Robotic-assisted, laparoscopic, and open incisional hernia repair: early outcomes from the Prospective Hernia Study.

PURPOSE: To provide a comparative analysis of short-term outcomes after open, laparoscopic, and robotic-assisted (RAS) ventral incisional hernia (VIH) repairs that include subject-reported pain medication usage and hernia-related quality of life (QOL). METHODS: Subjects were ≥ 18 years old and underwent elective open, laparoscopic or RAS VIH repair without myofascial release. Perioperative clinical outcomes through 30 days were analyzed as were prescription pain medication use and subject-reported responses to the HerQLes Abdominal QOL questionnaire. Observed differences in baseline characteristics were controlled using a weighted propensity score analysis to obviate potential selection bias (inverse probability of treatment weighting, IPTW). A p value < 0.05 was considered statistically significant. RESULTS: Three hundred and seventy-one subjects (RAS, n = 159; open, n = 130; laparoscopic, n = 82) were enrolled in the study across 17 medical institutions within the United States. Operative times were significantly different between the RAS and laparoscopic groups (126.2 vs 57.2, respectively; p < 0.001). Mean length of stay was comparable for RAS vs laparoscopic (1.4 ± 1.0 vs 1.4 ± 1.1, respectively; p = 0.623) and differed for the RAS vs open groups (1.4 ± 1.0 vs 2.0 ± 1.9, respectively; p < 0.001). Conversion rates differed between RAS and laparoscopic groups (0.6% vs 4.9%; p = 0.004). The number of subjects reporting the need to take prescription pain medication through the 2-4 weeks visit differed between RAS vs open (65.2% vs 79.8%; p < 0.001) and RAS vs laparoscopic (65.2% vs 78.75%; p < 0.001). For those taking prescription pain medication, the mean number of pills taken was comparable for RAS vs open (23.3 vs 20.4; p = 0.079) and RAS vs laparoscopic (23.3 vs 23.3; p = 0.786). Times to return to normal activities and to work, complication rates and HerQLes QOL scores were comparable for the RAS vs open and RAS vs laparoscopic groups. The reoperation rate within 30 days post-procedure was comparable for RAS vs laparoscopic (0.6% vs 0%; p = 0.296) and differed for RAS vs open (0.6% vs 3.1%; p = 0.038). CONCLUSIONS: Short-term outcomes indicate that open, laparoscopic, and robotic-assisted approaches are effective surgical approaches to VIH repair; however, each repair technique may demonstrate advantages in terms of clinical outcomes. Observed differences in the RAS vs laparoscopic comparison are longer operative time and lower conversion rate in the RAS group. Observed differences in the RAS vs open comparison are shorter LOS and lower reoperation rate through 30 days in the RAS group. The operative time in the RAS vs open comparison is similar. The number of subjects requiring the use of prescription pain medication favored the RAS group in both comparisons; however, among subjects reporting a need for pain medication, there was no difference in the number of prescription pain medication pills taken. While the study adds to the body of evidence evaluating the open, laparoscopic, and RAS approaches, future controlled studies are needed to better understand pain and QOL outcomes related to incisional hernia repair. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02715622.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Prospective, multicenter, pairwise analysis of robotic-assisted inguinal hernia repair with open and laparoscopic inguinal hernia repair: early results from the Prospective Hernia Study.

PURPOSE: To evaluate and compare peri-operative outcomes through 30 days, including pain and quality of life (QOL) through 3 months across three cohorts of inguinal hernia repair (IHR) patients (robotic-assisted, laparoscopic, and open IHR). METHODS: The Prospective Hernia Study is an ongoing, multicenter, comparative, open-label analysis of clinical and patient-reported outcomes from robotic-assisted surgery (RAS) versus open and RAS versus laparoscopic IHR procedures. Patient responses to the Carolinas Comfort Scale (CCS) questionnaire provided QOL outcomes. RESULTS: 504 enrolled patients underwent unilateral or bilateral IHR (RAS, n = 159; open, n = 190; laparoscopic, n = 155) at 17 medical institutions from May 2016 through December 2018. Propensity score matching provided a balanced comparison: RAS versus open (n = 112 each) and RAS versus laparoscopic (n = 80 each). Overall, operative times were significantly different between the RAS and laparoscopic cases (83 vs. 65 min; p < 0.001). Fewer RAS patients required prescription pain medication than either open (49.5% vs. 80.0%; p < 0.001) or laparoscopic patients (45.3% vs. 65.4%; p = 0.013). Median number of prescription pain pills taken differed for RAS vs. open (0.5 vs. 15.5; p = 0.001) and were comparable for RAS vs laparoscopic (7.0 vs. 6.0; p = 0.482) among patients taking prescribed pain medication. Time to return to normal activities differed for RAS vs. open (3 vs. 4 days; p = 0.005) and were comparable for RAS vs. laparoscopic (4 vs. 4 days; p = 0.657). Median CCS scores through 3 months were comparable for the three approaches. Postoperative complication rates for the three groups also were comparable. One laparoscopic case was converted to open. CONCLUSION: This study demonstrates that IHR can be performed effectively with the robotic-assisted, laparoscopic, or open approaches. There was no difference in the median number of prescription pain medication pills taken between the RAS and laparoscopic groups. A difference was observed in the overall number of patients reporting the need to take prescription pain medication. Comparable operative times were observed for RAS unilateral IHR patients compared to open unilateral IHR patients; however, operative times for RAS overall and bilateral subjects were longer than for open patients. Operative times were longer overall for RAS patients compared to laparoscopic patients; however, there was no difference in conversion and complication rate in the RAS vs. laparoscopic groups or the complication rate in the RAS vs. open group. Time to return to normal activities for RAS IHR patients was comparable to that of laparoscopically repaired patients and significantly sooner compared to open IHR patients.

Open versus robotic-assisted transabdominal preperitoneal (R-TAPP) inguinal hernia repair: a multicenter matched analysis of clinical outcomes.

PURPOSE: To compare the perioperative outcomes of initial, consecutive robotic-assisted transabdominal preperitoneal (R-TAPP) inguinal hernia repair (IHR) cases with consecutive open cases completed by the same surgeons. METHODS: Multicenter, retrospective, comparative study of perioperative results from open and robotic IHR using standard univariate and multivariate regression analyses for propensity score matched (1:1) cohorts. RESULTS: Seven general surgeons at six institutions contributed 602 consecutive open IHR and 652 consecutive R-TAPP IHR cases. Baseline patient characteristics in the unmatched groups were similar with the exception of previous abdominal surgery and all baseline characteristics were comparable in the matched cohorts. In matched analyses, postoperative complications prior to discharge were comparable. However, from post discharge through 30 days, fewer patients experienced complications in the R-TAPP group than in the open group [4.3% vs 7.7% (p = 0.047)]. The R-TAPP group had no reoperations post discharge through 30 days of follow-up compared with five patients (1.1%) in the open group (p = 0.062), respectively. Multivariate logistic regression analysis which demonstrated patient age > 65 years and the open approach were risk factors for complications within 30 days post discharge in the matched group [age > 65 years: odds ratio (OR) = 3.33 (95% CI 1.89, 5.87; p < 0.0001); open approach: OR = 1.89 (95% CI 1.05, 3.38; p = 0.031)]. CONCLUSIONS: In this matched analysis, R-TAPP provides similar postoperative complications prior to discharge and a lower rate of postoperative complications through 30 days compared to open repair. R-TAPP is a promising and reproducible approach, and may facilitate adoption of minimally invasive repairs of inguinal hernias.

Imatinib: a designer drug, another cutaneous complication.

A 55-year-old man with a history of mild psoriasis was started on imatinib for chronic myeloid leukaemia. He developed new nail dystrophy after treatment with an exacerbation of his psoriasis. Although not a contraindication for this drug, it should be remembered that psoriasis may worsen with imatinib.

Pacemaker shift in the gastric antrum of guinea-pigs produced by excitatory vagal stimulation involves intramuscular interstitial cells.

Intracellular recordings were made from isolated bundles of the circular muscle layer of guinea-pig gastric antrum and the responses produced by stimulating intrinsic nerve fibres were examined. After abolishing the effects of stimulating inhibitory nerve terminals with apamin and L-nitroarginine (NOLA), transmural nerve stimulation often evoked a small amplitude excitatory junction potential (EJP) and invariably evoked a regenerative potential. Neurally evoked regenerative potentials had similar properties to those evoked in the same bundle by direct stimulation. EJPs and neurally evoked regenerative potentials were abolished by hyoscine suggesting that both resulted from the release of acetylcholine and activation of muscarinic receptors. Neurally evoked regenerative potentials, but not EJPs, were abolished by membrane hyperpolarization, caffeine and chloride channel blockers. In the intact antrum, excitatory vagal nerve stimulation increased the frequency of slow waves. Simultaneous intracellular recordings of pacemaker potentials from myenteric interstitial cells (ICC(MY)) and slow waves showed that the onset of each pacemaker potential normally preceded the onset of each slow wave but vagal stimulation caused the onset of each slow wave to precede each pacemaker potential. Together the observations suggest that during vagal stimulation there is a change in the origin of pacemaker activity with slow waves being initiated by intramuscular interstitial cells (ICC(IM)) rather than by ICC(MY).

Selective knockout of intramuscular interstitial cells reveals their role in the generation of slow waves in mouse stomach.

1. Intracellular recording techniques were used to compare the patterns of electrical activity generated in the antral region of the stomachs of wild-type and W/W(V) mutant mice. Immunohistochemical techniques were used to determine the distribution of c-kit-positive interstitial cells of Cajal (ICC) within the same region of the stomach. 2. In wild-type mice interstitial cells were found at the level of the myenteric plexus (ICC(MY)) and distributed within the smooth muscle bundles (ICC(IM)). In these preparations slow waves, which consisted of initial and secondary components, were detected. 3. In W/WV mutant mice ICC(MY) could be identified at the level of the myenteric plexus but ICC(IM) were not detected within smooth muscle bundles. Intracellular recordings revealed that smooth muscle cells generated waves of depolarization; these lacked a secondary component. 4. These results indicate that the secondary regenerative component of a slow wave is generated by ICC(IM). Thus the depolarization arising from the pacemaker cells, ICC(MY), is augmented by ICC(IM), so causing a substantial membrane depolarization in the circular muscle layer. Rather than contributing directly to rhythmical electrical activity, smooth muscle cells appear to depolarize at the command of the two subpopulations of ICC.

Vagal inhibition in the antral region of guinea pig stomach.

The effects of vagal stimulation in the presence of a muscarinic antagonist were examined on three distinct rhythmically active cells located in guinea pig antrum. Vagal stimulation inhibited contractions of the circular muscle layer but did not change their rate of occurrence. With the use of intracellular recording techniques, these stimuli were found to initiate inhibitory junction potentials in the circular layer but produced smaller potential changes in driving and follower cells. Inhibition of the circular muscle layer involved two separate components. The dominant component was independent of changes in membrane potential and was abolished by nitro-L-arginine. After abolishing Ca(2+) entry into smooth muscle cells with a Ca(2+) antagonist, vagal stimulation continued to inhibit the residual contractions associated with each slow wave. When the cyclic changes in intracellular Ca(2+) concentration associated with each slow wave were measured, they were found to be unchanged by vagal stimulation. The observations suggest that vagal inhibition of stomach movements does not alter pacemaker activity in the stomach; rather, it results from a change in the sensitivity of smooth muscle contractile proteins to Ca(2+).

A patient determined general practice satisfaction questionnaire.

OBJECTIVES: To develop and explore the use of a patient satisfaction questionnaire based on patient perceptions of items which influence satisfaction and to explore patient and practitioner characteristics which influence the results. METHOD: Twenty focus groups identified 39 items which were then assembled into a questionnaire which was evaluated by attendees at 133 Australian general practices. MAIN OUTCOME MEASURES: Overall satisfaction with general practitioner services and the appropriateness of the 39 items identified by focus group participants; socio-demographic characteristics of patients and practitioners and the impact of these characteristics on the results; factor analysis of the relationship of the items to each other and to overall satisfaction. RESULTS: Questionnaires were completed by 12,605 patients of 133 general practices. Seventy-three percent of these patients reported they were overall very satisfied with the care they received and 26% were satisfied. There were five individual items for which an average of more than 10% of patients reported they were not satisfied: waiting time at the surgery (18%); ease of obtaining home visits (17%); ease of seeing the doctor out of normal hours (15%); cost of drugs (12%) and facilities for children in the waiting room (10%). Factors which were more likely to result in a report of patients being very satisfied included: patients being older; if patients had visited recently; if they had attended the practice for a long time; if they visited only one general practice and had more consultations in the past 12 months. Patients of solo practitioners were more likely to report they were satisfied with individual items and patients of practices of three or more practitioners were least likely. No significant differences between practices of different sizes in the level of overall satisfaction were detected. Factor analysis identified three major factors which we have described as containing interaction, technical and accessibility items. These three factors explained 44.4% of the variance in results. CONCLUSION: This project found the items patients identified were similar to those identified by practitioners, and reiterated previous findings that there is substantial variability in the levels of satisfaction reported by patients of Australian general practices.

The provision of preventive care by general practitioners measured by patient completed questionnaires.

The objective of this study was, by means of patient self-report, to measure the provision of preventive care to patients of a sample of Australian general practitioners. Patient-completed questionnaires from a consecutive sample of Australian general practitioners enrolled in the Quality Assurance and Continuing Medical Education Program of the Royal Australian College of General Practitioners were used. Patients were attendees at Australian general practices. The main outcome measures included the following: the provision of tetanus immunization within the last 10 years; blood pressure measurement within the last 12 months; cholesterol screening within the past 5 years; provision of adequate information to enable patients to stop smoking if they desired; discussion about the benefits of diet and exercise to enhance life, and about alcohol intake; provision of cervical smears in the past 2 years; provision of adequate instruction in breast self-examination and overall satisfaction with service provision. A total of 12,605 questionnaires from 133 general practices were completed. There was wide variability between practices in the reported provision of preventive care items including an average of 86% (range 36-100) of patients reporting the provision of blood pressure checking in the past 12 months, 62% (range 25-97%) reporting the provision of tetanus immunization in the past 10 years, and 63% (range 10-91%) reporting having had a cervical smear in the past 2 years. Patients who were very satisfied were more likely to have reported that they had received blood pressure measurement in the past 12 months, participated in discussions about the benefits of diet and exercise in enhancing life, and participated in discussions about alcohol intake and provision of adequate instruction in the technique of breast self-examination. Patient self-reporting identified variability between practitioners in the provision of preventive care conforming to accepted guidelines. Patients who reported that they were very satisfied or who regularly attend only one general practice reported the provision of more preventive care than those who were not very satisfied or who regularly visited two or more general practitioners.

Identification of rhythmically active cells in guinea-pig stomach.

1. When intracellular recordings were made from the antral region of guinea-pig stomach, cells with different patterns of electrical activity were detected. 2. One group of cells, slow-wave cells, generated slow waves which consisted of initial and secondary components. When filled with either Lucifer Yellow or neurobiotin, the cells identified as smooth muscle cells lying in the circular muscle layer. 3. A second group of cells, driving cells, generated large, rapidly rising, potential changes, driving potentials. They had small cell bodies with several processes. With neurobiotin, a network of cells was visualized that resembled c-kit positive interstitial cells of the myenteric region. 4. A third group of cells generated sequences of potential changes which resembled driving potentials but had smaller amplitudes and slow rates of rise. These cells resembled smooth muscle cells lying in the longitudinal muscle layer. 5. When simultaneous recordings were made from the driving and slow-wave cells, driving potentials and slow waves occurred synchronously. Current injections indicated that both cell types were part of a common electrical syncytium. 6. The initial component of slow waves persisted in low concentrations of caffeine, but the secondary component was abolished; higher concentrations shortened the duration of the residual initial component. Driving potentials continued in the presence of low concentrations of caffeine; moderate concentrations of caffeine shortened their duration. 7. Hence three different types of cells were distinguished on the basis of their electrical activity, their responses to caffeine and their structure. These were smooth muscle cells, lying in the longitudinal and circular layers, and interstitial cells in the myenteric region. The observations suggest that interstitial cells initiate slow waves.

Preventive care and continuity of attendance. Is there a risk?

OBJECTIVE: To explore whether there are associations between continuity of care and the provision of items of preventive care in Australian general practice. METHOD: Patient completed questionnaires from a 'consecutive' sample of Australian general practitioners enrolled in the Patient Participation Program of the Quality Assurance and Continuing Medical Education Program of the Royal Australian College of General Practitioners. MAIN OUTCOME MEASURES: An association was sought between the length of time patients reported attending their practitioner, whether they regularly attended more than one practice, and whether they were provided with preventive care. RESULTS: Data from 12,605 questionnaires, completed by patients from 133 practices throughout Australia found that patients who reported only visiting one practice on a regular basis were significantly more likely to report the provision of: blood pressure screening within the past 12 months; cholesterol screening in the past 5 years; adequate smoking cessation information if required; to have discussed the benefits of diet and exercise; to have received a cervical smear in the past 2 years; and to have received adequate instruction in the technique of breast self examination. Patients attending the same practices for longer periods were significantly more likely to have received the above items with the exception of adequate information to enable them to stop smoking if they desired; and cervical smears in the past 2 years. Such patients were less likely to report the provision of tetanus immunisation in the past 10 years and cervical smears in the past 2 years. CONCLUSIONS: Patients reporting greater continuity of care measured by only consulting at one practice or visiting the practice for a longer time period reported a greater provision of preventive care than patients who did not report these characteristics.

Xanthine oxidase activity in the circulation of rats following hemorrhagic shock.

Reactive oxygen metabolites generated from xanthine oxidase play an important role in the pathogenesis of ischemia-induced tissue injury. In a hemorrhagic shock model of ischemia-reperfusion, the intracellular enzyme xanthine oxidase was released into the vasculature. This intravascular source of superoxide (O2.-) and hydrogen peroxide (H2O2) interacted reversibly with glycosaminoglycans of vascular endothelium and markedly concentrated xanthine oxidase at cell surfaces, enhancing its ability to produce extensive damage to remote tissues. Rats were made hypotensive by hemorrhage, maintained for 2h, and reinfused with shed blood. Blood samples were obtained prior to hemorrhage and 15, 30, 60, and 90 min after reperfusion for determination of xanthine oxidase (XO), lactate dehydrogenase (LDH), and alanine transaminase (AST). These enzymes were not significantly elevated in control animals. Reperfusion after hemorrhage-induced ischemia resulted in significantly elevated AST and LDH in both low heparin (100 U/h) and high heparin (1000 U/h) groups. Xanthine oxidase was detected in the circulation only after 90 min reperfusion in the low heparin group and was elevated during the entire reperfusion period in the high heparin group. Studies with cultured vascular endothelium showed significant heparin-reversible binding of XO to cellular glycosaminoglycans. These results suggest that XO can gain access to the circulation following ischemia, where it then binds to the vascular endothelial cells to produce site-specific oxidant injury to organs remote from the site of XO release.

In situ hybridization of interleukin-1 in CD14-positive cells in rheumatoid arthritis.

Interleukin 1 (IL-1) has been implicated as an inflammatory mediator in rheumatoid arthritis (RA). Many cell types, including macrophages, lymphocytes, fibroblasts, and endothelial cells, can produce IL-1 and it is known that IL-1 production is under transcriptional control. It has, however, been difficult to define in vivo the predominant cellular source of this mediator in RA. Here, we have used the combination of in situ hybridization of mRNA and cellular immunophenotyping with monoclonal antibodies to show that the IL-1 beta gene is expressed predominantly by CD14-positive macrophages in synovial tissue from patients with RA. Synovial macrophages were also associated with the immunoreactive IL-1 peptide. These cells appear to be the major source of IL-1 beta within the rheumatoid synovium in vivo and must be regarded as playing a central role in the chronic inflammation and joint destruction of RA.

In situ hybridization of IL-6 in rheumatoid arthritis.

IL-6, an important mediator of the acute phase response, has been implicated in the pathogenesis of rheumatoid arthritis (RA). Many cell types including macrophages, T cells, B cells, endothelial cells and fibroblasts can produce this cytokine and production is largely regulated at the level of gene transcription or mRNA stabilization. In this paper we have first measured the levels of IL-6 activity in synovial fluid (SF) and serum from patients with RA and then localized IL-6-producing cells in the synovium by in situ hybridization combined with immunophenotyping. Patients with RA had raised levels of IL-6 in both SF and serum compared with patients with osteoarthritis and age-matched healthy controls. In individual RA patients tested serially after admission to hospital, serum IL-6 was initially raised and, unexpectedly, increased with clinical improvement. In situ hybridization of IL-6 mRNA showed positive cells both in the lymphocyte-rich aggregates and adjacent to small blood vessels. With immunophenotyping it was found that cells containing IL-6 mRNA were often in contact with CD14+ tissue macrophages and double immunophenotyping revealed that immunoreactive IL-6 was often associated with synovial T cells.

In situ hybridisation.

In situ hybridisation of mRNA in tissues or cell preparations is a powerful technique for studying gene expression. When combined with cell phenotyping with monoclonal antibodies it gives insights into the cellular basis of disease in vivo. The technique has also been used widely to identify foreign nucleic acids--for example, bacterial or viral, in host cells. The major disadvantages of this approach in the past have been that it was technically demanding, time consuming, and provided qualitative rather than quantitative results. Now, with the use of non-radioactive probes and improved imaging systems, the full potential of this form of molecular analysis is increasingly accessible and should generate rapid advances in many fields.

Interleukin 1 activity produced by human rheumatoid and normal dendritic cells.

Dendritic cells (DC) from the synovial inflammatory tissue and peripheral blood of patients with rheumatoid arthritis and from the peripheral blood of normal blood donors were compared with the autologous monocytes for their capacity to produce and release interleukin 1 (IL-1). Synovial DC often spontaneously released higher amounts of IL-1 activity than unstimulated and lipopolysaccharide-stimulated peripheral blood DC and monocytes. The IL-1 production by both DC and monocytes increased after stimulation with bacterial lipopolysaccharide. In contrast with synovial DC the peripheral blood DC from both patients with rheumatoid arthritis and normal controls released less IL-1 activity than peripheral blood monocytes did. Inhibition with an antiserum to IL-1 revealed that IL-1 production is important for the accessory activity of the peripheral blood DC. Thus human DC from inflammatory sites and peripheral blood produce IL-1 activity.