Validated machine learning tools to distinguish immune checkpoint inhibitor, radiotherapy, COVID-19 and other infective pneumonitis.

BACKGROUND: Pneumonitis is a well-described, potentially disabling, or fatal adverse effect associated with both immune checkpoint inhibitors (ICI) and thoracic radiotherapy. Accurate differentiation between checkpoint inhibitor pneumonitis (CIP) radiation pneumonitis (RP), and infective pneumonitis (IP) is crucial for swift, appropriate, and tailored management to achieve optimal patient outcomes. However, correct diagnosis is often challenging, owing to overlapping clinical presentations and radiological patterns. METHODS: In this multi-centre study of 455 patients, we used machine learning with radiomic features extracted from chest CT imaging to develop and validate five models to distinguish CIP and RP from COVID-19, non-COVID-19 infective pneumonitis, and each other. Model performance was compared to that of two radiologists. RESULTS: Models to distinguish RP from COVID-19, CIP from COVID-19 and CIP from non-COVID-19 IP out-performed radiologists (test set AUCs of 0.92 vs 0.8 and 0.8; 0.68 vs 0.43 and 0.4; 0.71 vs 0.55 and 0.63 respectively). Models to distinguish RP from non-COVID-19 IP and CIP from RP were not superior to radiologists but demonstrated modest performance, with test set AUCs of 0.81 and 0.8 respectively. The CIP vs RP model performed less well on patients with prior exposure to both ICI and radiotherapy (AUC 0.54), though the radiologists also had difficulty distinguishing this test cohort (AUC values 0.6 and 0.6). CONCLUSION: Our results demonstrate the potential utility of such tools as a second or concurrent reader to support oncologists, radiologists, and chest physicians in cases of diagnostic uncertainty. Further research is required for patients with exposure to both ICI and thoracic radiotherapy.

Modelling the transportation of marine plastics over the ocean surface by Cellular Automata.

This article describes a novel Cellular Automata (CA) model to predict the transportation of buoyant marine plastics. The proposed CA model provides a simpler and more affordable approach to a field where the computationally intensive Lagrangian particle-tracking models dominate. The transportation of marine plastics was investigated using well-defined, probabilistic rules governing the advection and diffusion processes. The CA model was applied to evaluate the impact of two input scenarios, namely a "population" and a "river" scenario. Of the sub-tropical gyres, a high percentage of buoyant plastics were found in the Indian gyre (population: 5.0 %; river: 5.5 %) and North Pacific gyre (population: 5.5 %; river: 7 %). These findings show good agreement with previously published results from particle-tracking models. The CA model could be a useful rapid-scenario assessment tool for the estimation marine plastic pollution prior to more in-depth studies on effective mitigation measures to, for example, reduce plastics waste.

Virtual reality and surgical oncology.

More than 80% of people diagnosed with cancer will require surgery. However, less than 5% have access to safe, affordable and timely surgery in low- and middle-income countries (LMICs) settings mostly due to the lack of trained workforce. Since its creation, virtual reality (VR) has been heralded as a viable adjunct to surgical training, but its adoption in surgical oncology to date is poorly understood. We undertook a systematic review to determine the application of VR across different surgical specialties, modalities and cancer pathway globally between January 2011 and 2021. We reviewed their characteristics and respective methods of validation of 24 articles. The results revealed gaps in application and accessibility of VR with a proclivity for high-income countries and high-risk, complex oncological surgeries. There is a lack of standardisation of clinical evaluation of VR, both in terms of clinical trials and implementation science. While all VR illustrated face and content validity, only around two-third exhibited construct validity and predictive validity was lacking overall. In conclusion, the asynchrony between VR development and actual global cancer surgery demand means the technology is not effectively, efficiently and equitably utilised to realise its surgical capacity-building potential. Future research should prioritise cost-effective VR technologies with predictive validity for high demand, open cancer surgeries required in LMICs.

Metastatic cancer masquerading as miliary tuberculosis in an immunocompetent young adult.

A healthy, immunocompetent South Asian man in his mid-20s, with a medical history of gastric ulcer, presented to Accident & Emergency with pleuritic chest pain, shortness of breath, fever, night sweats, weight loss, dry cough and asymptomatic iron deficiency anaemia. Following his initial assessment and investigations (chest X-ray, CT and blood tests), a diagnosis of miliary tuberculosis (TB) was made and empirical antimicrobial treatment started. However, subsequent microbiological testing, including urine, blood, induced sputum and lymph node sampling, was negative. Being interpreted as non-diagnostic, the antimicrobial therapy was continued. Following a clinical deterioration while on treatment, the patient's case was re-evaluated and further investigations, including a repeat CT and a liver biopsy, confirmed a diagnosis of stage IV (T1aN3bM1) gastric carcinoma. Our case highlights the diagnostic challenges in differentiating metastatic cancer from miliary TB. We also focus on possible cognitive biases that may have influenced the initial management decisions.

Acute to Subacute Atraumatic Entrapment Neuropathies in Patients With CMT1A: A Report of a Distinct Phenotypic Variant of CMT1A.

Charcot-Marie-Tooth type 1A (CMT1A) is typically characterised as a childhood-onset, symmetrical, length-dependent polyneuropathy with a gradual progressive clinical course. Acute to subacute neurological deterioration in CMT1A is rare, and has been reported secondary to overlap pathologies including inflammatory neuropathy. We identified two patients with CMT1A who presented with acute to subacute, atraumatic, entrapment neuropathies as an initial symptom. A superimposed inflammatory neuropathy was excluded. Both patients had a diffuse demyelinating polyneuropathy, with markedly low motor nerve conduction velocities (<20 m/s). In both patients, we demonstrated symptomatic and asymptomatic partial conduction blocks at multiple entrapment sites. Nerve ultrasound findings in our patients demonstrated marked diffuse nerve enlargement, more pronounced at non-entrapment sites compared to entrapment sites. We discuss ways to distinguish this condition from its other differentials. We propose pathophysiological mechanisms underlying this condition. We propose that CMT1A with acute to subacute, atraumatic, entrapment neuropathies to be a distinct phenotypic variant of CMT1A.

Risk factors for lumbosacral radiculoplexus neuropathy.

INTRODUCTION/AIMS: Recently, our group found an association between diabetes mellitus (DM) and lumbosacral radiculoplexus neuropathy (LRPN) in Olmsted County, Minnesota; we found a higher risk (odds ratio [OR], 7.91) for developing LRPN in diabetic compared with nondiabetic patients. However, the influence of other comorbidities and anthropomorphic variables was not studied. METHODS: Demographic and clinical data from 59 LRPN patients and 177 age/sex-matched controls were extracted using the Rochester LRPN epidemiological study. Differences between groups were compared by chi-square/Fisher exact test or Wilcoxon rank-sum test. Uni- and multivariate logistic regression analysis were performed. RESULTS: Factors predictive of LRPN on univariate analysis were DM (OR, 7.91; 95% confidence interval [CI], 4.11-15.21), dementia (OR, 6.36; 95% CI, 1.13-35.67), stroke (OR, 3.81; 95% CI, 1.32-11.01), dyslipidemia (OR, 2.844; 95% CI, 1.53-5.27), comorbid autoimmune disorders (OR, 2.72; 95% CI, 1.07-6.93), hypertension (OR, 2.25; 95% CI, 1.2-4.13), obesity (OR, 2.05; 95% CI, 1.11-3.8), body mass index (BMI) (OR, 1.1; 95% CI, 1.04-1.15), and weight (OR, 1.02; 95% CI, 1.009-1.037). On multivariate logistic regression analysis only DM (OR, 8.03; 95% CI, 3.86-16.7), comorbid autoimmune disorders (OR, 4.58; 95% CI, 1.45-14.7), stroke (OR, 4.13; 95% CI, 1.2-14.25), and BMI (OR, 1.07; 95% CI, 1.01-1.13) were risk factors for LRPN. DISCUSSION: DM is the strongest risk factor for the development of LRPN, followed by comorbid autoimmune disorders, stroke, and higher BMI. Altered metabolism and immune dysfunction seem to be the most influential factors in the development of LRPN.

Hereditary Transthyretin Amyloidosis- Clinical and Genetic Characteristics of a Multiracial South-East Asian Cohort in Singapore.

BACKGROUND AND AIMS: Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort. METHODS: Patients with genetically proven ATTRv amyloidosis were identified over a 13-year period (2007-2020) at the National Neuroscience Institute, Singapore. Clinical, laboratory, genotypic and electrophysiological features were retrospectively reviewed. RESULTS: 29 patients comprising Chinese, Malay, Burmese, Vietnamese and Indonesians with ATTRv amyloidosis were identified. Somatic neuropathy was the most common initial presentation, followed by carpal tunnel syndrome, autonomic dysfunction and cardiac dysfunction. ATTR-A97S (p.Ala117Ser) was the most common variant found in 14 patients, constituting 66.7%of ethnic Chinese patients and 48.3%of the entire cohort. Five patients had early-onset disease (age < 50 years) with the following variants: ATTR-V30M (p.Val50Met), ATTR-G47A (p.Gly67Ala), ATTR-S50I (p.Ser70Ile) and ATTR-A97S (p.Ala117Ser); one patient with ATTR-A97S (p.Ala117Ser) had isolated unilateral carpal tunnel syndrome with amyloid deposits identified on histological examination of the transverse carpal ligament. All early-onset patients had a positive parental history; two patients, with ATTR-S50I (p.Ser70Ile) and ATTR-Ala97Ser (p.Ala117Ser) respectively, demonstrated anticipation with mother-to-daughter inheritance. Amongst the 24 patients with late-onset disease (age≥50 years), two patients had novel variants, ATTR-G66D (p.Glu86Asp) and ATTR-A81V (p.Ala101Val) that were confirmed to be pathogenic based on the histological identification of transthyretin amyloid. Other identified variants included ATTR-V30M (p.Val50Met), ATTR-R34T (p.Arg54Thr), ATTR-S50I (p.Ser70Ile), ATTR-H88R (p.His108Arg) and ATTR-A97S (p.Ala117Ser). CONCLUSION: Our study further expands the genotypic and phenotypic knowledge regarding ATTRv amyloidosis.

Lumbosacral Radiculoplexus Neuropathy: Neurologic Outcomes and Survival in a Population-Based Study.

OBJECTIVE: To determine whether patients in the community with lumbosacral radiculoplexus neuropathy (LRPN) have milder neuropathy than referral patients, we characterized the outcomes and survival of population-based compared to referral-based LRPN cohorts. BACKGROUND: Previously, we found that the incidence of LRPN is 4.16/100,000/y, a frequency greater than other inflammatory neuropathies. The survival of patients with LRPN is uncharacterized. METHODS: Sixty-two episodes in 59 patients with LRPN were identified over 16 years (2000-2015). Clinical findings were compared to previous referral-based LRPN cohorts. Survival data were compared to those of age- and sex-matched controls. RESULTS: At LRPN diagnosis, median age was 70 years, median Neuropathy Impairment Score (NIS) 22 points, 92% had pain, 95% had weakness, 23% were wheelchair-bound, and median modified Rankin Scale score (mRS) was 3 (range 1-4). At last follow-up, median NIS improved to 17 points (p < 0.001) with 56% having ≥4 points improvement, 16% were wheelchair-bound, and median mRS was 2. Compared to referral-based LRPN cohorts, community patients with LRPN had less impairment, less bilateral disease (37% vs 92%), and less wheelchair usage (23% vs 49%). LRPN survival was 86% at 5 years and 55% at 10 years. Compared to age- and sex-matched controls, patients with LRPN had 76% increased risk of death (p = 0.016). In multivariate analysis, diabetes, age, stroke, chronic kidney disease, peripheral artery disease, and coronary artery disease were significant mortality risk factors but LRPN was not. CONCLUSION: LRPN is a painful, paralytic, asymmetric, monophasic, sometimes bilateral pan-plexopathy that improves over time but leaves patients with impairment. Although having LRPN increases mortality, this increase is probably due to comorbidities (diabetes) rather than LRPN itself.

Lumbosacral radiculoplexus neuropathy: Incidence and the association with diabetes mellitus.

OBJECTIVE: To determine the previously unknown incidence of lumbosacral radiculoplexus neuropathy (LRPN) and its association with diabetes mellitus (DM). METHODS: LRPN defined by clinical and electrophysiologic criteria was identified among Olmsted County, Minnesota, residents during a 16-year period (2000-2015) using the unique facilities of the Rochester Epidemiology Project. DM was ascertained using American Diabetes Association criteria. RESULTS: Of 1,892 medical records reviewed, 59 patients (33 men, 26 women) were identified as having LRPN. The median age was 70 years (range 24-88 years) and the median time of onset of symptoms to diagnosis was 2 months (range 1-72 months). DM was more frequent in patients with LRPN than in controls (39/59 vs 35/177, p < 0.001) but not in those with pre-DM (10/20 vs 55/142, p = 0.336). LRPN recurred in 3 patients with DM resulting in 62 LRPN episodes during the study period. The overall incidence of LRPN was 4.16/100,000/y (95% confidence interval [CI] 3.13-5.18). The incidences of LRPN among DM and non-DM groups were 2.79/100,000/y (95% CI 1.94-3.64) and 1.27/100,000/y (95% CI 0.71-1.83), respectively. The odds of LRPN among patients with DM and pre-DM was 7.91 (95% CI 4.11-15.21) and 1.006 (95% CI 1.004-1.012), respectively. CONCLUSIONS: LRPN incidence in Olmsted County of 4.16/100,000/y makes LRPN a common inflammatory neuropathy and is higher than that of other immune-mediated neuropathies (acute or chronic inflammatory demyelinating polyradiculoneuropathy, brachial plexus neuropathy) assessed within the same population. DM is a major risk factor for LRPN and thus justifies the continued classification of LRPN into diabetic and nondiabetic forms.

Predictors of thyroxine replacement following hemithyroidectomy in a south east Asian cohort.

BACKGROUND: Thyroxine replacement following a hemithyroidectomy is not commonly discussed during consent for the procedure as the risk of hypothyroidism is perceived to be low. METHODS: Retrospective review of 901 patients who underwent hemithyroidectomy at a tertiary referral institution during the period January 2000 to December 2015. The main outcome studied was the overall incidence of hypothyroidism and the associated risk factors. RESULTS: Hypothyroidism developed in 123 (13%) patients and 94 patients (10%) required hormone supplementation over a mean follow up of 21 months (range 1-168 months). Preoperative TSH of more than 2.5 was seen in 38 of 123 (31%) of patients. Presence of diffuse thyroiditis was the only independent risk factor on multivariate analysis (P = 0.002) found to be associated with the development of hypothyroidism. CONCLUSION: After thyroid lobectomy, approximately one in 10 patients requiring thyroid hormone treatment for hypothyroidism. Presence of diffuse thyroiditis is a significant risk factor for hypothyroidism.

A dysmorphic newborn with petechiae and a 'Big Heart'.

A male fetus was noted to have an isolated pericardial effusion. At birth, he had dysmorphic features of Down syndrome and extensive petechiae. He was diagnosed to have transient myeloproliferative disorder. The large pericardial effusion and TMD spontaneously resolved. At 4 years of age, he was diagnosed with acute megakaryoblastic leukaemia, underwent chemotherapy and achieved complete remission.

Monitoring of physiological parameters from multiple patients using wireless sensor network.

This paper presents a wireless sensor network system that has the capability to monitor physiological parameters from multiple patient bodies. The system uses the Medical Implant Communication Service band between the sensor nodes and a remote central control unit (CCU) that behaves as a base station. The CCU communicates with another network standard (the internet or a mobile network) for a long distance data transfer. The proposed system offers mobility to patients and flexibility to medical staff to obtain patient's physiological data on demand basis via Internet. A prototype sensor network including hardware, firmware and software designs has been implemented and tested. The developed system has been optimized for power consumption by having the nodes sleep when there is no communication via a bidirectional communication.

A wireless medical monitoring over a heterogeneous sensor network.

This paper presents a heterogeneous sensor network system that has the capability to monitor physiological parameters from multiple patient bodies by means of different communication standards. The system uses the recently opened medical band called MICS (Medical Implant Communication Service) between the sensor nodes and a remote central control unit (CCU) that behaves as a base station. The CCU communicates with another network standard (the internet or a mobile network) for a long distance data transfer. The proposed system offers mobility to patients and flexibility to medical staff to obtain patient's physiological data on demand basis via Internet. A prototype sensor network including hardware, firmware and software designs has been implemented and tested by incorporating temperature and pulse rate sensors on nodes. The developed system has been optimized for power consumption by having the nodes sleep when there is no communication via a bidirectional communication.

Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX adjuvant in women with cervical intraepithelial neoplasia.

PURPOSE: Persistent infection of cervical epithelium with "high risk" human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX adjuvant (HPV16 Immunotherapeutic) for patients with CIN. EXPERIMENTAL DESIGN: Patients with CIN (n = 31) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. RESULTS: Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. CONCLUSIONS: The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX adjuvant is safe and induces vaccine antigen specific cell mediated immunity.