Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England.

The Omicron variant of SARS-CoV-2 became the globally dominant variant in early 2022. A sub-lineage of the Omicron variant (BA.2) was identified in England in January 2022. Here, we investigated hospitalisation and mortality risks of COVID-19 cases with the Omicron sub-lineage BA.2 (n = 258,875) compared to BA.1 (n = 984,337) in a large cohort study in England. We estimated the risk of hospital attendance, hospital admission or death using multivariable stratified proportional hazards regression models. After adjustment for confounders, BA.2 cases had lower or similar risks of death (HR = 0.80, 95% CI 0.71-0.90), hospital admission (HR = 0.88, 95% CI 0.83-0.94) and any hospital attendance (HR = 0.98, 95% CI 0.95-1.01). These findings that the risk of severe outcomes following infection with BA.2 SARS-CoV-2 was slightly lower or equivalent to the BA.1 sub-lineage can inform public health strategies in countries where BA.2 is spreading.

Unresolved grief and its consequences. A nationwide follow-up of teenage loss of a parent to cancer 6-9 years earlier.

PURPOSE: The early loss of a parent is a tragedy and a serious life event. This study investigated grief resolution and morbidity in cancer-bereaved teenagers 6 to 9 years after the loss of a parent to cancer. METHODS: In a nationwide population-based study of 622 of 851 (73 %) youths who as teenagers 6 to 9 years earlier had lost a parent to cancer, we explored the magnitude of unresolved grief and its association with psychological and physiological morbidity. Participants answered a study-specific anonymous questionnaire including questions about if they had worked through their grief and about their current health. RESULTS: Six to nine years post-loss 49 % reported unresolved grief (8 % no and 41 % a little grief resolution). They had, in comparison with youths reporting resolved grief, statistically significantly elevated risks, e.g. for insomnia (sons' relative risk (RR) 2.3, 95 % CI 1.3-4.0; daughters' RR 1.7, 95 % CI 1.1-2.7), fatigue (sons' RR 1.8, 95 % CI 1.3-2.5; daughters' RR 1.4, 95 % CI 1.1-1.7) and moderate to severe depression, i.e. score >9, PHQ-9 (sons' RR 3.6, 95 % CI 1.4-8.8; daughters' RR 1.8, 95 % CI 1.1-3.1). Associations remained for insomnia in sons, exhaustion in daughters and fatigue in both sons and daughters when depression, negative intrusive thoughts and avoiding reminders of the parents' disease or death were included in a model. CONCLUSIONS: Approximately half of cancer-bereaved youth report no or little grief resolution 6 to 9 years post-loss, which is associated with fatigue, sleeping problems and depressive symptoms.

WATER EXERCISE COMPARED TO LAND EXERCISE OR STANDARD CARE IN FEMALE CANCER SURVIVORS WITH SECONDARY LYMPHEDEMA.

There are few studies showing that physical exercise can improve secondary lymphedema. We hypothesized that water exercise would be more effective than land exercise in reducing limb volume. Secondary objectives were joint movement, BMI, daily function, well-being, and body image. Limb volume was measured with circumference or was volumetric. Well-being and body image were measured with a study-specific questionnaire and daily function with DASH and HOOS questionnaires. Eighty-eight eligible patients with secondary lymphedema after breast or gynecological cancer participated in this controlled clinical intervention study. There was a higher proportion of women who participated in water exercises who reduced their secondary arm limb volume (p = 0.029), and there were also significant differences for BMI (p = 0.047) and self-reported frequency of swelling (p = 0.031) in the water exercise group after intervention. Women with arm lymphedema in the land exercise group improved DASH scores (p = 0.047) and outer rotation in the shoulder (p = 0.001). Our results suggest that to reduce objective and self-reported swelling, lymphedema patients may be offered water exercise training while to improve daily shoulder function, land exercises are preferred. To guide female cancer survivors with lymphedema to effective exercise resulting in reduced limb volume and improved function, adequate evidenced-based programs are needed.

Tips and tricks for intracorporeal robot-assisted urinary diversion.

Since 2003, Karolinska University Hospitals have performed totally intracorporeal robotic-assisted radical cystectomy (RARC) in carefully selected patients. As our technique has evolved, the proportion of patients undergoing RARC has progressively increased. Whilst open radical cystectomy remains the gold standard, several high-volume centres have now demonstrated that RARC is both feasible and safe. RARC comprises three stages: radical cystectomy, extended lymph node dissection and urinary diversion. The majority of centres in the United States currently perform RARC utilizing an extracorporeal approach for the urinary diversion stage, perceiving this to be a more accessible option with a reduced risk of complications. We assess the evidence for this perception, reviewing the literature and reporting the functional outcomes and complication rates for a totally intracorporeal RARC approach. We also describe our technique for both intracorporeal orthotopic neobladder and intracorporeal ileal conduit, identifying the potential hazard steps and the 'tips and tricks' to optimize outcomes.

Robot-assisted radical cystectomy with intracorporeal neobladder diversion: The Karolinska experience.

INTRODUCTION: The aim of this report is to describe our surgical technique of totally intracorporeal robotic assisted radical cystectomy (RARC) with neobladder formation. MATERIALS AND METHODS: Between December 2003 and March 2013, a total of 147 patients (118 male, 29 female) underwent totally intracorporeal RARC for urinary bladder cancer. We also performed a systematic search of Medline, Embase and PubMed databases using the terms RARC, robotic cystectomy, robot-assisted, totally intracorporeal RARC, intracorporeal neobladder, intracorporeal urinary diversion, oncological outcomes, functional outcomes, and complication rates. RESULTS: The mean age of our patients was 64 years (range 37-87). On surgical pathology 47% had pT1 or less disease, 27% had pT2, 16% had pT3 and 10% had pT4. The mean number of lymph nodes removed was 21 (range 0-60). 24% of patients had lymph node positive dAQ1isease. Positive surgical margins occurred in 6 cases (4%). Mean follow-up was 31 months (range 4-115 months). Two patients (1.4%) died within 90 days of their operation. Using Kaplan-Meier analysis, overall survival and cancer specific survival at 60 months was 68% and 69.6%, respectively. 80 patients (54%) received a continent diversion with totally intracorporeal neobladder formation. In the neobladder subgroup median total operating time was 420 minutes (range 265-760). Daytime continence and satisfactory sexual function or potency at 12 months ranged between 70-90% in both men and women. CONCLUSIONS: Our experience with totally intracorporeal RARC demonstrates acceptable oncological and functional outcomes that suggest this is a viable alternative to open radical cystectomy.

Self-perceived penile shortening after radical prostatectomy.

The postoperative effect on penile length after radical prostatectomy has been the subject of studies with conflicting results. We analyzed self-perceived penile shortening, quality of life and self-esteem after radical prostatectomy. In this cross-sectional study of a cohort of 1411 men who underwent a radical prostatectomy at Karolinska University Hospital between 2002 and 2006, we used a study-specific questionnaire. Patients and controls were asked about their perceived penile shortening by comparing present penile length now and at age 30 years. All subjects were also asked about their present quality of life and self-esteem. Patients were compared with 442 age-matched population-based controls. Among 1288 who underwent radical prostatectomy and answered the questionnaire (response rate 91%), 663 patients reported self-perceived penile shortening (55%), as compared with 85 (26%) of 350 men in the control group, corresponding to a relative risk (RR) of 2.1 (95% confidence interval (CI) 1.8-2.6) of self-perceived penile shortening compared with the age-matched control group. Age, grade of erectile dysfunction and angina were correlated with self-perceived penile shortening in both the operated and the control group. After adjustments for all of these mentioned potential confounders, we obtained a RR of 1.7 (95% CI 1.4-2.1) of self-perceived penile shortening compared with the controls. We also found that self-assessed penile shortening was associated with a RR of 1.2 (95% CI 1.1-1.3) for a low-to-moderate self-assessed quality of life and a RR of 1.2 (95% CI 1.1-1.4) for a low-to-moderate self estimation of self-esteem. Extensive nerve-sparing technique seems to be associated with less self-perceived penile shortening compared with radical prostatectomy with lower degree of nerve-sparing approach. These data indicate that radical prostatectomy is associated with self-perceived penile shortening and suggests that erectile function is a key factor in penile shortening.

Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study.

BACKGROUND: We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women. METHODS: We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records. RESULTS: Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms. CONCLUSION: Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.

Micromechanics of diffuse axonal injury: influence of axonal orientation and anisotropy.

Multiple length scales are involved in the development of traumatic brain injury, where the global mechanics of the head level are responsible for local physiological impairment of brain cells. In this study, a relation between the mechanical state at the tissue level and the cellular level is established. A model has been developed that is based on pathological observations of local axonal injury. The model contains axons surrounding an obstacle (e.g., a blood vessel or a brain soma). The axons, which are described by an anisotropic fiber-reinforced material model, have several physically different orientations. The results of the simulations reveal axonal strains being higher than the applied maximum principal tissue strain. For anisotropic brain tissue with a relatively stiff inclusion, the relative logarithmic strain increase is above 60%. Furthermore, it is concluded that individual axons oriented away from the main axonal direction at a specific site can be subjected to even higher axonal strains in a stress-driven process, e.g., invoked by inertial forces in the brain. These axons can have a logarithmic strain of about 2.5 times the maximum logarithmic strain of the axons in the main axonal direction over the complete range of loading directions. The results indicate that cellular level heterogeneities have an important influence on the axonal strain, leading to an orientation and location-dependent sensitivity of the tissue to mechanical loads. Therefore, these effects should be accounted for in injury assessments relying on finite element head models.

Sorting of regenerating rat sciatic nerve fibers with target-derived molecules.

The functional outcome of microsurgical repair of divided nerves is disappointing since many regenerating axons fail to reach appropriate targets. Sorting of regenerating axons according to target tissue might be used to improve functional regeneration. The aim of the present study is to see if regenerating axons can be sorted into functionally different bundles with target-derived molecules. The proximal stump of the adult rat sciatic nerve was sutured into the inlet of a silicon Y-tube. The two branches of the Y-tube were filled with agarose primed with filtrates prepared from skin and muscle homogenates from the operated rat. The tibial and sural nerves were inserted in the two branches of the Y-tube. Six weeks later the sciatic nerve axons showed vigorous regeneration into both branches. Electron microscopic examination of regenerated nerve segments showed numerous myelinated and unmyelinated axons. The proportion of myelinated axons was significantly larger in the muscle-gel branch than in the skin-gel branch. Retrograde tracing from the nerve regenerates with Fast Blue and Fluoro-Ruby showed that ventral horn neurons at L4-L5 segmental levels were preferentially labeled from the muscle-gel branch. Neurons in corresponding dorsal root ganglia were labeled from both Y-tube branches (no significant numerical difference). A few neurons of both types contained both tracers. Measurements revealed that sensory neurons labeled from the muscle-gel branch were significantly larger (mean perikaryal area 870 microm(2)) than neurons labeled from the skin-gel branch (mean area 580 microm(2)). We conclude that regenerating motor and sensory axons can be sorted with target-derived molecules.

The case of the unpopular pay plan.

Three years after launching the team-based Quality For All program, Top Chemical Company CEO Sam Verde was searching for a team-based compensation system that would reflect his company's new philosophy. With a committee gathered to discuss the issue, Verde confronts the fact that changing pay plans is an issue few people can agree on. "Very simply," explains vice president for compensation Gilbert Porterfield, "the plan is designed to give employees working on teams real incentives for constant improvement and overall excellence. The variable aspect of the system pays employees for the performance of their group." This doesn't sit well with the others. "It's going to punish teams like mine for the failings of others instead of rewarding us for the work we do and have already done," says packaging team representative Ruth Gibson. Another committee member feels that team-based anything is a "motivational happy land that doesn't square with how people really work." While Verde likes the proposed pay plan, he has doubts over whether his employees will accept the risk. Upper management has no problem basing 60% of its pay on TopChem's performance. But getting line employees to risk part of their salaries--even as little as 4%--on the ups and downs of the chemical industry may be more trouble than it's worth. Four experts on compensation reveal where Top Chemical went wrong in its plan and how Sam Verde might bring about change successfully.