A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia.

The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (ß-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

Transanal mesorectal excision: early outcomes in Australia and New Zealand.

BACKGROUND: Transanal total mesorectal excision (taTME) aims to overcome some of the technical challenges faced when operating on mid and low rectal cancers. Specimen quality has been confirmed previously, but recent concerns have been raised about oncological safety. This multicentre prospective study aimed to evaluate the safety of taTME among early adopters in Australia and New Zealand. METHODS: Data from all consecutive patients who had taTME for rectal cancer from July 2014 to February 2020 at six tertiary referral centres in Australasia were recorded and analysed. RESULTS: A total of 308 patients of median age of 64 years underwent taTME. Some 75.6 per cent of patients were men, and the median BMI was 26.8 kg/m2. The median distance of tumour from anal verge was 7 cm. Neoadjuvant chemoradiotherapy was administered to 57.8 per cent of patients. The anastomotic leak rate was 8.1 per cent and there was no mortality within 30 days of surgery. Pathological examination found a complete mesorectum in 295 patients (95.8 per cent), a near-complete mesorectum in seven patients (2.3 per cent), and an incomplete mesorectum in six patients (1.9 per cent). The circumferential resection margin and distal resection margin was involved in nine patients (2.9 per cent), and two patients (0.6 per cent) respectively. Over a median follow-up of 22 months, the local recurrence rate was 1.9 per cent and median time to local recurrence was 30.5 months. CONCLUSION: This study showed that, with appropriate training and supervision, skilled minimally invasive rectal cancer surgeons can perform taTME with similar pathological and oncological results to open and laparoscopic surgery.

Who gets Hartmann's reversed in a regional centre?

BACKGROUND: Many patients who undergo a Hartmann's procedure do not have their stoma reversed. We analysed parameters and co-morbidity scales to assess their accuracy in predicting likelihood of undergoing reversal. MATERIAL AND METHODS: Retrospective analysis of 165 patients from a prospective colorectal database who were discharged home following a Hartmann's procedure at Barwon Health (Geelong, Australia), a regional centre, between 2002 and 2010. Parameters measured included age, sex, time to reversal, ICU admission and pathology results were recorded. Patients' ASA, POSSUM and Elixhauser co-morbidity scales were retrospectively analysed. RESULTS: Reversal of Hartmann's was performed in 74/165 (45%) patients after a median of 294 days (range 70-902). Age (mean 58.5 vs 72.9 years, p < 0.001), ICU stay (34/74 vs 66/91, p < 0.001), ASA (p < 0.002), Elixhauser co-morbidity count (mean 1.14 vs 1.92, p < 0.002) and a malignant diagnosis (9/74 vs 31/91, p < 0.002) were all associated with a decreased reversal rate on univariate analysis. Age was the only parameter found to be significant on multivariate analysis. The complication rate was 23/74, with 7/74 noted to have major complications (Clavian-Dindo III-IV). Reasons for not reversing patients included age and co-morbidities, patient refusal, and malignant disease progression. CONCLUSIONS: More than half the patients undergoing a Hartmann's procedure did not proceed to a closure of their stoma. Age was the only parameter significant in predicting those patients undergoing reversal.

Eating marshmallows reduces ileostomy output: a randomized crossover trial.

AIM: Anecdotally, many ostomates believe that eating marshmallows can reduce ileostomy effluent. There is a plausible mechanism for this, as the gelatine contained in marshmallows may thicken small bowel fluid, but there is currently no evidence that this is effective. METHOD: This was a randomized crossover trial. Adult patients with well-established ileostomies were included. Ileostomy output was measured for 1 week during which three marshmallows were consumed three times daily, and for one control week where marshmallows were not eaten. There was a 2-day washout period. Patients were randomly allocated to whether the control or intervention week occurred first. In addition, a questionnaire was administered regarding patient's subjective experience of their ileostomy function. RESULTS: Thirty-one participants were recruited; 28 completed the study. There was a median reduction in ileostomy output volume of 75 ml per day during the study period (P = 0.0054, 95% confidence interval 23.4-678.3) compared with the control week. Twenty of 28 subjects (71%) experienced a reduction in their ileostomy output, two had no change and six reported an increase. During the study period, participants reported fewer ileostomy bag changes (median five per day vs six in the control period, P = 0.0255). Twenty of 28 (71%) reported that the ileostomy effluent was thicker during the study week (P = 0.023). Overall 19 (68%) participants stated they would use marshmallows in the future if they wanted to reduce or thicken their ileostomy output. CONCLUSION: Eating marshmallows leads to a small but statistically significant reduction in ileostomy output.

Renal transplantation in 4 patients with methylmalonic aciduria: a cell therapy for metabolic disease.

INTRODUCTION: Patients with methylmalonic acidemia (MMA) may develop many complications despite medical treatment, in particular, severe central nervous system damage and chronic kidney disease (CKD). A kidney transplant may partially correct the metabolic dysfunctions. Liver, kidney and combined liver-kidney transplantations have been advocated but no guidelines are available to identify the most suitable organ to transplant. PATIENTS AND METHODS: Four patients with MMA (mut° phenotype) received a kidney graft because of repeated metabolic decompensations, with progression to CKD in 3 patients (end-stage kidney disease in two patients and CKD stage III in one patient with an estimated glomerular filtration rate [eGFR] of 40ml/min/1.73m(2)) but normal renal function in one (eGFR of 93ml/min/1.73m(2)) before transplantation. RESULTS: The medium age at transplantation was 7.9y (5-10.2) and the median follow-up was 2.8years (1.8-4.6). Renal transplantation improved the relevant metabolic parameters in 4/4 patients and renal function in the patients with CKD. Plasma and urinary MMA levels immediately decreased and remained normal or subnormal (mean values of plasma MMA before transplantation 1530µmol/L versus 240µmol/L after transplantation, and mean values of urine MMA before transplantation 4700mmol/mol creatinine versus 2300mmol/mol creatinine after transplantation). No further acute metabolic decompensation was observed and protein-intake was increased from 0.60 to 0.83g/Kg/day. One patient transplanted at age 9.7years developed a hepatoblastoma at age 11years with subsequent neurological complications and eventually died. The three other patients are alive. Two of them remained neurologically stable. The 3rd patient who displayed choreoathetosis transiently improved his neurological condition immediately after transplantation and then remained stable. CONCLUSION: Kidney transplantation represents an interesting alternative therapeutic option in methylmalonic aciduria, for renal complications but also as a "cellular therapy" that may significantly reduce metabolic decompensations and hospitalizations. However, further neurological impairment remains possible.

The ideal ileal-pouch design: a long-term randomized control trial of J- vs W-pouch construction.

BACKGROUND: The IPAA has become established as the preferred technique for restoring intestinal continuity postproctocolectomy. The ideal pouch design has not been established. W-pouches may give better functional results owing to increased volume, whereas the J-pouch's advantage is its straightforward construction. We report short- and long-term results of an randomized control trial designed to establish the ideal pouch. DESIGN: Ninety-four patients were randomly assigned to J- and W-pouches (49:45) and assessed at 1 and 8.7 years postoperatively. Assessment was questionnaire based and designed to assess pouch function and patient quality of life. RESULTS: Eighty-five percent of patients were followed up at 1 year, and 68% were followed up at 8.7 years. At 1 year, there was a significant difference in 24-hour bowel movement frequency J- vs W-pouches 7 vs 5(p < 0.001) and in daytime frequency J- vs W-pouches 6 vs 4 (p < 0.001), with no difference in nocturnal function. At 9-year follow-up, function had equilibrated between the 2 groups: 24-hour bowel movement frequency J- vs W-pouches 6.5 vs 6 (p = 0.36), daytime frequency 5.5 vs 5 (p = 0.233), and nocturnal function 1 vs 1 (p = 0.987). Mean operating time of J- and W-pouches was 195 and 215 minutes (p < 0.05). All other parameters, pad usage, urgency, incontinence, and quality of life, did not differ significantly between groups. CONCLUSION: These data demonstrate that the theoretical functional advantage conferred on the W-pouch by its greater volume exists only in the short term and is of little consequence to patients' long-term quality of life. This advantage is attenuated as the pouches mature, resulting in no disparity in pouch function. This, combined with the more consistent, efficient, and easily taught construction of the J-pouch, should conclusively establish it as the optimum ileal-pouch design.

Enhanced recovery after surgery program for elective abdominal surgery at three Victorian hospitals.

The aim of this study was to evaluate the anaesthesia care of an enhanced recovery after surgery (ERAS) program for patients having abdominal surgical in Victorian hospitals. The main outcome measure was the number of ERAS items implemented following introduction of the ERAS program. Secondary endpoints included process of care measures, outcomes and hospital stay. We used a before-and-after design; the control group was a prospective cohort (n=154) representing pre-existing practice for elective abdominal surgical patients from July 2009. The introduction of a comprehensive ERAS program took place over two months and included the education of surgeons, anaesthetists, nurses and allied health professionals. A post-implementation cohort (n=169) was enrolled in early 2010. From a total of 14 ERAS-recommended items, there were significantly more implemented in the post-ERAS period, median 8 (interquartile range 7 to 9) vs 9 (8 to 10), P <0.0001. There were, however, persistent low rates of intravenous fluid restriction (25%) and early removal of urinary catheter (31%) in the post-ERAS period. ERAS patients had less pain and faster recovery parameters, and this was associated with a reduced hospital stay, geometric mean (SD) 5.7 (2.5) vs 7.4 (2.1) days, P=0.006. We found that perioperative anaesthesia practices can be readily modified to incorporate an enhanced recovery program in Victorian hospitals.

Mortality in pediatric renal transplantation: a study of the French pediatric kidney database.

OBJECTIVE AND METHODS: To assess patient survival in pediatric renal transplantation, we retrospectively reviewed 573 transplants in 553 patients, registered from 1995 to 2005. RESULTS: Mean age at transplantation was 9.9 years. Patient survival at 1, 5 and 10 years was respectively 99%, 97% and 96%. Death occurred at a median time of 2.6 years after transplantation. Long-term patient survival was significantly lower in recipients younger than 5 years old. Seventeen patients (3.1%) died. Two deaths occurred while under maintenance dialysis. Among the remaining patients, the two main causes of death were infections (33%) and malignancies (27%). Interestingly, initial disease-related complications were a major cause of death (34%). CONCLUSION: A low mortality rate was observed, with the majority of deaths due to malignancies and infections, and with a notable participation of complications related to the initial disease. No impact of cardiovascular disease was noted with the given follow-up period. Improvements in managing immunosuppression may contribute to reducing mortality in pediatric renal transplantation.

Training in the private sector: what works and how do we increase opportunities?

In Australia 61% of elective surgery takes place in private hospitals where current opportunities for surgical education and training (SET) are limited. The situation will shortly be compounded because of the large increase in local medical graduates, many of whom will aspire to be surgeons. How and where to train these extra surgeons to meet the expanding needs of the community must be addressed. Two models of private sector training are reviewed both of which involved combined training in both private and public sectors. Two second-year (SET 2) positions were created from one public hospital SET position by using the private sector for 3.5 days per week for 3 months of a 6-month rotation. The second model was applicable to post-fellowship training with a fairly even split between public and private sector responsibilities. In the first year, four registrars shared the two 6-month rotations for the SET 2 position. Trainees did the required minimum procedures (range 109-139) with primary operating targets of 20-25% (range 21-32%). The post-fellowship position in colorectal surgery was greatly enhanced by the private sector involvement with regard to operating experience as well as meeting part of the remuneration of the trainee. Successful models for training within the private sector in Australia can be found. To expand training in the private sector there will need to be a cultural shift in the perceptions of surgeons, patients, administrators, and trainees. Funding for posts may be available to those private hospitals that can meet the Royal Australasian College of Surgeons' accreditation standards for posts and hospitals.

Liver hepatoblastoma and multiple OXPHOS deficiency in the follow-up of a patient with methylmalonic aciduria.

A boy who was diagnosed with methylmalonic aciduria (MMA) at the age of 10 days developed persistent hepatomegaly and raised transaminases from the age of 4 years. He was subsequently diagnosed with Leigh syndrome and required a kidney transplantation for end-stage renal failure. A massive hepatoblastoma led to his death by the age of 11 years. Methylmalonyl-CoA mutase activity was undetectable on both cultured skin fibroblasts and kidney biopsy and multiple respiratory chain deficiency was demonstrated in the kidney. Mitochondrial dysfunction and/or post-transplant immunosuppressive therapy should be considered as a possible cause of liver cancer in this patient.

HIV vaccine efficacy trial participation: men who have sex with men's experiences of risk reduction counselling and perceptions of risk behaviour change.

Qualitative interviews were conducted with 35 men who have sex with men, enrolled in the world's first phase III HIV vaccine efficacy trial at five US sites, regarding their risk reduction counselling experiences and their perceptions of its impact on risk behaviour. Respondents ranged in age from 20 to 58 years and were predominately white (71.4%) in racial/ethnic origin. Systematic qualitative analysis revealed that a positive counselling experience meant having good rapport with clinic staff. Differences in attitudes toward counselling were related to either a personal approach of balancing an enjoyable sex life with safe sex behaviours (balancing risks) or accepting the consequences of risky sexual behaviour rather than making changes (risk homeostasis). Respondents seeking to balance risks indicated that they saw themselves engaging in safer sexual behaviour almost twice as often as in riskier behaviours. They perceived counselling and behavioural risk assessments to help increase their awareness of personal risk-taking behaviours. Conversely, those with a risk homeostasis approach reported that they had established sexual boundaries prior to trial participation that had thus far proven to be effective in avoiding HIV infection, and that they were comfortable with the level of risk taken. Thus, risk reduction counselling had little to no influence on their sexual practices. Some of these men also indicated that while they had not found the risk reduction information imparted to them by clinic staff to be novel, counselling was beneficial in reinforcing their HIV/AIDS and safe sex knowledge base.

Effects of growth hormone on growth factors after renal transplantation.

Growth retardation occurs frequently in renal transplanted children (RTx) and can be improved by growth hormone (GH) treatment. This study retrospectively examines the insulin-like growth factor-1 (IGF-1) and IGF binding protein (IGFBP) profile of ten growth-retarded children previously given renal allografts, after 1 year of GH treatment period. Ten prepubertal patients (nine boys and one girl) were investigated. They had a mean chronological age (CA) of 11.4 +/- 1.1 years and a mean bone age (BA) of 7.3 +/- 0.9 years. Mean height was -3.9 +/- 0.4 SD units below the mean for CA. The mean body mass index (BMI) was 16.9 +/- 0.6 and the mean inulin clearance was 36.5 +/- 4.9 ml/min/1.73 m2. Recombinant hGH was given at 4 IU/m2/day. Plasma GH, total and free IGF-1, IGFBP-2 and -3 were measured by specific radioimmunoassay (RIA). IGFBPs were characterized by SDS PAGE techniques and ligand and immunoblot analyses. Mean velocity was markedly increased (P < 0.01) after 1 year of GH therapy, expressed as SD score for BA. The range of growth response was wide. The total and free plasma IGF-1 increased (P < 0.01) by about 100% (mean values after GH therapy: 95.9 +/- 2.1 nM and 165 +/- 29 pM, respectively). Plasma IGFBP-3 concentrations increased by about 40% (mean value: 148 +/- 18 pM, P < 0.01), with a concomitant increase in both intact IGFBP-3 and its 30-kDa proteolytic fragment. There was no change in plasma IGFBP-2 concentration. Both mean values of inulin clearance and BMI were unchanged during the treatment. In view of the IGF-1/IGFBP concentration changes, there should have been an even better growth response to GH therapy in these patients. This strongly suggests IGF-1 insensitivity, probably as a result of corticosteroid therapy.

Long term results of liver-kidney transplantation in children with primary hyperoxaluria.

From 1990 to 2000, we performed eight liver-kidney transplants in eight children, aged 1-16 years, with end-stage renal failure (ESRF) due to primary hyperoxaluria (PH1). The duration of dialysis before transplantation ranged from 2 to 42 months (mean 14 months) and was <1 year in four patients. Only the first patient underwent postoperative hemodialysis; in the other five, we chose to induce maximal diuresis from the first hours with intravenous and intragastric hyperhydration (> or =3 l/m2 per day). High water intake with nocturnal tube hydration was maintained for 6 months to 5 years, as long as oxaluria exceeded 0.5 mmol/day. A quadruple sequential immunosuppressive regimen was used. Two patients died during liver graft surgery. The other six patients are alive and well, with a mean follow-up of 7.4 years (range 5-11 years). Patient and graft survival is 75% at 5 years. At latest follow-up, liver tests were normal in all six patients; creatinine clearance ranged from 55 to 95 ml/min per 1.73 m2 (mean=74). Oxaluria was lower than 0.4 mmol/day in all patients (mean=0.22). The six patients underwent 15 renal biopsies, 1-11 years after transplantation. Chronic transplant nephropathy was present in four patients and mild cyclosporin nephrotoxicity in another. No oxalate crystals were seen and repeat ultrasonography has been consistently normal in all patients. The three patients with bone oxalosis showed progressive complete healing of bone lesions. All six children or adolescents now live a normal life. From this series, we conclude that early combined liver-kidney transplantation is the treatment of choice for children with ESRF due to primary hyperoxaluria.

Role of the bladder in delayed failure of kidney transplants in boys with posterior urethral valves.

PURPOSE: There is a tendency toward less favorable long-term graft function in patients with posterior urethral valves than in controls. We studied the role of the bladder in boys who underwent transplantation by simultaneously evaluating renal graft and voiding function. MATERIALS AND METHODS: Between 1972 and 1994, 66 boys with posterior urethral valves underwent kidney transplantation. Of these boys 44 with a mean age of 9.7 years who retained a functional renal graft did not undergo any surgery on the lower urinary tract except for the initial treatment of posterior urethral valves. Long-term evaluation included a voiding questionnaire, radiological assessment and serum creatinine measurement. RESULTS: Average followup was 9.01 years (range 2.4 to 19.6). There was no voiding dysfunction symptomatology in 23 boys, while 3 (14.2%) and 8 (38.1%) of the remaining 21 had daytime and nighttime frequency, respectively. Dysuria and incontinence were present in 11 (52.4%) and 12 (57.1%) patients, respectively. Urodynamics in 11 cases revealed a mean bladder compliance plus or minus standard deviation of 11.3+/-2.8 ml./cm. water. In boys with a voiding disorder mean serum creatinine increased after 5 years of followup. At 10 years after kidney transplantation mean serum creatinine was 140.3+/-36.0 and 285.7+/-36.2 micromol./l. in asymptomatic boys and those with a voiding disorder, respectively (p<0.01). CONCLUSIONS: Valve bladder has a role in the deterioration of renal transplants in boys with posterior urethral valves. In those with a voiding disorder closer followup is needed, including urodynamic and radiological studies. Bladder dysfunction, such as hypocompliance and/or hyperreflexia, requires medical or surgical treatment.

Metastatic Crohn's disease: case report of an unusual variant and review of the literature.

PURPOSE: Metastatic Crohn's disease is a rare complication of Crohn's disease that has been infrequently reported in the literature. We report a case where submammary, inguinal, and perineal disease was observed in a patient many years after a proctocolectomy. The proliferative and polypoid morphology of the cutaneous lesions has not been previously described. In addition, this case describes severe cutaneous metastatic Crohn's disease in the absence of active gastrointestinal disease, which to our knowledge has not been reported in the literature. RESULTS: A 55-year-old female with a 25-year history of Crohn's disease was investigated and treated over a 12-month period for metastatic Crohn's disease involving the submammary, inguinal, and perineal areas. These proliferative lesions with erythema and ulceration were histologically consistent with metastatic Crohn's disease. Gram and Ziehl Nielsen stains revealed no pathogenic organisms. The use of topical solutions, antibiotics, immunosuppression, and surgery failed to produce any significant benefit. A review of 42 cases of metastatic Crohn's disease in the literature is reported. CONCLUSION: Cutaneous metastatic Crohn's disease has an extremely variable macroscopic appearance and may be a source of considerable morbidity. It can be present without other significant symptomatology, although it more commonly parallels gastrointestinal disease activity. There are no trials to guide current treatment, which is mainly based on anecdotal reporting.

Internet resources for dentistry: computer, Internet, reference, and sites for enhancing personal productivity of the dental professional.

At the onset of the new millennium the Internet has become the new standard means of distributing information. In the last two to three years there has been an explosion of e-commerce with hundreds of new web sites being created every minute. For most corporate entities, a web site is as essential as the phone book listing used to be. Twenty years ago technologist directed how computer-based systems were utilized. Now it is the end users of personal computers that have gained expertise and drive the functionality of software applications. The computer, initially invented for mathematical functions, has transitioned from this role to an integrated communications device that provides the portal to the digital world. The Web needs to be used by healthcare professionals, not only for professional activities, but also for instant access to information and services "just when they need it." This will facilitate the longitudinal use of information as society continues to gain better information access skills. With the demand for current "just in time" information and the standards established by Internet protocols, reference sources of information may be maintained in dynamic fashion. News services have been available through the Internet for several years, but now reference materials such as online journals and digital textbooks have become available and have the potential to change the traditional publishing industry. The pace of change should make us consider Will Rogers' advice, "It isn't good enough to be moving in the right direction. If you are not moving fast enough, you can still get run over!" The intent of this article is to complement previous articles on Internet Resources published in this journal, by presenting information about web sites that present information on computer and Internet technologies, reference materials, news information, and information that lets us improve personal productivity. Neither the author, nor the Journal endorses any of the sites or products listed, but include these references and links as a matter of convenience for its readers.