby increase the morbidity in these patients leading to prolonged rehabilitation. Subperiosteal inferior maxillectomy involves sparing of the uninvolved mucoperiosteum of the hard palate. This flap is used for closure of the oroantral fistula, which preserves the functional capabilities of the patient, such as speech, mastication and deglutination.MethodThis case series describes the experience of using the technique of mucosa-preserving subperiosteal inferior maxillectomy in five patients with mucormycosis.ResultsWith the technique used in this study, complete oronasal separation was achieved in all six patients. The overall surgery time was also decreased when compared with free tissue transfer. Patients also did not have to bear the weight of prosthesis.ConclusionMucoperiosteal palatal flap-preserving subperiosteal inferior maxillectomy is an excellent approach for all patients with mucormycosis and healthy palatal mucosa.

Aswin Anand Pai, Ajith Mohan, Esther Sathya Bama Benjamin, Raveen Stephen Stallon Illangeswaran, Infencia Xavier Raj, Nancy Beryl Janet, Arun Kumar Arunachalam, ML Kavitha, Uday Kulkarni, Anup J Devasia, NA Fouzia, Aby Abraham, Alok Srivastava, Biju George, Vikram Mathews, Anu Korula, Poonkuzhali Balasubramanian Department of Haematology, Christian Medical College, Vellore, Tamilnadu, IndiaCorrespondence: Poonkuzhali BalasubramanianDepartment of Haematology, Christian Medical College, Vellore, Tamilnadu, IndiaEmail bpoonkuzhali@cmcvellore.ac.inPurpose: Severe myelosuppression in patients with acute lymphoblastic leukemia (ALL) undergoing 6-MP-based maintenance therapy is attributed to TPMT gene polymorphisms, which is rare in Asian populations. This study aims to evaluate the role of selected polymorphisms in NUDT15, ITPA, and MRP4 genes in addition to TPMT in predicting 6-MP intolerance during ALL maintenance therapy.Patients and Methods: We screened for the presence of NUDT15&ast;3 (c.415 C>T, rs116855232); MRP4 c.2269 C>T (rs3765534), ITPA c.94 C>A (rs1127354) polymorphisms in addition to TPMT &ast;2 (rs1800462), &ast;3A (&ast;3B and &ast;3C; rs1800460 and rs1142345) in ALL patients with documented severe neutropenia (cohort-1; n=42). These polymorphisms were then screened in a prospective cohort of ALL patients (cohort-2; n=133) and compared with 6-MP dose reduction, early/late myelotoxicity.Results: Nineteen (45%) patients in cohort-1 and 18 (14%) in cohort-2 had NUDT15 c.415 C>T variant while 4 (3%) patients in cohort-2 had TPMT&ast;3C variant. Five (12%) in cohort-1 and 30 (24%) in cohort-2 had ITPA c.94 C>A variant while 9 (22%) and 15 (12%) had MRP4 c.2269 C>T variant in cohorts-1 and 2, respectively. All in cohort-1 and 36 (27%) in cohort-2 had severe myelotoxicity. Twenty-eight patients (66.6%) in cohort-1 and 40 (30%) patients in cohort-2 had significant 6-MP dose reduction. NUDT15 c.415 C>T variant explained severe myelotoxicity in 63% and 33% in cohort 1 and 2. TPMT&ast;3C and ITPA c.94 C>A variants also explained myelotoxicity in cohort-2 (Median ANC: 376 vs 1014 mm3; p=0.04 and 776 vs 1023 mm3; p=0.04 respectively). NUDT15 c.415 C>T polymorphism explained significant myelotoxicity (507 vs 1298 mm3; p< 0.0001) in the multivariate analysis as well (β=− 0.314, p< 0.0001).Conclusion: NUDT15 c.415 C>T (15&ast;3), TPMT&ast;3C, as well as ITPA c.94 C>A and MRP4 c.2269 C>T polymorphisms explain hematotoxicities. Preemptive genotype-based (NUDT15&ast;3, TPMT, ITPA c.94 C>A) 6-MP dosing could improve the outcome after maintenance therapy.Keywords: leukemia, mercaptopurine, myelotoxicity, pharmacogenomics

Background: Patrick Haglund in 1927 was the first one to describe Haglund’s deformity. This type of deformity is also known as retro-calcaneal exostosis. It is one of the causes of posterior heel pain. Several methods have been described for treatment including conservative measures and surgical measures. Aim of Study: The aim of this study is to evaluate results of surgical resection of Haglund's deformity by Achilles’s tendon splitting approach. Patients and Methods: In this prospective study, 21 cases with Haglund's deformity were treated with surgical resection through Achilles’s tendon splitting approach. Results: These cases were assessed according to AOFAS score, the functional results were graded as excellent in thirteen patients (61.9%), good in seven patients (33.3%), fair in one patient (4.8%), with no poor results. The excellent and good results were categorized as satisfactory ones while the fair results were said to be the unsatisfactory ones. Thus, satisfactory results were seen in 20 patients (95.2%), and the unsatisfactory ones were found in 1 patient (4.8%). Conclusion: This study proves that central splitting technique for the surgical treatment of Haglund's deformity is an effective treatment with good exposure of retrocalcaneal space, with reduced risk of vascular and nerve injury, and acceptable outcome.

Ashwin Parchani,1 K Vidhya,2 Prasan Kumar Panda,1 Vikram Singh Rawat,3 Yogesh Arvind Bahurupi,4 Deepjyoti Kalita,5 Harsh Kumar,2 Naveen Dr2 1Department of Medicine (Infectious Disease Division), All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 2All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 3Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 4Department of Community and Family Medicine, All India Institute of Medical Sciences (AIIMS), Rishikesh, India; 5Department of Microbiology, All India Institute of Medical Sciences (AIIMS), Rishikesh, IndiaCorrespondence: Prasan Kumar PandaDepartment of Medicine (Infectious Disease Division), Sixth Floor, College Block, All India Institute of Medical Sciences (AIIMS), Rishikesh, 249203, IndiaTel +91-9868999488Email motherprasanna@rediffmail.comPurpose: Disease pandemics are known to cause psychological distress. The ensuing mental health issues are not only restricted to the patients and their relatives/friends but affect the healthcare workers (HCWs) as well. Our study aims to assess these psychological trends during the COVID-19 pandemic between the two most affected population groups, that is, patients and frontline healthcare workers.Patients and Methods: A survey questionnaire, including scales to assess fear, anxiety, stress, depression – PSS 10, and DASS 21, was distributed and sent to all COVID-19 suspected/confirmed individuals and healthcare workers at a tertiary care center along with a second visit after 14 days of answering the first questionnaire and this continued as follow-up. Data were analyzed with the SPSS version 23 using various tests of significance.Results: In the community, COVID-19 patients in the age group 41– 50 with respiratory tract symptoms and those who were home isolated/quarantined experienced a greater tendency of mental health problems. Healthcare workers posted in COVID-19 designated areas of the hospital displayed higher levels of stress, anxiety, and depression.Conclusion: The high degree of uncertainty associated with novel pathogens has a profound effect on the psychological state of suspected/confirmed cases as well as healthcare workers. Within the community, individuals suspected of having COVID-19 display a significant mental health burden, while HCWs also experience an unprecedented amount of stress, anxiety, depression and fear during such enduring situations.Keywords: coronavirus disease 2019, fear, anxiety, depression, stress, survey, healthcare worker

Purpose Serious immune checkpoint inhibitor (ICI)-related neurotoxicity is rare. There is limited data on the specifics of care and outcomes of patients with severe neurological immune related adverse events (NirAEs) admitted to the Intensive Care Unit (ICU). Materials and methods Retrospective study of patients with severe NirAEs admitted to the ICU at 3 academic centers between January 2016 and December 2018. Clinical data collected included ICI exposure, type of NirAE (central [CNS] or peripheral nervous system [PNS) disorders), and patient outcomes including neurological recovery and mortality. Results Seventeen patients developed severe NirAEs. Eight patients presented with PNS disorders; 6 with myasthenia gravis (MG), 1 had a combination of MG and polyneuropathy and 1 had Guillain-Barre syndrome. Nine patients had CNS disorders (6 seizures and 5 had concomitant encephalopathy. During ICU admission, 65% of patients required mechanical ventilation, 35% vasopressors, and 18% renal replacement therapy. The median ICU and hospital length of stay were 7 (2–36) and 18 (4–80) days, respectively. Hospital mortality was 29%. At hospital discharge, 18% of patients made a full neurologic recovery, 41% partial recovery, and 12% did not recover. Conclusion Severe NirAEs while uncommon, can be serious or even life-threatening if not diagnosed and treated early.

Objective/Background The purpose of this study was to characterize the impact of household income disparities in the survival of patients with non-small cell lung cancer (NSCLC) presenting with brain metastasis on a population-based level. Methods This is a population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from 2010–2016 including 15,808 NSCLC patients presenting with brain metastasis. Results This study comprises 15,808 adult patients with NSCLC presenting with brain metastases having an age range 64 ± 10 years with 51% male, 76% white, 52% married, 61% insured, and with 85% of lung adenocarcinoma histopathology. The 1-, 2- and 5-year survival rates for living in the lower household income quartile were 21%, 10%, and 3%, respectively, for the second quartile 24%, 10%, and 3%; for the third quartile 28%, 14%, and 4%; and for the top quartile 31%, 17%, and 4%, respectively. Multivariate Cox proportional hazard analysis showed that living in a higher quartile household income county is associated with increased survival (P Conclusions This population-based study suggests that living in higher median household income counties is associated with increased survival time and reduced risk of mortality for patients with NSCLC who have brain metastases present at diagnosis, independent of other factors. These findings underscore the importance of ensuring adequate and easy access to care for all patients, irrespective of their economic background.

Objective The optimal antiplatelet regimen after lower extremity revascularization in patients with chronic limb-threatening ischemia (CLTI) is unknown because current recommendations are based on extrapolation of data from trials in coronary artery disease and stroke. Methods We identified all patients undergoing an elective lower extremity revascularization for CLTI in the Vascular Quality Initiative registry discharged on a mono antiplatelet agent (MAPT) or dual antiplatelet therapy (DAPT). Results From 2003 to 2018, 50,890 patients underwent revascularization procedures for CLTI, and were discharged on MAPT or DAPT. Of these, 33,781 patients underwent endovascular therapy (EVT), and 17,109 patients underwent open surgery (OS) procedures. The rate of major amputation at 30 days in the target limb in the EVT group was 0.3% and 0.4% in the OS group (P = .22). On Kaplan-Meier analyses, patients on MAPT at discharge had a higher risk of 1-year major amputation compared with DAPT after EVT but not after OS procedures. Patients on MAPT had lower overall survival and amputation-free survival at 30 days and 1 year compared with DAPT after both EVT and OS. At 1 year, the MAPT group was at higher risk for target lesion reintervention after EVT compared with the DAPT group (15.9% vs 13%; P = .0012). There was no significant difference in thrombosis at 1 year between the MAPT and DAPT groups either after EVT (3.9% vs 3.7%; P = .3048) or OS (3.1% vs 3.2%; P = .2893). On Cox regression analysis, DAPT was associated with improved survival but not major amputation after both EVT and OS. Conclusions In patients with CLTI, DAPT at the time of discharge has a positive impact on amputation-free survival and overall survival after both EVT and OS as well as target lesion reintervention after EVT. DAPT was not associated with a positive impact on major amputation after either EVT or OS.

Objective Joubert syndrome (JS) is a rare syndrome characterized by ataxia and the molar tooth sign (MTS) on imaging. The present study aims to explore the clinical and radiological features in a cohort of patients with JS.Methods This was a retrospective chart review of patients with JS evaluated by movement disorder specialists.Results Nine patients were included in the study. All patients had facial dysmorphism and ocular abnormalities, and 4 patients had dystonia. Ocular tilt reaction and alternate skew deviation (66%) were the most common ocular abnormalities. Horizontally aligned superior cerebellar peduncles were observed in all four patients with diffusion tensor imaging, with a lack of decussation in three. Exome sequencing performed in four patients revealed novel variants in the MKS1, CPLANE1, and PIBF1 genes.Conclusion Facial dysmorphism, ocular abnormalities and classical imaging findings were observed in all patients with JS. Apart from ataxia, dystonia and myoclonus are other movement disorders observed in JS.

Sameerpannag Ras (SPR) is a complex herbomineral formulation widely used in Ayurveda for stiffness in joints, cough, fever, headache, and respiratory symptoms like dyspnea. The metallic constituents of the formulation pose public health concerns; therefore, the current study was designed to evaluate the safety of the SPR in rats. In the present study, systematic preparation, characterization, and subacute oral toxicity of Sameerpannag Ras were performed. The formulation was prepared as per a standard protocol prescribed in the classical Ayurveda texts. The drug obtained was greenish-black with typical physicochemical properties. Energy-dispersive X-ray analysis (EDX) identified the sample with the presence of arsenic (As), sulphur (S), carbon (C), and mercury (Hg) predominantly. The subacute oral toxicity study of the formulation was conducted at different doses (6, 12, and 25 mg/kg BW) for 28 days on rats. No clinical signs and mortality were observed at any of the three doses in rats. The body weight, haematological, and biochemical parameters were comparable to the control animals. The histopathological examination revealed no significant pathological lesion in the vital organ except for mild changes in the intestinal villi of few rats at medium and higher doses. Overall, the study concluded that the formulation has no significant adverse effect and safe to use at the prescribed doses.

Diabetes mellitus is one of the major non-communicable diseases in India. Kamareddy district, with the support of Novartis under its Public Health Initiatives, has implemented secondary screening camps for subjects with higher risk of diabetes through screening under NPCDCS. In this analysis, we aim to identify the utility of the camps in monitoring diabetes management and early detection complications like diabetic retinopathy (DR). Seventeen camps were conducted in the rural Kamareddy district during Jun 2019 to Mar 2020. Subjects with RBS ≥ 140 mg/dl in the field screening were counselled and referred to the camps conducted as per schedule for further assessment through HbA1c, fundoscopy, ECG and lipid profile in an algorithm-based screening protocol. Twelve percent (24,965/208,685) of screened subjects had abnormal RBS and were referred to the camps. Of them, 9.2% (n = 2287; male = 1291; female = 996) could avail HbA1c testing in the camps, which consisted of 45% (1022) known diabetics. Forty-nine percent of the subjects belonged to age group 40–59 years (range: 6–88). Nearly one-third (34%) had HbA1c levels ≥ 7%. More than 63% of the known Diabetic subjects had HbA1c ≥ 7% indicating the need for strengthening treatment adherence (p

This study was done to assess the effect of sarcopenia and other risk factors on the postoperative morbidity and perioperative mortality of patients undergoing elective surgery for gastric cancer.This was a prospective cohort study comprising a single group of patients undergoing elective surgery for gastric cancer carried out in a tertiary care center in India. Patients diagnosed with gastric cancer underwent contrast-enhanced computed tomography preoperatively. Patients were considered sarcopenic when their skeletal muscle index (SMI) was 34.9 cmA total of 100 patients were included in the study. There was a high prevalence of sarcopenia (62%) among patients with gastric cancer who underwent elective surgery. However, sarcopenia was not associated with any postoperative complication (p 0.05) including 30-day mortality (p = 0.155), prolonged postoperative hospital stay (p = 0.876), or 30-day readmission rate (0.524). Among the variables considered, only esophagojejunostomy (p 0.001) was associated with a poor postoperative outcome.The present study showed that there was a high prevalence of sarcopenia (62%) in patients undergoing elective surgery for gastric cancer. However, it did not adversely affect the postoperative outcome. Among the variables considered, esophagojejunostomy alone was associated with a poor postoperative outcome.