Lead Time and Immortal Time Biases Impact the Calculation of Post-colonoscopy Colorectal Cancer Survival.

The World Endoscopy Organization (WEO) standardized the reporting of post-colonoscopy colorectal cancers (PCCRCs), which account for 7% to 10% of colorectal cancers (CRCs).1 PCCRCs are diagnosed 6 to 36 months after a false negative colonoscopy. Detected CRCs (dCRCs) are diagnosed ≤6 months after an index true positive colonoscopy.2 PCCRC prognosis is unclear, with outcomes reported as comparable,3 superior,4 or inferior5,6 to those of dCRC. Because WEO terminology defines cases relative to the index colonoscopy, conventional survival analyses of PCCRC are susceptible to lead time and immortal time biases. We evaluated the influence of these biases on mortality in a population-based retrospective cohort of 10,938 dCRCs (93.8%) and 717 PCCRCs (6.2%). This study was set within Kaiser Permanente Northern California (KPNC), a large integrated health system, whose members are similar in demographic and socioeconomic characteristics to the Northern California region.7.

Systematic review with meta-analysis: the prevalence of post-colonoscopy colorectal cancers using the World Endoscopy Organization nomenclature.

INTRODUCTION: Post-colonoscopy colorectal cancers (PCCRCs) have been proposed as a performance metric for colonoscopy quality assurance programs. Previously, there was no standardised terminology or reporting methods. In 2018, the World Endoscopy Organization (WEO) advised standardised definitions and prevalence calculation methodology. AIMS: To assess PCCRC burden using WEO standardised methods, to explore causes of heterogeneity, and to review changes in prevalence over time METHODS: We updated a prior systematic review by searching Ovid MEDLINE and EMBASE databases from 1 January 2013 to 31 January 2021 to identify population-based studies (or multicentre studies representative of the local population) reporting PCCRC prevalence (PROSPERO [CRD42020183796]). Two authors independently determined study eligibility, assessed quality, and extracted data. We estimated the PCCRC 3-year prevalence using WEO-recommended methodologies and investigated between-study sources of heterogeneity. We examined changes in prevalence over time. RESULTS: Fifteen studies reporting on 25 872 PCCRC cases met eligibility criteria. Pooled PCCRC 3 year prevalence was 8.2% (95% CI = 6.9%-9.4%, I2  = 98.2%) across four European studies using WEO precise methodology. Proximal PCCRC prevalence was greater than distal (9.7% [95% CI = 7.0%-12.4%] vs 5.4% [95% CI = 2.9%-7.8%], I2  = 99.2%). Seven studies reporting PCCRC rates over time showed no consistent trend: four showed a decrease, one an increase and two were unchanged. Between-study heterogeneity was high. CONCLUSIONS: Pooled 3-year PCCRC prevalence was 8.2% (95% CI = 6.9%-9.4%). Despite WEO standardised methodology to define and calculate PCCRC rates, there was significant heterogeneity among studies. Comparing rates between populations remains challenging and additional studies are needed to better understand the global PCCRC burden to inform quality assurance programs.

Dietary antioxidant intake and the risk of developing Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: We investigated in a cohort study, for the first time using 7-day food diaries (7-DFDs), for age-dependent inverse associations with antioxidants, which have anti-carcinogenic properties, and development of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). METHODS: A total of 24,068 well individuals completed 7-DFDs and donated blood. Vitamins C and E, carotenes, zinc and selenium intakes, and plasma vitamin C were measured. Participants were monitored for 15 years for BO and OAC. Hazard ratios (HRs) were estimated for: quintiles of intake and in participants younger and >=65 years at recruitment, the midpoint of BO peak prevalence. RESULTS: A total of 197 participants developed BO and 74 OAC. There were no significant associations between antioxidants and BO or OAC in the whole cohort or if >65 years at recruitment. In participants <65 years, for BO, there was an inverse trend across plasma vitamin C quintiles (trend HR = 0.82; 95% CI = 0.71-0.96, P = 0.01), OAC for plasma vitamin C (trend HR = 0.58; 95% CI = 0.37-0.92, P = 0.02) and for dietary vitamins C and E (trend HR = 0.71 95% CI = 0.51-0.99, P = 0.04 and trend HR = 0.70; 95% CI = 0.51-0.96; P = 0.03). CONCLUSIONS: Data supports a role for dietary antioxidants prevent BO and OAC, perhaps at the earlier stages of carcinogenesis.

Renal infarction due to spontaneous dissection of the renal artery: an unusual cause of non-visceral type abdominal pain.

A 44-year-old man presented with very severe right upper quadrant pain of sudden onset. This was exacerbated by movement but unaffected by food or defaecation. It was continuous-day and night -but resolved over a 1-week period. The physical examination was normal at presentation, by which time the pain had resolved. His white cell count, alanine transaminase and C reactive protein were elevated but normalised after 10 days. An abdominal CT showed low density lesions in the right kidney consistent with segmental infarcts. CT angiogram showed a dissection of the right renal artery. The patient remained asymptomatic and normotensive when reviewed 1 month later.

Novel mutations in NPHP4 in a consanguineous family with histological findings of focal segmental glomerulosclerosis.

Nephronophthisis is a form of autosomal recessive hereditary cystic kidney disease that typically progresses to end-stage renal disease by early adulthood. Conversely, focal segmental glomerulosclerosis is a histological glomerular phenotype that can be familial, primary (idiopathic), or secondary to a multitude of pathological processes affecting the kidney, including such tubulointerstitial diseases as nephronophthisis. Mutations in 6 distinct nephronophthisis genes have been described to date. We describe a consanguineous Filipino family with 2 novel sequence variants in the NPHP4 gene. Affected individuals presented with end-stage renal disease and histological features of focal segmental glomerulosclerosis on biopsy. They also had atypical radiological findings, making the clinical diagnosis of the genetic syndrome difficult. Furthermore, although ocular abnormalities and hearing loss were described previously, this is the first report of hepatic disease in patients with mutations in NPHP4. The diagnosis of nephronophthisis was made by means of mutational analysis of the NPHP4 gene after isolation of a region of homozygosity in affected individuals by using whole-genome single-nucleotide polymorphism analysis. Because establishment of the correct diagnosis has implications for therapeutic interventions, prognosis, and, in the case of heritable diseases, appropriate genetic counseling for affected individuals and their families, this report emphasizes the importance of obtaining meticulous clinical information, considering alternative diagnoses, and, when possible, performing genetic evaluation to confirm the diagnosis. We outline an approach to patients with hereditary kidney disease, focusing specifically on the molecular genetic techniques available to evaluate such families and determine a chromosomal region of interest and, subsequently, the diagnosis.

The effect of intravenous fluid replacement on the response to mannitol in experimental cerebral edema: an analysis of intracranial pressure, serum osmolality, serum electrolytes, and brain water content.

Albino rabbits that had undergone a cryogenic insult over the left parieto-occipital cortex were analyzed for serum osmolality, serum electrolytes, brain water content, and intracranial pressure (ICP) following either a baseline infusion of intravenous (i.v.) fluid (45 mL total) for 3 hours or above-maintenance isotonic saline (73.5 +/- 12 mL or 90.5 +/- 1.5 mL) and mannitol therapy. The subgroups were compared amongst themselves and to sham-operated controls. Serum osmolality was elevated in the higher-dose mannitol subgroup compared with maintenance i.v. fluids subgroup (1 g/kg/h vs 1 g/kg/3 h; p < 0.05), accompanied by an insignificant reduction of serum sodium. A significant reduction in brain water in the injured left hemisphere was seen following high-dose mannitol in the subgroup that received less i.v. (maintenance) fluids than the group that received above-maintenance i.v. fluids (p < 0.025). No reduction in brain water was seen in the subgroup that received above-maintenance i.v. fluids (non-treated groups). Reduction of ICP was not found in the lower mannitol dose group. We conclude that the ability of mannitol to reduce cerebral edema is related to the total amount of i.v. fluid replacement. This implies that the amount of i.v. crystalloid fluid that is administered to patients with cerebral edema and raised ICP requiring mannitol for control needs to be carefully monitored.

Infective Endocarditis in Patients with Kidney Failure: Chronic Dialysis and Kidney Transplant.

Physicians who treat patients with infective endocarditis (IE) are encountering a growing number of dialysis and kidney transplant patients. Both groups have 30 to 100 times higher risk of IE, with 1-year mortalities of 40% to 60%. The predominant organisms causing IE are gram positive, with 60% to 80% of cases due to Staphylococcus aureus, and another 10% to 20% of cases due to coagulase-negative staphylococci. Renal transplant patients may develop fungal IE, but this risk is primarily in the first 3 months after transplant. In addition to blood cultures, transesophageal echocardiogram is the most useful diagnostic examination for IE in these patients. Initial antibiotic therapy, pending final culture and antibiotic susceptibility results, should provide coverage against the most common organisms and allow for the potential of either methicillin or vancomycin-resistant species. Removal of infected hemodialysis access devices and at least 4 to 6 weeks of intravenous antibiotics are recommended. Antibiotic prophylaxis against IE has been recommended for all dialysis and renal transplant patients, but this strategy is controversial and unproven.

The treatment of Candida albicans shunt infections.

Cerebrospinal fluid shunting procedures are performed for the treatment of hydrocephalus. Infection of ventriculoperitoneal shunts may create significant clinical management issues in these patients. The majority of these infections are bacterial, but occasionally a Candida albicans shunt infection may occur. We report two patients who acquired Candida albicans shunt infection and discuss their clinical presentation, management, and successful outcome. The treatment with or without removal of the shunt and the correct dosage and route of administration of the antifungal agents is not well documented. The dilemma of treatment of Candida albicans shunt infections in these patients and review of the limited literature on this subject are the subjects of this report.

Carboplatin is effective therapy for young children with progressive optic pathway tumors: a Pediatric Oncology Group phase II study.

The Pediatric Oncology Group conducted a phase II study to evaluate the activity of carboplatin in children 5 years or younger with progressive optic pathway tumors (OPTs). Of the 51 patients accrued to this study, 1 was not eligible because the child was older than 6 years. Fifty patients were eligible and had either neuro-imaging or symptomatic evidence of progressive OPTs. Twenty-one of 50 had evidence of neurofibromatosis type I (NF-1). Therapy consisted of carboplatin 560 mg/m2 at 4-week intervals. Patients with stable disease or better after two courses were continued on therapy for 18 months or until progressive disease. Of the 50 eligible children, 39 had stable disease or better, and 34 completed the 18-month therapy. Our data are sufficient to conclude that the proportion of objective responses (complete, partial, or minor response or stable disease) exceeded 30% (P < 0.00001), and the approximate 95% confidence interval estimate of the objective response rate was 0.665 to 0.895. Twenty-one patients went off protocol because of progressive disease. Fifteen patients progressed during the 18-month therapy, and 6 patients progressed after completing therapy. Six children died with progressive disease. Major toxicities were neutropenia and thrombocytopenia, and 3 children experienced allergic reactions. Carboplatin is active and safe for the treatment of young children with progressive OPTs. The addition of other potentially active drugs may further increase the event-free survival for these children.

Pediatric head injury: what is unique and different.

Pediatric head injury has unique issues that make patient management and outcome different from that of adult head injury. The differences may be classified in various categories. The mechanism of injury may be that of accidental or non-accidental trauma, and in the latter, repeated secondary insults will affect patient management and outcome. Age related aspects will determine a greater or lesser degree of craniocervical junction injuries (disproportionate cranial size to trunk in infancy and early childhood). Other factors are potential underlying congenital anomalies, physiological factors (cerebrovascular reactivity and blood flow), differing support systems needed from that of adults for neuro imaging and specialized medical, nursing and allied health care support. Pediatric rehabilitation and educational needs and goals are different to that of adult head injury. Neurological recovery in non-accidental trauma is uniformly poor, when compared to accidental trauma. Pediatric head injury has unique requirements in early field management, hospital management, rehabilitation and educational needs, as well as community re-entry programmes.

Cutaneomeningospinal angiomatosis (Cobb syndrome) with tethered cord.

A newborn presented with a skin-covered lumbar mass with a subcutaneous hemangioma and on a magnetic resonance image (MRI) revealed a tethered spinal cord with a local mass. The mass had signal characteristics compatible with a lipoma. An initial diagnosis of a lipomeningocele with tethered cord was made, and the patient underwent surgical exploration and subtotal resection of the mass. A follow-up MRI revealed that the cord was still tethered, but an additional mass was present. The initial mass with signal characteristics of lipomatous tissue was accompanied by a low-signal mass in the lumbosacral canal, ventral to the cord, and bilateral enlargement of the foramina at the lumbosacral level. Because of a concern for an intraspinal tumor, a second operative intervention was performed. Multiple biopsies of the mass inside the spinal cord, the nerve roots and at the level of the foramina revealed angiomas that had similar pathology in all the specimens. A partial resection of the masses and a release of the tethered cord was performed by sectioning the thickened filum terminale. The diagnosis of Cobb's syndrome was made. The unique association of a tethered cord and the Cobb syndrome is reported here.

Suprasellar germinoma associated with Cushing's disease and diabetes insipidus in a child.

Cushing's disease is described in a child with a suprasellar germinoma. The patient presented with all of the classic stigmata of Cushing's disease as well as diabetes insipidus, but after surgical resection of the lesion was found to have pathology incompatible with an ACTH-secreting tumor. We believe that this is the first reported incidence of Cushing's disease associated with a suprasellar germinoma. The implications of this unusual association are discussed.

Spinal hamartomas: a distinct clinical entity.

OBJECT: Congenital spinal hamartomas are defined as tumors of well-differentiated mature elements situated in an abnormal location. In this report, the authors document the clinical and pathological features of spinal hamartomas in 10 patients. METHODS: Ten patients presented with midline dorsal malformations at birth, initially diagnosed as teratomas or myelomeningoceles. The locations of the masses were variable: two were located in the thoracic region, four at the thoracolumbar junction, two in the lumbar region, one at the lumbosacral junction, and one in the sacral region. The results of the neurological examination were normal in nine patients. All but one mass had intact skin and seven had palpable bone components. Neuroimaging studies revealed widening of the spinal canal, heterotopic bone located dorsally in some patients, and varying degrees of involvement of the intraspinal contents. During surgery, six patients were found to have involvement of the spinal cord or cauda equina. The pathological characteristics of the masses included three or more of the following: bone, cartilage, synovial membrane, urinary tract tissue, cyst wall, yellow or brown fat, and nerves. The well-differentiated cellular elements, which formed mature structures, along with the absence of primitive cellular components and neoplastic characteristics are more consistent with a diagnosis of hamartoma than teratoma. CONCLUSIONS: In this series, the authors describe a lesion that is overt on physical examination, yet can have occult spinal canal involvement. Complete neurosurgical evaluation is essential to provide appropriate treatment and prognosis.

The Surgical Isolation Bubble System and patient temperature during ventriculoperitoneal shunt insertion in preterm and term newborn infants.

The ultraclean air environment in a plastic isolator has been used in cerebrospinal fluid shunt interventions in an attempt to reduce the incidence of infections. The blower that maintains a continuous flow of filtered air in the operative field may create body temperature changes. In this study we assessed the temperature before, during and at the end of the operation in preterm and term infants in whom ventriculoperitoneal shunts were being placed. There were 12 preterm and 9 term infants. The duration of the operative intervention ranged from 25 to 50 min. In the preterm infants the mean initial temperature was 36.2+/-0.2 degrees C, and the final temperature was 35.7+/-0.2 degrees C. This difference was not significant. The initial temperature in the term infants was 36.26+/-0.2 degrees C, and the final temperature was 35.9+/-0.3 degrees C, also not significantly different. The surgical isolation bubble system does not alter the temperature of preterm and term infants significantly during ventriculoperitoneal shunt procedures performed within the operative times seen in this study.

Ventriculoperitoneal shunts for hydrocephalus: a focus group discussion on the selection of shunt systems in pediatrics. A report of the Pediatric Neurosurgery Research Group meeting, December 1992.

As part of the Continuing Quality Improvement Study, phase I, 12 pediatric neurosurgeons participated in a discussion group to respond to the various issues related to selection of ventriculoperitoneal shunt systems in their practice. It was estimated that between then all the 12 participants performed approximately 1200 shunt procedures per year in the USA. The data were analyzed by grid and fish-bone charts as part of the data collection. All 12 participants indicated that they preferred a reservoir in the shunt system, 8 of them indicating that they preferred this for a manual test of the system. Three indicated that they did not routinely manipulate the system for testing. One participant stated that he placed a reservoir within the shunt system primarily to prevent migration of the ventricular catheter. Nine neurosurgeons indicated that they employed cranial valves in their shunt systems, and three indicated that they employed slit-end peritoneal catheters only. In reference to Delta valves, nine participants indicated that they employed them on occasions. In reference to pressure in the valve system, one participant employed high-pressure valves at all times, five employed only medium-pressure systems, and the remaining six always employed low-pressure valves. All 12 neurosurgeons stated that the incidence of symptomatic slit ventricle in their practices was between 1% and 5%, in their mind irrespective of the system used. It was concluded that any form of ventriculoperitoneal shunt, with or without valves, with slit-end valves or cranial valves seemed to work equally well in the hands of a dedicated pediatric neurological surgeon.(ABSTRACT TRUNCATED AT 250 WORDS)