Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants.

Peripheral artery disease (PAD) is characterized by varying severity of arterial stenosis, exercise induced claudication, malperfused tissue precluding normal healing and skeletal muscle dysfunction. Revascularization interventions improve circulation, but post-reperfusion changes within the skeletal muscle are not well characterized. This study investigates if revascularization enhanced hemodynamics increases walking performance with concurrent improvement of mitochondrial function and reverses abnormal skeletal muscle morphological features that develop with PAD. Fifty-eight patients completed walking performance testing and muscle biopsy before and 6 months after revascularization procedures. Muscle fiber morphology, desmin structure, and mitochondria respiration assessments before and after the revascularization were evaluated. Revascularization improved limb hemodynamics, walking function, and muscle morphology. Qualitatively not all participants recovered normal structural architecture of desmin in the myopathic myofibers after revascularization. Heterogenous responses in the recovery of desmin structure following revascularization may be caused by other underlying factors not reversed with hemodynamic improvements. Revascularization interventions clinically improve patient walking ability and can reverse the multiple subcellular functional and structural abnormalities in muscle cells. Further study is needed to characterize desmin structural remodeling with improvements in skeletal muscle morphology and function.

Early experience with venous arterialization for limb salvage in no-option patients with chronic limb-threatening ischemia.

OBJECTIVE: Chronic limb-threatening ischemia (CLTI) is associated with adverse limb outcomes and increased mortality. However, a small subset of the CLTI population will have no feasible conventional methods of revascularization. In such cases, venous arterialization (VA) could provide an alternative for limb salvage. The objective of the present study was to review the outcomes of VA at our institution. METHODS: We performed a single-institution review of 41 patients who had been followed up prospectively and had undergone either superficial or deep VA. The data collected included patient demographics, comorbidities, VA technique (endovascular vs hybrid), and WIfI (wound, ischemia, and foot infection) limb staging. Data were collected at 1-month, 6-month, and 1-year intervals and included the following outcomes: patency, wound healing, major adverse limb events, major amputation, and death. Descriptive statistics were used for analysis. RESULTS: The study group included 41 patients who had undergone successful open hybrid superficial or deep endovascular VA; 21 (51.2%) had undergone a purely endovascular procedure and 20 (48.8%), hybrid VA. The WIfI clinical stage was as follows: stage 4, 33 (80.5%); stage 3, 6 (14.6%); and stage 2, 1 (2.4%). Of the 41 patients, 24 (58.5%) had completed follow-up at 6 months and 16 (39%) at 1 year. At 1 year, the VA primary patency was 28.6% (95% confidence interval [CI], 0.15%-0.43%), primary assisted patency was 44.3% (95% CI, 0.27%-0.60%), and secondary patency was 67% (95% CI, 0.49%-0.80%). The complete wound healing rate was 2.7% (n = 1) at 1 month, 62.5% (n = 15) at 6 months, and 18.8% (n = 3) at 1 year. Overall wound healing at 1 year was 46.3% (n = 19). The number of major adverse limb events at 1 year was 15 (36.5%) and included 8 reinterventions (19.5%) and 7 major amputations (17%). The number of deaths was zero (0%) at 1 month and four (19%) at 6 months. Two deaths (9.5%) were attributed to COVID-19 (coronavirus disease 2019). No further deaths had occurred within 1 year. The limb salvage survival probability at 1 year was 81%. CONCLUSIONS: These findings suggest that for a select subset of CLTI patients presenting with a high WIfI clinical limb stage and no viable options for conventional open or endovascular arterial revascularization, superficial and deep VA are feasible options to achieve limb salvage.

Extent of heel ulceration influences the outcomes in patients with isolated infrapopliteal limb threatening critical ischemia.

BACKGROUND: The aim of the present study was to assess the effects of the extent of heel ulceration on the outcomes of limb threatening critical ischemia due to isolated infrapopliteal disease. METHODS: A retrospective review identified 989 patients with isolated infrapopliteal disease and heel ulceration treated from 2001 to 2018. The heel was defined as the back of the foot, extending from the Achilles tendon to around the plantar surface and covering the apex of the calcaneum bone. Heel ulceration was categorized into three groups by area: <5 cm2, 5 to 10 cm2, and >10 cm2. The interventions were endovascular, open bypass, major amputation, and wound care. An intention-to-treat analysis by patient group was performed. The 30-day outcomes and amputation-free survival (AFS; survival without a major amputation) were evaluated. RESULTS: Of the 989 patients, 384 (58% male; average age, 65 years; n = 768 vessels) had undergone isolated endovascular tibial intervention, 124 (45% male; average age, 59 years) had undergone popliteal tibial vein bypass for limb threatening critical ischemia, 219 (52% male; average age, 67 years) had undergone major amputation, and 242 (49% male; average age, 66 years) had received wound care. No difference was found in the 30-day major adverse cardiac events in the endovascular and open bypass groups, with significantly more events in the major amputation group (P = .03). The 30-day major adverse limb events and 30-day amputation rates were equivalent between the open bypass and endovascular groups. The 5-year AFS rate was superior in the open bypass group (37% ± 8%; mean ± standard error of the mean) compared with the endovascular group (27% ± 9%; P = .04). The wound care group had a 5-year AFS rate of 20% ± 9%, which was not significantly different from that of the endovascular group. Patients with heel ulcers of <5 cm2 had better AFS (47% ± 8%) than those with 5- to 10- cm2 heel ulceration (24% ± 9%). Heel ulcers >10 cm2 were associated with markedly worse 5-year AFS outcomes (0% ± 0%). The presence of end-stage renal disease, osteomyelitis, uncontrolled diabetes (hemoglobin A1c >10%), and/or frailty combined with a heel ulcer >10 cm2 were predictive of poor AFS. CONCLUSIONS: An increasing heel ulcer area combined with osteomyelitis and systemic comorbidities was associated with worsening 30-day outcomes and 5-year AFS, irrespective of the therapy chosen.

Implications of early failure of isolated endovascular tibial interventions.

BACKGROUND: Endovascular tibial interventions for chronic limb-threatening ischemia are frequent, but the implications of early failure (≤30 days) of an isolated tibial intervention are still unclear. The aim of this study was to examine the patient-centered outcomes after early failure of isolated tibial artery intervention. METHODS: A database of patients undergoing lower extremity endovascular interventions between 2007 and 2017 was retrospectively queried. Patients with chronic limb-threatening ischemia (Rutherford classes 4, 5, and 6) were selected, and failures within 30 days were identified. Lack of technical success at the time of the procedure was an exclusion. Intention-to-treat analysis by patient was performed. Patient-oriented outcomes of clinical efficacy (absence of recurrent symptoms, maintenance of ambulation, and absence of major amputation), amputation-free survival (survival without major amputation), and freedom from major adverse limb events (MALEs; above-ankle amputation of the index limb or major reintervention [new bypass graft, jump or interposition graft revision]) were evaluated. RESULTS: There were 1779 patients (58% male; average age, 65 years; 2898 vessels) who underwent tibial intervention for chronic limb-threatening ischemia; 284 procedures (16%) were early failures. In the early failure group, 124 cases (44%) were considered immediate (<24 hours), and 160 cases (56%) failed within the first 30 days after intervention. The two modes of failure were hemodynamic failure (47%) and progression of chronic limb-threatening ischemia (53%). Bypass after early failure was successful in patients with adequate vein, target vessel of ≥3 mm, and good inframalleolar runoff. Progression of symptoms was associated with major amputation in patients with Rutherford class 5 and class 6 disease. Presentation with diabetes and end-stage renal disease were identified as independent clinical predictors for early failure. Lesion calcification, reference vessel diameter <3 mm, lesion length >300 mm, and poor inframalleolar runoff were identified as independent anatomic predictors for early failure and increased MALEs. Early failure was predictive of poor long-term clinical efficacy (11% ± 9% vs 39% ± 8% at 5 years, mean ± standard error of the mean, early vs no early failure; P = .01) and amputation-free survival (16% ± 9% vs 47% ± 9% at 5 years, mean ± standard error of the mean, early vs no early failure; P = .02). CONCLUSIONS: Both clinical and anatomic factors can predict early failure of endovascular therapy for isolated tibial disease. Early failure significantly increases 30-day major amputation and 30-day MALEs and is associated with poor long-term patient-centered outcomes.

Short-term contemporary outcomes for staged versus primary lower limb amputation in diabetic foot disease.

BACKGROUND: Major lower extremity amputations remain among the most common procedures performed by vascular surgeons in patients with diabetes and its associated peripheral vascular disease. After major amputation, this population commonly suffers from high readmission rates, increased wound complications, and conversion to more proximal major amputations. These events impact quality in terms of cost, resources, and subjective quality of life. The aim of this study is to compare outcomes between primary lower extremity above-ankle amputations (primary amputation [PA]) and staged ankle guillotine amputations followed by interval formalization to an above-ankle amputation (staged amputation [SA]) for nonsalvageable infected diabetic foot disease. METHODS: A retrospective review of all de novo major lower extremity amputations performed by the vascular surgery service at a single institution between January 2014 and March 2017 was performed. Inclusion criteria were diabetic patients with foot gangrene who underwent a major de novo above- or below-knee amputation. Amputations for trauma, acute limb ischemia, or malignancy were excluded. Per institutional practice, SA was performed for uncontrolled infection and/or infection with uncontrolled diabetes, and PA was performed in the absence of active infection and in stable diabetes. The primary outcome measure was 30-day freedom from conversion to a higher level amputation. Secondary outcome measures were 30-day stump complications, 30-day readmissions, 30-day major adverse cardiovascular events, and 30-day mortality. RESULTS: One hundred sixteen patients met the inclusion criteria. Sixty-eight percent were male, 18% were active smokers, 30% had end-stage renal disease, and 22% had congestive heart failure. Sixty-one patients underwent SA, and 55 patients underwent PA. The two cohorts were well-matched by demographics and comorbidities. Consistent with the institutional practice, 57% of SA patients met two or more systemic inflammatory response syndrome criteria at presentation compared with 24% of PA patients (P = .0003). There were no 30-day mortalities. There was no significant difference in major adverse cardiovascular events between the groups (2% vs 4%; SA vs PA, respectively; P = .6). The average length of stay did not significantly differ between SA and PA (mean of 14 ± 8 days vs 11 ± 11 days; P = .1). SA patients had a lower rate of 30-day readmission (7% vs 27%; P = .005) and 30-day unplanned conversion to higher level amputation (2% vs 13%; P = .026) compared with PA patients. CONCLUSIONS: In the setting of infected diabetic foot disease, a staged lower extremity amputation achieves quality outcomes superior to a one-stage amputation, despite the former cohort's greater illness acuity level. SA should be considered in all diabetic patients presenting with active foot infection.

A prospective randomized study of the efficacy of "Turning Point," an inpatient violence intervention program.

BACKGROUND: From 2002 to 2011, there were more than 17,000 shootings in Philadelphia. "Turning Point," Temple University Hospital's inpatient violence intervention program, takes advantage of the teachable moment that occurs after violent injury. In addition to receiving traditional social work services, Turning Point patients watch their trauma bay resuscitation video and a movie about violence, meet with a gunshot wound survivor and an outpatient case manager, and also undergo psychiatric assessment. The purpose of this study was to determine the efficacy of Turning Point in changing attitudes toward guns and violence among victims of penetrating trauma. METHODS: This prospective randomized study was conducted from January 2012 to January 2014. Patients who sustained a gunshot or stab wound were randomized to standard of care, which involved traditional social work services only, or Turning Point. The Attitudes Toward Guns and Violence Questionnaire was administered to assess attitude change. Analysis was performed with repeated-measures analysis of variance. A p < 0.05 was significant. RESULTS: A total of 80 of a potential 829 patients completed the study (40 standard of care, 40 Turning Point). The most common reason for exclusion was anticipated length of stay being less than 48 hours. The two groups were similar with respect to most demographics. Unlike the standard-of-care group, the Turning Point group demonstrated a 50% reduction in aggressive response to shame, a 29% reduction in comfort with aggression, and a 19% reduction in overall proclivity toward violence. CONCLUSIONS: Turning Point is effective in changing attitudes toward guns and violence among victims of penetrating trauma. Longer follow-up is necessary to determine if this program can truly be a turning point in patients' lives. LEVEL OF EVIDENCE: Therapeutic/care management study, level II.

"Permissive hypoventilation" in a swine model of hemorrhagic shock.

BACKGROUND: Many penetrating trauma patients in severe hemorrhagic shock receive positive pressure ventilation (PPV) upon transport to definitive care, either by intubation (INT) or bag-valve mask (BVM). Using a swine hemorrhagic shock model that simulates penetrating trauma, we proposed that severely injured patients may have better outcomes with "permissive hypoventilation," where manual breaths are not given and oxygen is administrated passively via face mask (FM). We hypothesized that PPV has harmful physiologic effects in severe low-flow states and that permissive hypoventilation would result in better outcomes. METHODS: The carotid arteries of Yorkshire pigs were cannulated with a 14-gauge catheter. One group of animals (n = 6) was intubated and manually ventilated, a second received PPV via BVM (n = 7), and a third group received 100% oxygen via FM (n = 6). After placement of a Swan-Ganz catheter, the carotid catheters were opened, and the animals were exsanguinated. The primary end point was time until death. Secondary end points included central venous pressure, cardiac output, lactate levels, serum creatinine, CO2 levels, and pH measured in 10-minute intervals. RESULTS: Average survival time in the FM group (50.0 minutes) was not different from the INT (51.1 minutes) and BVM groups (48.5 minutes) (p = 0.84). Central venous pressure was higher in the FM group as compared with the INT 10 minutes into the shock phase (8.3 mm Hg vs. 5.2 mm Hg, p = 0.04). Drop in cardiac output (p < 0.001) and increase in lactate (p < 0.05) was worse in both PPV groups throughout the shock phase. Creatinine levels were higher in both PPV groups (p = 0.04). The FM group was more hypercarbic and acidotic than the two PPV groups during the shock phase (p < 0.001). CONCLUSION: Although permissive hypoventilation leads to respiratory acidosis, it results in less hemodynamic suppression and better perfusion of vital organs. In severely injured penetrating trauma patients, consideration should be given to immediate transportation without PPV.

Cyclical pattern of non-nutritive sucking in normal and high-risk neonates

En este trabajo se determinaron patrones de ciclos de succión mediante registros de la presión de succión en recién nacidos a término, prematuro normal y recién nacido con patología(hipoxia al nacer). Además, se establecieron asociaciones entreestos patrones y algunos parámetros clínicos, con el propósito de valorar la capacidad de alimentación, para orientar la estimulación específica y favorecer el alta de internación en mejorescondiciones de salud. Se evaluó a 75 neonatos de ambos sexos con consentimiento firmado, agrupados según su condición al nacer. Se determinó el peso corporal y el scorede Apgar. Se obtuvieron los registros de valores máximos y mínimos de presión utilizando un aparato “ad-hoc” (de presión-succión) que permitió medir el número de ciclos de succión. Los datos fueron analizados estadísticamente con un nivel de significación p<0.05. Los valores máximos de presiónsucciónpresentaron variaciones entre los grupos analizados. Los valores más altos de presión y el mayor número de ciclos de succión se observó en nacidos a término. Los prematuros mostraron valores de presión más bajos y menor cantidad de ciclos de succión, lo que posibilitó establecer un patrón específicopara estos grupos. Los hipoxiados exhibieron una gran variabilidad en ambos parámetros. En los neonatos normales y pretérmino hubo una correlación directa y significativa entrelos ciclos de succión y los valores de Apgar a los cinco minutos. El grupo de recién nacidos con patología debido a hipoxia no mostró la misma asociación. Estos resultados constituyen unaimportante herramienta que contribuirá a mejorar la nutrición materna neonatal y optimizar la calidad de vida de los recién nacidos de alto riesgo en nuestro medio