Renal cell carcinoma (RCC) is a kidney neoplasm that accounts for 85% of cases and has complex genetic pathways that affect its development and progression. RCC metastasis can occur in 20%-50% of patients and usually affects distant organs. Gastric metastases (GM) from RCC are rare and present as polyp-like growths in the submucosal layer, accounting for 0.2%-0.7% of cases. This case report describes an 84-year-old female with Furhman grade II ccRCC who presented with an atherothrombotic ischemic stroke and gastrointestinal bleeding nine years post-radical nephrectomy. Gastroscopy revealed a 12mm pseudopedicled gastric lesion with ulceration and bleeding, diagnosed as metastatic ccRCC. The discussion focuses on the rarity, diagnostic challenges, and prognostic elements of gastric metastasis from RCC. The median survival after detecting digestive metastasis varies widely, and the mechanisms include direct invasion and dissemination through lymphatic, transcelomic, or hematogenous routes. Prognostic markers encompass patient history, symptoms, time since RCC diagnosis, overall health, and genetic factors. Surgical removal of gastric lesions and targeted therapy are treatment options that can improve survival. This case report highlights the need for further research to enhance diagnostic and treatment strategies for this rare aspect of RCC pathophysiology.

The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is a diagnostic tool used to help clinicians identify necrotizing fasciitis (NF) in its early stages. This tool uses six laboratory values including the patient\'s white blood cell count, C-reactive protein level, serum sodium level, creatinine level, and hemoglobin level to help with risk stratification. Each of these laboratory values is assigned a point value and the total score is used to determine the likelihood that a patient has NF, with a score of 6 or higher considered to be strongly indicative. The LRINEC score has gained popularity in recent years, having been included in guidelines and society recommendations for the management of NF. However, some studies have challenged the validity of the LRINEC score. Prompt and accurate diagnosis of NF is imperative given the associated mortality rate, which can be as high as 30%-40%, especially if the diagnosis is delayed. We present a case of a patient with a delayed diagnosis of NF that was initially missed in the early stages in the setting of a low LRINEC, however, growing clinical suspicion eventually led to an accurate diagnosis and management.

Introduction Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne zoonotic disease. Sporadic outbreaks of CCHF occur in endemic regions, including Pakistan. The clinical spectrum of the illness varies from asymptomatic seroconversion to severe disease which may end in death. The treatment is supportive, including blood and blood products. There is multi-organ involvement in CCHF including acute hepatitis, thrombocytopenia, coagulopathy, acute kidney injury (AKI), and encephalopathy. Hematological and biochemical parameters may identify patients at substantial risk of worse outcomes. Early detection of the disease and forecasting the clinical course may be helpful. This case series aims to evaluate the trends of hematological and biochemical parameters among the survivors and non-survivors of CCHF. Methods All consecutive patients aged 16 years and above admitted to the isolation unit of Hayatabad Medical Complex, Peshawar, Pakistan between 1st July and 30th July 2022 with the diagnosis of CCHF were included in this case series. The diagnosis of CCHF was made by detecting viral ribonucleic acid by a polymerase chain reaction. For all patients, age, gender, address, occupation, clinical presentation, history of contact with animals, and travel history were recorded. All the vitals were taken regularly. The hematological (complete blood count) and biochemical parameters (serum creatinine, alanine aminotransferase (ALT), and C-reactive protein (CRP)) were documented daily. The blood group was determined for all the cases. Results Out of 17 cases, the majority (16 cases, 94.1%) were male and butchers (eight cases, 47.1%) by profession. All cases had significant contact with animals. Four patients (23.5%) died. Three out of the four non-survivors (75%) had ALT < 5 times the upper limit of normal with a static pattern of liver enzymes without much decline in ALT till death. One non-survivor (25%) had marked elevation of ALT at presentation, which had a declining trend till death. Seven out of 13 survivors (53.8%) had moderate to marked elevation in the level of ALT at presentation. The ALT showed a downward trend during the course of illness in all these patients. The remaining survivors (six out of 13, 46.2%) had a mild elevation of ALT and 50% of them showed improvement in the ALT level during hospitalization. All patients had thrombocytopenia at presentation. None of the non-survivors showed a persistent increase in the platelet count, and three cases remained severely thrombocytopenic at the time of death. However, the trend in platelet count among all the survivors was increasing. The CRP level in the majority (three out of four cases, 75%) of the non-survivors remained elevated till death, while all survivors showed a progressive decline in CRP level. A majority (11 out of 17 cases) had blood group B. Half of the non-survivors (two out of four cases) and the majority of the survivors (nine out of 13 cases) had blood group B. AKI was found in all non-survivors, while all the survivors had normal renal function throughout the course. Conclusion A persistently raised ALT and CRP level, a persistently low or decreasing platelet count, and AKI were associated with mortality. Blood group B was the commonest blood group among patients of CCHF, which is not reflective of the blood group distribution of the general population from which this case series has been reported.

This study aimed to characterise the clinicopathological features and prognostic factors of a large cohort of Hungarian patients with adrenocortical cancer diagnosed between 2000-2021.
This retrospective study included seventy-four patients (27 men and 47 women) with histologically confirmed adrenocortical cancer in a single tertiary referral endocrine centre. Descriptive statistics were performed, providing summaries of selected clinical and pathological parameters. Clinicopathological factors contributing to overall survival were analysed.
The median age of patients was 48,5 years (17-84 years) at diagnosis. The majority of cases were diagnosed at ENSAT stage II (39,2%) and stage IV (33,8%). At diagnosis, the median tumour size was 9,0 cm (4,5-20 cm). In 47 patients (71,6%), the tumour was hormonally active. The median overall survival and the 5-year survival rate were 23,5 months (95% CI, 17-30,5 months) and 18,3%, respectively. Primary tumour resection was performed in 68 patients (91,8%); R0 surgical resection was achieved in 30 patients. In univariate Cox regression model, tumours with stages III and IV, high proliferative activity (Ki67-index > 10%), R1-R2 surgical resection state and hormonal activity were associated with poorer survival. Cortisol excess, both isolated and combined with androgen production, was associated with poorer survival. Fifty-five patients were treated with mitotane. The overall survival of patients achieving therapeutic mitotane plasma concentration was significantly better compared to those who never reached it [27.0 (2-175) months vs 18.0 (2-83) months; p<0.05)]. The median age, the distribution of gender, ENSAT stage, resection state and Ki67-index did not differ between these two groups. The time needed to reach the therapeutic range of serum mitotane was 96.5 days (95% CI, 75-133 days).
Our results confirm previous data that disease stage, mitotic activity, the resection state and the mitotane treatment achieving therapeutic concentration are the most critical parameters influencing the prognosis of adrenocortical cancer. Our data suggest that hormonal activity may be more frequent than described previously, and it is a strong and independent prognostic factor of overall survival. To our knowledge, this is the first single-centre study confirming the prognostic importance of achieving therapeutic mitotane concentration.

Digital health metrics promise to advance the understanding of impaired body functions, for example in neurological disorders. However, their clinical integration is challenged by an insufficient validation of the many existing and often abstract metrics. Here, we propose a data-driven framework to select and validate a clinically relevant core set of digital health metrics extracted from a technology-aided assessment. As an exemplary use-case, the framework is applied to the Virtual Peg Insertion Test (VPIT), a technology-aided assessment of upper limb sensorimotor impairments. The framework builds on a use-case-specific pathophysiological motivation of metrics, models demographic confounds, and evaluates the most important clinimetric properties (discriminant validity, structural validity, reliability, measurement error, learning effects). Applied to 77 metrics of the VPIT collected from 120 neurologically intact and 89 affected individuals, the framework allowed selecting 10 clinically relevant core metrics. These assessed the severity of multiple sensorimotor impairments in a valid, reliable, and informative manner. These metrics provided added clinical value by detecting impairments in neurological subjects that did not show any deficits according to conventional scales, and by covering sensorimotor impairments of the arm and hand with a single assessment. The proposed framework provides a transparent, step-by-step selection procedure based on clinically relevant evidence. This creates an interesting alternative to established selection algorithms that optimize mathematical loss functions and are not always intuitive to retrace. This could help addressing the insufficient clinical integration of digital health metrics. For the VPIT, it allowed establishing validated core metrics, paving the way for their integration into neurorehabilitation trials.

Metastatic clear cell renal cell cancer (mccRCC) portends a poor prognosis and urgently requires better clinical tools for prognostication as well as for prediction of response to treatment. Considerable investment in molecular risk stratification has sought to overcome the performance ceiling encountered by methods restricted to traditional clinical parameters. However, replication of results has proven challenging, and intratumoural heterogeneity (ITH) may confound attempts at tissue-based stratification.
We investigated the influence of confounding ITH on the performance of a novel molecular prognostic model, enabled by pathologist-guided multiregion sampling (n = 183) of geographically separated mccRCC cohorts from the SuMR trial (development, n = 22) and the SCOTRRCC study (validation, n = 22). Tumour protein levels quantified by reverse phase protein array (RPPA) were investigated alongside clinical variables. Regularised wrapper selection identified features for Cox multivariate analysis with overall survival as the primary endpoint.
The optimal subset of variables in the final stratification model consisted of N-cadherin, EPCAM, Age, mTOR (NEAT). Risk groups from NEAT had a markedly different prognosis in the validation cohort (log-rank p = 7.62 × 10-7; hazard ratio (HR) 37.9, 95% confidence interval 4.1-353.8) and 2-year survival rates (accuracy = 82%, Matthews correlation coefficient = 0.62). Comparisons with established clinico-pathological scores suggest favourable performance for NEAT (Net reclassification improvement 7.1% vs International Metastatic Database Consortium score, 25.4% vs Memorial Sloan Kettering Cancer Center score). Limitations include the relatively small cohorts and associated wide confidence intervals on predictive performance. Our multiregion sampling approach enabled investigation of NEAT validation when limiting the number of samples analysed per tumour, which significantly degraded performance. Indeed, sample selection could change risk group assignment for 64% of patients, and prognostication with one sample per patient performed only slightly better than random expectation (median logHR = 0.109). Low grade tissue was associated with 3.5-fold greater variation in predicted risk than high grade (p = 0.044).
This case study in mccRCC quantitatively demonstrates the critical importance of tumour sampling for the success of molecular biomarker studies research where ITH is a factor. The NEAT model shows promise for mccRCC prognostication and warrants follow-up in larger cohorts. Our work evidences actionable parameters to guide sample collection (tumour coverage, size, grade) to inform the development of reproducible molecular risk stratification methods.