Continuous Subcutaneous Delivery of rhPTH(1-84) and rhPTH(1-34) by Pump in Adults With Hypoparathyroidism.

Context: Continuous subcutaneous infusion of recombinant parathyroid hormone (rhPTH) through a pump has been proposed as a therapeutic alternative for patients with chronic hypoparathyroidism who remain symptomatic or hypercalciuric on conventional treatment (calcium and active vitamin D) or daily injections of rhPTH(1-84) or rhPTH(1-34). However, the real-world evidence of the outcome of this novel therapy is limited. Case Descriptions: We report the clinical and biochemical outcomes of 12 adults with hypoparathyroidism (11 women, age 30-70 years, and 1 man, age 30 years) from 3 different clinical sites in the United States who were transitioned from conventional therapy to daily injections of rhPTH(1-84) or rhPTH(1-34) and then switched to continuous administration of rhPTH(1-84)/rhPTH(1-34) via pump therapy. In most patients, mean serum calcium concentrations increased while on PTH pump therapy compared with both conventional therapy (in 11 patients) and single/multiple daily rhPTH injections (in 8 patients). Despite this, 10 patients had lower median 24-hour urinary calcium levels while on PTH pump therapy compared with prior therapy (mean ± SD difference: -130 ± 222 mg/24 hours). All patients reported a qualitative decrease in hypocalcemic symptoms while receiving pump therapy. Three patients had pod failure at least once, and 1 patient developed an infusion site reaction. Conclusion: In this case series of 12 patients with chronic hypoparathyroidism treated with rhPTH(1-84)/rhPTH(1-34) administered via a pump, improvement in clinical and biochemical parameters were observed in the majority of the patients. Our observations indicate benefits of pump administration of rhPTH that warrant further investigation.

Safety and Efficacy of Inpatient Infliximab Rescue Therapy for Acute Crohn's Disease Flares.

PURPOSE: Describe the safety, complications, and need for urgent surgery in patients requiring inpatient rescue infliximab for acute Crohn's disease (CD) flare. BACKGROUND: Infliximab is increasingly used for patients hospitalized with acute severe ulcerative colitis as rescue therapy; however, optimal management for patients hospitalized for CD flares remains unclear. METHODS: A single-institution retrospective study of patients aged 18+ admitted from 2008 to 2020 with acute Crohn's flare requiring induction of rescue infliximab therapy. Outcomes included postoperative and medication-related complications and need for urgent surgery. RESULTS: 52 patients were included in analysis; 8% required surgery on index admission, and 19% required surgery within 90 days of infliximab. Postoperative complications included 1 anastomotic leak, 3 superficial wound infections, 3 prolonged ileus, and 1 urinary infection. There were no adverse reactions to infliximab infusion, and medical complication rates were low. Patients with penetrating disease were more likely to undergo surgery within 90 days of infliximab (43% vs 8%; P = .01). Mean LOS was longer for patients undergoing surgery within 90 days of therapy compared to those who did not (13.4 vs 8.3 days, P = .04). CONCLUSION: Inpatient rescue infliximab is safe for treating acute Crohn's disease flare in addition to standard steroid therapy. The majority of patients hospitalized with Crohn's flare requiring rescue infliximab avoided surgery with low postoperative and medication-related complications. More research is needed to clarify the optimal rescue infliximab therapy dosage.

Effects of the interplay between topology and function of an integrated urban development on patterns of user movement.

With the advent of distributed multi-sensory networks of devices, vast troves of real-time data can be gathered about our interactions with the built environment. These rich data sets can be mined to achieve improved and informed data-driven designs of buildings, neighborhoods, and potentially entire cities. Among those, integrated developments have the peculiarity of combining multiple functions within a compact space and, as such, behave as microcosms of a city that can help address the problem of urban sprawl and density. However, a general lack of data and framework about integrated developments hinders our ability to test design hypotheses about the complex interplay between heterogeneity in both space and function. Here, we apply a data-driven approach to analyze the joint influence of topology and function on user movement within a state-of-the-art integrated development in Singapore. Specifically, we leverage the network representation of the building and use movement data collected from 51 individuals over a month. We show evidence of correlation (40%) between the spatial network features and human movement at the building level. We are also able to quantify the relationship between the functional and spatial components of the integrated development through user movement. Previous studies have shown a 60% or higher correlation between the topology and human movement at the city or country scales. Our moderate correlation, therefore, implies that more factors influencing user movement are at play. The heterogeneity in the spatial function introduced trips with diverse origins and destinations. A further data-driven analysis integrating origins and destinations reveals both qualitative and quantitative means of studying the relationship between the built environment and the processes that take place in them.

Transorbital and endonasal resection of a rare orbital ectopic atypical meningioma.

A female patient in her early 20s presented with increasing proptosis of her left eye over 2 months. She had no other signs of diplopia, pain or visual loss on initial presentation. Subsequent imaging of her orbits revealed a medial rectus tumour. A transorbital open biopsy of this tumour was non-diagnostic/inconclusive, hence a combined transorbital and endonasal resection of this tumour was performed. Histopathology of the resected tumour revealed an unusual inflammatory-rich spindle cell neoplasm, which was determined to be a primary orbital ectopic atypical meningioma. These tumours are exceedingly rare, with only case reports/series reported in the literature. Complete surgical resection with margins is the proposed treatment. The role of radiotherapy is still controversial. More studies are required to improve our knowledge of this condition.

Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking.

Gut microbiota can adapt to their host environment by rapidly acquiring new mutations. However, the dynamics of this process are difficult to characterize in dominant gut species in their complex in vivo environment. Here we show that the fine-scale dynamics of genome-wide transposon libraries can enable quantitative inferences of these in vivo evolutionary forces. By analyzing >400,000 lineages across four human Bacteroides strains in gnotobiotic mice, we observed positive selection on thousands of cryptic variants - most of which were unrelated to their original gene knockouts. The spectrum of fitness benefits varied between species, and displayed diverse tradeoffs over time and in different dietary conditions, enabling inferences of their underlying function. These results suggest that within-host adaptations arise from an intense competition between numerous contending variants, which can strongly influence their emergent evolutionary tradeoffs.

What care do people with dementia receive at the end of life? Lessons from a retrospective clinical audit of deaths in hospital and other settings.

BACKGROUND: The need for better end-of-life care for people with dementia has been acknowledged. Existing literature suggests that people dying with dementia have less access to palliative care, yet little is known about the care provided to people with dementia at the end of life. This study aimed to establish evidence related to end-of-life care for people dying with dementia in hospital compared to other settings. METHODS: A retrospective clinical audit of people who had a diagnosis of dementia and had accessed services within a local health district, who died between 2015 and 2019, was conducted. A total of 705 people were identified, and a subset of 299 people randomly selected for manual audit. Chi-square p-values were used to compare the place of death, and a t-test or non-parametric test was used to assess the significance of the difference, as appropriate. Measures of functional decline within one month of death were assessed using mixed effects logistic regression models. RESULTS: The characteristics of people differed by place of death, with people who died in hospital more likely to be living at home and to not have a spouse. Less than 1 in 5 people had advance care directives or plans. Many were still being actively treated at the time of death: almost half of people who died in hospital had an investigation in their final 72 hours, less than half of people were coded as receiving palliative care at death, and more than 2 in 3 people did not get access to specialist palliative care. Declining function was associated with the terminal phase. CONCLUSION: This study provides novel insights for those providing end-of-life care for people with dementia. Healthcare professionals and policy makers should consider how demographic characteristics relate to the places people with dementia receive end-of-life care. The care provided to people with dementia in the last year of their life highlights the need for more support to prepare advance care documentation and timely consideration for palliative care. Changes in markers of nutritional status and function in people with advanced dementia may help with identification of terminal phases.

Microbial co-occurrences on catheters from long-term catheterized patients.

Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected by chance. We find that for many patients, the microbial species composition between collection periods is similar. In a subset of patients, we find that the most frequently sampled bacteria, Escherichia coli and Enterococcus faecalis, co-localize on catheter samples. Further, co-culture of paired isolates recovered from the same patients reveals that E. coli significantly augments E. faecalis growth in an artificial urine medium, where E. faecalis monoculture grows poorly. These findings suggest novel strategies to collapse polymicrobial CAUTI in long-term catheterized patients by targeting mechanisms that promote positive co-associations.

Improving end-of-life care for people with dementia: a mixed-methods study.

BACKGROUND: Improving palliative and end-of-life care for people with dementia is a growing priority globally. This study aimed to integrate multiple perspectives on end-of-life care for people with dementia and carers, to identify clinically relevant areas for improvement. METHODS: The mixed-methods study involved surveys, interviews, and workshops with two participant groups: healthcare professionals and carers (individuals who provided care and support to a family member or friend). Healthcare professionals were invited to complete an online adapted version of the Australian Commission on Safety and Quality in Health Care, End-of-Life Care Toolkit: Clinician Survey Questions. Carers completed a hard copy or online adapted version of the Views of Informal Carers-Evaluation of Services (Short form) (VOICES-SF) questionnaire. Interview schedules were semi-structured, and workshops followed a co-design format. Findings were integrated narratively using a weaving approach. RESULTS: Five areas in which we can improve care for people with dementia at the end of life, were identified: 1) Timely recognition of end of life; 2) Conversations about palliative care and end of life; 3) Information and support for people with dementia and carers; 4) Person-and-carer-centred care; 5) Accessing quality, coordinated care. CONCLUSIONS: There are multiple areas where we can improve the quality of end-of-life care people with dementia receive. The findings demonstrate that the heterogeneous and challenging experiences of living with and caring for people with dementia necessitate a multidisciplinary, multifaceted approach to end-of-life care. The identified solutions, including care coordination, can guide local development of co-designed models of end-of-life care for people with dementia.

Primary pulmonary enteric adenocarcinoma presenting as a solitary skull mass.

Pulmonary enteric adenocarcinoma (PEAC) is a rare, aggressive variant of lung adenocarcinoma with early metastatic potential. We present the case of a male smoker in his 50s who presented with right-sided numbness, pain and headache. Imaging revealed a destructive skull base mass invading the right sphenoid sinus. Histopathology was consistent with PEAC. The diagnosis was metastatic PEAC with a distant spread to the skull and represents the first case reported in the literature. We present an associated literature review of the clinical presentation, histological features and management of PEAC with skull metastasis. Metastasis should be considered when evaluating any persistent cranial lesion. Diagnosis requires thorough clinical, radiological and pathological assessment. Treatment involves surgical resection, chemoradiation and targeted therapy. Prognosis directly correlates with clinical stage at presentation. This case highlights the importance of careful evaluation of skull lesions, even in patients without known primary malignancy. Early diagnosis and multimodal therapy may improve outcomes.

Therapeutic challenges in small cell carcinoma of the larynx.

Primary small cell neuroendocrine carcinoma (SCNC) of the larynx is a rare subtype of laryngeal cancer, accounting for less than 1% of all laryngeal tumours. It most commonly affects smokers in their fifth to sixth decade of life and is characterised by a high incidence of advanced disease at presentation and an aggressive clinical course. Here we present a case of SCNC of the larynx, presenting initially with dysphonia, and an associated literature review collating current knowledge regarding therapeutic approaches. After review of 260 cases in the literature we determined a disease-specific survival of 33.1%. Combined chemoradiotherapy is currently the recommended first-line treatment option.

Expression of Melan-A in cutaneous granular cell tumours: a diagnostic pitfall.

Morphological overlap exists between cutaneous granular cell tumours (GCT) and malignant melanoma, with the melanocyte-specific markers HMB45 and Melan-A commonly used to support the diagnosis of melanoma. We recently encountered several cases of GCT in our practice showing strong expression of Melan-A. The aim of this study was to establish the prevalence of positive immunohistochemical staining for Melan-A and HMB45 in a series of unequivocal GCTs. We also aimed to assess the prevalence of staining for PRAME (PReferentially expressed Antigen in MElanoma), a marker expressed in >80% of primary melanomas as well as many non-melanocytic tumours. A total of 20 cutaneous/subcutaneous GCTs were evaluated using Melan-A, HMB45 and PRAME immunohistochemistry. Staining for Melan-A and HMB45 was scored using a semiquantitative scale from 0 (absent) to 3+ (staining present in >50% of tumour cells). PRAME expression was recorded as either positive (>75% of cell nuclei staining) or negative. Melan-A expression was observed in four GCTs (20%), with strong and diffuse (3+) staining seen in two cases (10%), both from anogenital areas. Weak patchy nuclear PRAME expression was seen in every case, interpreted to be negative. HMB45 was also negative in all cases (100%). Our study demonstrates that Melan-A expression can be strong and diffuse in a subset of otherwise unequivocal cutaneous GCTs, which may cause diagnostic confusion with malignant melanoma. HMB45 and PRAME did not stain any of the GCTs in our series.

Strength-based cognitive-behavioural therapy and peer-to-peer support in the recovery process for people with schizophrenia: A randomised control trial.

BACKGROUND AND AIMS: Dysfunctional cognition and negative symptoms in schizophrenia are associated with persistently low social functioning and quality of life (QoL). Recovery interventions report only a modest effect in improving social functioning and QoL. This study examined the therapeutic effects and pathways of interventions using strength-based cognitive-behavioural therapy (SBCBT) and peer-to-peer support (PSP) approaches. METHODS: A randomised control trial compared SBCBT, PSP and TAU (treatment-as-usual) by recruiting 127 individuals with schizophrenia spectrum disorders and low social functioning. RESULTS: The three-group comparison found SBCBT produced improved social functioning and social support at post-intervention and 6-month follow-up while PSP reported improved social QoL and defeatist beliefs, but none remained at 6-month follow-up. Unsurprising, no improvement was found in any areas for TAU, both at post-test and 6-month follow-up. Regarding mechanisms of change, improvements in hope and personal recovery consistently and significantly accounted for improvements in social functioning and many aspects of QoL of participants, thus indicating the important contribution of hope and personal recovery in strength-based interventions for people with schizophrenia. CONCLUSION: This rigorously designed study provides the first few solid empirical evidence on the effectiveness of SBCBT and PSP in recovery from schizophrenia and provides initial evidence of the linkage between dysfunctional cognition, hope and recovery in schizophrenia.

Testicular Radiomics To Predict Pathology At Time of Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminomatous Germ Cell Tumor.

INTRODUCTION: Testicular germ cell tumors are the most common malignancy in young adult males. Patients with metastatic disease receive standard of care chemotherapy followed by retroperitoneal lymph node dissection for residual masses >1cm. However, there is a need for better preoperative tools to discern which patients will have persistent disease after chemotherapy given low rates of metastatic germ cell tumor after chemotherapy. The purpose of this study was to use radiomics to predict which patients would have viable germ cell tumor or teratoma after chemotherapy at time of retroperitoneal lymph node dissection. PATIENTS AND METHODS: Patients with nonseminomatous germ cell tumor undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) between 2008 and 2019 were queried from our institutional database. Patients were included if prechemotherapy computed tomography (CT) scan and postchemotherapy imaging were available. Semiqualitative and quantitative features of residual masses and nodal regions of interest and radiomic feature extractions were performed by 2 board certified radiologists. Radiomic feature analysis was used to extract first order, shape, and second order statistics from each region of interest. Post-RPLND pathology was compared to the radiomic analysis using multiple t-tests. RESULTS: 45 patients underwent PC-RPLND at our institution, with the majority (28 patients) having stage III disease. 24 (53%) patients had teratoma on RPLND pathology, while 2 (4%) had viable germ cell tumor. After chemotherapy, 78%, 53%, and 33% of patients had cystic regions, fat stranding, and local infiltration present on imaging. After radiomic analysis, first order statistics mean, median, 90th percentile, and root mean squares were significant. Strong correlations were observed between these 4 features;a lower signal was associated with positive pathology at RPND. CONCLUSIONS: Testicular radiomics is an emerging tool that may help predict persistent disease after chemotherapy.

Kinase expression in angiomatoid fibrous histiocytoma: panTRK is commonly expressed in the absence of NTRK rearrangement.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumour of intermediate (rarely metastasising) malignant potential, which harbours EWSR1/FUS gene fusions. These tumours can express anaplastic lymphoma kinase (ALK) in the absence of gene rearrangement or copy number alteration and can also coexpresses Pan-TRK immunohistochemistry (IHC). All EWSR1/FUS-rearranged AFH were retrieved from the files of three institutions and Pan-TRK (EPR17341), ALK and BRAF V600E IHC were performed. Fourteen AFH cases were identified, which included three cases of intracranial mesenchymal tumours with FET-CREB fusions. PanTRK and ALK positive immunostaining was identified in 9 (64.2%) and 12 (85.7%) cases, respectively. No NTRK or ALK translocations or increased copy number/amplification were identified in all eight cases which had fluorescence in situ hybridisation and/or next generation sequencing for NTRK1-3 and ALK available for assessment. None of the cases expressed BRAF-V600E.Although our study is limited, our report is the first to document PanTRK expression in AFH in the absence of identifiable NTRK1-3 gene alterations.

Recurrent Lateral Abdominal Wall Hernias: Options for Reconstruction.

Management of lateral abdominal wall hernias presents a surgical challenge, and best management is controversial. Flank hernias as a surgical sequela occur more commonly, whereas flank hernias resulting from trauma are a rare occurrence. In this article, we present a review of the literature and a case of flank hernia presenting after trauma and recurring after repair. An anchored suture repair was performed and reinforced by the addition of a polyester underlay mesh.

Improved stone quality of life in patients with an obstructing ureteral stone on alpha-blocker medical expulsive therapy.

PURPOSE: Though controversial, alpha blockers are used widely for ureteral stone passage. However, its effects on the patient-reported Quality of life (QOL) is unknown. We compared the QoL of patients on alpha-blocker medical expulsive therapy (MET) to patients not on MET (noMET) utilizing the validated Wisconsin Stone Quality of Life (WISQOL). METHODS: This prospective study included patients prescribed either MET or noMET after presentation with symptomatic, obstructing ureteral stones. The treatment arm was decided at the point of care by the initial treating physician and included analgesia and antiemetics. Tamsulosin (0.4 mg daily) was prescribed for the MET group. The WISQOL survey was administered at baseline, 7-, 14-, 21- and 28-days following discharge from the ED or until stone expulsion. RESULTS: 197 patients were enrolled, of which 116 (59.2%) completed questionnaires for analysis, 91 in the MET group and 25 in noMET. Average ureteral stone size was 4.7 mm (SD 1.8) and 3.1 mm (SD 1.0) for MET and noMET, respectively. Of completed surveys, 105 (90%) were completed at day 7, 67 (57.6%) at day 14, 53 (45.7%) at day 21, and 40 (34.5%) at day 28. MET was associated with improved QoL scores across all WISQOL domains compared to noMET. Stone size, age, race, sex, comorbidity score and a prior stone history were not associated with reduced QoL. CONCLUSIONS: The use of MET was associated with improved QOL on all WISQOL metrics compared to noMET patients. Improved stone QOL may be an indication of alpha-blocker therapy in patients with ureteral stone colic.

Patients' Acceptability and Satisfaction With Teleconsultation for Pelvic Floor Exercises for Stress Urinary Incontinence During COVID-19.

OBJECTIVES: This was the first urogynaecology specialty nurse teleconsultation offered by a public hospital during COVID-19 for learning pelvic floor exercises. This study assessed patients' perception, acceptance, and satisfaction using 2 validated questionnaires. METHODS: In total, 25 patients with stress urinary incontinence attended the teleconsultation via videoconferencing in April 2022, and completed the Telemedicine Perception Questionnaire (TMPQ) and Telemedicine Satisfaction Questionnaire (TSQ). The TMPQ was a 17-item, 5-point Likert scale questionnaire for assessing the acceptability of telemedicine. The TSQ was a 14-item, 5-point Likert scale questionnaire for assessing satisfaction with teleconsultation. The higher the score, the greater the acceptance and satisfaction. Information on demographics, symptom severity by Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7, internet access, and transport arrangements were included. RESULTS: Participants had a mean age of 54.6 ± 7.37 years. Their mean Urogenital Distress Inventory-6 score was 40.60/100 (SD = 17.83) and Impact Questionnaire-7 was 27.90/100 (SD = 19.83). Pre-teleconsultation mean TMPQ score was 59.16 ± 5.78/85. Post-teleconsultation mean score was 64.92 ± 5.21/85, which was 3.64 higher (t = 3.642, df = 24, P = 0.001), indicating a significant increase in positive perception and acceptability. There were fewer concerns with the usage (P = 0.017) and reliability (P = 0.003) of technology, while there was increased agreement that teleconsultation is cost-saving for the health care system (P = 0.003) and offers easier access to health care providers (P = 0.006) after the teleconsultation. Mean TSQ score was 59.85 ± 9.46/70. CONCLUSION: Our pilot study demonstrated positive perception, high acceptability, and satisfaction from patients' first teleconsultation experience. Further multi-centre studies with the inclusion of a control group would help in understanding patients' needs and for service planning.

Optimizing Outcomes in Lymphedema Reconstruction.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe current surgical techniques for treating primary and secondary lymphedema. 2. Optimize the surgical care of patients with lymphedema. SUMMARY: Over the past decade, significant advances have been made in the surgical treatment of lymphedema. The most notable changes have been the reintroduction and evolution of physiologic techniques, including lymphovenous bypass-sometimes referred to as lymphovenous anastomosis in the literature-and vascularized lymph node transplant. These surgical modalities are now often used as first-line surgical options or may be combined with nonphysiologic approaches, including direct excision and suction-assisted lipectomy. Surgeons continue to debate the most appropriate sequence and combination of surgical treatment, particularly for patients at both extremes of the severity spectrum. Furthermore, debate remains around the need to apply different treatment approaches for patients with upper versus lower extremity involvement and primary versus secondary cause. In this article, we provide a summary of the surgical techniques currently used for both primary and secondary lymphedema and provide our recommendations for optimizing the surgical care of patients with lymphedema.