Lymphatic expression of the proliferation marker Ki67 is linked to sentinel node positivity, recurrence and mortality in primary cutaneous melanoma.

Lymphangiogenesis is a precursor to lymphovascular invasion, and may therefore signal a higher risk of metastasis and mortality in primary cutaneous melanoma. This retrospective longitudinal study aimed to evaluate whether emergent lymphangiogenesis, as measured through co-expression of endothelial proteins with the proliferation marker Ki67, was associated with poorer prognosis in a cohort of patients with single primary cutaneous melanoma. We screened all patients with a single locally invasive primary cutaneous melanoma who received sentinel lymph node biopsy at a tertiary dermatology centre in Brisbane, Australia between 1994 and 2007. Primary melanoma sections were stained via Opal multiplex immunofluorescence, and categorized according to the presence of Ki67 within either CD31+ or D2-40+ endothelial cells. Multivariate Cox regression modelling was used to evaluate associations between endothelial Ki67 positivity and clinical outcomes, with adjustment for age, sex, Breslow depth, ulceration, and anatomical location. Overall, 264 patients were available for analysis, with a median follow-up duration of 7.1 years. The presence of D2-40+ /Ki67+ co-expression was associated with greater melanoma-specific mortality (adjusted hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.33-3.10; p = 0.001) and recurrence (adjusted HR: 1.70; 95% CI: 1.33-3.10; p = 0.001) relative to absence. CD31+ /Ki67+ co-expression was not prognostic in this cohort. Lymphatic proliferation, as measured through D2-40+ /Ki67+ co-expression, predicted greater melanoma-specific mortality and recurrence in this cohort of primary cutaneous melanoma.

Cat-scratch disease masquerading as post-transplant lymphoproliferative disorder.

Lymphadenopathy in an immunosuppressed patient raises the quintessential diagnostic dilemma: infection or malignancy? We present the case of a transplant recipient on anti-rejection prophylaxis admitted with acute fever, malaise and a swollen right axillary node. The patient had pancytopenia and tested positive for Epstein-Barr virus; nodal core biopsy demonstrated atypical plasma cell infiltration, immediately raising suspicion for post-transplant lymphoproliferative disorder. However, excisional biopsy and Bartonella henselae serology clarified a final diagnosis of cat-scratch disease-a potentially fatal zoonosis requiring a disparate treatment regimen. Here, we explore this patient's investigations, hospital course and recovery, with an emphasis on recognizing and differentiating these diagnostic mimics in post-transplant practice.

pSTAT5 is associated with improved survival in patients with thick or ulcerated primary cutaneous melanoma.

Identifying prognostic biomarkers to predict clinical outcomes in stage I and II cutaneous melanomas could guide the clinical application of adjuvant and neoadjuvant therapies. We aimed to investigate the prognostic value of phosphorylated signal transducer and activator of transcription 5 (pSTAT5) as a biomarker in early-stage melanoma. This study evaluated all initially staged Ib and II melanoma patients undergoing sentinel node biopsy at a tertiary centre in Brisbane, Australia between 1994 and 2007, with survival data collected from the Queensland Cancer Registry. Primary melanoma tissue from 189 patients was analysed for pSTAT5 level through immunohistochemistry. Cox regression modelling, with adjustment for sex, age, ulceration, anatomical location, and Breslow depth, was applied to determine the association between pSTAT5 detection and melanoma-specific survival. Median duration of follow-up was 7.4 years. High pSTAT5 detection was associated with ulceration and increased tumour thickness. However, multivariate analysis indicated that high pSTAT5 detection was associated with improved melanoma-specific survival (hazard ratio: 0.15, 95% confidence interval: 0.03-0.67) as compared to low pSTAT5 detection. This association persisted when pSTAT5 detection was limited to immune infiltrate or the vasculature, as well as when sentinel node positivity was accounted for. In this cohort, staining for high-pSTAT5 tumours identified a subset of melanoma patients with increased survival outcomes as compared to low-pSTAT5 tumours, despite the former having higher-risk clinicopathological characteristics at diagnosis. pSTAT5 is likely an indicator of local immune activation, and its detection could represent a useful tool to stratify the risk of melanoma progression.

Symptomatic scrotal-inguino-retroperitoneal lymphocele in a kidney transplant patient-to drain but how to drain?

Scrotal-inguino-retroperitoneal (SIR) lymphocele is a rare complication following kidney transplant. This entity is characterized by a tract originating in the retroperitoneal space, through the inguinal canal and scrotum following lymph hydrodissection. Systematic review investigating SIR lymphocele yielded cases with open fenestration of the sac into the peritoneum as treatment. We described a case report of a male in his 60s with a functioning kidney transplant and SIR lymphocele, which was successfully managed in the short term with percutaneous drainage of the collection. However, the collection recurred and computed tomography scan showed a multiloculated collection that prompted surgical management. Intraoperatively, the encapsulated fluid-filled tract was excised and a drain was placed, which was removed 48 h later. The patient wore a hernia belt for 6 weeks as support. He had no recurrence of his lymphocele following serial reviews for 9 months now.

State-Level Prevalence and Associates of Opioid Dependence in the USA.

Traditionally, opioid-related disease burden was primarily due to heroin use. However, increases in extra-medical (or non-medicinal use of prescription opioids; NMPOs) use has precipitated the current overdose epidemic in North America. We aim to examine the state-level prevalence of heroin and NMPO dependence and their associations with opioid-related mortality and state-level socio-demographic profiles. Data were pooled from the 2005-2014 National Survey on Drug Use and Health (NSDUH). We examine opioid-related mortality from CDC WONDER (Cause of Death database) by the past year prevalence of DSM-IV heroin and NMPO dependence, by age and sex, and their associations with state-level socio-demographic characteristics from census data. State-level rates of heroin dependence were associated with opioid-related death rates in young and mid-aged adults, while rates of NMPO dependence were associated with opioid-related death rates across all ages. The prevalence of heroin dependence was positively associated with state-level GDP/capita and urbanity. State-level NMPO dependence prevalence was associated with higher unemployment, lower GDP/capita, and a lower high-school completion rate. The prevalence of heroin and NMPO dependence are associated with a broad range of geographical and socio-demographic groups. Taking a wider view of populations affected by the opioid epidemic, inclusive interventions for all are needed to reduce opioid-related disease burden.

Exploring Symptom Fluctuations and Triggers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Novel Patient-Centred N-of-1 Observational Designs: A Protocol for a Feasibility and Acceptability Study.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition of unknown aetiology associated with a range of disabling symptoms, including post-exertional malaise, chronic fatigue, musculoskeletal pain, orthostatic intolerance, unrefreshing sleep, and cognitive dysfunction. ME/CFS is a heterogeneous disorder, with significant variation in symptom type and severity between individuals, as well as within individuals over time. The diversity of ME/CFS symptom presentation makes management challenging; treatments supported by data from randomised controlled trials may not work for all individuals due to the variability in experienced symptoms. Studies using quantitative N-of-1 observational designs involve repeated outcome measurements in an individual over time and can generate rigorous individual-specific conclusions about symptom patterns and triggers in individuals with ME/CFS. This study aims to explore the feasibility and acceptability of using novel patient-centred N-of-1 observational designs to explore symptom fluctuations and triggers in ME/CFS at the individual level. METHODS AND ANALYSIS: Individuals with a medical diagnosis of ME/CFS will be recruited through ME/CFS patient organisations to participate in a series of patient-centred N-of-1 observational studies. Using a wrist-worn electronic diary, participants will complete ecological momentary assessments of fatigue, stress, mood, and cognitive demand, three times per day for a period of 6-12 weeks. Personally relevant symptoms and triggers will also be incorporated into the questionnaire design. Physical activity will be objectively measured via an integrated accelerometer. Feasibility and acceptability outcomes will be assessed including the percentage of diary entries completed, as well as recruitment and retention rate, feasibility of analysing and interpreting the data collected, and participant views about participation elicited via a post-study semi-structured interview. DISCUSSION: This study will assess the feasibility and acceptability of patient-centred N-of-1 observational studies to assess diseases with complex presentations such as ME/CFS, as well as provide individual-level evidence about fluctuations and triggers of ME/CFS symptoms that may aid self-management. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12618001898246. Registered on 22 November 2018.

A critical decision point: Short- and long-term outcomes of older surgical patients admitted to a Queensland intensive care unit.

OBJECTIVES: Critical care admission is a pivotal juncture for older patients undergoing surgery. We aimed to identify the in-hospital and postdischarge outcomes of older postsurgical patients (≥65 years) admitted to the intensive care unit (ICU). METHODS: We collected clinical, morbidity and survival data on all patients aged ≥65 years postsurgically admitted to a tertiary metropolitan ICU between 2014 and 2019. RESULTS: Within this older cohort (n = 370), the oldest patients (≥85 years) had the highest 1-year mortality (RR: 4.00; P < 0.001). Major surgery (RR: 5.67; P < 0.001), emergency surgery (RR: 2.89; P < 0.001) and APACHE III score ≥50 (RR: 2.63; P < 0.001) were associated with reduced 1-year survival. CONCLUSIONS: APACHE III score and surgery subtype are strong predictors of post-ICU mortality and may be useful to preoperatively stratify whether surgery and subsequent ICU admission are in patients' best interests. These data may also inform prospective discussions regarding end-of-life care and advanced care planning.

Comparing pregabalin and gabapentin for persistent neuropathic pain: A protocol for a pilot N-of-1 trial series.

BACKGROUND: Evidence-based management of neuropathic pain is commonly ineffective due to the large variability in response between cases. Patients often have to trial several drugs before finding one that provides adequate relief, leading to increased costs and worsened outcomes. There is thus a need for tools to guide and streamline prescribing decisions in neuropathic pain. N-of-1 trials provide a potentially precise and economical method of selecting between multiple interventions in an individual patient, and merit a feasibility assessment for use in clinical pain practice. AIMS: We aim to evaluate the feasibility of N-of-1 trials to compare pregabalin and gabapentin for individual presentations of neuropathic pain. METHODS: This is a double-blinded multiple crossover study, with recruitment from existing patients at an outpatient pain clinic in New South Wales, Australia. Participants will undergo three 4-week treatment pairs, comprising 2 weeks of pregabalin (150-600 mg/day) and 2 weeks of gabapentin (900-3600 mg/day), in an individually randomised order. Intervention doses will be derived from participants' existing treatment dose. Medications will be taken orally three times daily. The primary outcome will be pain intensity; measures will be self-reported daily in patient diaries. After completing all three cycles, participants and their physicians will be presented with the results of the trial to form an informed decision about their treatment. DISCUSSION: As a stable yet debilitating condition, neuropathic pain is especially amenable to an N-of-1 study design. A successful trial would represent a significant quality of life improvement for the patient, possibly extending over the course of their lifetime.

A delicate balance: Psychotropic polypharmacy and anti-cholinergic use are correlated with fall incidence in Australian inpatients with dementia.

BACKGROUND: Persons with dementia commonly experience a range of behavioural and psychological symptoms, including agitation, aggression, perceptual disturbances, and depression. While psychotropic medications are regularly prescribed to mitigate these symptoms, these agents also carry a broad adverse effect profile. This study aimed to characterize psychotropic medication use in patients with dementia, as well as identify prescribing factors associated with falls in this cohort. METHODS: This retrospective study collected longitudinal demographic and medication data from all patients admitted to a neuro-cognitive unit at an Australian metropolitan hospital over a 2-year period. Psychotropic polypharmacy and psychotropic agent use per patient-fortnight were investigated for their association with inpatient falls. RESULTS: All patients (n = 147) were prescribed at least one psychotropic medication, with 96% receiving anti-psychotic medications and 90% receiving benzodiazepines. Patient fall rate was significantly associated with anticholinergic drug use (Incidence rate ratio: 2.2; P < .001), as well as concomitant use of ≥5 daily psychotropic agents (Incidence rate ratio: 3.1; P = .001). CONCLUSIONS: Patients with dementia are routinely prescribed a wide variety of psychotropic medications. Use of anticholinergic drugs and psychotropic polypharmacy are correlated with fall incidence in persons with dementia.