Maternal and neonatal outcomes of COVID-19 in a high-risk pregnant cohort with and without HIV.

BACKGROUND: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously. OBJECTIVES: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV. METHODS: We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m2) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV. RESULTS: One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n=61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p<0.001). Neonatal outcomes were favourable. No significant differences in COVID-19 risk factors, disease severity, and maternal/neonatal outcome were noted for PLHIV v. those without HIV. CONCLUSIONS: In this cohort of high-risk pregnant women, the impact of COVID-19 was severe, significantly increasing maternal mortality risk compared with baseline rates. Virally suppressed HIV infection was not associated with worse COVID-19 outcomes in pregnancy.

Analysis of synovial biomarkers with a multiplex protein microarray in patients with PJI undergoing revision arthroplasty of the hip or knee joint.

INTRODUCTION: Diagnosing a (low-grade) periprosthetic joint infection (PJI) after hip or knee arthroplasty remains a diagnostic challenge. The aim of this study was to evaluate the utility of using a novel multiplex protein microarray system for synovial biomarkers in determining PJI in patients undergoing revision knee or hip arthroplasty. MATERIALS AND METHODS: The individual synovial fluid levels of 12 cytokines (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, GM-CSF, TNF-α, and INF-γ) were analysed with a novel multiplex protein microarray system in 32 patients undergoing revision hip (n = 22) or knee (n = 10) arthroplasty. Cases were classified into septic and aseptic groups on basis of pre- and interoperative findings: [PJI (n = 14) vs. non-PJI (n = 18)]. Receiver operator characteristic (ROC) curves were calculated to assess the discriminatory strength of the individual parameters. A multiple regression model was used to determine the utility of using a combination of the tested cytokines to determine the infection status. RESULTS: The levels of all of the evaluated cytokines were significantly elevated in the PJI-group. Best sensitivity and specificity were found for IL-6, followed by IL-1b, IL-10, and IL-17. The multiple regression models revealed a combination of IL-2, IL-4, IL-5, IL6, lL-12, and GM-CSF to be associated with the best sensitivity (100%) and specificity (88.9%) for a cut-off value of 0.41, with a likelihood ratio of 9.0. CONCLUSION: Analysis of individual synovial fluid cytokine levels showed both high sensitivity and high specificity in diagnosing PJI. A combined model using several cytokines showed even higher sensitivity and specificity in diagnosing PJI and could thus be a useful predictive tool to determine the probability of PJI in patients with a painful prosthesis. LEVEL OF EVIDENCE: Diagnostic IV.

Case report: Traumatic lingual hematoma.

We describe a case of traumatic lingual hematoma in a patient on dual antiplatelet therapy. After securing the airway, bilateral lingual artery embolization successfully halted expanding hematoma formation. Patient subsequently required tracheostomy for continued airway edema. Although patient course was wrought with postoperative complications, we review this case to illustrate how prompt hematoma evacuation and embolization can resolve significant vasovagal bradycardia and hypotension secondary to expansile lingual hematoma.

Evaluation of the accuracy of nine electronic apex locators by using Micro-CT.

AIM: To determine the accuracy of locating the apical constriction using apex locators. METHODOLOGY: Extracted teeth were micro-CT scanned preoperatively to localize the apical constriction. Electronic length measurements of 91 root canals were made using nine electronic apex locators (EAL) connected to a mounting model. Distances from the major foramen were recorded at each scale bar of the EALs, and a file was fixed in the canal at a position indicated by each EAL to be the apical constriction. A second micro-CT scan was conducted, and distances from the file tip to constriction and major foramen were calculated for each EAL. The accuracy of EALs was determined with a tolerance of 0.1, 0.25, 0.5 and 1 mm, and the 95% confidence interval was used to compare the EALs. A rank analysis was performed in which measurements beyond the major foramen were considered as inaccurate. RESULTS: Regardless of the type of teeth, there was no significant difference in the accuracy of determining the apical constriction and major foramen between the nine EALs within a tolerance of ±0.5 mm and 1 mm, but there was a significant difference for the tolerances of ±0.1 and 0.25 mm. The highest ranks close to the constriction (98% and 94%) and to the major foramen (86% and 73%) were observed in Dentaport ZX and Elements Diagnostic Unit, respectively. Overestimation of working length beyond the major foramen was observed in all EALs (5% to 71%) when the scale for the major foramen, as recommended by the manufacturers, was used. However, when the scale for the constriction was used, only 3% of the measurements were beyond the major foramen. CONCLUSION: Electronic apex locators were able to determine the apical constriction. Using EALs to determine the major foramen led to overestimation of the working length. Therefore, it may be recommended to use the EAL scale of the constriction.

Validity of longitudinal sections for determining the apical constriction.

AIM: To validate the use of longitudinal sections against cross sections using micro-CT for disclosing the topography and location of the apical constriction. METHODOLOGY: Seventy extracted human teeth with 117 completely developed roots were micro-CT scanned and reconstructed at a voxel size of 27 µm. The 3DSlicer program was used to navigate the longitudinal sections parallel to the long axis of the canal and also to rotate and tilt the views. Each root canal was evaluated in both mesio-distal and bucco-lingual planes. Constriction topographies were identified as described in the literature. In each canal, the number of different topographies detected was recorded. Further, serial cross-sectional analysis of the apical portion of the canal was performed. Reconstructed plots of canal areas were assessed to locate the constriction and determine its form. A descriptive analysis of both longitudinal and cross section methods was conducted. In each canal, the frequency of constriction forms was calculated in the mesio-distal or bucco-lingual aspects and the 99% confidence interval was computed. RESULTS: When both aspects of the longitudinal sections were pooled, all root canals had two or more topographies and consequently different locations of the apical constriction. In contrast, cross-sectional analysis constantly yielded one constriction form per canal. CONCLUSION: Compared to cross-sectional analysis, longitudinal sections of the root canal conveyed inconsistent results regarding the topography and the location of the apical constriction.

Maturational, comorbid, maternal and discharge domain impact on preterm rehospitalizations: a comparison of planned and unplanned rehospitalizations.

OBJECTIVE: To determine the predictive value of (1) maternal, (2) maturational, (3) comorbid and (4) discharge domains associated with preterm infant rehospitalization. STUDY DESIGN: Retrospective, cohort study of preterm infants discharged home from a level IV neonatal intensive care unit. Rates of unplanned and planned 6-month readmissions were assessed. The four domains were modeled incrementally and separately to predict relative and combined contributions to the readmission risk. RESULT: Out of 504 infants, 5% had 30-day readmissions (22 unplanned, three planned). By 6 months, 13% were rehospitalized (52 unplanned, 15 planned). Sixty-seven infants had 96 readmission events with 30% of readmission events elective. The four domains together predicted 78% of total 1-month, all 6-month and unplanned 6-month readmissions. Discharge complexity was as predictive as comorbidity in all models. CONCLUSION: These four-domain models were more predictive than single domains. Many total readmission events were planned, suggesting parsing planned and unplanned rehospitalizations may benefit quality-improvement efforts.

Older siblings as potential supervisors of younger siblings: sibling supervisors' recognition of injury-risk behaviours and beliefs about supervisee risk taking and potential injury outcomes.

BACKGROUND: Past research has shown that increased injury risk for supervisees during sibling supervision is in part due to the supervision practices of older siblings. METHODS: The current study used a photo sorting task to examine older siblings' recognition of injury-risk behaviours, their perceived likelihood of supervisees engaging in, or being injured while engaging in, these behaviours, and awareness of past risk-taking behaviours of supervisees. Mothers completed the same measures and an interview about sibling supervision in the home. RESULTS: Mothers reported that sibling supervision occurred most frequently in the kitchen, living room, and children's bedrooms, for approximately 39 min/day, and that the more time the children spent together in a room, the more frequently the older sibling supervised the younger one. The most common reasons mothers gave for why sibling supervision was allowed included beliefs that the older child knows about hazards and unsafe behaviours and that the child could provide adequate supervision. Photo sort results revealed that older siblings were able to correctly identify about 98% of risk behaviours, with these scores significantly higher than what mothers expected (79%). However, compared with mothers, older siblings were less aware of risk behaviours that their younger siblings had engaged in previously. In addition, mothers rated supervisees as 'fairly likely' both to engage in risk behaviours and to experience an injury if they tried these behaviours, whereas sibling supervisors rated both supervisee risk behaviour and injury outcomes as 'not likely' to occur. CONCLUSION: Older siblings showed good knowledge of hazards but failed to realize that younger children often engage in injury-risk behaviours. Efforts to improve the supervision practices of sibling supervisors need to include changing their perception of supervisees' injury vulnerability and potential injury severity, rather than targeting to increase knowledge of injury-risk behaviours per se.

Dosimetric effects of energy spectrum uncertainties in radiation therapy with laser-driven particle beams.

Laser-driven particle acceleration is a potentially cost-efficient and compact new technology that might replace synchrotrons or cyclotrons for future proton or heavy-ion radiation therapy. Since the energy spectrum of laser-accelerated particles is rather wide, compared to the monoenergetic beams of conventional machines, studies have proposed the usage of broader spectra for the treatment of at least certain parts of the target volume to make the process more efficient. The thereby introduced additional uncertainty in the applied energy spectrum is analysed in this note. It is shown that the uncertainty can be categorized into a change of the total number of particles, and a change in the energy distribution of the particles. The former one can be monitored by a simple fluence detector and cancels for a high number of statistically fluctuating shots. The latter one, the redistribution of a fixed number of particles to different energy bins in the window of transmitted energies of the energy selection system, only introduces smaller changes to the resulting depth dose curve. Therefore, it might not be necessary to monitor this uncertainty for all applied shots. These findings might enable an easier uncertainty management for particle therapy with broad energy spectra.

Modifying proton fluence spectra to generate spread-out Bragg peaks with laser accelerated proton beams.

Currently, energy spectra of laser accelerated proton beams are far from being monoenergetic. For their application in radiation therapy, energy selection systems using magnetic fields have been proposed to single out particles with the desired energy. These systems allow the choice of protons between a lowest and a highest energy. In this work, we present a slight modification that allows us to influence the relative number of particles per energy bin. In fact, the transmitted spectrum can be shaped in such a way that it corresponds to a full spread out Bragg peak delivered simultaneously. This change of the spectrum can be achieved by inserting suitably formed scattering material at the central plane of the energy selection system where the particles are separated in space depending on their energy. With the help of Monte Carlo simulations we analysed both simple wedge geometries and various stacks of lead slices. We found that these configurations can provide energy spectra that naturally produce spread out Bragg peaks within one laser shot. This increases the particle efficiency of the whole system and makes laser accelerated protons more suitable for radiation therapy.

Radiofrequency ablation treatment of refractory carcinoid hepatic metastases.

BACKGROUND: Our institution has experienced excellent success using hepatic artery embolization for treating symptoms and slowing tumor progression for patients with unresectable hepatic metastases for carcinoid tumors. Our previous treatment strategies used hepatic artery embolization alone, examining control of symptoms and dependence on octreotide therapy. However, some patients exhibit hepatic metastases that are unresponsive to embolization. This report describes the use of radiofrequency ablation (RFA) as salvage treatment for these refractory metastases. METHODS: Thirteen patients with unresectable bilobar hepatic metastases from biochemically confirmed carcinoid tumors were treated with selective hepatic artery embolization using Lipiodol/Gelfoam between 1994 and 2000. Three patients developed symptoms resistant to embolization treatment resulting from progression of existing metastases or development of new metastases. These patients underwent surgical exploration and intraoperative ultrasound of their refractory lesions, followed by treatment with RFA. Tumor size, symptoms of carcinoid syndrome, and octreotide requirements were monitored postoperatively. RESULTS: Median follow-up for the three patients treated with RFA was 6 months. During the first 3-month interval following RFA, all three patients demonstrated decrease in the size of treated lesions. Using our previously developed symptom scoring system, all three patients demonstrated decreased symptoms following treatment. One patient was able to discontinue octreotide treatment, and the other two patients required decrease octreotide dosages. CONCLUSIONS: This study demonstrates that utilization of RFA treatment for carcinoid metastases refractory to hepatic artery embolization may represent a useful adjunct for symptomatic control, decreased octreotide dependence, and slowing of disease progression.

Local excision and postoperative radiation therapy for rectal adenocarcinoma.

Sixty-seven patients with early-stage adenocarcinoma of the rectum who had lesions thought to be unsuitable for either local excision alone or endocavitary irradiation were treated with local excision followed by postoperative radiation therapy. The purpose of this study was to evaluate the effectiveness of local excision followed by radiation therapy for treatment of rectal adenocarcinoma. The patients were treated between 1974 and 1999; follow-up time was 6 to 273 months (median, 65 months). All living patients had follow-up for at least 2 years. The indications for postoperative irradiation included equivocal or positive margins, invasion of the muscularis propria, endothelial-lined space invasion, poorly differentiated histology, and perineural invasion. Cox proportional hazards regression analysis was performed using six explanatory variables including tumor size, configuration (exophytic vs. ulcerative), histologic differentiation, pathologic T stage, endothelial-lined space invasion, and margin status. The time interval between treatment and development of recurrent disease was in the range of 11 to 48 months. The 5-year results were as follows: local-regional control, 86%; ultimate local-regional control, 93%; distant metastasis-free survival, 93%; absolute survival, 80%; and cause-specific survival, 90%. When the Cox proportional hazards regression analysis was performed for these endpoints, margin status influenced absolute survival (P = 0.0074), cause-specific survival (P = 0.0405), and ultimate local-regional control (P = 0.0439). Tumor configuration marginally influenced cause-specific survival (P = 0.0577). None of the variables had an influence on the endpoints' local-regional control, ultimate local-regional control with sphincter preservation, or distant metastasis. Five patients (7%) had severe complications; no complication was fatal. Local excision and postoperative radiation therapy results in a high probability of local-regional control and survival for selected patients with relatively early-stage rectal adenocarcinoma. Patients with ulcerative tumors may have a lower likelihood of cause-specific survival.

The pain-related negative difference potential: a direct measure of central pain pathway activity or of interactions between the innocuous somatosensory and pain pathways?

Negative difference potential (NDP) is a sural nerve-evoked scalp potential derived by subtracting potentials elicited at the pain threshold level from those elicited at supra-pain threshold levels. Our recent work examined the possibility that the NDP reflects a pain-related inhibition of neurons in the innocuous somatosensory pathways. Although failing to find any evidence for this inhibition, these studies do present the possibility that the NDP reflects an attention- and/or task-related decrease in the innocuous somatosensory activity that is elicited by the noxious electrical stimulus. To test this hypothesis, 35 healthy subjects were given three attention/task relevance conditions presented in counterbalanced order: rate the subjective magnitude of the painful aspects of the noxious electrical stimulus; rate the subjective magnitude of the non-painful aspects of the noxious electrical stimulus; and, ignore the stimulus. Neither changes in attention nor the task relevance of the non-painful aspects of the stimulus had any effect on NDP amplitude. These data demonstrate that the NDP does not reflect an attention- or task-related modulation of innocuous somatosensory activity. Rather, our evidence to date suggests that the NDP is generated by activity in the central pain pathways.

Paraplegia following intraoperative celiac plexus injection.

The technique for percutaneous and open neurolytic celiac plexus injection, using ethanol or phenol, for relief of intractable pancreatic cancer pain has been well described. Prospective randomized studies, demonstrating safety and efficacy with few complications, have led to widespread acceptance and use of this palliative procedure. The complications of neurolytic celiac plexus injection are rare, and are usually minor. However, transient or permanent paraplegia has been reported previously in 10 cases. The case described herein represents the third reported case of permanent paraplegia following open intraoperative neurolytic celiac plexus injection using 50% ethanol. The literature surveying the indications for this procedure, routes of administration, known complications, and their pathophysiology are reviewed.

Laparoscopic adrenalectomy for nonmalignant disease: improved safety, morbidity, and cost-effectiveness.

BACKGROUND: Laparoscopic adrenalectomy has rapidly gained widespread acceptance for treatment of benign adrenal neoplasms. A number of authors have compared various anatomic approaches to laparoscopic adrenalectomy, comparing length of inpatient stay, transfusion requirements, and perioperative complications. Separate studies have found inpatient stay reduced 40-60% with the use of laparoscopic adrenalectomy vs. an open procedure. METHODS: There have been no studies designed specifically to examine and compare perioperative morbidity, length of stay, and patient charges in patients undergoing laparoscopic adrenalectomy. This report examines the Johns Hopkins Hospital experience with laparoscopic adrenalectomy in 22 patients, comparing length of stay, perioperative morbidity, and patient charges. These data are compared with those seen in 17 patients undergoing open adrenalectomy within our institution and 70 patients at all other nonfederal hospitals in the state of Maryland. RESULTS: Outcomes after laparoscopic versus open adrenalectomy were compared. Resumption of diet (1.6 vs. 6.1 days), independent activity (1.6 vs. 7.9 days), inpatient length of stay (1.7 vs. 7.8 days), and total hospital patient charges ($8,698 vs. $12,610) were all significantly reduced in patients undergoing laparoscopic adrenalectomy at our institution. Similar findings were obtained when our data were compared against adrenalectomy performed at other hospitals within the state of Maryland. Length of stay (1.7 vs. 8.9 days) and total hospital patient charges ($8,698 vs. $13,867) were both significantly reduced compared to state-wide data in patients treated with laparoscopic adrenalectomy. CONCLUSIONS: Although a technically challenging procedure, laparoscopic adrenalectomy provides clear advantages over open procedures for the vast majority of adrenal neoplasms. Our data support the conclusion that laparoscopic adrenalectomy should be considered for all patients with benign adrenal neoplasms.

Innocuous-related sural nerve-evoked and finger-evoked potentials generated in the primary somatosensory and supplementary motor cortices.

OBJECTIVE: Our earlier work revealed two components of the somatosensory evoked potential, which we have labeled SP1 and SP4a, that appear to be generated by neurons involved in the innocuous aspects of somatosensation. The objective of the present study was to examine a hypothesis developed in our earlier work, namely that SP1 and SP4a are generated in the primary somatosensory cortex. METHODS: The dipole source localization method was applied to SP1 and SP4a evoked by electrical stimulation of the fingers and of the sural nerve in 20 subjects. The subjects rated the subjective magnitude of each stimulus on a 9 point scale. RESULTS: The finger-evoked and sural nerve-evoked SP1 were best-fit by single sources located in the primary somatosensory cortex (SI) hand and foot areas, respectively. Both the finger-evoked and the sural nerve-evoked SP4a, on the other hand, were best-fit by a single source located in the supplementary motor area (SMA). CONCLUSIONS: These results are consistent with our hypothesis that SP1 reflects the activity of SI neurons that are involved in innocuous somatosensation. SP4a is not generated in SI as we originally hypothesized, but rather in the SMA. The SP4a amplitude-stimulus intensity function and the dependence of the SP4a source location on the evoking stimulus site and not the hand registering the magnitude rating suggests that SP4a reflects the response of SMA neurons to afferent input from the innocuous somatosensory pathways. Hence, SP4a may be generated by SMA activity involved in the sensory-guided selection and/or generation of motor responses.

Evidence that the anterior cingulate and supplementary somatosensory cortices generate the pain-related negative difference potential.

OBJECTIVE: The pain-related negative difference potential (NDP) is derived by subtracting sural nerve-evoked somatosensory evoked potentials elicited at the pain threshold level from those elicited at supra-pain threshold levels. This experiment evaluated a hypothesis derived from our earlier work, namely that the NDP is generated by pain-related activity in the primary somatosensory (SI) cortex. METHODS: The dipole source localization method was applied to NDPs evoked by electrical stimulation of the finger and of the sural nerve in 20 subjects. RESULTS: Comparison of several one-, two- and three-source configurations demonstrated that both the finger-evoked NDP and the sural nerve-evoked NDP are best-fit by two sources, with one located in or near the anterior cingulate cortex and the other in or near the supplementary somatosensory area. CONCLUSIONS: Both the anterior cingulate cortex and the supplementary somatosensory area receive afferent projections from medial thalamic nuclei that receive nociceptive inputs, and both have been shown to respond to noxious stimulation. Hence, although the results of this experiment did not confirm our hypothesis that the NDP is generated in SI, they are consistent with the hypothesis that the NDP is generated in the supraspinal pain pathways.

Control of fecal incontinence: continued success with the Malone procedure.

BACKGROUND: Our center has previously reported the use of the Malone antegrade continence enema procedure in children. The procedure involves bringing the appendix to the surface of the abdominal wall to provide a nonrefluxing catheterizable channel that enables antegrade colonic lavage for the control of fecal incontinence. METHODS: This report critically evaluates 23 patients treated for fecal incontinence with up to 6 years of follow-up. After operation, specific scoring criteria were used for assessment. Success in surgical technique, control of fecal soiling, and improvement in quality of life were evaluated. RESULTS: More than 85% of patients achieved maximal or near-maximal scores in all three categories. Postoperative complications remain a relevant concern when this procedure is undertaken, but we have found that significant postoperative complications are few and can be minimized by meticulous follow-up. CONCLUSIONS: Overall, the Malone antegrade continence enema procedure has been shown to be safe and highly effective. There is the potential for wider application in older age groups where sphincter and pelvic floor muscles have been compromised as a result of trauma or cancer surgery.