Narrative review of prostate cancer grading systems: will the Gleason scores be replaced by the Grade Groups?

The Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic approaches. In particular, in the 2014 Conference, it was recognized that there were weaknesses with the original and the 2005 ISUP modified Gleason systems. Based on the results of a research conducted by Prof. JI Epstein and his group, a new grading system was proposed by the ISUP in order to address some of such deficiencies: i.e., the five distinct Grade Groups (GGs). Since 2014, results of studies have been published by different groups and societies, including the Genitourinary Pathology Society (GUPS), giving additional support to the prognostic role of the architectural Gleason patterns and, in particular, of the GGs. A revised GG system, taking into account the percentage of Gleason pattern (GP) 4, cribriform and intraductal carcinoma, tertiary GP 5, and reactive stroma grade, has shown to have some advantages, however not ready for adoption in the current practice. The aim of this contribution was to review the major updates and recommendations regarding the GPs and GSs, as well as the GGs, trying to give an answer to the following questions: “How has the grade group system been used in the routine?” and “will the Gleason scoring system be replace by the grade groups?” We also discussed the potential implementation in the future of molecular pathology and artificial intelligence in grading to further define risk groups in patients with PCa.     

Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review

In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.     

Public health challenges and opportunities after COVID-19

With hindsight, the main weakness behind the ineffective response to the coronavirus disease 2019 (COVID-19) pandemic in some countries has been the failure to understand, and take account of, the multilayered systemic interdependencies that spread the effects of the pandemic across social, technological, economic and health-care dimensions. For example, to respond to the COVID-19 pandemic, all people were required to rapidly adjust to social distancing and travel restrictions. Such a complex behavioural response entails adaptation to achieve a full recovery from the systemic shock. To capitalize on the positive effects of disruption to the status quo, much more complex socioeconomic modelling needs to be considered when designing and evaluating possible public health interventions that have major behavioural implications. We provide a simple example of how this reasoning may highlight generally unacknowledged connections and interdependencies and guide the construction of scenarios that can inform policy decisions to enhance the resilience of society and tackle existing societal challenges.     

Pneumonectomy for benign disease

Pneumonectomy for benign disease of the lung is a rather infrequent intervention. A retrospective study based on 1900 pulmonary resections performed in our institute up to 1998, identified a total of 15 patients submitted to pneumonectomy for non-neoplastic disease. Indications were chronic infections in 11 cases, congenital malformations in 2 cases, left primary bronchial stenosis caused by closed thoracic trauma one in case and gunshot wound in one case. Access to the lung was obtained in all cases by a classic postero-lateral thoracotomy: intra-pericardial ligature was required in five cases and in one patient an extrapleural pneumonectomy was performed. The intra-operative mortality was 20% and the average time of hospitalization 27 days. One patient, operated for pulmonary tuberculosis, developed a broncopleural fistula requiring a second operation. In conclusion, the use of pneumonectomy for non-neoplastic diseases presents serious problems and may be associated with major complications.     

Association between large aortic arch atheromas and high-intensity transient signals in elderly stroke patients

BACKGROUND AND PURPOSE: Aortic arch atheromas (AAs) have been shown to be a risk factor for ischemic stroke (IS) in the elderly because of their potential for cerebral embolization. However, the association between AAs and the presence of cerebral microemboli has not been clearly established. The aim of this study was to determine whether large AAs are associated with an increased frequency of high-intensity transient signals (HITS) in elderly patients with IS. METHODS: We performed bitemporal simultaneous HITS monitoring of both middle cerebral arteries in 62 consecutive elderly patients with acute IS (mean age 72.5+/-8.8 years, 65% men). In 16 patients, one or both temporal windows were inadequate; therefore, the analysis of HITS was performed in the remaining 46 patients. All patients underwent omniplane transesophageal echocardiography (TEE), and they had no significant extracranial or intracranial artery disease and no cardiac prosthetic valves. Large AA was defined as > or = 4 mm in thickness. Complex AA was defined as ulcerated or mobile, regardless of plaque thickness. HITS monitoring was performed within 24 hours of TEE and analyzed by an experienced neurologist-sonographer blinded to TEE findings. A 9-dB threshold was chosen to discriminate HITS from background Doppler signal. The HITS counts in the left and in the right middle cerebral arteries were added and reported as a total number of HITS in 30 minutes. RESULTS: HITS were detected in 14 (78%) of 18 patients with large AAs versus 8 (29%) of 28 patients with no or small AAs (odds ratio [OR] 8.8, 95% CI 2.2 to 34.8; P=0. 001). The association was also present in 27 patients with no other cardiac embolic sources, such as atrial fibrillation, patent foramen ovale, spontaneous echo contrast, and thrombus (7 of 10 patients with large AAs versus 3 of 17 patients with small or no AA; OR 10.9, 95% CI 1.7 to 68.5; P=0.013). Complex AAs were associated with a higher frequency of HITS than were noncomplex AAs (6 of 6 patients with complex AAs versus 15 of 39 patients with noncomplex AAs; OR 2. 6, 95% CI 1.7 to 3.9; P=0.005). CONCLUSIONS: HITS are significantly associated with large AAs in elderly stroke patients. This observation may support the causal role of large AAs in IS.     

TRISS unexpected survivors--a statistical phenomenon or a clinical reality?

Data from patients treated in Pennsylvania-accredited trauma centers during 1989 were analyzed. TRISS expected and unexpected survivors (1.6% of all survivors) differed in many ways. Unexpected survivors were more than twice as likely to have been transferred from a nondesignated trauma center (45.8% vs. 22.8%, p < 0.001). Unexpected survivors had significantly higher frequencies of motor vehicle injuries (56.2% vs. 38.3%, p < 0.001), pedestrian injuries (9.6% vs. 5.4%, p < 0.01), and gunshot wounds (7.3% vs. 4.7%, p < 0.01). Expected survivors were injured more frequently in falls (26.1% vs. 10.8%, p < 0.001) and were less frequently male (64.5% vs. 75%, p < 0.001). Unexpected survivors had significantly longer average hospital stay (29.6 s vs. 9.3 days, p < 0.001) and more frequent (98.8% vs. 36.8%, p < 0.001) and longer average stays in the ICU (13.3 s vs. 4.1 days, p < 0.001). The percentage of unexpected survivors discharged to rehabilitation centers (61.9%) was significantly greater than that for expected survivors (8.7%), (p < 0.001). Unexpected survivors were more frequently judged "completely dependent" in five measures of functional disability than expected survivors. We conclude that unexpected survivors are a seriously injured and clinically relevant patient set, not just a statistical phenomenon.     

Predictors of resource use after acute hospitalization: the Northern Manhattan Stroke Study

OBJECTIVE: To determine demographic and clinical predictors of discharge destinations following acute care hospitalization for stroke in the community of northern Manhattan. METHODS: A group of 893 patients (mean age, 70 +/- 12 years; 56% women; 51% Hispanic, 30% African-American, 19% white) who survived acute care hospitalization for a first ischemic stroke were followed prospectively. Stroke severity was assessed by the NIH Stroke Scale and categorized as mild (< or = 5), moderate (6 to 13), and severe (> or = 14). Polytomous logistic regression was used to determine predictors for rehabilitation and nursing home placement versus returning home. RESULTS: Among the survivors of acute stroke care hospitalization, 611 (68%) patients were discharged to their homes, 168 (19%) to rehabilitation, and 114 (13%) to nursing homes. Patients with moderate and severe neurologic deficits had more than a threefold increased risk of being sent to a nursing home and more than an eightfold increased risk of being sent to rehabilitation. Age over 65 and cognitive impairment were associated with placement to a nursing home (age over 65: OR, 2.4; 95% CI, 1.0 to 5.6; cognitive impairment: OR, 2.9; 95%, CI 1.4 to 5.7), and rehabilitation (age over 65: OR, 1.8; 95% CI, 1.1 to 2.9; cognitive impairment: OR, 2.9; 95% CI, 1.4 to 5.7). CONCLUSION: Our results demonstrated that one-third of patients with acute stroke from the community of northern Manhattan required placement in a temporary or a long-term disability care institution following acute care hospitalization. Severity of stroke is an important factor that influences discharge planning following acute care hospitalization and its reduction can improve health care resource usage.     

Chlamydia pneumoniae and the risk of first ischemic stroke : The Northern Manhattan Stroke Study

BACKGROUND AND PURPOSE: Serological evidence of infection with Chlamydia pneumoniae has been associated with cardiovascular disease in multiple epidemiological studies. The data on its association with ischemic stroke are limited. We sought to determine whether chronic C pneumoniae infection is associated with ischemic stroke in a multi-ethnic population. METHODS: The Northern Manhattan Stroke Study contains a population-based, case-control study component. Cases had first ischemic stroke and matched control subjects were derived through random digit dialing. Titers of IgG, IgA, and IgM antibodies specific for C pneumoniae were measured with the use of microimmunofluorescence, and titers >/=1:16 were considered positive. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjustment for medical, behavioral, and socioeconomic factors. RESULTS: Eighty-nine cases and 89 control subjects were selected. Mean age among cases was 68.5+/-12.8 years; 53% were women and 15% of the subjects were white, 28% were black, and 54% were Hispanic. Elevated C pneumoniae IgA titers were significantly associated with risk of ischemic stroke after adjusting for other stroke risk factors (adjusted OR 4. 51, 95% CI 1.44 to 14.06). IgG titers were less strongly associated with stroke risk (adjusted OR 2.59, 95% CI 0.87 to 7.75). The association of IgA with stroke risk was detected in both younger and older groups, in men and women, and in whites, blacks, and Hispanics. There was also a significant continuous increase in risk associated with the log-transformation of the titer for IgA (adjusted OR 1.32, 95% CI 1.05 to 1.66) but not IgG. CONCLUSIONS: Serological evidence of chronic infection with C pneumoniae is associated with risk of ischemic stroke in an urban, multi-ethnic population. IgA titers may be a better marker of this risk than are IgG titers. This association is independent of other vascular disease risk factors. Further prospective epidemiological studies of the effect of this infection on stroke risk are warranted.